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Sample records for human consensus interferon-alpha

  1. Secretion of human interferon alpha 2b by Streptomyces lividans.

    Science.gov (United States)

    Pimienta, E; Fando, R; Sánchez, J C; Vallin, C

    2002-02-01

    Biologically active human interferon alpha 2b (HuIFNalpha-2b) was secreted into the culture medium by Streptomyces lividans transformed with recombinant plasmids coding for HuIFNalpha-2b fused to the Streptomyces exfoliatus M11 lipase A signal sequence. Levels were low, 15 or 100 ng/ml, depending on the plasmid used. Neither processed nor unprocessed HuIFNalpha-2b was detected in cell lysates of the transformants secreting the recombinant product. However, the secreted recombinant product was found to partially degrade when cultures reached the stationary phase by the action of an, as yet, unidentified mycelium-associated factor. Experimental evidence suggests that the degrading factor is related to mycelium-associated proteolytic activity.

  2. 78 FR 46593 - Prospective Grant of Start-up Exclusive License: Kits for the Detection of Human Interferon-Alpha...

    Science.gov (United States)

    2013-08-01

    ... the Detection of Human Interferon-Alpha Subtypes and Allotypes AGENCY: National Institutes of Health...-2008/0), titled ``Compositions for Detecting Human Interferon- Alpha Subtypes and Methods of Use'', to.... This technology relates to use of kits for the detection of human interferon-alpha subtypes and...

  3. MOLECULAR CLONING AND HETEROLOGOUS EXPRESSION OF HUMAN INTERFERON ALPHA2b GENE

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    I. Made Artika

    2013-01-01

    Full Text Available Human alpha Interferons (hIFNα have been shown to have antiviral, antiproliferative and immunomodulatory activities. The human interferon alpha2b (hIFNα2b, is one of the human interferon alpha2 sub variants, naturally synthesized as a polypeptide of 188 amino acid residues, the first 23 residues of which represents a signal peptide. In the present study, the hIFNα2b gene was expressed after being fused with Glutathione S-Transferase (GST gene. The hIFNα2b gene was amplified from human genomic DNA by using a pair of specific primers, cloned into an Escherichia coli expression vector and expressed in E. coli cells under the direction of the tac promoter. The expressed protein was purified using a one-step affinity chromatography column containing immobilized gluthatione-bound resin. The purified protein was shown to react specifically with anti-human-interferon-alpha antibody, confirming that the protein was the human interferon alpha molecule. This strategy has the potential to be used as an alternative mean for production of pure human interferon α proteins for therapeutic purposes and for further studies on their molecular characterization and mechanism of action.

  4. Expression of biologically active human interferon alpha 2 in aloe vera

    Science.gov (United States)

    We have developed a system for transgenic expression of proteins in Aloe Vera. Using this approach we have generated plants expressing the human gene interferon alpha 2, IFNa2. IFNa2 is a small secreted cytokine that plays a vital role in regulating the body’s immune response to viral infections a...

  5. Interferon-alpha induces transient suppressors of cytokine signalling expression in human T cells

    DEFF Research Database (Denmark)

    Brender, C; Nielsen, M; Röpke, C;

    2001-01-01

    The suppressors of cytokine signalling (SOCS) proteins comprise a newly identified family of negative feedback regulators of cytokine signalling. SOCS expression is differentially induced upon cytokine stimulation in different cell types. Here we show that interferon-alpha (IFNalpha) is a potent...... induction neither CIS, SOCS-1, nor SOCS-2 expression levels declined after 6 h. In conclusion, we provide the first evidence that IFNalpha induces SOCS expression in human T cells. Moreover, we show that IFNalpha and IL-2 induce distinct patterns of expression kinetics, suggesting that dynamic changes...

  6. Synergism between human tumor necrosis factor and human interferon-alpha: effects on cells in culture.

    Science.gov (United States)

    Orita, K; Ando, S; Kurimoto, M

    1987-08-01

    The cytostatic and cytotoxic effects of highly purified natural human tumor necrosis factor (HuTNF-alpha) and natural human interferon-alpha (HuIFN-alpha) on 23 cell lines were studied in vitro. Natural HuTNF-alpha showed cytostatic and cytotoxic effects on PC-9, KHG-2, HT-1197, KG-1 and L-929 cells, and HuIFN-alpha showed both effects on KHG-2 and Daudi cells. A mixture of HuTNF-alpha and HuIFN-alpha (1:1, by unit) showed cytostatic and cytotoxic effects on HuTNF-alpha- or HuIFN-alpha-resistant cell lines such as KB, KATO-III, HEp-2, P-4788, as well as on HuTNF-alpha- or HuIFN-alpha-susceptible cells. Thus, the combined preparation of HuTNF-alpha and HuIFN-alpha expanded the spectrum of sensitive cells. The dosage of the mixed preparation required to produce 50% inhibition of cell growth was less than 20% of that of HuTNF-alpha or HuIFN-alpha alone. These results indicate that the cytostatic and cytotoxic effects of HuTNF-alpha and HuIFN-alpha are synergistically enhanced when they are administered together.

  7. Synergism between human tumor necrosis factor and human interferon-alpha: effects on cells in culture.

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    Orita,Kunzo

    1987-08-01

    Full Text Available The cytostatic and cytotoxic effects of highly purified natural human tumor necrosis factor (HuTNF-alpha and natural human interferon-alpha (HuIFN-alpha on 23 cell lines were studied in vitro. Natural HuTNF-alpha showed cytostatic and cytotoxic effects on PC-9, KHG-2, HT-1197, KG-1 and L-929 cells, and HuIFN-alpha showed both effects on KHG-2 and Daudi cells. A mixture of HuTNF-alpha and HuIFN-alpha (1:1, by unit showed cytostatic and cytotoxic effects on HuTNF-alpha- or HuIFN-alpha-resistant cell lines such as KB, KATO-III, HEp-2, P-4788, as well as on HuTNF-alpha- or HuIFN-alpha-susceptible cells. Thus, the combined preparation of HuTNF-alpha and HuIFN-alpha expanded the spectrum of sensitive cells. The dosage of the mixed preparation required to produce 50% inhibition of cell growth was less than 20% of that of HuTNF-alpha or HuIFN-alpha alone. These results indicate that the cytostatic and cytotoxic effects of HuTNF-alpha and HuIFN-alpha are synergistically enhanced when they are administered together.

  8. Influence of carbohydrates on the stability and structure of a hyperglycosylated human interferon alpha mutein.

    Science.gov (United States)

    Ceaglio, Natalia; Etcheverrigaray, Marina; Kratje, Ricardo; Oggero, Marcos

    2010-08-01

    Protein physical and chemical instability is one of the major challenges in the development of biopharmaceuticals during every step of the process, ranging from production to final delivery. This is particularly applicable to human recombinant interferon alpha-2b (rhIFN-alpha2b), a pleiotropic cytokine currently used worldwide for the treatment of various cancer and chronic viral diseases, which presents a poor stability in solution. In previous studies, we have demonstrated that the introduction of four N-glycosylation sites in order to construct a heavily glycosylated IFN variant (4N-IFN) resulted in a markedly prolonged plasma half-life which was reflected in an enhanced therapeutic activity in mice in comparison with the commercial non-glycosylated rhIFN-alpha2b (NG-IFN). Herein, we evaluated the influence of glycosylation on the in vitro stability of 4N-IFN towards different environmental conditions. Interestingly, the hyperglycosylated cytokine showed enhanced stability against thermal stress, acid pH and repetitive freeze-thawing cycles in comparison with NG-IFN. Besides, microcalorimetric analysis indicated a much higher melting temperature of 4N-IFN, also demonstrating a higher solubility of this variant as denoted by the absence of precipitation at the end of the experiment, in contrast with the NG-IFN behaviour. Furthermore, far-UV circular dichroism (CD) spectrum of 4N-IFN was virtually superimposed with that of NG-IFN, indicating that the IFN structure was not altered by the addition of carbohydrate moieties. The same conclusion could be inferred from limited proteolysis studies. Our results suggest that glycoengineering could be a useful strategy for protecting rhIFN-alpha2b from inactivation by various external factors and for overcoming aggregation problems during the production process and storage.

  9. Extended interferon-alpha therapy accelerates telomere length loss in human peripheral blood T lymphocytes.

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    Joel M O'Bryan

    Full Text Available BACKGROUND: Type I interferons have pleiotropic effects on host cells, including inhibiting telomerase in lymphocytes and antiviral activity. We tested the hypothesis that long-term interferon treatment would result in significant reduction in average telomere length in peripheral blood T lymphocytes. METHODS/PRINCIPAL FINDINGS: Using a flow cytometry-based telomere length assay on peripheral blood mononuclear cell samples from the Hepatitis-C Antiviral Long-term Treatment against Cirrhosis (HALT-C study, we measured T cell telomere lengths at screening and at months 21 and 45 in 29 Hepatitis-C virus infected subjects. These subjects had failed to achieve a sustained virologic response following 24 weeks of pegylated-interferon-alpha plus ribavirin treatment and were subsequently randomized to either a no additional therapy group or a maintenance dose pegylated-IFNα group for an additional 3.5 years. Significant telomere loss in naïve T cells occurred in the first 21 months in the interferon-alpha group. Telomere losses were similar in both groups during the final two years. Expansion of CD8(+CD45RA(+CD57(+ memory T cells and an inverse correlation of alanine aminotransferase levels with naïve CD8(+ T cell telomere loss were observed in the control group but not in the interferon-alpha group. Telomere length at screening inversely correlated with Hepatitis-C viral load and body mass index. CONCLUSIONS/SIGNIFICANCE: Sustained interferon-alpha treatment increased telomere loss in naïve T cells, and inhibited the accumulation of T cell memory expansions. The durability of this effect and consequences for immune senescence need to be defined.

  10. Use of recombinant human interferon alpha-2a in the management of a dog with epitheliotropic lymphoma.

    Science.gov (United States)

    Tzannes, Sophia; Ibarrola, Patricia; Batchelor, Daniel J; Burrow, Rachel D; Blackwood, Laura

    2008-01-01

    An 8-year-old, mixed-breed dog with preputial epitheliotropic lymphoma was initially treated with cyclophosphamide, vincristine, and prednisolone. A short-term partial response was followed by disease progression after 4 weeks. Recombinant human interferon alpha-2a was administered starting at week 7. The interferon therapy resulted in rapid resolution of clinical signs and a 10-week disease-free interval. The lymphoma recurred at 17 weeks and did not respond to rescue chemotherapy. Additional oral lesions were treated with localized radiotherapy followed by increased dosages of interferon. This additional interferon treatment resulted in another 12 weeks of stable disease.

  11. Evaluation of Adverse Effects of Mutein Forms of Recombinant Human Interferon Alpha-2b in Female Swiss Webster Mice

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    H. Rachmawati

    2013-01-01

    Full Text Available Purpose. We successfully developed recombinant human interferon alpha-2b (rhIFN-α2b and mutein forms through the site-directed mutagenesis technique. The mutein forms were developed by substituting cysteins at positions 2 and 99 with aspartic acids. The potential adverse effects of these rhIFN-α2bs were assessed by acute and subchronic studies. Methods. In the acute study, rhIFN-α2bs were subcutaneously administered to mice at a single dose of 97.5 μg/kg, 975 μg/kg, and 9.75 mg/kg BW and were observed for 14 days. In the subchronic study, single dose of 1.95 μg/kg and 19.5 μg/kg, respectively, was given subcutaneously every 3 days for 45 days. Results. No death as well as abnormality in body weight, behavior, presentation of main organs, and value of plasma SGPT and SGOT was observed. Wild type and mutein rhIFN-α2bs did not show significant adverse effects at dose up to 9.75 mg/kg BW. Administration of these rhIFN-α2bs given repeatedly did not induce any adverse effect. Conclusion. These results suggest that our rhIFN-α2bs are safe. However, further study is still needed to clarify the safety issue before use in clinical trial.

  12. Interferon alpha2 recombinant and epidermal growth factor modulate proliferation and hypusine synthesis in human epidermoid cancer KB cells.

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    Caraglia, M; Passeggio, A; Beninati, S; Leardi, A; Nicolini, L; Improta, S; Pinto, A; Bianco, A R; Tagliaferri, P; Abbruzzese, A

    1997-06-15

    We previously found that interferon alpha2 recombinant (IFNalpha) increases the expression of epidermal growth factor receptor (EGF-R) in the human epidermoid cancer KB cell line. Here we report the effects of IFNalpha and epidermal growth factor (EGF) on KB cell cycle kinetics. IFNalpha (1000 i.u./ml) for 48 h decreased the S-phase fraction and diminished the expression of Ki67 and proliferating cell nuclear antigen on KB cells. Incubation of IFNalpha-treated KB cells with 10 nM EGF for 12 h reversed these effects. We then studied several biochemical markers of cell proliferation. Ornithine decarboxylase activity was decreased to about one-tenth by IFNalpha and partly restored by EGF. Hypusine is contained only in eukaryotic initiation factor 5A and its levels are correlated with cell proliferation. IFNalpha decreased hypusine synthesis by 75%; exposure of cells to EGF for 12 h restored hypusine synthesis almost completely. We also studied the effects of IFNalpha on the cytotoxicity of the recombinant toxin TP40, which inhibits elongation factor 2 through EGF-R binding and internalization. IFNalpha greatly enhanced the TP40-induced inhibition of protein synthesis in KB cells. In conclusion, IFNalpha, which affects protein synthesis machinery and increases EGF-R expression, enhances the tumoricidal activity of TP40 and hence could be useful in the setting of anti-cancer therapy.

  13. Immunostimulatory effects of natural human interferon-alpha (huIFN-alpha) on carps Cyprinus carpio L.

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    Watanuki, Hironobu; Chakraborty, Gunimala; Korenaga, Hiroki; Kono, Tomoya; Shivappa, R B; Sakai, Masahiro

    2009-10-15

    Human interferon-alpha (huIFN-alpha) is an important immunomodulatory substance used in the treatment and prevention of numerous infectious and immune-related diseases in animals. However, the immunostimulatory effects of huIFN-alpha in fish remain to be investigated. In the current study, the immune responses of the carp species Cyprinus carpio L. to treatment with huIFN-alpha were analyzed via measurement of superoxide anion production, phagocytic activity and the expression of cytokine genes including interleukin-1beta, tumor necrosis factor-alpha and interleukin 10. Low doses of huIFN-alpha were administered orally once a day for 3 days, and sampling was carried out at 1, 3 and 5 days post-treatment. Our results indicate that a low dose of huIFN-alpha significantly increased phagocytic activity and superoxide anion production in the carp kidney. The huIFN-alpha-treated fish also displayed a significant upregulation in cytokine gene expression. The current study demonstrates the stimulatory effects of huIFN-alpha on the carp immune system and highlights the immunomodulatory role of huIFN-alpha in fish.

  14. Interferon-alpha-2a is a potent inhibitor of hormone secretion by cultured human pituitary adenomas

    NARCIS (Netherlands)

    L.J. Hofland (Leo); W.W. de Herder (Wouter); M. Waaijers (Marlijn); J. Zuijderwijk; P. Uitterlinden (Piet); P.M. van Koetsveld (Peter); S.W.J. Lamberts (Steven)

    1999-01-01

    textabstractInterferon-alpha (IFN alpha) may exert direct inhibitory effects on cell proliferation and on the production of different peptide hormones. We investigated the effect of IFN alpha on hormone production by 15 GH-secreting pituitary adenomas, 4 clinically nonf

  15. 13 native human interferon-alpha species assessed for immunoregulatory properties

    DEFF Research Database (Denmark)

    Heron, I; Hokland, M; Berg, K

    1983-01-01

    Human leukocytes treated with Sendai virus yield interferon predominantly of the alpha-type (HuIFN-alpha). Successful attempts to purify these "native" species have been performed and the final analysis, which included an SDS-PAGE disclosed 13 stained and separated IFN-proteins in the molecular w...

  16. Interferon alpha regulates MAPK and STAT1 pathways in human hepatoma cells

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    Ren Hao

    2011-04-01

    Full Text Available Abstract Background Signaling events triggered by interferon (IFN account for the molecular mechanisms of antiviral effect. JAK-STAT pathway plays a critical role in IFN signaling, and other pathways are also implicated in IFN-mediated antiviral effect. Changes in mitogen-activated protein kinase (MAPK and STAT1 pathways were evaluated in human hepatoma cells Huh7 and HepG2 upon IFN alpha treatment. Results Phosphorylation of ERK was significantly and specifically up-regulated, whereas enhanced phosphorylation of upstream kinase MEK was unobservable upon IFN alpha treatment. A mild increase in p38 MAPK, SAPK/JNK and downstream target ATF-2 phosphorylation was detectable after exposure to IFN alpha, indicating differential up-regulation of the MAPK signaling cascades. Moreover, STAT1 phosphorylation was strongly enhanced by IFN alpha. Conclusion IFN alpha up-regulates MAPK and STAT1 pathways in human hepatoma cells, and may provide useful information for understanding the IFN signaling.

  17. Enhanced expression in vivo of HLA-ABC antigens and beta 2-microglobulin on human lymphoid cells induced by human interferon-alpha in patients with lung cancer. Enhanced expression of class I major histocompatibility antigens prior to treatment

    DEFF Research Database (Denmark)

    Nissen, Mogens Holst; Plesner, T; Larsen, J K

    1985-01-01

    The effect of cloned human interferon-alpha (IFN-alpha) on the expression of HLA-ABC antigens (HLA-ABC) and beta 2-microglobulin (beta 2m) on human peripheral lymphoid cells in vivo was studied by cytofluorometry using monoclonal antibodies and fluorescein-labelled rabbit anti-mouse immunoglobulin...

  18. MicroRNA Expression Profiling by Bead Array Technology in Human Tumor Cell Lines Treated with Interferon-Alpha-2a

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    Siegrist Fredy

    2009-01-01

    Full Text Available Abstract MicroRNAs are positive and negative regulators of eukaryotic gene expression that modulate transcript abundance by specific binding to sequence motifs located prevalently in the 3' untranslated regions of target messenger RNAs (mRNA. Interferon-alpha-2a (IFNα induces a large set of protein coding genes mediating antiproliferative and antiviral responses. Here we use a global microarray-based microRNA detection platform to identify genes that are induced by IFNα in hepatoma- or melanoma-derived human tumor cell lines. Despite the enormous differences in expression levels between these models, we were able to identify microRNAs that are upregulated by IFNα in both lines suggesting the possibility that interferon-regulated microRNAs are involved in the transcriptional repression of mRNA relevant to cytokine responses.

  19. Overproduction, purification and characterization of human interferon alpha2a-human serum albumin fusion protein produced in methilotropic yeast Pichia pastoris

    Science.gov (United States)

    Ningrum, R. A.; Santoso, A.; Herawati, N.

    2017-05-01

    Human interferon alpha2a (hIFNα2a) is a therapeutic protein that used in cancer and hepatitis B/C therapy. The main problem of using hIFNα-2a is its short elimination half life due to its low molecular weight. Development of higher molecular weight protein by albumin fusion technology is a rational strategy to solve the problem. In our previous research we constructed an open reading frame (ORF) encoding hIFNα2a-human serum albumin (HSA) fusion protein that expressed in Pichia pastoris (P. pastoris) protease deficient strain SMD1168. This research was performed to overproduce, purify and characterize the fusion protein. To overproduce the protein, cultivation was performed in buffered complex medium containing glyserol (BMGY) for 24 h and protein overproduction was applied in buffered complex medium containing methanol (BMMY) for 48 hours at 30°C. The fusion protein was purified by blue sepharose affinity chromatography. Molecular weight characterization by SDS PAGE corresponds with its theoretical size, 85 kDa. Western blot analysis demonstrated that the fusion protein was recognized by anti hIFNα2 and anti HSA monoclonal antibody as well. Amino acid sequence of the fusion protein was determined by LC MS/MS2 mass spectrometry with trypsin as proteolitic enzyme. There were three fragments that identified as hIFNα2a and seven fragments that identified as HSA. Total identified amino acids were 150 residues with 20% coverage from total residues. To conclude, hIFNα2a-HSA fusion protein was overproduced, purified and characterized. Characterization based on molecular weight, antibody recognition and amino acid sequence confirmed that the fusion protein has correct identity as theoretically thought.

  20. [Interferon alpha antibodies show no cross reactions with typical autoantibodies].

    Science.gov (United States)

    Görg, S; Klouche, M; Wilhelm, D; Kirchner, H

    1993-04-01

    Patients treated with natural human interferon alpha develop anti-interferon antibodies (IFN-AB) only in very rare cases. By contrast, patients with autoimmune disorders are able to generate high-titered IFN-AB against endogenous interferon alpha. One explanation for the development of auto-IFN-AB could be cross-reactivity with typical autoimmune antigens. We investigated the cross-reactivity of 3 high-titered IgG IFN-AB of female autoimmune patients (aged 32, 36, 74 years; two severe cases of SLE, one case of autoimmune thyroiditis) as well as 25 low-titered natural IgM IFN-AB of healthy blood donors (aged 19-48 years). Typical autoimmune antigens including dsDNA, ENA, as well as natural interferon beta and recombinant interferon gamma are not able to inhibit binding of IFN-AB to interferon alpha in an ELISA test system. Preincubation of sera containing either dsDNA antibodies (dsDNA-AB) (24 patients), thyroid peroxidase (TPO-AB) (9 patients) or thyroglobulin (TG-AB) (12 patients) with interferon alpha resulted in no change in the respective autoantibody titer. These data suggest that there is no cross-reactivity between IFN-alpha-AB and dsDNA-AB, TPO-AB or TG-AB. Thus, an explanation for the occurrence of IFN-AB in autoimmune disorders cannot be found in a cross-reaction between interferon alpha with typical autoimmune antigens.

  1. Anti-hepatitis B virus activity and mechanisms of recombinant human serum albumin-interferon-alpha-2b fusion protein in vitro and in vivo.

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    Bingfa, Xu; Qinglin, Fan; Hui, Huang; Canjun, Wang; Wei, Wei; Lihua, Song

    2009-01-01

    To evaluate the anti-hepatitis B virus (anti-HBV) effects and mechanisms of recombinant human serum albumin-interferon-alpha-2b fusion protein (rHSA-IFNalpha-2b) in vitro and in vivo. The inhibiting effects on HBV replication were examined in the HepG2 2.2.15 cell line and in ducks, and the expressions of signal transducers and transactivator 1 (STAT1), IFN-stimulated gene factor 3 (ISGF3) and 2',5'-oligoadenylate synthetase 1 (OAS1) were investigated by the reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis. In vitro,at concentrations from 0.075 to 1.2 nmol/l, rHSA-IFNalpha-2b inhibited the releases of extracellular hepatitis B surface antigen, hepatitis B e antigen and HBV DNA in a dose-dependent manner; rHSA- IFNalpha-2b also increased the levels of STAT1, ISGF3 and OAS1. In vivo, rHSA-IFNalpha-2b reduced the levels of alanine aminotransferase, aspartate aminotransferase, total bilirubin and duck hepatitis B virus (DHBV) DNA in the sera of DHBV-infected ducks. We provide the first evidence that rHSA-IFNalpha-2b significantly inhibits HBV replication in HepG2 2.2.15 cells and in ducks, and that the antiviral effect of rHSA-IFNalpha-2b in vivo is more potent than that of IFNalpha-2b. The anti-HBV mechanism probably operates by triggering the JAK-STAT signaling pathway and increasing the expression of OAS1. Copyright 2009 S. Karger AG, Basel.

  2. Antitumor effects of human interferon-alpha 2b secreted by recombinant bacillus Calmette-Guérin vaccine on bladder cancer cells

    Institute of Scientific and Technical Information of China (English)

    Guo-qing DING; Yan-lan YU; Zhou-jun SHEN; Xie-lai ZHOU; Shan-wen CHEN; Guo-dong LIAO; Yue ZHANG

    2012-01-01

    Objective:Our objective was to construct a recombinant bacillus Calmette-Guénn vaccine (rBCG) that secretes human interferon-alpha 2b (IFNα-2b) and to study its immunogenicity and in vitro antitumor activity against human bladder cancer cell lines T24 and T5637.Methods:The signal sequence BCG Ag85B and the gene IFNα-2b were amplified from the genome of BCG and human peripheral blood,respectively,by polymerase chain reaction (PCR).The two genes were cloned in Escherichia coli-BCG shuttle-vector pMV261 to obtain a new recombinant plasmid pMV261-Ag85B-IFNα-2b.BCG was transformed with the recombinant plasmid by electroporation and designated rBCG-IFNα-2b.Mononuclear cells were isolated from human peripheral blood (PBMCs) and stimulated with rBCG-IFNα-2b or wild type BCG for 3 d,and then cultured with human bladder cancer cell lines T24 and T5637.Their cytotoxicities were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay.Results:BCG was successfully transformed with the recombinant plasmid pMV261-Ag85B-IFNα-2b by electroporation and the recombinant BCG (rBCG-IFNα-2b) was capable of synthesizing and secreting cytokine IFNα-2b.PBMC proliferation was enhanced significantly by rBCG-IFNα-2b,and the cytotoxicity of PBMCs stimulated by rBCG-IFNα-2b to T24 and T5627 was significantly stronger in comparison to wild type BCG.Conclusions:A recombinant BCG,secreting human IFNα-2b (rBCG-IFNα-2b),was constructed successfully and was superior to control wild type BCG in inducing immune responses and enhancing cytotoxicity to human bladder cancer cell lines T24 and T5637.This suggests that rBCG-IFNα-2b could be a promising agent for bladder cancer patients in terms of possible reductions in both clinical dosage and side effects of BCG immunotherapy.d enhancng c

  3. Interferon-alpha caused reversible parkinsonism.

    Science.gov (United States)

    Lu, Chieh-Sheng; Kao, Wei-Yau; Lin, Jiann-Chyun; Chang, Ping-Ying

    2015-01-01

    Interferon has been used to treat chronic viral hepatitis and several malignancies. However, it may cause various neuropsychiatric adverse effects including parkinsonism. We report a rare case of interferon alpha-2a therapy-related parkinsonism in a 67-year-old man with metastatic papillary renal cell carcinoma and our experience of using Tc-99m-TRODAT-1 single photon emission computed tomography (SPECT) as a tool for evaluation of parkinsonism. Physicians should be alert to the possibility of interferon alpha-2a-related parkinsonism.

  4. Interferon alpha association with neuromyelitis optica

    DEFF Research Database (Denmark)

    Asgari, Nasrin; Voss, Anne; Steenstrup, Troels;

    2013-01-01

    Interferon-alpha (IFN- α ) has immunoregulatory functions in autoimmune inflammatory diseases. The goal of this study was to determine occurrence and clinical consequences of IFN- α in neuromyelitis optica (NMO) patients. Thirty-six NMO and 41 multiple sclerosis (MS) patients from a population...

  5. Interferon-alpha induced Raynaud's syndrome.

    Science.gov (United States)

    Kruit, W H; Eggermont, A M; Stoter, G

    2000-11-01

    The cytokine interferon-alpha (IFN-alpha) is increasingly prescribed for a number of indications, especially viral hepatitis and several malignancies. Two patients are described who developed Raynaud's syndrome during treatment with IFN-alpha as adjuvant therapy for high-risk melanoma. With a review of the available literature the symptomatology, possible pathophysiologic mechanisms and treatment options are discussed.

  6. Induced and down-regulated proteins in the human cultured hairy cell leukemia line JOK-1 and the Burkitt's lymphoma cell line Daudi during incubation with interferon-alpha: a kinetic study

    DEFF Research Database (Denmark)

    Madsen, P S; Nielsen, B; Jensen, A W

    1992-01-01

    To elucidate the mechanism of action of interferon-alpha (IFN-alpha), the effect on cell proliferation and protein synthesis in the human hairy cell leukemia line JOK-1 and the Burkitt's lymphoma cell line Daudi were investigated. While Daudi cells were inhibited in proliferation and in total...... that the changes in JOK-1 cells were only temporary (within 8-16 h) and small to moderate in magnitude (less than four-fold). In Daudi cells, the changes for two of these polypeptides were early (within 2 h), for most of them prolonged (at least 24 h), and for three of them of great magnitude (between 6- and 30...... protein synthesis, no effect was seen on JOK-1 cells. However, high-resolution two-dimensional gel electrophoresis showed that four polypeptides were induced in JOK-1 cells after IFN-alpha incubation, while an additional 11 were induced and two down-regulated in Daudi cells. Kinetic studies revealed...

  7. Differential involvement of 5-HT(1A) and 5-HT(1B/1D) receptors in human interferon-alpha-induced immobility in the mouse forced swimming test.

    Science.gov (United States)

    Zhang, Hongmei; Wang, Wei; Jiang, Zhenzhou; Shang, Jing; Zhang, Luyong

    2010-01-01

    Although Interferon-alpha (IFN-alpha, CAS 9008-11-1) is a powerful drug in treating several viral infections and certain tumors, a considerable amount of neuropsychiatric side-effects such as depression and anxiety are an unavoidable consequence. Combination with the selective serotonin (5-HT) reuptake inhibitor (SSRI) fluoxetine (CAS 56296-78-7) significantly improved the situation. However, the potential 5-HT(1A) receptor- and 5-HT(1B) receptor-signals involved in the antidepressant effects are still unclear. The effects of 5-HT(1A) receptor- and 5-HT(1B) receptor signals were analyzed by using the mouse forced swimming test (FST), a predictive test of antidepressant-like action. The present results indicated that (1) fluoxetine (administrated intragastrically, 30 mg/kg; not subactive dose: 15 mg/kg) significantly reduced IFN-alpha-induced increase of the immobility time in the forced swimming test; (2) 5-HT(1A) receptor- and 5-HT(1B) receptor ligands alone or in combination had no effects on IFN-alpha-induced increase of the immobility time in the FST; (3) surprisingly, WAY 100635 (5-HT(1A) receptor antagonist, 634908-75-1) and 8-OH-DPAT(5-HT(1A) receptor agonist, CAS 78950-78-4) markedly enhanced the antidepressant effect of fluoxetine at the subactive dose (15 mg/kg, i. g.) on the IFN-alpha-treated mice in the FST. Further investigations showed that fluoxetine combined with WAY 100635 and 8-OH-DPAT failed to produce antidepressant effects in the FST. (4) Co-application of CGS 12066A (5-HT(1B) receptor agonist, CAS 109028-09-3) or GR 127935 (5-HT(1B/1D) receptor antagonist, CAS 148642-42-6) with fluoxetine had no synergistic effects on the IFN-alpha-induced increase of immobility time in FST. (5) Interestingly, co-administration of GR 127935, WAY 100635 and fluoxetine significantly reduced the IFN-alpha-induced increase in immobility time of FST, being more effective than co-administration of WAY 100635 and fluoxetine. All results suggest that (1) compared to

  8. Interferon-alpha mediates restriction of human immunodeficiency virus type-1 replication in primary human macrophages at an early stage of replication.

    Directory of Open Access Journals (Sweden)

    Kelly M Cheney

    Full Text Available Type I interferons (IFNα and β are induced directly in response to viral infection, resulting in an antiviral state for the cell. In vitro studies have shown that IFNα is a potent inhibitor of viral replication; however, its role in HIV-1 infection is incompletely understood. In this study we describe the ability of IFNα to restrict HIV-1 infection in primary human macrophages in contrast to peripheral blood mononuclear cells and monocyte-derived dendritic cells. Inhibition to HIV-1 replication in cells pretreated with IFNα occurred at an early stage in the virus life cycle. Late viral events such as budding and subsequent rounds of infection were not affected by IFNα treatment. Analysis of early and late HIV-1 reverse transcripts and integrated proviral DNA confirmed an early post entry role for IFNα. First strand cDNA synthesis was slightly reduced but late and integrated products were severely depleted, suggesting that initiation or the nucleic acid intermediates of reverse transcription are targeted. The depletion of integrated provirus is disproportionally greater than that of viral cDNA synthesis suggesting the possibility of a least an additional later target. A role for either cellular protein APOBEC3G or tetherin in this IFNα mediated restriction has been excluded. Vpu, previously shown by others to rescue a viral budding restriction by tetherin, could not overcome this IFNα induced effect. Determining both the viral determinants and cellular proteins involved may lead to novel therapeutic approaches. Our results add to the understanding of HIV-1 restriction by IFNα.

  9. Interferon Alpha Association with Neuromyelitis Optica

    Directory of Open Access Journals (Sweden)

    Nasrin Asgari

    2013-01-01

    Full Text Available Interferon-alpha (IFN-α has immunoregulatory functions in autoimmune inflammatory diseases. The goal of this study was to determine occurrence and clinical consequences of IFN-α in neuromyelitis optica (NMO patients. Thirty-six NMO and 41 multiple sclerosis (MS patients from a population-based retrospective case series were included. Expanded Disability Status Scale (EDSS score and MRI findings determined disease activity. Linear regression was used to assess the effects of the level of IFN-α on disability (EDSS. IFN-α was determined by sensitive ELISA assays. IFN-α was detectable in sera from 9/36 NMO patients, significantly more often than in the MS group (2/41 (P=0.0197. A higher frequency of IFN-α was observed in NMO patients with acute relapse compared to NMO patients in remission (P<0.001 and compared to the MS patients with relapse (P=0.010. In NMO patients, the levels of IFN-α were significantly associated with EDSS (P=0.0062. It may be concluded that IFN-α was detectable in a subgroup of NMO patients. Association of IFN-α levels with clinical disease activity and severity suggests a role for IFN-α in disease perpetuation and may provide a plausible explanation for a negative effect of IFN-1 treatment in NMO patients.

  10. Interferon alpha-induced reduction in the values of myeloid-derived suppressor cells in melanoma patients

    Directory of Open Access Journals (Sweden)

    Stanojević Ivan

    2015-01-01

    Full Text Available Background/Aim. Interaction between tumor cells and host’s immunoregulatory cells in creation of microenvironment that supports tumor progression is the focus of numerous investigations in recent years. Myeloid-derived suppressor cells (MDSCs are heterogeneous population of immature dendritic cells, macrophages and granulocytes. In cancer patients, these cells accumulate in tumor microenvironment, tumor-draining lymph nodes, peripheral blood and the liver and their numbers correlate with the stage of the disease and the metastatic disease. The aim of the study was to investigate the effect of interferon alpha on MDSCs percentage in peripheral blood of melanoma patients. Methods. The interferon treated melanoma patients were given subcutaneously interferon alpha, in optimal dose, for a period of at least 6 months before the analysis. Blood samples were collected from the melanoma patients (n = 91 and the age/sex matched healthy controls (n = 8. The following anti-human monoclonal antibodies were used for immunostaining: anti-CD15-FITC, anti-CD33-PE, anti-CD45-ECD, anti-HLA-DR PE/Cy5, anti-CD14-FITC, anti-CD16-PE and anti-CD11b-PE. Results. Comparison of myeloid-derived suppressor cells values in the stage 2 melanoma patients with and without interferon alpha therapy did not show a significant difference. When we compared the MDSCs values in the patients within stage 3 melanoma, we found a significant difference in granulocytic subset values between the interferon alpha-treated and the untreated group. Comparison of values of all suppressor cells populations between the interferon alpha-treated patients and healthy controls showed a significant increase in suppressor cells percentage in the melanoma patients. The granulocytic and total MDSCs values were significantly lower in the interferon alpha treated melanoma patients with progression in comparison with untreated patients with stable disease. Conclusion. We confirmed that interferon alpha

  11. Interferon alpha for treatment of chronic myeloid leukemia

    DEFF Research Database (Denmark)

    Simonsson, Bengt; Hjorth-Hansen, Henrik; Bjerrum, Ole Weis

    2011-01-01

    Treatment of chronic myeloid leukemia (CML) with interferon-alpha (IFN-a) was introduced in the early 1980s. Several clinical trials showed a survival advantage for patients treated with IFN-a compared to conventional chemotherapy. Some patients achieved longstanding complete cytogenetic remissions...

  12. Interferon alpha for treatment of chronic myeloid leukemia

    DEFF Research Database (Denmark)

    Simonsson, Bengt; Hjorth-Hansen, Henrik; Bjerrum, Ole Weis

    2011-01-01

    Treatment of chronic myeloid leukemia (CML) with interferon-alpha (IFN-α) was introduced in the early 1980s. Several clinical trials showed a survival advantage for patients treated with IFN-α compared to conventional chemotherapy. Some patients achieved longstanding complete cytogenetic remissions...

  13. Local synthesis of interferon-alpha in lupus nephritis is associated with type I interferons signature and LMP7 induction in renal tubular epithelial cells.

    Science.gov (United States)

    Castellano, Giuseppe; Cafiero, Cesira; Divella, Chiara; Sallustio, Fabio; Gigante, Margherita; Pontrelli, Paola; De Palma, Giuseppe; Rossini, Michele; Grandaliano, Giuseppe; Gesualdo, Loreto

    2015-03-22

    Type I interferons are pivotal in the activation of autoimmune response in systemic lupus erythematous. However, the pathogenic role of interferon-alpha in patients affected by lupus nephritis remains uncertain. The aim of our study was to investigate the presence of a specific interferon signature in lupus nephritis and the effects of interferon-alpha at renal level. We performed immunohistochemical analysis for MXA-protein and in situ hybridization to detect interferon-alpha signature and production in human lupus nephritis. Through microarray studies, we analyzed the gene expression profile of renal tubular epithelial cells, stimulated with interferon-alpha. We validated microarray results through real-time polymerase chain reaction, flow cytometry on renal tubular epithelial cells, and through immunohistochemical analysis and confocal microscopy on renal biopsies. Type I interferons signature was characterized by MXA-specific staining in renal tubular epithelial cells; in addition, in situ hybridization showed that renal tubular epithelial cells were the major producers of interferon-alpha, indicating a potential autocrine effect. Whole-genome expression profile showed interferon-alpha induced up-regulation of genes involved in innate immunity, protein ubiquitination and switching to immunoproteasome. In accordance with the in vitro data, class IV lupus nephritis showed up-regulation of the immunoproteasome subunit LMP7 in tubular epithelial cells associated with type I interferon signature. Our data indicate that type I interferons might have a pathogenic role in lupus nephritis characterized by an autocrine effect of interferon-alpha on renal tubular epithelial cells. Therefore we hypothesize that inhibition of type I interferons might represent a therapeutic target to prevent tubulo-interstitial damage in patients with lupus nephritis.

  14. Successful treatment of provisional cutaneous mastocytosis with interferon alpha

    Directory of Open Access Journals (Sweden)

    Andrea Rosario

    2016-01-01

    Full Text Available Mastocytosis is a disorder characterized by the clonal proliferation of mast cells and their accumulation in skin, bone marrow, liver, and spleen. Cutaneous mastocytosis presents in children in over 90% of the cases and any cutaneous manifestation in an adult is the earliest sign of the systemic disease. A 45-year-old patient presented with itchy dark lesions over the body since childhood and Darier's sign was positive. Skin biopsy showed features of mastocytosis and immunohistochemistry was positive for CD34. Since the patient was refractory to treatment with antihistamines and psoralen-ultraviolet A therapy, injections of interferon alpha were given – 3 million IU twice weekly subcutaneously as they have been proven to improve constitutional symptoms. Very few reports of successful treatment of cutaneous mastocytosis using interferon alpha have been published.

  15. Complete remission of multiple myeloma after autoimmune hemolytic anemia: possible association with interferon-alpha.

    Science.gov (United States)

    Gesundheit, Benjamin; Zelig, Orly; Shapira, Michael Y; Ackerstein, Aliza; Avgil, Meytal; Or, Reuven

    2007-06-01

    A patient with multiple myeloma (MM) was being maintained on human recombinant interferon-alpha (INF-alpha) after VAD and autologous bone marrow transplantation (pretreated with melphalan). An episode of immune thrombocytopenia and (Coombs positive) autoimmune hemolytic anemia (AIHA) was noted while on maintenance INF-alpha, which remitted when it was withdrawn. Following this event, he achieved a state of stable disease that persists (more than 3 years) with no specific myeloma treatment. This sequence of events suggests a relationship between an immunological reaction induced by INF-alpha and the prolonged phase of stable disease.

  16. Use of intralesional interferon-alpha for the treatment of recalcitrant oral warts in patients with AIDS: a report of 4 cases.

    Science.gov (United States)

    Lozada-Nur, F; Glick, M; Schubert, M; Silverberg, I

    2001-12-01

    Four human immunodeficiency virus-positive homosexual men with 2- to 4.5-year histories of recurrent oral warts that had failed to respond to conventional surgical and other treatment modalities were offered treatment with interferon-alpha. All had multiple or large oral warts, 3 had skin warts, 2 had a history of anal warts, and 1 had penile lesions. All 4 patients were treated with a combination of intralesional and subcutaneous interferon-alpha. Adverse side effects were dose-related, mild, and transient; they included flulike symptoms (3 patients), hair loss and tachycardia (1 patient), and transient changes in the white blood cell count. All patients responded to therapy and remained free of disease up to 42 months. Intralesional injection with interferon-alpha appears to provide excellent clinical control for recurrent, multiple, and extensive oral warts in the human immunodeficiency virus-positive population, and is a useful adjunct to initial surgical removal of oral warts.

  17. Chronic inflammatory demyelinating polyneuropathy after treatment with interferon-alpha.

    Science.gov (United States)

    Hirotani, Makoto; Nakano, Hitoshi; Ura, Shigehisa; Yoshida, Kazuto; Niino, Masaaki; Yabe, Ichiro; Sasaki, Hidenao

    2009-01-01

    Interferon-alpha (IFN-alpha), though widely used for the treatment of chronic viral hepatitis, may be associated with the occurrence of autoimmune disorders. In this case report, a patient with chronic hepatitis C virus infection had chronic inflammatory demyelinating polyneuropathy (CIDP) after the initiation of IFN-alpha therapy. The neurological symptoms of this patient continued to progress even though the treatment with IFN-alpha had been withdrawn; the symptoms improved dramatically following treatment with intravenous immunoglobulin. This case may therefore provide an important clue to understand the immune mechanism of CIDP and IFN-alpha.

  18. Controlled-release interferon alpha 2b, a new member of the interferon family for the treatment of chronic hepatitis C.

    Science.gov (United States)

    Jansen, Peter L M; De Bruijne, Joep

    2012-01-01

    Combination therapy with pegylated interferon alpha (Peg-interferon) and ribavirin is currently the cornerstone of antiviral therapy for chronic hepatitis C. Monotherapy with Peg-interferon still is important for the treatment of chronic hepatitis B. With the advent of new therapies, protease inhibitors for chronic hepatitis C and nucleotide inhibitors for chronic hepatitis B, there remains a need for interferon-based therapies. The side effects of Peg-interferon are a main disadvantage and represent a stumbling block for many patients to enter and continue therapy. In this review, the authors will discuss controlled-release interferon alpha 2b (CR2b) (Locteron®, Biolex Therapeutics, Pittsboro, NC, USA), a new slow-release interferon alpha 2b preparation for the treatment of chronic viral hepatitis. Other alternative interferons will also be discussed. CR2b is a slow-release microsphere preparation for the administration of plant-derived recombinant human interferon alpha 2b. Compared with Peg-interferon, treatment with CR2b shows less flu-like reactions and less depression, and is at least as effective as conventional Peg-interferon-based therapy in patients with chronic hepatitis C. CR2b has the added advantage of biweekly instead of once weekly administration. CR2b appears to cause more neutropenia than Peg-interferon alpha 2b. This may be due to higher trough serum levels of CR2b at the end of a dosing interval. The bone marrow effects of CR2b closely resemble those published for the registered Peg-interferon alpha 2a. CR2b appears to have at least comparable efficacy with fewer side effects than current registered Peg-interferons.

  19. Targeted Therapies: Bevacizumab and interferon-alpha in metastatic renal-cell carcinoma.

    Science.gov (United States)

    Bukowski, Ronald M

    2009-05-01

    Rini and colleagues provide additional data on bevacizumab and interferon-alpha in clear-cell carcinoma of the kidney; a comparison of these results with the findings from contemporary trials suggests that bevacizumab and interferon-alpha is another clinically useful treatment option for patients with metastatic renal-cell carcinoma.

  20. Interferon-alpha induced depressive-like behavior in rats

    DEFF Research Database (Denmark)

    Fischer, C. W.; Liebenberg, N.; Elfving, B.

    2013-01-01

    Background: A subpopulation of individuals with major depressive disorder (MDD) show increased levels of peripheral inflammatory biomarkers, indicating an association of MDD with a chronically activated immune system. Administration of the immune stimulating cytokine, interferon-alpha (IFN......-(alpha)), also used in the treatment of cancer and hepatitis, commonly leads to neuropsychiatric side effects with approximately 16- 45% of patients developing depressive-like symptoms during the course of therapy. Given that treatmentresistant depression has been associated with increased levels of inflammatory...... markers, the development of an inflammation-induced model of depression is highly relevant. Aim: The objective of this study was to investigate whether IFN-(alpha) can induce a chronic low-grade inflammatory state in rats, and whether this may lead to a depressive phenotype. Methods: Male Sprague...

  1. Consensus on consensus: a synthesis of consensus estimates on human-caused global warming

    Science.gov (United States)

    Cook, John; Oreskes, Naomi; Doran, Peter T.; Anderegg, William R. L.; Verheggen, Bart; Maibach, Ed W.; Carlton, J. Stuart; Lewandowsky, Stephan; Skuce, Andrew G.; Green, Sarah A.; Nuccitelli, Dana; Jacobs, Peter; Richardson, Mark; Winkler, Bärbel; Painting, Rob; Rice, Ken

    2016-04-01

    The consensus that humans are causing recent global warming is shared by 90%-100% of publishing climate scientists according to six independent studies by co-authors of this paper. Those results are consistent with the 97% consensus reported by Cook et al (Environ. Res. Lett. 8 024024) based on 11 944 abstracts of research papers, of which 4014 took a position on the cause of recent global warming. A survey of authors of those papers (N = 2412 papers) also supported a 97% consensus. Tol (2016 Environ. Res. Lett. 11 048001) comes to a different conclusion using results from surveys of non-experts such as economic geologists and a self-selected group of those who reject the consensus. We demonstrate that this outcome is not unexpected because the level of consensus correlates with expertise in climate science. At one point, Tol also reduces the apparent consensus by assuming that abstracts that do not explicitly state the cause of global warming (‘no position’) represent non-endorsement, an approach that if applied elsewhere would reject consensus on well-established theories such as plate tectonics. We examine the available studies and conclude that the finding of 97% consensus in published climate research is robust and consistent with other surveys of climate scientists and peer-reviewed studies.

  2. Treatment with interferon-alpha delays disease in swine infected with a highly virulent CSFV strain.

    Science.gov (United States)

    Fernandez-Sainz, I; Ramanathan, P; O'Donnell, V; Diaz-San Segundo, F; Velazquez-Salinas, L; Sturza, D F; Zhu, J; de los Santos, T; Borca, M V

    2015-09-01

    Interferon-alpha (IFNα) can effectively inhibit or abort a viral infection within the host. It has been reported that IFN induction and production is hindered during classical swine fever virus (CSFV) infection. Most of those studies have been performed in vitro, making it difficult to elucidate the actual role of IFNs during CSFV infection in swine. Here, we report the effect of IFNα treatment (delivered by a replication defective recombinant human adenovirus type 5, Ad5) in swine experimentally infected with highly virulent CSFV strain Brescia. Treatment with two different subtypes of IFNα delayed the appearance of CSF-related clinical signs and virus replication although it did not prevent lethal disease. This is the first report describing the effect of IFNα treatment during CSFV infection in swine. Published by Elsevier Inc.

  3. The rebound effect in the treatment of complex hemangioma with interferon alpha 2A

    Directory of Open Access Journals (Sweden)

    Jaime Anger

    Full Text Available The authors report the case of an infant with an extensive face hemangioma with subglottic airway obstruction which had been successfully treated with interferon alpha 2A but then reoccurred with the same dimensions and airway blockage after treatment was abruptly interrupted. The authors suggest the implementation of a standard procedure for the interruption of interferon alpha 2A treatment in order to avoid this rebound effect and advise on the need for further studies to properly evaluate dosage and administration parameters for interferon alpha 2A in the treatment of difficult hemangioma.

  4. Histological outcome of chronic hepatitis B in children treated with interferon alpha

    OpenAIRE

    Elzbieta, Sobaniec-Lotowska Maria; Marek, Lebensztejn Dariusz

    2005-01-01

    AIM: To evaluate the effect of interferon alpha (IFN-α) treatment on the liver histology in children with chronic hepatitis B and to evaluate the usefulness of various histological scoring systems of liver histology in this group of patients.

  5. Interferon alpha-2a as alternative treatment for conjunctival squamous cell carcinoma.

    Science.gov (United States)

    Cruzado-Sánchez, D; Salas-Diaz, M; Tellez, W A; Alvarez-Matos, S E; Serpa-Frías, S

    2017-05-15

    A 35 year-old male patient with a history of HIV infection characterized by progressive tumour growth in bulbar conjunctiva of the left eye, corresponding to conjunctival squamous cell carcinoma that responded to treatment with interferon alpha-2a. Interferon alpha-2b has been used at conjunctival level as a topical immunomodulator treatment, with complete remission of epithelial neoplasms being observed. However, there have not been any previous publications on the use of interferon alpha-2a, which differs from interferon alpha-2b in a single amino acid, for the treatment of conjunctival squamous cell carcinoma. Copyright © 2017 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

  6. Tenofovir disoproxil fumarate therapy for chronic hepatitis B in human immunodeficiency virus/hepatitis B virus-coinfected individuals for whom interferon-alpha and lamivudine therapy have failed.

    Science.gov (United States)

    Ristig, Maria B; Crippin, Jeffrey; Aberg, Judith A; Powderly, William G; Lisker-Melman, Mauricio; Kessels, Lisa; Tebas, Pablo

    2002-12-15

    A significant proportion of human immunodeficiency virus (HIV) infected patients are coinfected with hepatitis B virus (HBV). Currently available treatments for chronic hepatitis B (interferon [IFN]-alpha and lamivudine [3TC]) have limited long-term utility because of side effects or of the development of resistance. Tenofovir disoproxil fumarate (TDF) is a nucleotide analog with excellent activity in vitro against HBV, which is also active against 3TC-resistant HBV variants. In this 24-week pilot study, the anti-HBV activity of TDF was prospectively evaluated in a cohort of 6 HIV coinfected subjects for whom 3TC and IFN therapy had previously failed. At baseline, all patients were taking 3TC or FTC and were hepatitis B surface antigen and hepatitis B e antigen positive; 4 had cirrhosis. Baseline HBV load was 7.95 log(10) copies/mL. By weeks 12 and 24, HBV load had decreased by 3.1 log(10) copies/mL and 4.3 log(10) copies/mL, respectively. There was a transient increase of transaminases after the initiation of treatment. No patient developed HBe antibodies. TDF is a very promising drug for the treatment of chronic hepatitis B in HIV-infected individuals.

  7. Stat2 binding to the interferon-alpha receptor 2 subunit is not required for interferon-alpha signaling.

    Science.gov (United States)

    Nguyen, Vinh-Phúc; Saleh, Abu Z M; Arch, Allison E; Yan, Hai; Piazza, Flavia; Kim, John; Krolewski, John J

    2002-03-22

    The interferon-alpha (IFNalpha) receptor consists of two subunits, the IFNalpha receptor 1 (IFNaR1) and 2 (IFNaR2) chains. Following ligand binding, IFNaR1 is phosphorylated on tyrosine 466, and this site recruits Stat2 via its SH2 domain. In contrast, IFNaR2 binds Stat2 constitutively. In this study we have characterized the Stat2-IFNaR2 interaction and examined its role in IFNalpha signaling. Stat2 binds the major IFNaR2 protein but not a variant containing a shorter cytoplasmic domain. The interaction does not require a STAT SH2 domain. Both tyrosine-phosphorylated and non-phosphorylated Stat2 bind IFNaR2 in vitro; however, relatively little phosphorylated Stat2 associates with IFNaR2 in vivo. In vitro binding assays defined IFNaR2 residues 418-444 as the minimal interaction domain and site-specific mutation of conserved acidic residues within this domain disrupted in vitro and in vivo binding. An IFNaR2 construct carrying these mutations was either (i) overexpressed in 293T cells or (ii) used to complement IFNaR2-deficient U5A cells. Unexpectedly, the activity of an IFNalpha-dependent reporter gene was not reduced but, instead, was enhanced up to 2-fold. This suggests that this particular IFNaR2-Stat2 interaction is not required for IFNalpha signaling, but might act to negatively inhibit signaling. Finally, a doubly truncated recombinant fragment of Stat2, spanning residues 136-702, associated with IFNaR2 in vitro, indicating that the interaction with IFNaR2 is direct and occurs in a central region of Stat2 marked by a hydrophobic core.

  8. Liver-targeting of interferon-alpha with tissue-specific domain antibodies.

    Science.gov (United States)

    Coulstock, Edward; Sosabowski, Jane; Ovečka, Milan; Prince, Rob; Goodall, Laura; Mudd, Clare; Sepp, Armin; Davies, Marie; Foster, Julie; Burnet, Jerome; Dunlevy, Gráinne; Walker, Adam

    2013-01-01

    Interferon alpha (IFNα) is used for the treatment of hepatitis C infection and whilst efficacious it is associated with multiple adverse events including reduced leukocyte, erythrocyte, and platelet counts, fatigue, and depression. These events are most likely caused by systemic exposure to interferon. We therefore hypothesise that targeting the therapeutic directly to the intended site of action in the liver would reduce exposure in blood and peripheral tissue and hence improve the safety and tolerability of IFNα therapy. We genetically fused IFN to a domain antibody (dAb) specific to a hepatocyte restricted antigen, asialoglycoprotein receptor (ASGPR). Our results show that the murine IFNα2 homolog (mIFNα2) fused to an ASGPR specific dAb, termed DOM26h-196-61, could be expressed in mammalian tissue culture systems and retains the desirable biophysical properties and activity of both fusion partners when measured in vitro. Furthermore a clear increase in in vivo targeting of the liver by mIFNα2-ASGPR dAb fusion protein, compared to that observed with either unfused mIFNα2 or mIFNα2 fused to an isotype control dAb VHD2 (which does not bind ASGPR) was demonstrated using microSPECT imaging. We suggest that these findings may be applicable in the development of a liver-targeted human IFN molecule with improved safety and patient compliance in comparison to the current standard of care, which could ultimately be used as a treatment for human hepatitis virus infections.

  9. Control of islet intercellular adhesion molecule-1 expression by interferon-alpha and hypoxia.

    Science.gov (United States)

    Chakrabarti, D; Huang, X; Beck, J; Henrich, J; McFarland, N; James, R F; Stewart, T A

    1996-10-01

    The ability of interferon-alpha (IFN-alpha) to induce the adhesion molecules that characterize the islets of patients with type I diabetes has been investigated. We have found that all tested recombinant IFN-as will induce major histocompatibility complex (MHC) class I on arterial endothelial cells. Some but not all IFN-as will induce intercellular adhesion molecule-1 (ICAM-1). However, there is only a transient and modest increase in VCAM on arterial endothelial cells. IFN-alpha has very little effect on endothelial MHC class II expression but will induce these proteins on monocytes. Thus, there is a close concordance between the biological actions of IFN-alpha and the appearance of those adhesion molecules induced in the islets of patients with type I diabetes. IFN-alpha is also produced in normal human islets during short-term cultures, probably as a result of the ischemia present at the center of the islet. This induction of IFN-alpha by hypoxia may explain the previously reported spontaneous induction of ICAM-1 in human islets and may also be a contributing factor to the failure of islet grafts.

  10. Sustained major molecular response on interferon alpha-2b in two patients with polycythemia vera

    DEFF Research Database (Denmark)

    Larsen, T.S.; Pallisgaard, N.; Andersen, M.T.

    2008-01-01

    Quantitative assessment of the JAK2 V617F allele burden during disease evolution and ongoing myelosuppressive treatment is likely to be implemented in the future clinical setting. Interferon alpha has demonstrated efficacy in treatment of both chronic myeloid leukemia and the Philadelphia...... chromosome negative chronic myeloproliferative disorders. Reductions in the JAK2 V617F allele burden in patients treated with pegylated interferon alpha-2a (Peg-IFN-2a) have been demonstrated, although follow-up was relatively short. We report here the first profound and sustained molecular responses...... with a JAK2 V617F allele burden below 1.0% in two patients with polycythemia vera treated with interferon alpha-2b (IFN-2b). Discontinuation of IFN-2b in one of the patients was followed by a sustained long-lasting (12 months of follow-up) major molecular response Udgivelsesdato: 2008/10...

  11. A Computational Model of Inhibition of HIV-1 by Interferon-Alpha.

    Directory of Open Access Journals (Sweden)

    Edward P Browne

    Full Text Available Type 1 interferons such as interferon-alpha (IFNα inhibit replication of Human immunodeficiency virus (HIV-1 by upregulating the expression of genes that interfere with specific steps in the viral life cycle. This pathway thus represents a potential target for immune-based therapies that can alter the dynamics of host-virus interactions to benefit the host. To obtain a deeper mechanistic understanding of how IFNα impacts spreading HIV-1 infection, we modeled the interaction of HIV-1 with CD4 T cells and IFNα as a dynamical system. This model was then tested using experimental data from a cell culture model of spreading HIV-1 infection. We found that a model in which IFNα induces reversible cellular states that block both early and late stages of HIV-1 infection, combined with a saturating rate of conversion to these states, was able to successfully fit the experimental dataset. Sensitivity analysis showed that the potency of inhibition by IFNα was particularly dependent on specific network parameters and rate constants. This model will be useful for designing new therapies targeting the IFNα network in HIV-1-infected individuals, as well as potentially serving as a template for understanding the interaction of IFNα with other viruses.

  12. A Computational Model of Inhibition of HIV-1 by Interferon-Alpha.

    Science.gov (United States)

    Browne, Edward P; Letham, Benjamin; Rudin, Cynthia

    2016-01-01

    Type 1 interferons such as interferon-alpha (IFNα) inhibit replication of Human immunodeficiency virus (HIV-1) by upregulating the expression of genes that interfere with specific steps in the viral life cycle. This pathway thus represents a potential target for immune-based therapies that can alter the dynamics of host-virus interactions to benefit the host. To obtain a deeper mechanistic understanding of how IFNα impacts spreading HIV-1 infection, we modeled the interaction of HIV-1 with CD4 T cells and IFNα as a dynamical system. This model was then tested using experimental data from a cell culture model of spreading HIV-1 infection. We found that a model in which IFNα induces reversible cellular states that block both early and late stages of HIV-1 infection, combined with a saturating rate of conversion to these states, was able to successfully fit the experimental dataset. Sensitivity analysis showed that the potency of inhibition by IFNα was particularly dependent on specific network parameters and rate constants. This model will be useful for designing new therapies targeting the IFNα network in HIV-1-infected individuals, as well as potentially serving as a template for understanding the interaction of IFNα with other viruses.

  13. Sustained major molecular response on interferon alpha-2b in two patients with polycythemia vera

    DEFF Research Database (Denmark)

    Larsen, Thomas Stauffer; Bjerrum, O W; Pallisgaard, N

    2008-01-01

    chromosome negative chronic myeloproliferative disorders. Reductions in the JAK2 V617F allele burden in patients treated with pegylated interferon alpha-2a (Peg-IFN-2a) have been demonstrated, although follow-up was relatively short. We report here the first profound and sustained molecular responses...... with a JAK2 V617F allele burden below 1.0% in two patients with polycythemia vera treated with interferon alpha-2b (IFN-2b). Discontinuation of IFN-2b in one of the patients was followed by a sustained long-lasting (12 months of follow-up) major molecular response....

  14. LONG-TERM TREATMENT WITH INTERFERON-ALPHA-2B FOR SEVERE PRURITUS IN PATIENTS WITH POLYCYTHEMIA-VERA

    NARCIS (Netherlands)

    MULLER, EW; DEWOLF, JTM; EGGER, R; WIJERMANS, PW; HUIJGENS, PC; HALIE, MR; VELLENGA, E

    Pruritus is a major clinical problem in patients with polycythaemia vera (PV). Conventional symptomatic treatment is unsatisfactory. Recently, a favourable effect of interferon-alpha on pruritus in patients with PV has been reported. Also, interferon-alpha suppresses the increased haemopoiesis in

  15. LONG-TERM TREATMENT WITH INTERFERON-ALPHA-2B FOR SEVERE PRURITUS IN PATIENTS WITH POLYCYTHEMIA-VERA

    NARCIS (Netherlands)

    MULLER, EW; DEWOLF, JTM; EGGER, R; WIJERMANS, PW; HUIJGENS, PC; HALIE, MR; VELLENGA, E

    1995-01-01

    Pruritus is a major clinical problem in patients with polycythaemia vera (PV). Conventional symptomatic treatment is unsatisfactory. Recently, a favourable effect of interferon-alpha on pruritus in patients with PV has been reported. Also, interferon-alpha suppresses the increased haemopoiesis in PV

  16. Chronic myeloid leukemia and interferon-alpha : a study of complete cytogenetic responders

    NARCIS (Netherlands)

    Bonifazi, F; de Vivo, A; Rosti, G; Guilhot, F; Guilhot, J; Trabacchi, E; Hehlmann, R; Hochhaus, A; Shepherd, PCA; Steegmann, JL; Kluin-Nelemans, HC; Thaler, J; Simonsson, B; Louwagie, A; Reiffers, J; Mahon, FX; Montefusco, E; Alimena, G; Hasford, J; Richards, S; Saglio, G; Testoni, N; Martinelli, G; Tura, S; Baccarani, M

    2001-01-01

    Achieving a complete cytogenetic response (CCgR) is a major target in the treatment of chronic myeloid leukemia (CIVIL) with interferon-alpha (IFN-alpha), but CCgRs are rare. The mean CCgR rate is 13%, in a range of 5% to 33%. A collaborative study of 9 European Union countries has led to the

  17. Is combination therapy with lamivudine and interferon-alpha superior to monotherapy with either drug?

    NARCIS (Netherlands)

    van Nunen, A B; Janssen, H L; Wolters, L M; Niesters, H G; de Man, R A; Schalm, S W

    2001-01-01

    For the treatment of chronic hepatitis B (CHB) two drugs have been licensed world-wide: interferon-alpha (IFN) and lamivudine. Both drugs significantly increase the hepatitis B e-antigen (HBeAg) seroconversion rate, but a sustained treatment response occurs in less than 40% of patients. To explore w

  18. Expression of the interferon-alpha/beta-inducible bovine Mx1 dynamin interferes with replication of rabies virus.

    Science.gov (United States)

    Leroy, M; Pire, G; Baise, E; Desmecht, D

    2006-03-01

    Rabies is a fatal anthropozoonotic viral infection of the central nervous system that remains a serious public health problem in many countries. As several animal cases of spontaneous survival to infection were reported and because type 1 interferons were shown to protect against the virus, it was suggested that innate resistance mechanisms exist. Among the antiviral proteins that are synthesized in response to interferon-alpha/beta stimulation, Mx proteins from several species are long known to block the replication of vesicular stomatitis virus (VSV). As both VSV and rabies virus belongs to the Rhabdoviridae family, this study was started with the aim to establish whether the anti-VSV activity of a mammalian Mx protein could be extended to rabies virus. This question was addressed by inoculating the virus onto a bovine Mx1 or human MxA-expressing Vero cell clone. Plaque formation was unambiguously blocked, and viral yields were reduced 100- to 1000-fold by bovine Mx1 expression for both SAG2 and SADB19 viral strains. In opposition, only SAG2 strain could be inhibited by the expression of human MxA protein. The effect of both proteins expression was then evaluated at the viral protein expression level. Again, boMx1 was able to repress protein expression in both strain, whereas only SAG2 proteins were inhibited in human MxA-expressing cells. These results suggest that protection conferred by interferon-alpha/beta against rabies could be, at least partially, attributable to the Mx pathway. Alternatively, bovine Mx1 could be unique in its ability to repress rabies virus which, if confirmed in vivo, would open an avenue for the development of new antirabies therapeutic strategies.

  19. Liver-targeting of interferon-alpha with tissue-specific domain antibodies.

    Directory of Open Access Journals (Sweden)

    Edward Coulstock

    Full Text Available Interferon alpha (IFNα is used for the treatment of hepatitis C infection and whilst efficacious it is associated with multiple adverse events including reduced leukocyte, erythrocyte, and platelet counts, fatigue, and depression. These events are most likely caused by systemic exposure to interferon. We therefore hypothesise that targeting the therapeutic directly to the intended site of action in the liver would reduce exposure in blood and peripheral tissue and hence improve the safety and tolerability of IFNα therapy. We genetically fused IFN to a domain antibody (dAb specific to a hepatocyte restricted antigen, asialoglycoprotein receptor (ASGPR. Our results show that the murine IFNα2 homolog (mIFNα2 fused to an ASGPR specific dAb, termed DOM26h-196-61, could be expressed in mammalian tissue culture systems and retains the desirable biophysical properties and activity of both fusion partners when measured in vitro. Furthermore a clear increase in in vivo targeting of the liver by mIFNα2-ASGPR dAb fusion protein, compared to that observed with either unfused mIFNα2 or mIFNα2 fused to an isotype control dAb VHD2 (which does not bind ASGPR was demonstrated using microSPECT imaging. We suggest that these findings may be applicable in the development of a liver-targeted human IFN molecule with improved safety and patient compliance in comparison to the current standard of care, which could ultimately be used as a treatment for human hepatitis virus infections.

  20. Construction and Expression of Eukaryotic Expression Vector of Mature Polypeptide of Duck Interferon Alpha Gene

    Institute of Scientific and Technical Information of China (English)

    PEI Fucheng; LI Jingpeng; LI Lu; ZHANG Jianguang; REN Guiping

    2006-01-01

    To study biological activities of Duck Interferon Alpha (DuIFN-α) and prepare antivirus medicine, the eukaryotic expression vector of mature polypeptide of Duck Interferon Alpha (mDuIFN-α) gene was constructed and expressed in insect cell. By means of PCR technique, the mDuIFN-α gene was cloned from pMD-18-duIFN-αrecombinant. The gene was then inserted to pGEM-T vector and identified by restriction endonuclease analysis and sequencing. The mDuIFN-α gene was ligated with the eukaryotic expression vector pMelBacA, then transfected into Sf9cell line. Recombinant polypeptide was effectively expressed in insect cell and its molecular weight was 34 ku.

  1. Neuropsychiatric complications associated with interferon - alpha -2b treatment of malignant melanoma.

    LENUS (Irish Health Repository)

    Enudi, W

    2012-02-01

    Several adverse effects have been associated with interferon alpha 2b treatment and neuropsychiatric effects have also been commonly reported. Psychosis and mood disorders have been described in the literature. This case report is of a 30 year old man with malignant melanoma stage 3a who was receiving adjuvant alpha 2b interferon and developed a manic episode two weeks post switching after one month of treatment on a high dose to a low dose. There was no previous psychiatric illness and no known family history of mental illness. This is in keeping with previous reports that mania has been observed in patients undergoing interferon treatment especially after significant dose-reduction or treatment breaks. Mania induced by interferon responds well to antimanic drugs .Since interferon alpha 2b is now commonly used in the treatment of malignant melanoma and other conditions, the need to be aware of its neuropsychiatric complications is essential.

  2. Neuropsychiatric complications associated with interferon - alpha -2b treatment of malignant melanoma.

    LENUS (Irish Health Repository)

    Enudi, W

    2009-08-01

    Several adverse effects have been associated with interferon alpha 2b treatment and neuropsychiatric effects have also been commonly reported. Psychosis and mood disorders have been described in the literature. This case report is of a 30 year old man with malignant melanoma stage 3a who was receiving adjuvant alpha 2b interferon and developed a manic episode two weeks post switching after one month of treatment on a high dose to a low dose. There was no previous psychiatric illness and no known family history of mental illness. This is in keeping with previous reports that mania has been observed in patients undergoing interferon treatment especially after significant dose-reduction or treatment breaks. Mania induced by interferon responds well to antimanic drugs .Since interferon alpha 2b is now commonly used in the treatment of malignant melanoma and other conditions, the need to be aware of its neuropsychiatric complications is essential.

  3. Long-term therapy of interferon-alpha induced pulmonary arterial hypertension with different PDE-5 inhibitors: a case report

    Directory of Open Access Journals (Sweden)

    Baumann Gert

    2005-09-01

    Full Text Available Abstract background Interferon alpha2 is widely used in hepatitis and high-risk melanoma. Interferon-induced pulmonary arterial hypertension as a side effect is rare. Case presentation We describe a melanoma patient who developed severe pulmonary arterial hypertension 30 months after initiation of adjuvant interferon alpha2b therapy. Discontinuation of interferon did not improve pulmonary arterial hypertension. This patient could be treated successfully with phosphodiesterase-5 inhibitor therapy. Conclusion This is only the 5th case of interferon-induced pulmonary arterial hypertension and the first documented case where pulmonary arterial hypertension was not reversible after termination of interferon alpha2 therapy. If interferon alpha2 treated patients develop respiratory symptoms, pulmonary arterial hypertension should be considered in the differential diagnosis. For these patients phosphodiesterase-5 inhibitors, e.g. sildenafil or vardenafil, could be an effective therapeutic approach.

  4. Attempted suicide in two patients with chronic hepatitis C while being treated with Interferon-alpha

    Directory of Open Access Journals (Sweden)

    Seyed-Moayed Alavian

    2004-04-01

    Full Text Available A 36-years old man was treated with Peg-interferon (PEGASYS and ribavirin to controlof Hepatitis C experienced a suicide attempt and was admitted to hospital. Another casetreated by PDferon B® attempted to suicide by consumption more than 100 tablet ofFluxetin. Fortunately their family rescued them. Both of them had a history of depressionand interferon-alpha deepened it. These are the first reports of suicide attempt after treatmentwith PEGASYS and PDferon B® from Iran

  5. Linear IgA bullous dermatosis induced by interferon-alpha 2a.

    Science.gov (United States)

    Kocyigit, P; Akay, B N; Karaosmanoglu, N

    2009-07-01

    Linear Ig A bullous dermatosis (LABD) is an acquired autoimmune subepidermal blistering disorder with linear deposits of IgA along the basement membrane zone. Its cause is unclear, although it appears to have an immune-mediated basis. Idiopathic, systemic disorder-related, and rarely drug-induced forms of LABD have been described. We describe a case of LABD associated with interferon-alpha 2A used for the treatment of Kaposi's sarcoma.

  6. Intensive Farmaco- Surveillance of Interferon Alpha 2b Recombinant in Multiple Sclerosis.

    Directory of Open Access Journals (Sweden)

    Leslie Pérez Ruiz

    2007-12-01

    Full Text Available Background: The interferon alpha 2b recombinant, produced in Cuba, is used in the treatment of different illnesses, such as the multiple sclerosis. For its commercialization it is needed to know its safety scope. Objective: To assess the adverse reactions of interferon alpha 2b recombinant in the treatment of multiple sclerosis. Method: During the period between 1996 and 2006, 70 clinical histories and data collection notebooks of patients included in the randomized double blind national clinical trial phase IV were revised. This trial was developed in the Clinic of Multiple Sclerosis of the Hospital "Dr. Gustavo Aldereguía Lima" in Cienfuegos. With regard to the total of manifested adverse reactions we analyzed type, length, and use of a given treatment to counteract them, intensity level (light, moderate, serious or lethal and causality level (definitive, probable, possible, conditional or not related. Results: 53 patients out of the total presented 207 adverse reactions to interferon. The most frequent were: fever, migraine, chills, arthralgia, asthenia and myalgia, being most of them moderate collateral effects of definitive character. In 197 patients the outcome was favorable. Conclusion: The use of the interferon alpha 2b recombinant was safe in the treatment of the multiple sclerosis in these patients. 

  7. The effects of pegylated interferon--alpha2B on mumps orchitis.

    Science.gov (United States)

    Pal, Goutam

    2013-09-01

    To evaluate the effects of pegylated Interferon--alpha2B on mumps orchitis, 80 patients suffering from mumps orchitis, were randomly assigned into 2 groups of 40 patients each. In the first group patients received pegylated interferon--alpha2B and the other group did not, acting as controls. All were confirmed by mumps IgM (ELISA) and evaluated by testis size, semen analysis and hormone level. In the first group, the symptoms resolved within average 2.2 days and testicular size returned to normal within average 5.3 days but in 2nd group, those returned to normal within average 5.7 days and 10.2 days respectively. In the 1st group, oligospermia was detected in 11 patients and subsequently returned to normal in all patients and there was no testicular atrophy. In the 2nd group oligospermia was detected in 13 patients and were persistently low in 3 patients and testicular atrophy detected in 2 patients. The results indicated the beneficial role of pegylated interferon--alpha2B in preventing infertility from mumps orchitis.

  8. Thyroid hormonal disturbances related to treatment of hepatitis C with interferon-alpha and ribavirin

    Directory of Open Access Journals (Sweden)

    Debora Lucia Seguro Danilovic

    2011-01-01

    Full Text Available OBJECTIVE: To characterize thyroid disturbances induced by interferon-alpha and ribavirin therapy in patients with chronic hepatitis C. INTRODUCTION: Interferon-alpha is used to treat chronic hepatitis C infections. This compound commonly induces both autoimmune and non-autoimmune thyroiditis. METHODS: We prospectively selected 26 patients with chronic hepatitis C infections. Clinical examinations, hormonal evaluations, and color-flow Doppler ultrasonography of the thyroid were performed before and during antiviral therapy. RESULTS: Of the patients in our study, 54% had no thyroid disorders associated with the interferon-alpha therapy but showed reduced levels of total T3 along with a decrease in serum alanine aminotransferase. Total T4 levels were also reduced at 3 and 12 months, but free T4 and thyroid stimulating hormone (TSH levels remained stable. A total of 19% of the subjects had autoimmune interferon-induced thyroiditis, which is characterized by an emerge of antithyroid antibodies or overt hypothyroidism. Additionally, 16% had non-autoimmune thyroiditis, which presents as destructive thyroiditis or subclinical hypothyroidism, and 11% remained in a state of euthyroidism despite the prior existence of antithyroidal antibodies. Thyrotoxicosis with destructive thyroiditis was diagnosed within three months of therapy, and ultrasonography of these patients revealed thyroid shrinkage and discordant change in the vascular patterns. DISCUSSION: Decreases in the total T3 and total T4 levels may be related to improvements in the hepatocellular lesions or inflammatory changes similar to those associated with nonthyroidal illnesses. The immune mechanisms and direct effects of interferon-alpha can be associated with thyroiditis. CONCLUSION: Interferon-alpha and ribavirin induce autoimmune and non-autoimmune thyroiditis and hormonal changes (such as decreased total T3 and total T4 levels, which occur despite stable free T4 and TSH levels. A thyroid

  9. Interferon-alpha induced depressive-like behavior in rats

    DEFF Research Database (Denmark)

    Fischer, C. W.; Liebenberg, N.; Elfving, B.

    2013-01-01

    -Dawley rats (n=40, mean weight 328.3 (plus or minus) 1.55 g) received daily subcutaneous injections with human recombinant IFN-(alpha) (1null106 U/kg/day) or vehicle (saline) for one week. After six days, animals were tested either 1h or 24 hours after injection for depressive-like behavior using......-effects including depression can be induced. The finding in this study that IFN-(alpha)-treated rats show depressive-like behavior supports this notion, and indicates that IFN-(alpha) treatment in rats could represent a viable inflammationinduced animal model of depression. Several theories have been suggested...... the saccharin preference test (SPT) and Forced Swim test (FST), which respectively measure anhedonia and behavioral despair in rodents. Results: IFN-a did not induce sickness behavior, indicated by similar body weight, food and water intake, temperature measurement and locomotor activity between the groups...

  10. Interferon-alpha in the treatment of Philadelphia-negative chronic myeloproliferative neoplasms. Status and perspectives

    DEFF Research Database (Denmark)

    Hasselbalch, Hans Carl; Larsen, Thomas Stauffer; Riley, Caroline Hasselbalch;

    2011-01-01

    The Philadelphia-negative chronic myeloproliferative neoplasms encompass essential thrombocythemia (ET), polycythemia vera (PV) and primary myelofibrosis (PMF). A major break-through in the understanding of the pathogenesis of these neoplasms occurred in 2005 by the discovery of the JAK2 V617F...... shown that interferon-alpha (IFN-alpha) induces complete haematological remissions in a large proportion of the patients. However, its use in clinical practice has unfortunately been limited due to side effects with high drop-out rates in most studies. Recently, IFN-alpha2 has been shown to induce deep...

  11. Rapid progression to cardiac tamponade in Erdheim-Chester disease despite treatment with interferon alpha.

    Science.gov (United States)

    Nakhleh, Afif; Slobodin, Gleb; Elias, Nizar; Bejar, Jacob; Odeh, Majed

    2016-07-01

    Erdheim-Chester disease (ECD) is a rare form of non-Langerhans histiocytosis with heterogeneous clinical manifestations. The most common presentation is bone pains typically involving the long bones. Approximately 75% of the patients develop extraskeletal involvement. Cardiac involvement is seen in up to 45% of the patients, and although, pericardial involvement is the most common cardiac pathology of this rare disease, cardiac tamponade due to ECD has been very rarely reported. We describe a case of a patient found to have ECD with multi-organ involvement and small pericardial effusion, which progressed to cardiac tamponade despite treatment with interferon alpha.

  12. Removing a Cystein Group On Interferon Alpha 2b at Position 2 and 99 does Not Diminish Antitumor Activity of the Protein, Even Better.

    Science.gov (United States)

    Rachmawati, Heni; Jessica, Adhitya; Sumirtaputra, Yeyet Cahyati; Retnoningrum, Debbie Sofie; Adlia, Amirah; Ningrum, Ratih Asmana

    2016-01-01

    Interferon alpha 2b is the only standard therapeutic protein for hepatitis virus infections. Further study demonstrated that this protein also posseses antitumor activity in several cancerous organs. One main pathway of this antitumor activity is mediated through antiproliferation as well as proapoptotic effects. Previously, we have successfully developed recombinant human interferon alpha 2b (rhIFNα2b) by using a synthetic gene. In addition, two mutein forms of rhIFNα2b were generated to improve the characteristics of this protein. Two point mutations showed better pharmacokinetic profiles than one point mutation as well as the native form. In the present study, this mutein form was studied for ist antitumor effect in vitro using HepG2 cells. As a comparison, the native form as well as a commercial rIFNα2b were used. Several parameters were investigated including the MTT assay, cell viability test, cell cycle using flow cytometric analysis, and the genes and protein expressions involved in cell growth. The latest was observed to study the mechanism of rhIFNα2b. There was no significant difference in the MTT assay and cell viability after cells were treated with both forms of rhIFNα2b. However, the mutein rhIFNα2b tended to show better proapoptotic activity reflected by flow cytometric data, protein expression of pSTAT1, and DNA expression of caspase 3.

  13. Vaniprevir with pegylated interferon alpha-2a and ribavirin in treatment-naïve patients with chronic hepatitis C

    DEFF Research Database (Denmark)

    Manns, Michael P; Gane, Edward; Rodriguez-Torres, Maribel

    2012-01-01

    Vaniprevir (MK-7009) is a macrocyclic hepatitis C virus (HCV) nonstructural protein 3/4A protease inhibitor. The aim of the present phase II study was to examine virologic response rates with vaniprevir in combination with pegylated interferon alpha-2a (Peg-IFN-α-2a) plus ribavirin (RBV). In this......Vaniprevir (MK-7009) is a macrocyclic hepatitis C virus (HCV) nonstructural protein 3/4A protease inhibitor. The aim of the present phase II study was to examine virologic response rates with vaniprevir in combination with pegylated interferon alpha-2a (Peg-IFN-α-2a) plus ribavirin (RBV...

  14. Effects of adenoviral delivered interferon-alpha on porcine reproductive and respiratory syndrome virus infection in swine.

    Science.gov (United States)

    Type I interferons, such as interferon alpha (IFN-alpha), contribute to innate antiviral immunity by promoting production of antiviral mediators and also play a role in the adaptive immune response. Porcine reproductive and respiratory syndrome (PRRS) is one of the most devastating and costly diseas...

  15. Tolerance and antiviral effects of high-dose interferon-alpha B/D in patients with chronic hepatitis B

    NARCIS (Netherlands)

    Rasch, MC; Schellekens, H; van Dijck, CMM; Haagsma, EB; Michielsen, PP; van Buuren, AHJAM; Stotter, H; van Hattum, J

    1998-01-01

    A novel recombinant interferon-alpha B/D hybrid was applied to assess tolerability, antiviral effect, and biological activity in chronic hepatitis B. The study was designed as an open nonrandomized trial. Treatment comprised a two-week run-in phase with 16 MU three times a week followed by 14 weeks

  16. Acute pancreatitis associated with pegylated interferon-alpha-2a therapy in chronic hepatitis C.

    Science.gov (United States)

    Choi, Jong Wook; Lee, June Sung; Paik, Woo Hyun; Song, Tae Jun; Kim, Jung Wook; Bae, Won Ki; Kim, Kyung-Ah; Kim, Jung Gon

    2016-03-01

    Chronic hepatitis C virus (HCV) infection is a major cause of liver cirrhosis and hepatocellular carcinoma. Combination therapy of pegylated interferon-alpha (PEG-IFN-α) and ribavirin (RBV) is a current standard treatment for chronic HCV infection in Korea, which has considerable adverse effects. Acute pancreatitis is a rare complication of PEG-IFN-α administration. We report a case of a 62-year-old female who experienced acute pancreatitis after 4 weeks of PEG-IFN-α-2a and RBV combination therapy for chronic HCV infection. The main cause of the acute pancreatitis in this case was probably PEG-IFN-α rather than RBV for several reasons. A few cases have been reported in which acute pancreatitis occurred during treatment with PEG-IFN-α-2b. This is the first report of acute pancreatitis associated with PEG-IFN-α-2a in Korea.

  17. Effective treatment with interferon-alpha in chronic recurrent multifocal osteomyelitis.

    Science.gov (United States)

    Andersson, R

    1995-10-01

    Chronic recurrent multifocal osteomyelitis (CRMO) is a rare disease of unknown etiology characterized by multiple osteomyelitic changes in the predominantly metaphysial regions of long bones. It was first described by Giedon et al. in 1972. Cultures for all known microorganisms are negative. Pain is the most common symptom, and sometimes soft tissue swelling is present. Patients are usually treated with nonsteroidal antiinflammatory drugs (NSAIDs) or corticosteroids and respond, at least partly, to these treatments. CRMO is most commonly seen in children and is in the majority of cases self-limiting but has a protracted course of several years. Some patients have a more prolonged disease period, as in the patient reported here. Treatment with corticosteroids in children has the risk of causing growth retardation as a potential adverse effect, and alternative treatments are of great interest. In the actual paper, a successful treatment with interferon-alpha 2b in a 34-year-old man with CRMO is presented.

  18. Increased depressive ratings in patients with hepatitis C receiving interferon-alpha-based immunotherapy are related to interferon-alpha-induced changes in the serotonergic system.

    Science.gov (United States)

    Bonaccorso, Stefania; Marino, Valentina; Puzella, Antonella; Pasquini, Massimo; Biondi, Massimo; Artini, Marco; Almerighi, Cristiana; Verkerk, Robert; Meltzer, Herbert; Maes, Michael

    2002-02-01

    There is now evidence that repeated administration of interferon-alpha (IFN-alpha) to patients with chronic active hepatitis and cancers induces depressive symptoms. There is also evidence that induction of the cytokine network modulates the serotonergic system and that major depression is related to activation of the cytokine network and disturbances in the serotonergic metabolism. The aims of this study were to examine the effects of IFN-alpha-based immunotherapy on the development of depressive symptoms in relation to its effects on plasma tryptophan and kynurenine and serum serotonin (5-HT). Eighteen patients affected by chronic active hepatitis C were treated with IFN-alpha (3-6 million units subcutaneously three to six times a week for 6 months) and had measurements of the previous parameters before starting immunotherapy and 2, 4, 16, and 24 weeks later. Severity of depression and anxiety were measured with the Montgomery-Asberg Depression Rating Scale (MADRS) and the Hamilton Rating Scale for Anxiety (HAM-A) scale, respectively. Immunochemotherapy with IFN-alpha (1) significantly increased the MADRS and HAM-A scores and serum kynurenine concentrations and (2) significantly reduced plasma tryptophan and serum 5-HT concentrations. IFN-alpha-based immunotherapy significantly increased the kynurenine per tryptophan quotient, which estimates the activity of indoleamine 2,3-dioxygenase, the major tryptophan-catabolizing enzyme, which is induced by IFNs. There are significant relationships between the IFN-alpha-induced changes in the MADRS score and serum kynurenine (positive) and 5-HT (negative) concentrations. Immunotherapy with IFN-alpha significantly increases the severity of depressive symptoms. The latter is related to changes in the serotonergic system, such as depletion of serum 5-HT and induction of the catabolism of tryptophan to kynurenine. It is suggested that the IFN-alpha-induced changes in the serotonergic turnover could play a role in the

  19. Topical Delivery of Interferon Alpha by Biphasic Vesicles: Evidence for a Novel Nanopathway across the Stratum Corneum

    Energy Technology Data Exchange (ETDEWEB)

    Foldvari, M.; Badea, B; Wettig, S; Baboolal, D; Kumar, P; Creagh, A; Haynes, C

    2010-01-01

    Noninvasive delivery of macromolecules across intact skin is challenging but would allow for needle-free administration of many pharmaceuticals. Biphasic vesicles, a novel lipid-based topical delivery system, have been shown to deliver macromolecules into the skin. Investigation of the delivery mechanism of interferon alpha (IFN {alpha}), as a model protein, by biphasic vesicles could improve understanding of molecular transport through the stratum corneum and allow for the design of more effective delivery systems. The interaction of biphasic vesicles with human skin and isolated stratum corneum membrane was investigated by confocal microscopy, differential scanning calorimetry (DSC) and small- and wide-angle X-ray scattering (SAXS and WAXS). Confocal microscopy revealed that biphasic vesicles delivered IFN {alpha} intercellularly, to a depth of 70 {micro}m, well below the stratum corneum and into the viable epidermis. DSC and SAXS/WAXS data suggest that the interaction of biphasic vesicles with SC lipids resulted in the formation of a three-dimensional cubic Pn3m polymorphic phase by the molecular rearrangement of intercellular lipids. This cubic phase could be an intercellular permeation nanopathway that may explain the increased delivery of IFN {alpha} by biphasic vesicles. Liposomes and submicrometer emulsion (the individual building blocks of biphasic vesicles) separately and methylcellulose gel, an alternative topical vehicle, did not induce a cubic phase and delivered low amounts of IFN {alpha} below the stratum corneum. Molecular modeling of the cubic Pn3m phase and lamellar-to-cubic phase transitions provides a plausible mechanism for transport of IFN {alpha}. It is hypothesized that induction of a Pn3m cubic phase in stratum corneum lipids could make dermal and transdermal delivery of other macromolecules also possible.

  20. Clinical Utility of Serum Interleukin-8 and Interferon-Alpha in Thyroid Diseases

    Directory of Open Access Journals (Sweden)

    Toral P. Kobawala

    2011-01-01

    Full Text Available Serum interleukin-8 (IL-8 and interferon-alpha (IFN-α levels have been estimated from a total of 88 individuals of which 19 were disease-free healthy individuals, and 69 were patients with thyroid diseases: goitre (N=21, autoimmune diseases (N=16, and carcinomas (N=32. Both IL-8 and IFN-α were significantly higher in all the patients as compared to healthy individuals. Serum IL-8 levels showed significant positive correlation with disease stage in thyroid cancer patients. Higher serum IL-8 levels were associated with advanced disease stage while no significant correlation was observed between serum IFN-α levels and any of the clinicopathological parameters. IL-8 and IFN-α significantly correlated with each other in anaplastic carcinoma patients. Finally concluding, monitoring the serum IL-8 and IFN-α levels can help differentiate patients with thyroid diseases from healthy individuals, and IL-8 seems to have a role in the pathogenesis of thyroid diseases and may represent a target for innovative diagnostic and therapeutic strategies.

  1. Interferon-alpha induced thyroid dysfunction: three clinical presentations and a review of the literature.

    Science.gov (United States)

    Koh, L K; Greenspan, F S; Yeo, P P

    1997-12-01

    Three patients who developed symptomatic, autoimmune-mediated thyroid dysfunction during treatment with interferon-alpha (IFN-alpha) for chronic active hepatitis C with liver cirrhosis, age-related macular degeneration with foveal involvement, and chronic myelogenous leukemia, respectively, are described. The first two patients developed autoimmune hypothyroidism that required thyroxine replacement, and the third developed autoimmune thyroiditis with transient thyrotoxicosis. The clinical manifestations were protean, and required a high index of suspicion for diagnosis, the failure of which led to significant morbidity. A literature review revealed that the mean incidence of IFN-alpha induced thyroid dysfunction was 6%. Spontaneous resolution occurred in more than half with discontinuation of IFN-alpha treatment. Hypothyroidism was induced more frequently than hyperthyroidism. At least one positive thyroid autoantibody titer was found in 17% of patients receiving IFN-alpha. Risk factors for developing thyroid dysfunction with IFN-alpha treatment were female sex, underlying malignancy or hepatitis C, higher doses of IFN-alpha for longer durations, combination immunotherapy (especially with interleukin-2), and the presence of thyroid autoantibodies prior to or during treatment.

  2. Enabling low cost biopharmaceuticals: high level interferon alpha-2b production in Trichoderma reesei.

    Science.gov (United States)

    Landowski, Christopher P; Mustalahti, Eero; Wahl, Ramon; Croute, Laurence; Sivasiddarthan, Dhinakaran; Westerholm-Parvinen, Ann; Sommer, Benjamin; Ostermeier, Christian; Helk, Bernhard; Saarinen, Juhani; Saloheimo, Markku

    2016-06-10

    The filamentous fungus Trichoderma reesei has tremendous capability to secrete over 100 g/L of proteins and therefore it would make an excellent host system for production of high levels of therapeutic proteins at low cost. We have developed T. reesei strains suitable for production of therapeutic proteins by reducing the secreted protease activity. Protease activity has been the major hindrance to achieving high production levels. We have constructed a series of interferon alpha-2b (IFNα-2b) production strains with 9 protease deletions to gain knowledge for further strain development. We have identified two protease deletions that dramatically improved the production levels. Deletion of the subtilisin protease slp7 and the metalloprotease amp2 has enabled production levels of IFNα-2b up to 2.1 and 2.4 g/L, respectively. With addition of soybean trypsin protease inhibitor the level of production improved to 4.5 g/L, with an additional 1.8 g/L still bound to the secretion carrier protein. High levels of IFNα-2b were produced using T. reesei strains with reduced protease secretion. Further strain development can be done to improve the production system by reducing protease activity and improving carrier protein cleavage.

  3. In-vitro antiviral efficacy of ribavirin and interferon-alpha against canine distemper virus.

    Science.gov (United States)

    Carvalho, Otávio V; Saraiva, Giuliana L; Ferreira, Caroline G T; Felix, Daniele M; Fietto, Juliana L R; Bressan, Gustavo C; Almeida, Márcia R; Silva Júnior, Abelardo

    2014-10-01

    Canine distemper is a highly contagious disease with high incidence and lethality in the canine population. The objective of this study was to evaluate the efficacy of antiviral action with ribavirin (RBV), interferon-alpha (IFNα), and combinations of RBV and IFNα against canine distemper virus (CDV). Vero cells inoculated with CDV were treated with RBV, IFNα, and combinations of these drugs. The efficacy to inhibit viral replication was evaluated by adding the compounds at different times to determine which step of the viral replicative process was affected. Both drugs were effective against CDV in vitro. The IFNα was the most active compound, with an average IC50 (50% inhibitory concentration) value lower than the IC50 of the RBV. Ribavirin (RBV) was more selective than IFNα, however, and neither drug showed extracellular antiviral activity. The combination of RBV and IFNα exhibited antiviral activity for the intra- and extracellular stages of the replicative cycle of CDV, although the intracellular viral inhibition was higher. Both RBV and IFNα showed high antiviral efficacy against CDV, and furthermore, RBV + IFNα combinations have shown greater interference range in viral infectivity. These compounds could potentially be used to treat clinical disease associated with CDV infection.

  4. Interferon alpha induces establishment of alphaherpesvirus latency in sensory neurons in vitro.

    Directory of Open Access Journals (Sweden)

    Nick De Regge

    Full Text Available BACKGROUND: Several alphaherpesviruses, including herpes simplex virus 1 (HSV-1 and pseudorabies virus (PRV, establish lifelong latency in neurons of the trigeminal ganglion (TG. Although it is thought that efficient establishment of alphaherpesvirus latency is based on a subtle interplay between virus, neurons and the immune system, it is not clear which immune components are of major importance for the establishment of latency. METHODOLOGY/PRINCIPAL FINDINGS: Here, using an in vitro model that enables a natural route of infection, we show that interferon alpha (IFNalpha has the previously uncharacterized capacity to induce a quiescent HSV-1 and PRV infection in porcine TG neurons that shows strong similarity to in vivo latency. IFNalpha induced a stably suppressed HSV-1 and PRV infection in TG neurons in vitro. Subsequent treatment of neurons containing stably suppressed virus with forskolin resulted in reactivation of both viruses. HSV and PRV latency in vivo is often accompanied by the expression of latency associated transcripts (LATs. Infection of TG neurons with an HSV-1 mutant expressing LacZ under control of the LAT promoter showed activation of the LAT promoter and RT-PCR analysis confirmed that both HSV-1 and PRV express LATs during latency in vitro. CONCLUSIONS/SIGNIFICANCE: These data represent a unique in vitro model of alphaherpesvirus latency and indicate that IFNalpha may be a driving force in promoting efficient latency establishment.

  5. Histological outcome of chronic hepatitis B in children treated with interferon alpha

    Institute of Scientific and Technical Information of China (English)

    Sobaniec-Lotowska Maria Elzbieta; Lebensztejn Dariusz Marek

    2005-01-01

    AIM: To evaluate the effect of interferon alpha (IFN-α)treatment on the liver histology in children with chronic hepatitis B and to evaluate the usefulness of various histological scoring systems of liver histology in this group of patients.METHODS: Fibrosis stage and inflammation grade were assessed according to Batts and Ludwig, Ishak et al., and METAVIR (only fibrosis stage) before and 12 mo after IFN-α treatment termination in 93 children aged 2-16years with chronic hepatitis B.RESULTS: None of the three numerical scoring systems for liverfibrosis showed statistically significant differences in liver fibrosis, while evolution of inflammatory activity revealed statistically significant improvement in the whole group of children with chronic hepatitis B treated with IFN-α and in responders. Significantly positive correlations were found between fibrosis stage and inflammation grade in the respective scoring systems.CONCLUSION: Treatment with IFN-α did not improve histological fibrosis but decreased inflammatory activity in children with chronic hepatitis B. The three semiquantitative scoring systems seem to be comparable in the estimation of the inflammation grade and fibrosis stage in this group of children.

  6. Plasmacytoid dendritic cells accumulate and secrete interferon alpha in lymph nodes of HIV-1 patients.

    Directory of Open Access Journals (Sweden)

    Clara Lehmann

    Full Text Available Circulating plasmacytoid dendritic cells (pDC decline during HIV-1 infection, but at the same time they express markedly higher levels of interferon alpha (IFNalpha, which is associated with HIV-1 disease progression. Here we show an accumulation of pDC in lymph nodes (LN of treatment-naïve HIV-1 patients. This phenomenon was associated with elevated expression of the LN homing marker, CCR7, on pDC in peripheral blood of HIV-1 patients, which conferred increased migratory capacity in response to CCR7 ligands in ex vivo functional assays. LN-homed pDC of HIV-1 patients presented higher CD40 and lower BDCA2 levels, but unchanged CD83 and CD86 expression. In addition, these cells expressed markedly higher amounts of IFNalpha compared to uninfected individuals, and were undergoing faster rates of cell death. These results demonstrate for the first time that in asymptomatic, untreated HIV-1 patients circulating pDC up-regulate CCR7 expression, accumulate in lymph nodes, and express high amounts of IFNalpha before undergoing cell death. Since IFNalpha inhibits cell proliferation and modulates immune responses, chronically high levels of this cytokine in LN of HIV-1 patients may impair differentiation and immune function of bystander CD4(+ T cells, thus playing into the mechanisms of AIDS immunopathogenesis.

  7. Interferon-alpha (Intron A) upregulates urokinase-type plasminogen activator receptor gene expression.

    Science.gov (United States)

    Wu, Shanshan; Murrell, George A C; Wang, Yao

    2002-07-01

    The regulation of urokinase plasminogen activator receptor (uPAR) gene expression by interferon-alpha (IFN-alpha, or Intron A) and interferon-gamma (IFN-gamma) was studied in a HCT116 colon cancer cell line. uPAR mRNA levels were increased in a dose- and time-dependent manner in cells stimulated with IFN-alpha or IFN-gamma. uPAR protein levels reflected IFN-alpha and IFN-gamma induction of uPAR mRNA production. Cycloheximide, a protein synthesis inhibitor, also induced uPAR mRNA accumulation either alone or in combination with IFN-alpha or IFN-gamma, suggesting that the effect on uPAR mRNA levels activated by IFN-alpha or IFN-gamma does not require de novo protein synthesis. Both sodium butyrate and amiloride inhibited the uPAR mRNA levels induced by IFN-alpha or IFN-gamma. These results may provide useful information for the treatment of patients receiving IFN-alpha or IFN-gamma.

  8. Evaluation criteria of rat hepatocytes transcriptome analysis under the influence of interferon alpha by DNA microarray

    Directory of Open Access Journals (Sweden)

    Kuklin A. V.

    2013-10-01

    Full Text Available The changes induced in transcriptome of rat hepatocytes treated with interferon alpha (IFN during three and six hours were analyzed by DNA microarray. Aim. To conduct a stepwise analysis of the results of microarray experiment and to determine whether they meet/fail to the conventional requirements. Methods. The files obtained after scanning microarrays were subjected to the analysis in statistical environment R by Bioconductor’s packages «affy», «simpleaffy», «affyPLM» and BRB Array Tools software for paired T-test. Results. All microarrays had quality metrics lying within recommended ranges, passed quality control, were normalized and are comparable with each other. The T-test revealed 28 and 124 differentially expressed genes after three and six hours of cells cultivation with IFNα , respectively. Conclusions. The obtained data meet the conventional criteria of quality and are applicable for further evaluation of their biological significance. The R-codes used in this study can be used for the analysis of the microarrays data.

  9. Pharmacokinetic Characteristics, Pharmacodynamic Effect and In Vivo Antiviral Efficacy of Liver-Targeted Interferon Alpha

    Science.gov (United States)

    Rycroft, Daniel; Sosabowski, Jane; Coulstock, Edward; Davies, Marie; Morrey, John; Friel, Sarah; Kelly, Fiona; Hamatake, Robert; Ovečka, Milan; Prince, Rob; Goodall, Laura; Sepp, Armin; Walker, Adam

    2015-01-01

    Interferon alpha (IFNα) is used for the treatment of hepatitis B virus infection, and whilst efficacious, it is associated with multiple adverse events caused by systemic exposure to interferon. We therefore hypothesise that targeting IFN directly to the intended site of action in the liver would reduce exposure in blood and peripheral tissue and hence improve the safety and tolerability of IFNα therapy. Furthermore we investigated whether directing IFN to the reservoir of infection in the liver may improve antiviral efficacy by increasing local concentration in target organs and tissues. Our previous results show that the mIFNα2 fused to an ASGPR specific liver targeting antibody, DOM26h-196-61, results in a fusion protein which retains the activity of both fusion partners when measured in vitro. In vivo targeting of the liver by mIFNα2-DOM26h-196-61, hereafter referred to as targeted mIFNα2, was observed in microSPECT imaging studies in mice. In this study we show by pharmacokinetic analysis that antibody mediated liver-targeting results in increased uptake and exposure of targeted mIFNα2 in target tissues, and correspondingly reduced uptake and exposure in systemic circulation, clearance organs and non-target tissues. We also show that cytokine activity and antiviral activity of liver-targeted IFN is observed in vivo, but that, contrary to expectations, liver-targeting of mIFNα2 using ASGPR specific dAbs actually leads to a reduced pharmacodynamic effect in target organs and lower antiviral activity in vivo when compared to non-targeted mIFNα2-dAb fusions. PMID:25689509

  10. Pharmacokinetic characteristics, pharmacodynamic effect and in vivo antiviral efficacy of liver-targeted interferon alpha.

    Directory of Open Access Journals (Sweden)

    Daniel Rycroft

    Full Text Available Interferon alpha (IFNα is used for the treatment of hepatitis B virus infection, and whilst efficacious, it is associated with multiple adverse events caused by systemic exposure to interferon. We therefore hypothesise that targeting IFN directly to the intended site of action in the liver would reduce exposure in blood and peripheral tissue and hence improve the safety and tolerability of IFNα therapy. Furthermore we investigated whether directing IFN to the reservoir of infection in the liver may improve antiviral efficacy by increasing local concentration in target organs and tissues. Our previous results show that the mIFNα2 fused to an ASGPR specific liver targeting antibody, DOM26h-196-61, results in a fusion protein which retains the activity of both fusion partners when measured in vitro. In vivo targeting of the liver by mIFNα2-DOM26h-196-61, hereafter referred to as targeted mIFNα2, was observed in microSPECT imaging studies in mice. In this study we show by pharmacokinetic analysis that antibody mediated liver-targeting results in increased uptake and exposure of targeted mIFNα2 in target tissues, and correspondingly reduced uptake and exposure in systemic circulation, clearance organs and non-target tissues. We also show that cytokine activity and antiviral activity of liver-targeted IFN is observed in vivo, but that, contrary to expectations, liver-targeting of mIFNα2 using ASGPR specific dAbs actually leads to a reduced pharmacodynamic effect in target organs and lower antiviral activity in vivo when compared to non-targeted mIFNα2-dAb fusions.

  11. Interferon-alpha-2b induces autophagy in hepatocellular carcinoma cells through Beclin1 pathway

    Institute of Scientific and Technical Information of China (English)

    Jun Zhao; Ming-Li Wang; Zeng Li; Dong-Mei Gao; Yu Cai; Jun Chang; Shi-Ping Wang

    2014-01-01

    Objective:To determine whether Interferon-alpha-2b (IFN-α2b) can modulate the autophagic response in hepatocellular carcinoma cells. Methods:Hepatocellular carcinoma cells were treated with IFN-α2b. Autophagy was assessed by acridine orange staining, GFP-LC3 dotted assay, transmission electron microscopy and immunoblotting. Results:Acridine orange staining showed that IFN-α2b triggered the accumulation of acidic vesicular and autolysosomes in HepG2 cells. hTe acridine orange HepG2 cell ratios were (4.3±1.0)%, (6.9±1.4)%, and (13.1±2.3)%, respectively, atfer treatment with 100, 1,000, and 10,000 IU/mL IFN-α2b for 48 h. A markedly punctate pattern was observed in HepG2 cells treated with 10,000 IU/mL IFN-α2b for 48 h, but only diffuse and weakly lfuorescent GFP-LC3 puncta was observed in control cells. HepG2 cells treated with 10,000 IU/mL IFN-α2b for 48 h developed autophagosome-like characteristics, including single-or double-membrane vacuoles containing intact and degraded cellular debris. The Beclin1 and LC3-II protein expression was up-regulated by IFN-α2b treatment. Conclusion:Autophagy can be induced in a dose-dependent manner by treatment with IFN-α2b in HepG2 cells, and the Beclin1 signaling pathway was stimulated by IFN-α2b.

  12. Minocycline treatment ameliorates interferon-alpha-induced neurogenic defects and depression-like behaviors in mice

    Directory of Open Access Journals (Sweden)

    Lian-Shun eZheng

    2015-01-01

    Full Text Available Interferon-alpha (IFN-α is a proinflammatory cytokine that is widely used for the treatment of chronic viral hepatitis and malignancy, because of its immune-activating, antiviral, and antiproliferative properties. However, long-term IFN-α treatment frequently causes depression, which limits its clinical utility. The precise molecular and cellular mechanisms of IFN-α-induced depression are not currently understood. Neural stem cells (NSCs in the hippocampus continuously generate new neurons, and some evidence suggests that decreased neurogenesis plays a role in the neuropathology of depression. We previously reported that IFN-α treatment suppressed hippocampal neurogenesis and induced depression-like behaviors via its receptors in the brain in adult mice. However, it is unclear how systemic IFN-α administration induces IFN-α signaling in the hippocampus. In this study, we analyzed the role of microglia, immune cells in the brain, in mediating the IFN-α-induced neurogenic defects and depressive behaviors. In vitro studies demonstrated that IFN-α treatment induced the secretion of endogenous IFN-α from microglia, which suppressed NSC proliferation. In vivo treatment of adult mice with IFN-α for five weeks increased the production of proinflammatory cytokines, including IFN-α, and reduced neurogenesis in the hippocampus. Both effects were prevented by simultaneous treatment with minocycline, an inhibitor of microglial activation. Furthermore, minocycline treatment significantly suppressed IFN-α-induced depressive behaviors in mice. These results suggest that microglial activation plays a critical role in the development of IFN-α-induced depression, and that minocycline is a promising drug for the treatment of IFN-α-induced depression in patients, especially those who are low responders to conventional antidepressant treatments.

  13. Thyroid disorders in patients with chronic hepatitis C using interferon-alpha and ribavirin therapy

    Directory of Open Access Journals (Sweden)

    Luis Jesuino de Oliveira Andrade

    2011-08-01

    Full Text Available OBJECTIVE: To investigate the frequency of thyroid disorders (TD in patients with chronic hepatitis C before and during interferon-alpha (IFN-α and ribavirin (RIB treatment. STUDY DESIGN: Prospective study. PATIENTS AND METHODS: We prospectively studied 65 anti-HCV and viral RNA positive patients. Free thyroxine, thyroid-stimulating hormone, and thyroid peroxidase antibodies (TPO-Ab were systematically tested at entry (m0, week 12 (m3 and week 24 (m6 of treatment. RESULTS: Mean age of the 65 patients (38 females and 27 males was 49.61 ± 11.83 years. Seven (10.76% patients presented baseline thyroid disorders (m0, three had thyroid dysfunction, and four were TPO-Ab positive. Thyroid disorders occurred in the first 12 weeks of treatment in 11 (16.92% patients, four with thyroid dysfunction, and seven with TPO-Ab positive (m3. A total of 18 patients (27.69% developed TD after 24 weeks of treatment, 7 with thyroid dysfunction, and 11 with TPO-Ab positive (m6. The relative risk of developing hypothyroidism found in this study was 1.3 (95% CI: 1.1 to 1.6, hyperthyroidism 1.2 (95% CI: 1.1 to 1.4, and TPO-Ab positivity 7.6 (95% CI: 3.9 to 14.5. The study showed a significant association between female sex and thyroid disease (p = 0.009. CONCLUSION: Thyroid dysfunction and autoimmune TD were observed during IFN-α and RIB therapy.

  14. Changes in serum and histology of patients with chronic hepatitis B after interferon alpha-2b treatment

    Institute of Scientific and Technical Information of China (English)

    Hong-Lei Han; Zhen-Wei Lang

    2003-01-01

    AIM: Chronic hepatitis B is a serious health problem.Interferon has long been used to treat Chronic hepatitis B.To evaluate the effects of interferon on chronic hepatitis Bbetter, we designed the study to investigate the changes insera and liver histology of patients with chronic hepatitis Bafter interferon alpha-2b treatment.METHODS: Twenty-four patients with chronic hepatitis Bwere enrolled in this study. They all received interferon alpha-2b treatment as following: 3 million units, i.m.. t.i.w., for 18weeks. Sera of all patients were obtained respectively forevaluation of ALT, HBsAg, HBcAg, HBeAg, HBV DNA andTIMP-1 before and afterinterferon treatment, also a liverbiopsy pre- and post-treatment was performed forcomparison of HAI, HBsAg, HBcAg, HBeAg, TIMP-1 andactivated HSC in the liver tissue.RESULTS: Patients who had normalization of serum ALTand seroconversion of HBeAg and/or HBV DNA (blothybridization) after treatment were defined as responders.The response rate in this study group was 37.5 % (7/24).Compared to pretreatment, the serum HBV DNA and TIMP-1 decreased significantly (P<0.05), so did the HAI, HBo Ag,HBeAg, TIMP-1 and activated HSC (P<0.05).CONCLUSION: The significant decrease in HBV DNA insera, the seroconversion of HBeAg, and the decrease ofviral expression in liver indicated that interferon alpha-2btreatment can inhibit viral replication. The normalization ofALT in sera and the improvement of HAI in liver showedthat interferon alpha-2b can improve the liver histology ofpatients with chronic hepatitis B. At the same time, interferonalpha-2b treatment can reduce the TIMP-1 in serum andliver and decrease the number of activated HSC, which mayallievate or inhibit hepatic fibrosis. Although the responserate was unsatisfactory, interferon play a benefical role onpatients with chronic hepatitis B in other respects. We stillneed further studies to improve the therapy effects.

  15. Simultaneous development of diabetic ketoacidosis and Hashitoxicosis in a patient treated with pegylated interferon-alpha for chronic hepatitis C

    Institute of Scientific and Technical Information of China (English)

    Aspasia S Soultati; Spyridon P Dourakis; Alexandra Alexopoulou; Melanie Deutsch; Athanasios J Archimandritis

    2007-01-01

    Classical interferon-alpha has been shown to be correlated with the development of a variety of autoimmune disorders. A 38 year-old female patient developed simultaneously diabetic ketoacidosis and hyperthyroidism 5 mo following initiation of treatment with pegylated interferon-α and ribavirin for chronic hepatitis C. High titers of glutamic acid decarboxylase,antinuclear and thyroid (thyroid peroxidase and thyroglobulin) antibodies were detected. Antiviral treatment was withdrawn and the patient was treated with insulin for insulin-dependent diabetes mellitus and propranolol for hyperthyroidism. Twelve months after cessation of pegylated interferon-α therapy the patient was euthyroid without any medication but remained insulin-dependent.

  16. Modelling Adaptive Learning Behaviours for Consensus Formation in Human Societies

    Science.gov (United States)

    Yu, Chao; Tan, Guozhen; Lv, Hongtao; Wang, Zhen; Meng, Jun; Hao, Jianye; Ren, Fenghui

    2016-06-01

    Learning is an important capability of humans and plays a vital role in human society for forming beliefs and opinions. In this paper, we investigate how learning affects the dynamics of opinion formation in social networks. A novel learning model is proposed, in which agents can dynamically adapt their learning behaviours in order to facilitate the formation of consensus among them, and thus establish a consistent social norm in the whole population more efficiently. In the model, agents adapt their opinions through trail-and-error interactions with others. By exploiting historical interaction experience, a guiding opinion, which is considered to be the most successful opinion in the neighbourhood, can be generated based on the principle of evolutionary game theory. Then, depending on the consistency between its own opinion and the guiding opinion, a focal agent can realize whether its opinion complies with the social norm (i.e., the majority opinion that has been adopted) in the population, and adapt its behaviours accordingly. The highlight of the model lies in that it captures the essential features of people’s adaptive learning behaviours during the evolution and formation of opinions. Experimental results show that the proposed model can facilitate the formation of consensus among agents, and some critical factors such as size of opinion space and network topology can have significant influences on opinion dynamics.

  17. Psychosocial assessment and monitoring in the new era of non-interferon-alpha hepatitis C virus treatments

    Institute of Scientific and Technical Information of China (English)

    Paul; J; Rowan; Nizar; Bhulani

    2015-01-01

    Chronic hepatitis C virus(HCV) is a global concern. With the 2014 Food and Drug Administration approvals of two direct-acting antiviral(DAA) regimens, ledipasvir/sofosbuvir regimen and the ombitasvir/paritaprevir/ritonavir and dasabuvir regimen, we may now be in the era of all-pill regimens for HCV. Until this development, interferon-alpha along with Ribavirin has remained part of the standard of care for HCV patients. That regimen necessitates psychosocial assessment of factors affecting treatment eligibility, including interferon-alpharelated depressive symptoms, confounding psychiatric conditions, and social aspects such as homelessness affecting treatment eligibility. These factors have delayed as much as 70% of otherwise eligible candidates from interferon-based treatment, and have required treating physicians to monitor psychiatric as well as medical side effects throughout treatment. Allpill DAA regimens with the efficaciousness that would preclude reliance upon interferon-alpha or ribavirin have been anticipated for years. Efficacy studies for these recently approved DAA regimens provide evidence to assess the degree that psychosocial assessment and monitoring will be required. With shorter treatment timelines, greatly reduced side effect profiles, and easier regimens, psychosocial contraindications are greatly reduced. However, current or recent psychiatric comorbidity, and drug-drug interactions with psychiatric drugs, will require some level of clinical attention. Evidence from these efficacy studies tentatively demonstrate that the era of needing significant psychosocial assessment and monitoring may be at an end, as long as a manageable handful of clinical issues are managed.

  18. Influence of bovine serum albumin on the secondary structure of interferon alpha 2b as determined by far UV circular dichroism spectropolarimetry.

    Science.gov (United States)

    Johnston, Michael J W; Nemr, Kayla; Hefford, Mary A

    2010-03-01

    Many therapeutic biologics are formulated with excipients, including the protein excipient human serum albumin (HSA), to increase stability and prevent protein aggregation and adsorption onto glass vials. One biologic formulated with albumin is interferon alpha-2b (IFN alpha-2b). As is the case with other therapeutic biologics, the increased structural complexity of IFN alpha-2b compared to a small molecule drug requires that both the correct chemical structure (amino acid sequence) and also the correct secondary and tertiary structures (3 dimensional fold) be verified to assure safety and efficacy. Although numerous techniques are available to assess a biologic's primary, secondary and tertiary structures, difficulties arise when assessing higher order structure in the presence of protein excipients. In these studies far UV circular dichroism spectropolarimetry (far UV-CD) was used to determine the secondary structure of IFN alpha-2b in the presence of a protein excipient (bovine serum albumin, BSA). We demonstrated that the secondary structure of IFN alpha-2b remains mostly unchanged at a variety of BSA to IFN alpha-2b protein ratios. A significant difference in alpha helix and beta sheet content was noted when the BSA to IFN alpha-2b ratio was 5:1 (w/w), suggesting a potential conformational change in IFN alpha-2b secondary structure when BSA is in molar excess.

  19. Phase II Study of Adjuvant Immunotherapy with the CSF-470 Vaccine Plus Bacillus Calmette–Guerin Plus Recombinant Human Granulocyte Macrophage-Colony Stimulating Factor vs Medium-Dose Interferon Alpha 2B in Stages IIB, IIC, and III Cutaneous Melanoma Patients: A Single Institution, Randomized Study

    Directory of Open Access Journals (Sweden)

    José Mordoh

    2017-05-01

    Full Text Available The irradiated, allogeneic, cellular CSF-470 vaccine plus Bacillus Calmette–Guerin (BCG and recombinant human granulocyte macrophage-colony stimulating factor (rhGM-CSF is being tested against medium-dose IFN-α2b in stages IIB–III cutaneous melanoma (CM patients (pts after surgery in an open, randomized, Phase II/III study. We present the results of the Phase II part of the ongoing CASVAC-0401 study (ClinicalTrials.gov: NCT01729663. Thirty-one pts were randomized to the CSF-470 vaccine (n = 20 or to the IFN-α2b arm (n = 11. During the 2-year treatment, immunized pts should receive 13 vaccinations. On day 1 of each visit, 1.6 × 107 irradiated CSF-470 cells plus 106 colony-forming units BCG plus 100 µg rhGM-CSF were administered intradermally, followed on days 2–4 by 100 µg rhGM-CSF. IFN-α2b pts should receive 10 million units (MU/day/5 days a week for 4 weeks; then 5 MU thrice weekly for 23 months. Toxicity and quality of life (QOL were evaluated at each visit. With a mean and a maximum follow-up of 39.4 and 83 months, respectively, a significant benefit in the distant metastasis-free survival (DMFS for CSF-470 was observed (p = 0.022. Immune monitoring showed an increase in antitumoral cellular and humoral response in vaccinated pts. CSF-470 was well tolerated; 20/20 pts presented grades 1–2 dermic reactions at the vaccination site; 3/20 pts presented grade 3 allergic reactions. Other adverse events (AEs were grade 1. Pts in the IFN-α2b arm presented grades 2–3 hematological (7/11, hepatic (2/11, and cardiac (1/11 toxicity; AEs in 9/11 pts forced treatment interruptions. QOL was significantly superior in the vaccine arm (p < 0.0001. Our results suggest that CSF-470 vaccine plus BCG plus GM-CSF can significantly prolong, with lower toxicity, the DMFS of high-risk CM pts with respect to medium-dose IFN-α2b. The continuation of a Phase III part of the CASVAC-0401 study is encouraged.

  20. [Chronic inflammatory demyelinating polyneuropathy after treatment with pegylated interferon alpha 2b in a patient with HIV/HCV coinfection: case report].

    Science.gov (United States)

    Bassetti, Bil Randerson; Trés, Eduardo Sturzeneker; Ciríaco, Jovana Gobbi Marchesi; Pinto Neto, Lauro Ferreira Silva

    2010-01-01

    Chronic inflammatory demyelinating polyneuropathy has a strong association with HIV and HCV infection. A rare association between chronic inflammatory demyelinating polyneuropathy and hepatitis C treatment with pegylated interferon alpha was described recently. We described the first case of chronic inflammatory demyelinating polyneuropathy associated with pegylated interferon alpha 2b in a white man infected with HIV and HCV. The patient recovered completely with the use of intravenous hyperimmune immunoglobulin. Infectologists and hepatologists should be alert regarding this rare and serious association, which requires immediately drug discontinuation and early treatment.

  1. The Spanish human papillomavirus vaccine consensus group: a working model.

    Science.gov (United States)

    Cortés-Bordoy, Javier; Martinón-Torres, Federico

    2010-08-01

    Successful implementation of Human Papillomavirus (HPV) vaccine in each country can only be achieved from a complementary and synergistic perspective, integrating all the different points of view of the diverse related professionals. It is this context where the Spanish HPV Vaccine Consensus Group (Grupo Español de Consenso sobre la Vacuna VPH, GEC-VPH) was created. GEC-VPH philosophy, objectives and experience are reported in this article, with particular attention to the management of negative publicity and anti-vaccine groups. Initiatives as GEC-VPH--adapted to each country's particular idiosyncrasies--might help to overcome the existing barriers and to achieve wide and early implementation of HPV vaccination.

  2. Long-term efficacy and safety of interferon-alpha-2B in patients with mumps orchitis.

    Science.gov (United States)

    Yapanoglu, Turgut; Kocaturk, Huseyin; Aksoy, Yilmaz; Alper, Fatih; Ozbey, Isa

    2010-12-01

    The aim of this study was to determine long-term efficacy and safety subcutaneous injection of interferon-alpha-2B in patients with mumps orchitis in terms of testicular volume and other testicular functions. Mumps orchitis was evaluated in 37 patients. Patients were hospitalized and administered 1 × 3,000,000 IU subcutaneous injection of interferon-alpha-2B daily for 7 days. The testicular volumes of all the patients were measured by ultrasonography in the 18th month following treatment termination. The testes volumes were evaluated by descriptive statistics as percentages. Patients were divided into three groups according to testes volumes and differences between the involved and non-involved testicles. Group I included patients with normal testes volume (> 12 ml) and a difference between testes of less than 2 ml or 20%; Group II (atrophic groups) included patients with testes volume of less than 12 ml; and Group III (hypotrophic groups) included patients with testes volume of greater than 12 ml and a difference between testes of more than 2 ml or 20%. Groups were compared in terms of results of semen analysis and serum follicle stimulating hormone (FSH) and luteinizing hormone (LH) levels. Patients' ages ranged between 17 and 41 years (mean: 28.3 years). A total of nine atrophy cases were identified. Sixteen patients were determined to have hypotrophic testes with a difference of 2-10 ml or 20% between the involved and non-involved testicles, despite the absence of testicular atrophy. A comparison of groups revealed that sperm density, total sperm count, total motile sperm count, and motility percentage were significantly higher in Group I than in the other groups, while serum FSH and LH levels were lower in Group I than in the other groups. Although the use of interferon-alpha-2B appears to prevent testicular atrophy and protect testicular function, it leads to a considerable difference in the volume between testicles and a significant loss of testicular

  3. The impact of the combination of baseline risk group and cytogenetic response on the survival of patients with chronic myelold leukemia treated with interferon-alpha

    NARCIS (Netherlands)

    Hasford, J; Pfirrmann, M; Shepherd, P; Guilhot, J; Hehlmann, R; Mahon, FX; Kluin-Nelemans, HC; Ohnishi, K; Steegmann, JL; Thaler, J

    Background and Objectives. This study was aimed at examining major cytogenetic response (MCR) as a valid predictor of the course of chronic myeloid leukemia (CML) and at assessing the survival of CML patients treated with interferon alpha (IFN) in dependence on the combination of MCR (yes or no)

  4. Randomized study on hydroxyurea alone versus hydroxyurea combined with low-dose interferon-alpha 2b for chronic myeloid leukemia

    NARCIS (Netherlands)

    Kluin-Nelemans, JC; Delannoy, A; Louwagie, A; Le Cessie, S; Hermans, J; van der Burgh, JF; Hagemeijer, AM; Van den Berghe, H

    1998-01-01

    Interferon-alpha (IFN-alpha) is considered the standard therapy for chronic myeloid leukemia (CML) patients not suitable for allogeneic stem cell transplantation. From 1987 through 1992, 195 patients in the Benelux with recent untreated CML were randomized between low-dose IFN-alpha 2b (3 MIU, 5 day

  5. The long-term effect of treatment with interferon-alpha 2a in chronic hepatitis B

    DEFF Research Database (Denmark)

    Krogsgaard, K

    1998-01-01

    This study was performed to evaluate the long-term effects of interferon-alpha 2a (IFN-alpha 2a) vs no treatment in patients with chronic hepatitis B and to determine whether viral clearance, following therapy or occurring spontaneously, was sustained. Patients originating from three previously...... published multicentre, randomized, controlled trials were analysed. Information about survival and response during long-term follow-up was available in 340 (73%) and 308 (66%) of 469 randomized patients respectively. Response to therapy (viral clearance) was defined as: loss of hepatitis B virus (HBV) DNA...... and loss of hepatitis B e antigen (HBeAg) and improvement in alanine aminotransferase level. Scheduled treatment-free follow-up was 12 months in all studies. Median long-term follow-up time after inclusion in the individual studies was 4.7 years (range: 0.2-7.5 years). Viral clearance after IFN-alpha 2a...

  6. Improved scar in postburn patients following interferon-alpha2b treatment is associated with decreased angiogenesis mediated by vascular endothelial cell growth factor.

    Science.gov (United States)

    Wang, Jianfei; Chen, Hong; Shankowsky, Heather A; Scott, Paul G; Tredget, Edward E

    2008-07-01

    Hypertrophic scar (HTS) after thermal injury is a dermal fibroproliferative disorder, which leads to considerable morbidity. Previous clinical studies from our laboratory have suggested that interferon-alpha2b (IFN-alpha2b) improves scar quality as a result of the suppression of fibroblast function. More recently, our work has demonstrated that the improvement of scar in patients with HTS after IFN-alpha2b treatment may be associated with a decreased number of fibrocytes and/or altered fibrocyte function. In this study, we report that the improvement of HTS after IFNalpha-2b treatment may be associated with a decrease in angiogenesis. Using immunohistochemistry, we demonstrate an increase in angiogenesis in HTS compared to normal skin, and also show an increase in the expression of vascular endothelial cell growth factor (VEGF) in HTS. Subsequently, we demonstrate a significant reduction in angiogenesis in HTS tissue from patients after treatment with systemic IFN-alpha2b. By using a [3H] thymidine incorporation assay, we demonstrate that IFN-alpha2b suppresses the proliferation of human umbilical vein endothelial cells (HUVECs) in a dose-dependent manner. In addition, IFN-alpha2b inhibits VEGF-induced proliferation and tube formation by using HUVECs. All these effects may be a result of the blocking of VEGF receptor expression on endothelial cells by IFN-alpha2b. Taken together with previous results, the present study suggests that the improvement of scar quality in HTS patients after IFN-alpha2b treatment may also be associated with decreased angiogenesis in HTS. The current in vitro results may provide some insights into the scar improvement that is seen with systemic IFN-alpha2b treatment.

  7. Intrahepatic expression of interferon alpha & interferon alpha ...

    African Journals Online (AJOL)

    kemrilib

    Egypt. Patients with cirrhosis secondary to chronic HCV infection are at increased risk ... kinases to the Interferon receptors, Type 1 and. Type II. IFN-α and IFN-β have a common receptor .... columns was performed and Mann Whitney Non-.

  8. Rome Consensus Conference - statement; human papilloma virus diseases in males.

    Science.gov (United States)

    Lenzi, Andrea; Mirone, Vincenzo; Gentile, Vincenzo; Bartoletti, Riccardo; Ficarra, Vincenzo; Foresta, Carlo; Mariani, Luciano; Mazzoli, Sandra; Parisi, Saverio G; Perino, Antonio; Picardo, Mauro; Zotti, Carla Maria

    2013-02-07

    Human Papillomavirus (HPV) is a very resistant, ubiquitous virus that can survive in the environment without a host. The decision to analyse HPV-related diseases in males was due to the broad dissemination of the virus, and, above all, by the need to stress the importance of primary and secondary prevention measures (currently available for women exclusively). The objective of the Consensus Conference was to make evidence-based recommendations that were designed to facilitate the adoption of a standard approach in clinical practice in Italy. The Sponsoring Panel put a series of questions to the members of the Scientific Committee who prepared a summary of the currently available information, relevant for each question, after the review and grading of the existing scientific literature. The summaries were presented to a Jury, also called multidisciplinary Consensus Panel, who drafted a series of recommendations. The prevalence of HPV in males ranges between 1.3-72.9%;. The prevalence curve in males is much higher than that in females and does not tend to decline with age. Women appear to have a higher probability of acquiring HPV genotypes associated with a high oncogenic risk, whereas in males the probability of acquiring low- or high-risk genotypes is similar. The HPV-related diseases that affect males are anogenital warts and cancers of the penis, anus and oropharynx. The quadrivalent vaccine against HPV has proved to be effective in preventing external genital lesions in males aged 16-26 years in 90.4%; (95%; CI: 69.2-98.1) of cases. It has also proved to be effective in preventing precancerous anal lesions in 77.5%; (95%; CI: 39.6-93.3) of cases in a per-protocol analysis and in 91.7%; (95%; CI: 44.6-99.8) of cases in a post-hoc analysis. Early ecological studies demonstrate reduction of genital warts in vaccinated females and some herd immunity in males when vaccine coverage is high, although males who have sex with males gained no benefit at all. Males with

  9. An extremely rare case of delusional parasitosis in a chronic hepatitis C patient during pegylated interferon alpha-2b and ribavirin treatment

    Institute of Scientific and Technical Information of China (English)

    Geert Robaeys; Jozef De Bie; Marc Van Ranst; Frank Buntinx

    2007-01-01

    During treatment of chronic hepatitis C patients with interferon and ribavirin, a lot of side effects are described. Twenty-three percent to 44% of patients develop depression. A minority of patients evolve to psychosis. To the best of our knowledge, no cases of psychogenic parasitosis occurring during interferon therapy have been described in the literature. We present a 49-year-old woman who developed a delusional parasitosis during treatment with pegylated interferon alpha-2b weekly and ribavirin. She complained of seeing parasites and the larvae of fleas in her stools. This could not be confirmed by any technical examination. All the complaints disappeared after stopping pegylated interferon alpha-2b and reappeared after restarting it. She had a complete sustained viral response.

  10. The genetic differences with whole genome linkage disequilibrium mapping between responder and non-responder in interferon-alpha and ribavirin combined therapy for chronic hepatitis C patients.

    Science.gov (United States)

    Chen, P-J; Hwang, Y; Lin, C G-J; Wu, Y-J; Wu, L S-H

    2008-04-01

    Interferon-alpha and ribavirin combined therapy has been a mainstream treatment for hepatitis C infection. The efficacy of this combined treatment is around 30% to 60%, and the factors affecting the responsiveness are still poorly defined. Our study is intended to investigate the genetic differences between responder and non-responder patients. The genome-wide linkage disequilibrium screening for loci associated with genetic difference between two patient groups was conducted by using 382 autosomal short tandem repeat (STR) markers involving 92 patients. We have identified 19 STR markers displaying different allele frequencies between the two patient groups. In addition, based on their genomic location and biological function, we selected the CD81 and IL15 genes to perform single nucleotide polymorphism genotyping. In conclusion, this study may provide a new approach for identifying the associated polymorphisms and the susceptible loci for interferon-alpha and ribavirin combined therapy in patients with chronic hepatitis C.

  11. Efficacy of interferon alpha- 2b with or without ribavirin in thalassemia major patients with chronic hepatitis C virus infection: A randomized, double blind, controlled, parallel group trial

    Directory of Open Access Journals (Sweden)

    Hamid Kalantari

    2010-01-01

    Full Text Available Background: The aim of this study was to evaluate the effectiveness of monotherapy with interferon alpha- 2b and combination therapy with interferon alpha- 2b plus ribavirin on chronic hepatitis C infection in thalassaemic patients. Methods: In parallel group randomized, double blind, controlled trial, 32 thalassaemic patients with chronic hepatitis C infection completed the study. In a random fashion, one group was treated with three million units of interferon alpha- 2b three times a week plus ribavirin (800- 1200 mg daily. The second group received interferon alpha- 2b alone. Treatment duration was 24- 48 weeks. Primary efficacy variables were HCV RNA after treatment and sustained viral response (SVR six months after treatment. Results: The mean age of patients was 22 ± 7.4 years; 19 (59.4% were male and 13 (40.6 were female. At the end of treatment, no statistically significant differences were found between the groups in HCV RNA and AST. The proportion of patients with SVR six months after treatment was significantly greater in the monotherapy group (90.9% than in the combination therapy group (44.4%; p = 0.049. A significant difference in mean of ALT was also obtained at the end of treatment between monotherapy and combination therapy groups (30.4 ± 19.2 and 60.1 ± 48.9, respectively; p = 0.02. Response rates were not associated with genotype and severity of hepatitis C infection in both groups. Conclusions: These results suggest that monotherapy may be considered as the first- line therapy in patients with thalassemia.

  12. Budd-Chiari syndrome and heparin-induced thrombocytopenia in polycythemia vera: Successful treatment with repeated TIPS and interferon alpha

    Directory of Open Access Journals (Sweden)

    Akoum Riad

    2009-01-01

    Full Text Available Polycythemia vera (PV is a common cause of Budd-Chiari syndrome (BCS and portal vein thrombosis (PVT. The postpartum period is a precipitating cofactor. An additional heparin-induced thrombocytopenia/thrombosis (HIT/T leads to a life-threatening condition in which transjugular intrahepatic portosystemic shunting (TIPS seems to be the only life-saving procedure. We describe the case of a subacute BCS and PVT in the late postpartum period. The diagnosis was established using CT scan, MRI, and Doppler ultrasonography of abdominal vessels and the laboratory findings were compatible with PV. After a successful creation of TIPS, a HIT/T worsened the hemorrhagic and thrombotic picture. TIPS procedure was successfully repeated and heparin was replaced with Fondaparinux and then vitamin K antagonist. The treatment with interferon alpha-2A, started after the normalization of liver functions, resulted in a complete remission within 6 months. The JAK2 V617F mutation clone remained undetectable after 2 years′ follow-up.

  13. Interferon alpha in the treatment of chronic hepatitis C in children: a meta-analysis [correction of metanalysis].

    Science.gov (United States)

    Di Ciommo, V; Russo, P; Ravà, L; Caprino, L

    2003-05-01

    Children with chronic hepatitis C may be ideal candidates for treatment with interferon alpha (IFNalpha) as they have liver disease at an early stage. However, adverse drug reactions need to be considered. The aim of this study was to conduct a systematic review of literature on interferon therapy of chronic hepatitis C in children, and to perform a meta-analysis of pooled data. A computerized search gave 18 articles on IFNalpha therapy in children with chronic hepatitis C; after exclusion of uncontrolled trials and of trials including patients with comorbidities, data from two studies could be pooled (48 patients). The outcomes assessed were biochemical, defined as normalization of alanine transaminase, and virologic, defined as HCV-RNA loss, both sustained at 24 months after enrollment. Results of the studies were homogenous. Risk difference was 37% (95%CI: 12.9-61) in favour of IFNalpha treated children for sustained biochemical response, and 36.8% (95%CI: 14.3-59.3) in favour of treated children for sustained HCV clearance, respectively. The differences were highly significant (P = 0.007 and P = 0.004, respectively). The histological end-point, as well as side-effects, could not be analysed, due to lack of data. This review identifies the poor methodology of the majority of the published trials. The study provides support for the efficacy of IFNalpha in improving both biochemical and virologic outcomes in chronic hepatitis C in children, but evidence is confined to these surrogate end-points.

  14. Interferon-alpha-induced destructive thyroiditis followed by Graves' disease in a patient with chronic hepatitis C: a case report.

    Science.gov (United States)

    Kim, Bu Kyung; Choi, Young Sik; Park, Yo Han; Lee, Sang Uk

    2011-12-01

    Interferon-induced thyroiditis (IIT) is a major clinical problem for patients receiving interferon-alpha (IFN-α) therapy. But, destructive thyroiditis followed by Graves' disease associated with IFN-α therapy is very rarely reported. Herein, we report a rare case of pegylated IFN-α (pegIFN-α) induced destructive thyroiditis followed by Graves' disease in a patient with HCV infection. A 31-yr-old woman suffered from chronic active hepatitis C and was treated with pegIFN-α and ribavirin for 12 months. Results of a thyroid function test and autoantibody levels were normal before IFN-α therapy was initiated. Destructive thyrotoxicosis appeared seven months after the initiation of IFN-α therapy, followed by Graves' thyrotoxicosis two months after the cessation of therapy. The diagnoses of destructive thyroiditis and Graves' disease were confirmed by the presence of TSH receptor antibodies in addition to Tc-99m scintigraphy findings. The patient's antithyroglobulin antibody titer increased gradually during IFN-α therapy and remained weakly positive after IFN-α therapy was discontinued.

  15. B-Cell-Activating Factor Affects the Occurrence of Thyroid Autoimmunity in Chronic Hepatitis C Patients Treated with Interferon Alpha

    Directory of Open Access Journals (Sweden)

    Yusuke Kajiyama

    2012-01-01

    Full Text Available Chronic hepatitis C (CHC patients frequently suffer from thyroid disorders during interferon therapy. However, the mechanism remains unclear. In this study, we investigated the association between serum B-cell-activating factor belonging to the TNF family (BAFF levels and the presence of antithyroid peroxidase antibody (anti-TPO in CHC patients treated with pegylated interferon alpha and ribavirin combination therapy. Six months after the therapy, anti-TPO antibody was detected in 10 (males, 1; females, 9 of 50 patients. The mean age of these patients was higher than that of the anti-TPO-negative patients (61 yr versus 55 yr. Before treatment, the serum BAFF levels of the anti-TPO-positive patients were higher than those of the anti-TPO-negative patients. After starting therapy, the serum BAFF levels of both the anti-TPO-positive and -negative patient groups were elevated. Our findings suggest that the serum BAFF concentration before therapy can predict the risk of thyroid autoimmunity in elderly female patients with CHC.

  16. Interferon-alpha in viral and bacterial gastroenteritis: a comparison with C-reactive protein and interleukin-6.

    Science.gov (United States)

    Mangiarotti, P; Moulin, F; Palmer, P; Ravilly, S; Raymond, J; Gendrel, D

    1999-06-01

    The aim of the study was to identify serum markers able to differentiate bacterial and viral origin in acute diarrhoea. Interferon-alpha (INF-alpha), C-reactive protein (CRP) and interleukin-6 were determined on admission in the sera of 119 children aged between 1 mo and 14 y who were hospitalized for rotavirus (n = 60) or bacterial diarrhoea (Salmonella spp. 39 cases, Shigella spp. 15 cases, Campylobacter jejuni 5 cases). CRP concentration was >10 mg/l in 48.3% of children with viral gastroenteritis and 86.4% of children with bacterial gastroenteritis. IL6 concentration was >100 pg/ml in 11.7% and 26.3% of cases, respectively. INF-alpha was detected in 79.1% of children with rotavirus (sens 79%) and in 3.5% (spec 93%) with bacterial gastroenteritis. However the INF-alpha assay takes 48 h and pathogens are often identified from stools before interferon results are available. We found that serum markers are not discriminating enough to differentiate between viral and bacterial gastroenteritis in emergency cases.

  17. Single-dose pharmacokinetics and safety of pegylated interferon-alpha2b in patients with chronic renal dysfunction.

    Science.gov (United States)

    Gupta, Samir K; Pittenger, Amy L; Swan, Suzanne K; Marbury, Thomas C; Tobillo, Emlyn; Batra, Vijay; Sack, Marshall; Glue, Paul; Jacobs, Sheila; Affrime, Melton

    2002-10-01

    This study evaluates the pharmacokinetics and safety of pegylated interferon-alpha2b (PEG-Intron) following a single-dose subcutaneous injection into subjects with normal renal function, subjects with chronic renal impairment, and patients on hemodialysis. In this open-label, single-dose, parallel group study, subjects were divided into five groups according to their degree of renal function: four groups as defined by measured creatinine clearance and a fifth hemodialysis dependent group. They received 1 microg/kg PEG-Intron subcutaneously after a 10-hour fast. Pharmacokinetic and safety assessments were performed up to 168 hours postdose. Hemodialysis patients had a second PEG-Intron dose 12 hours prior to a hemodialysis session. PEG-Intron pharmacokinetic parameters (AUCtf, Cmax, and t1/2) increased progressively as CL(CR) declined. All subjects reported at least one adverse event, which were typical of those reported after alpha-interferon administration (e.g., flu-like symptoms, headache). Single-dose PEG-Intron administration to volunteers with normal renal function and chronic renal impairment was safe and well tolerated. In patients with CL(CR) < 30 ml/min, AUCand Cmax values were increased 90% compared with controls, while half-life was increased by up to 40% over controls. Based on the relationship between PEG-Intron apparent clearance and CL(CR), renal clearance accountsfor less than half of its total clearance. Hemodialysis did not affect PEG-Intron apparent clearance.

  18. Topical interferon alpha-2B topic as the first therapeutic option in a clinical case of conjunctival intraepithelial neoplasia.

    Science.gov (United States)

    Pagán Carrasco, S; Arranz Maestro, D

    2017-09-01

    Conjunctival intraepithelial neoplasia is a pre-malignant lesion of the ocular surface. It can be treated with topical interferon alpha-2b (INF α-2b) as first choice. A 71-year-old man referred for corneal-conjunctival, gelatinous lesion in the left eye (LE) with an area of almost 270°. The clinical diagnosis was compatible with a corneal-conjunctival intraepithelial neoplasia. Topical treatment was started with INF α-2b at a dose of one million international units (IU)/ml, 4 times/day for 4 months, with remission being achieved. The isolated use of topical INF α-2b is an effective treatment as a first option in the case of corneal-conjunctival intraepithelial neoplasia, positioning itself as a form of effective and safe treatment compared to other therapeutic options. Surgical excision and use of other chemotherapy agents could lead to severe limbic deficits and other side effects. Copyright © 2017 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

  19. Expression of bcl-2 protein in chronic hepatitis C: Effect of interferon alpha 2b with ribavirin therapy

    Institute of Scientific and Technical Information of China (English)

    Panasiuk Anatol; Prokopowicz Danuta; Dzieciol Janusz; Panasiuk Bozena

    2005-01-01

    AIM: Mechanisms responsible for persistence of HCV infection and liver damage in chronic hepatitis C are not clear. Apoptosis is an important form of host immune response against viral infections. Anti-apoptotic proteinbcl-2 expression on liver tissue as well as the influence of interferon alpha 2b (IFNα2b) and ribavirin (RBV) were analyzed in patients with chronic hepatitis C. METHODS: In 30 patients with chronic hepatitis C (responders - R and non-responders - NR) treated with IFNα2b+RBV, protein bcl-2 was determined in hepatocytes and in liver associated lymphocytes before and after the treatment.RESULTS: The treatment diminished bcl-2 protein accumulation in liver cells in_patients with hepatitis C (P<0.05). Before and after the therapy, we detected bcl-2 protein in R in 87±15% and 83±20% of hepatocytes andin 28± 18% and 26±10% of liver-associated lymphocytes, respectively. In NR, the values before treatment decreased from 94±32% to 88±21% of hepatocytes and 39±29% to 28±12% of lymphocytes with bcl-2 expression. There was no statistical correlation between bcl-2 expression on liver tissue with inflammatory activity, fibrosis and biochemical parameters before and after the treatment.CONCLUSION: IFNα2b+RBV treatment, by bcl-2 protein expression decrease, enables apoptosis of hepatocytes and associated liver lymphocytes, which in turn eliminate hepatitis C viruses.

  20. Interferon-alpha restrains growth and invasive potential of hepatocellular carcinoma induced by hepatitis B virus X protein

    Institute of Scientific and Technical Information of China (English)

    Jian-Qing Yang; Guang-Dong Pan; Guang-Ping Chu; Zhen Liu; Qiang Liu; Yi Xiao; Lin Yuan

    2008-01-01

    AIM: To investigate the effects of interferon-alpha (IFN-α) to restrain the growth and invasive potential of hepatocellular carcinoma (HCC) induced by hepatitis B virus (HBV) X protein.METHODS: The pcDNA3.1-HBx plasmid was transfected into Chang cells by Lipofectamine In vitro,and Chang/HBx was co-cultured with IFN-α.Cell survival growth curve and donogenicity assay were used to test the growth potential of Chang/pcDNA3.1,Chang/Hbxand IFN-a-Chang/HBx in vitro.Growth assay in nude mice was used to detect the growth potential of Chang/pcDNA3.1,Chang/HBx and IFN-α-Chang/HBx in vivo.Wound healing and transwell migration assays were used to detect the invasive ability of Chang/pcDNA3.1,Chang/HBx and IFN-α-Chang/HBx.RESULTS: Compared with CCL13 cells transfected with pcDNA3.1,CCL13 with stable expression of hepatitis B virus X protein showed the characteristics of malignant cells with high capability of growth and invasion by detecting their growth curves,colony forming efficiency,wound healing,transwell migration assays and growth assays in nude mice.Its capability of growth and invasion could be controlled by IFN-α.CONCLUSION: IFN-α can restrain the growth and invasive potential of HCC cells induced by HBx protein,which has provided an experimental basis for IFN-αtherapy of HCC.

  1. Interferon alpha therapy for hepatitis C: treatment completion and response rates among patients with substance use disorders

    Directory of Open Access Journals (Sweden)

    Loftis Jennifer M

    2007-01-01

    Full Text Available Abstract Background Individuals with substance use disorders (SUDs are at increased risk for hepatitis C viral infection (HCV, and few studies have explored their treatment responses empirically. The objective of this study was to assess interferon alpha therapy (IFN completion and response rates among patients with HCV who had a history of comorbid SUDs. More data is needed to inform treatment strategies and guidelines for these patients. Using a medical record database, information was retrospectively collected on 307,437 veterans seen in the Veterans Integrated Service Network 20 (VISN 20 of the Veterans Healthcare Administration (VHA between 1998 and 2003. For patients treated with any type of IFN (including regular or pegylated IFN or combination therapy (IFN and ribavirin who had a known HCV genotype, IFN completion and response rates were compared among patients with a history of SUD (SUD+ Group and patients without a history of SUD (SUD- Group. Results Odds ratio analyses revealed that compared with the SUD- Group, the SUD+ Group was equally likely to complete IFN therapy if they had genotypes 2 and 3 (73.1% vs. 68.0%, and if they had genotypes 1 and 4 (39.5% vs. 39.9%. Within the sample of all patients who began IFN therapy, the SUD- and SUD+ groups were similarly likely to achieve an end of treatment response (genotypes 2 and 3, 52.8% vs. 54.3%; genotypes 1 and 4, 24.5% vs. 24.8% and a sustained viral response (genotypes 2 and 3, 42.6% vs. 41.1%; genotypes 1 and 4: 16.0% vs. 22.3%. Conclusion Individuals with and without a history of SUD responded to antiviral therapy for HCV at similar rates. Collectively, these findings suggest that patients who have co-morbid SUD and HCV diagnoses can successfully complete a course of antiviral therapy.

  2. Evolution and predictive factors of thyroid disorder due to interferon alpha in the treatment of hepatitis C

    Institute of Scientific and Technical Information of China (English)

    Moana Gelu-Simeon; Aurore Burlaud; Jacques Young; Gilles Pelletier; Catherine Buffet

    2009-01-01

    AIM: To study predictive factors of thyroid dysfunction associated with interferon-alpha (IFNα) therapy in chronic hepatitis C (CHC) and to describe its long-term evolution in a large population without previous thyroid dysfunction.METHODS: We performed a follow-up of thyroid function and detection of thyroid antibodies in 301patients treated for CHC with IFNα from 1999 to 2004.RESULTS: Thyroid disorder developed in 30/301 (10%)patients with a mean delay of 6 ± 3.75 mo: 13 patients had hyperthyroidism, 11 had hypothyroidism, and 6had biphasic evolution. During a mean follow-up of 41.59 ± 15.39 mo, 9 patients with hyperthyroidism,3 with hypothyroidism, and 4 with biphasic evolution normalized thyroid function in 7.88 ± 5.46 mo. Recovery rate of dysthyroidism was not modified by treatment discontinuation, but was better for patients with negative thyroid antibodies before antiviral treatment ( P = 0.02). Women had significantly more dysthyroidism ( P= 0.05). Positive thyroid peroxidase and thyroglobulin antibodies were more frequent before antiviral treatment in patients who developed dysthyroidism ( P < 0.0003 and P = 0.0003, respectively). In a multivariate model, low fibrosis was found to be a predictive factor of dysthyroidism ( P = 0.039).CONCLUSION: In this monocentric population of CHC,dysthyroidism, especially hyperthyroidism, developed in 10% of patients. Low fibrosis was found to be apredictive factor of dysthyroidism. Thyroid disorder recovered in 16/30 patients (53%) and recovery was better in the non-autoimmune form.

  3. Interferon-alpha suppressed granulocyte colony stimulating factor production is reversed by CL097, a TLR7/8 agonist.

    LENUS (Irish Health Repository)

    Tajuddin, Tariq

    2012-02-01

    BACKGROUND AND AIM: Neutropenia, a major side-effect of interferon-alpha (IFN-alpha) therapy can be effectively treated by the recombinant form of granulocyte colony stimulating factor (G-CSF), an important growth factor for neutrophils. We hypothesized that IFN-alpha might suppress G-CSF production by peripheral blood mononuclear cells (PBMCs), contributing to the development of neutropenia, and that a toll-like receptor (TLR) agonist might overcome this suppression. METHODS: Fifty-five patients who were receiving IFN-alpha\\/ribavirin combination therapy for chronic hepatitis C virus (HCV) infection were recruited. Absolute neutrophil counts (ANC), monocyte counts and treatment outcome data were recorded. G-CSF levels in the supernatants of PBMCs isolated from the patients and healthy controls were assessed by enzyme-linked immunosorbent assay following 18 h of culture in the absence or presence of IFN- alpha or the TLR7\\/8 agonist, CL097. RESULTS: Therapeutic IFN-alpha caused a significant reduction in neutrophil counts in all patients, with 15 patients requiring therapeutic G-CSF. The reduction in ANC over the course of IFN-alpha treatment was paralleled by a decrease in the ability of PBMCs to produce G-CSF. In vitro G-CSF production by PBMCs was suppressed in the presence of IFN-alpha; however, co-incubation with a TLR7\\/8 agonist significantly enhanced G-CSF secretion by cells obtained both from HCV patients and healthy controls. CONCLUSIONS: Suppressed G-CSF production in the presence of IFN-alpha may contribute to IFN-alpha-induced neutropenia. However, a TLR7\\/8 agonist elicits G-CSF secretion even in the presence of IFN-alpha, suggesting a possible therapeutic role for TLR agonists in treatment of IFN-alpha-induced neutropenia.

  4. [Enhanced porcine interferon-alpha production by Pichia pastoris by methanol/sorbitol co-feeding and energy metabolism shift].

    Science.gov (United States)

    Wang, Huihui; Jin, Hu; Gao, Minjie; Dai, Keke; Dong, Shijuan; Yu, Ruisong; Li, Zhen; Shi, Zhongping

    2012-02-01

    Porcine interferon-alpha (pIFN-alpha) fermentative production by recombinant Pichia pastoris was carried out in a 10-L bioreactor to study its metabolism changes and effects on fermentation under different inducing strategies, by analyzing the change patterns of the corresponding metabolism and energy regeneration. The results show that the specific activities of alcohol oxidase (AOX), formaldehyde dehydrogenase (FLD) and formate dehydrogenase (FDH) largely increased when reducing temperature from 30 degrees C to 20 degrees C under pure methanol induction, leading significant enhancements in methanol metabolism, formaldehyde dissimilatory energy metabolism and pIFN-alpha antiviral activity. The highest pIFN-alpha antiviral activity reached 1.4 x 10(6) IU/mL, which was about 10-folds of that obtained under 30 degrees C induction. Using methanol/sorbitol co-feeding strategy at 30 degrees C, the major energy metabolism energizing pIFN-alpha synthesis shifted from formaldehyde dissimilatory energy metabolism pathway to TCA cycle, formaldehyde dissimilatory pathway was weakened and accumulation of toxic intermediate metabolite-formaldehyde was relieved, and methanol flux distribution towards to pIFN-alpha synthesis was enhanced. Under this condition, the highest pIFN-alpha antiviral activity reached 1.8 x 10(7) IU/mL which was about 100-folds of that obtained under pure methanol induction at 30 degrees C. More important, enhanced pIFN-alpha production with methanol/sorbitol co-feeding strategy could be implemented under mild conditions, which greatly reduced the fermentation costs and improved the entire fermentation performance.

  5. Anti-viral effect of interferon-alpha on bovine viral diarrhea virus.

    Science.gov (United States)

    Sentsui, H; Takami, R; Nishimori, T; Murakami, K; Yokoyama, T; Yokomizo, Y

    1998-12-01

    To get basic information to control persistent virus infection among domestic animals by cytokines, the antiviral activity of four natural human cytokines against bovine viral diarrhea virus (BVDV) was evaluated. Normal bovine peripheral blood mononuclear leukocytes (PBML) and fetal bovine muscular cells (FBMC) were treated with varying doses of human interferon (IFN)-alpha, IFN-gamma, tumor necrosis factor (TNF)-alpha and TNF-beta. The antiviral activity in treated cells was measured by the titration of virus infectivity in comparison with non-treated controls. IFN-alpha significantly suppressed virus growth in both PBML and FBMC. The growth of two cytopathogenic and two noncytopathogenic strains was suppressed in the presence of more than 10(3) u/ml of IFN-alpha. Addition of either TNF-alpha or TNF-beta to IFN-alpha did not potentiate the suppressive effect. IFN-alpha also suppressed the replication of BVDV in PBML from cattle persistently infected with BVDV.

  6. Modulation of gene expression in MHCC97 cells by interferon alpha

    Institute of Scientific and Technical Information of China (English)

    Wei-Zhong Wu; Hui-Chuan Sun; Lu Wang; Jie Chen; Kang-Da Liu; Zhao-You Tang

    2005-01-01

    AIM: To elucidate the molecular mechanisms of the inhibitory effects of IFN-α on tumor growth and metastasis in MHCC97 xenografts.METHODS: Three thousand international units per milliliter of IFN-α-treated and -untreated MHCC97 cells were enrolled for gene expression analysis using cDNA microarray. The mRNA levels of several differentially expressed genes in cDNA microarray were further identified by Northern blot and RT-PCR.RESULTS: A total of 190 differentially expressed genes including 151 IFN-α-repressed and 39 -stimulated genes or expressed sequence tags from 8 464 known human genes were found to be regulated by IFN-α in MHCC97.With a few exceptions, mRNA levels of the selected genes in RT-PCR and Northern blot were in good agreement with those in cDNA microarray.CONCLUSION: IFN-α might exert its complicated antitumor effects on MHCC97 xenografts by regulating the expression of functional genes involved in cell metabolism, proliferation, morphogenesis, angiogenesis,and signaling.

  7. Association of chronic hepatitis C with major depressive disorders: irrespective of interferon-alpha therapy

    Directory of Open Access Journals (Sweden)

    Chessa Luchino

    2007-10-01

    Full Text Available Abstract Background Mood and anxiety symptoms in chronic hepatitis C (CHC may be related to the patient awareness of the diagnosis and prognosis, to side effects induced by interferon (IFN-alpha treatment, as well as to substance abuse. However, the observation of metabolic alterations in patients with CHC has led to hypothesize a direct effect of hepatitis C virus (HCV on brain function. This study was aimed at elucidating whether CHC is associated with specific anxiety or mood disorders independently of confounding factors. Methods Patient cohort: consecutive patients, 135 with CHC and 76 with chronic hepatitis B (CHB. Exclusion criteria: previous treatment with IFN-alpha, co-infection with HCV and hepatitis B virus, infection with human immunodeficiency virus, drug or alcohol abuse, or malignancies. Controls: subjects without evidence of hepatitis randomly extracted from the database of a previous epidemiological study; they were divided into two groups of 540 (332 males and 304 (220 males as controls for patients with CHC and CHB, respectively. The psychiatric diagnosis was formulated by means of the Composite International Diagnostic Interview Simplified carried out by a physician according to DSM-IV criteria. Results A higher lifetime prevalence of major depressive disorder (MDD was observed among CHC compared to CHB or controls. The risk of MDD was not statistically different between CHB and controls. Both the CHC and CHB groups showed a significantly higher frequency of panic disorder when compared to controls. No statistical differences were observed in the prevalence of general anxiety disorder and social phobia when CHC or CHB were compared to controls. Conclusion The present study provides the first evidence of an association between CHC and MDD, diagnosed on the basis of well-defined international criteria. This association is independent of treatment with IFN-alpha and is not influenced by substance or alcohol abuse. By contrast

  8. Recombinant interleukin-2 and interferon alpha immunotherapy following autologous bone marrow transplantation. A case report of cardiovascular toxicity with serial echocardiographic evaluation.

    Science.gov (United States)

    Schechter, D; Nagler, A; Ackerstein, A; Nassar, H; Admon, D; Naparstek, E; Rein, A J

    1992-01-01

    The most serious side effects of recombinant interleukin-2 (rIL-2) and recombinant interferon-alpha (rIFN alpha) immunotherapy are cardiovascular disturbances, including systemic hypotension, left-ventricular dysfunction and pulmonary edema. We present a 25-year-old female who developed reversible cardiogenic shock during intermediate dose rIL-2 and low dose rIFN alpha therapy. Rapid clinical improvement occurred after intravenous fluid and dopamine support. A serial echocardiographic evaluation, which has not been described previously in this setting, is reported.

  9. Leadership, consensus decision making and collective behaviour in humans.

    Science.gov (United States)

    Dyer, John R G; Johansson, Anders; Helbing, Dirk; Couzin, Iain D; Krause, Jens

    2009-03-27

    This paper reviews the literature on leadership in vertebrate groups, including recent work on human groups, before presenting the results of three new experiments looking at leadership and decision making in small and large human groups. In experiment 1, we find that both group size and the presence of uninformed individuals can affect the speed with which small human groups (eight people) decide between two opposing directional preferences and the likelihood of the group splitting. In experiment 2, we show that the spatial positioning of informed individuals within small human groups (10 people) can affect the speed and accuracy of group motion. We find that having a mixture of leaders positioned in the centre and on the edge of a group increases the speed and accuracy with which the group reaches their target. In experiment 3, we use large human crowds (100 and 200 people) to demonstrate that the trends observed from earlier work using small human groups can be applied to larger crowds. We find that only a small minority of informed individuals is needed to guide a large uninformed group. These studies build upon important theoretical and empirical work on leadership and decision making in animal groups.

  10. Performance of human groups in social foraging: the role of communication in consensus decision making.

    Science.gov (United States)

    King, Andrew J; Narraway, Claire; Hodgson, Lindsay; Weatherill, Aidan; Sommer, Volker; Sumner, Seirian

    2011-04-23

    Early hominids searched for dispersed food sources in a patchy, uncertain environment, and modern humans encounter equivalent spatial-temporal coordination problems on a daily basis. A fundamental, but untested assumption is that our evolved capacity for communication is integral to our success in such tasks, allowing information exchange and consensus decisions based on mutual consideration of pooled information. Here we examine whether communication enhances group performance in humans, and test the prediction that consensus decision-making underlies group success. We used bespoke radio-tagging methodology to monitor the incremental performance of communicating and non-communicating human groups (small group sizes of two to seven individuals), during a social foraging experiment. We found that communicating groups (n = 22) foraged more effectively than non-communicating groups (n = 21) and were able to reach consensus decisions (an 'agreement' on the most profitable foraging resource) significantly more often than non-communicating groups. Our data additionally suggest that gesticulations among group members played a vital role in the achievement of consensus decisions, and therefore highlight the importance of non-verbal signalling of intentions and desires for successful human cooperative behaviour.

  11. Interferon alpha plus ribavirin combination treatment of Japanese chronic hepatitis C patients with HCV genotype 2: A project of the Kyushu University Liver Disease Study Group

    Institute of Scientific and Technical Information of China (English)

    Norihiro Furusyo; Akihide Masumoto; Shinji Shimoda; Kazuhiro Takahashi; Koichi Azuma; Jun Hayashi; Kyushu University Liver Disease Study Group; Masaki Katoh; Yuichi Tanabe; Eiji Kajiwara; Toshihiro Maruyama; Junya Shimono; Hironori Sakai; Makoto Nakamuta; Hideyuki Nomura

    2006-01-01

    AIM: To determine the efficacy of an interferon alpha and ribavirin combination treatment for Japanese patients infected with hepatitis C virus (HCV) of genotype 2,a multi-center study was retrospectively analyzed.METHODS: In total, 173 patients with HCV genotype 2stared to receive interferon-alpha subcutaneously thrice a week and 600-800 mg of ribavirin daily for 24 wk.RESULTS: The overall sustained virological response (SVR), defined as undetectable HCV RNA in serum, 24wk after the end of treatment, was remarkably high by 84.4%, (146/173) by an intention-to-treat analysis. A significant difference in SVR was found between patients with and without the discontinuation of ribavirin (46.9%vs 92.9 %), but no difference was found between those with and without a dose reduction of ribavirin. A significant difference in SVR was also found between patients with less than 16 wk and patients with 16 or more weeks of ribavirin treatment (34.8 % vs 92.0 %).CONCLUSION: The 24-wk interferon and ribavirin treatment is highly effective for Japanese patients with HCV genotype 2. The significant predictor of SVR is continuation of the ribavirin treatment for up to 16weeks.

  12. Seven-years follow-up on trial of Interferon alpha in patients with HCV RNA positive chronic hepatitis C

    Institute of Scientific and Technical Information of China (English)

    Bao Zhang Tang; Lin Zhuarg; Jing You; Hong Bing Zhang; Lu Zhang

    2000-01-01

    AIM To study the long-term efficiency of therapy with Interferon alpha (IFN-a) in patients with HCVRNA positive chronic hepatitis C.METHODS Ten patients were enrolled in the study, whose age 31 -62 years (mean 53 years), course 6- 72months (mean 24 months), of whom, 6 patients with mild CHC, 4 moderate CHC. All patients receivedIFN-a 3 MU three times weekly for six to twelve months, and then followed up for seven years after the endof treatment. The results of hepatic functions and HCV RNA at the end of treatment and follow-up period inall patients were observed.RESULTS ( At the end of treatment, clinical symptoms recovered obviously in all patients, virologicalresponse (defined as HCV RNA loss) occurred in 5 of 7 (71.4%) patients (60 years old). At the end of follow-up, the rates of HCV RNA loss were 42.9% (3/7)and 33.3% (1/3), respectively, in these group. Virological sustained response (defined as HCV RNA loss atthe end of treatment and follow-up) occurred in 3 of 6 (50%) patients (6 - 12 month-course) and in 1 of 4(25%) patients (> 12 month-course). A sustained HCV RNA response was observed in 2 of 7 (28.6%)patients with IFN-a therapy for 6m and in 2 of 3 (66.7%) patients with IFN-a therapy for more than 6 m. Ofall patients, 4 patients with sustained HCV RNA response were mild CHC, 4 patients with sustained HCVRNA positive were mild CHC (2 patients), moderate CHC (2 patients), respectively; other 2 patients withHCV RNA loss at the end of treatment but recurred at the end of follow-up, were moderate CHC. ②Biochemically sustained response (defined as ALT normalization at the end of treatment and follow-up) wasobserved in 5 out of 10 (50%) patients, and these 5 patients were mild CHC, of whom, 4 patients with HCVRNA sustained negative, 1 patient with HCV RNA loss and then recurred again. Two patients with ALTnormalization at the end of follow-up were one mild CHC, one moderate CHC, respectively. Other 3patients with no response were moderate CHC, of whom, 2

  13. [Expert consensus on induction of human embryonic stem cells into tenocytes].

    Science.gov (United States)

    Chen, Xiao; Zou, Xiaohui; Yu, Guangyan; Fu, Xin; Cao, Tong; Xiao, Yin; Ouyang, Hongwei

    2016-03-01

    Embryonic stem cells have unlimited proliferative capacity, which may provide a source of tendon stem/progenitor cells for tissue engineering. Experts of International Science and Technology Collaborative Program of Ministry of Science and Technology have developed a protocol consensus on differentiation of human embryonic stem cells into the tendon cells. The consensus recommends a protocol of two-step generation of human embryonic stem cells into tendon cells: the human embryonic stem cells are first differentiated into mesenchymal stem cells on different material surfaces; then with the scaffold-free tissue engineering tendon formed by high-density planting, the mesenchymal stem cells are induced into tendon cells under static or dynamic mechanical stimulation in vivo and in vitro. Tissue engineering tendon established in vitro by the protocol can be used as a model in toxicological analysis and safety evaluation of tendon-relevant small molecule compounds, medical materials and drugs.

  14. Consensus hologram QSAR modeling for the prediction of human intestinal absorption.

    Science.gov (United States)

    Moda, Tiago L; Andricopulo, Adriano D

    2012-04-15

    Consistent in silico models for ADME properties are useful tools in early drug discovery. Here, we report the hologram QSAR modeling of human intestinal absorption using a dataset of 638 compounds with experimental data associated. The final validated models are consistent and robust for the consensus prediction of this important pharmacokinetic property and are suitable for virtual screening applications. Copyright © 2012 Elsevier Ltd. All rights reserved.

  15. Therapy with interferon-alpha and ribavirin for chronic hepatitis C virus infection upregulates membrane HLA-ABC, CD86, and CD28 on peripheral blood mononuclear cells.

    Science.gov (United States)

    Cheng, Pin-Nan; Wei, Ya-Ling; Chang, Ting-Tsung; Chen, Jiann-Shiuh; Young, Kung-Chia

    2008-06-01

    Multiple interferon-stimulated genes (ISGs) involving T-cell activation are upregulated during initial interferon-alpha-based therapy for chronic hepatitis C virus (HCV) infection. However, the long-term impact on therapeutic outcome in patients remains unknown. In this study, the effects of anti-HCV therapy on the surface expression of HLA-ABC, CD86, and CD28 were longitudinally assessed. These proteins are integral membrane receptors of antigen presentation and triggering of costimulatory signals for activating CD8+ T cells. Peripheral blood mononuclear cells were collected at baseline and post-treatment for 1 day, and 2, 4, 12, and 24 weeks, respectively. This treatment led to a time-related elevation of membrane levels of HLA-ABC and CD86 on B-cells and monocytes in patients with a sustained response (n = 23), but not in those without (n = 8). Meanwhile, upregulation of CD28 on CD4+ and CD8+ T cells was comparable in both groups of sustained responders and non-responders. Steady increases in the B cells' surface and intracellular HLA-ABC were observed, thus, the surface-to-intracellular ratios did not alter over the period of treatment. Furthermore, multivariate analysis shows that increased HLA-ABC on monocytes by week 12 correlates significantly with sustained response (P = 0.033). In conclusion, differential modulation of T-cell activation ISGs, such as HLA-ABC and CD86 might correlate with the outcome of interferon-alpha-based therapy in chronic hepatitis C patients.

  16. A Consensus Tree Approach for Reconstructing Human Evolutionary History and Detecting Population Substructure

    Science.gov (United States)

    Tsai, Ming-Chi; Blelloch, Guy; Ravi, R.; Schwartz, Russell

    The random accumulation of variations in the human genome over time implicitly encodes a history of how human populations have arisen, dispersed, and intermixed since we emerged as a species. Reconstructing that history is a challenging computational and statistical problem but has important applications both to basic research and to the discovery of genotype-phenotype correlations. In this study, we present a novel approach to inferring human evolutionary history from genetic variation data. Our approach uses the idea of consensus trees, a technique generally used to reconcile species trees from divergent gene trees, adapting it to the problem of finding the robust relationships within a set of intraspecies phylogenies derived from local regions of the genome. We assess the quality of the method on two large-scale genetic variation data sets: the HapMap Phase II and the Human Genome Diversity Project. Qualitative comparison to a consensus model of the evolution of modern human population groups shows that our inferences closely match our best current understanding of human evolutionary history. A further comparison with results of a leading method for the simpler problem of population substructure assignment verifies that our method provides comparable accuracy in identifying meaningful population subgroups in addition to inferring the relationships among them.

  17. A consensus network of gene regulatory factors in the human frontal lobe

    Directory of Open Access Journals (Sweden)

    Stefano eBerto

    2016-03-01

    Full Text Available Cognitive abilities, such as memory, learning, language, problem solving, and planning, involve the frontal lobe and other brain areas. Not much is known yet about the molecular basis of cognitive abilities, but it seems clear that cognitive abilities are determined by the interplay of many genes. One approach for analyzing the genetic networks involved in cognitive functions is to study the coexpression networks of genes with known importance for proper cognitive functions, such as genes that have been associated with cognitive disorders like intellectual disability (ID or autism spectrum disorders (ASD. Because many of these genes are gene regulatory factors (GRFs we aimed to provide insights into the gene regulatory networks active in the human frontal lobe. Using genome wide human frontal lobe expression data from 10 independent data sets, we first derived 10 individual coexpression networks for all GRFs including their potential target genes. We observed a high level of variability among these 10 independently derived networks, pointing out that relying on results from a single study can only provide limited biological insights. To instead focus on the most confident information from these 10 networks we developed a method for integrating such independently derived networks into a consensus network. This consensus network revealed robust GRF interactions that are conserved across the frontal lobes of different healthy human individuals. Within this network, we detected a strong central module that is enriched for 166 GRFs known to be involved in brain development and/or cognitive disorders. Interestingly, several hubs of the consensus network encode for GRFs that have not yet been associated with brain functions. Their central role in the network suggests them as excellent new candidates for playing an essential role in the regulatory network of the human frontal lobe, which should be investigated in future studies.

  18. A Consensus Network of Gene Regulatory Factors in the Human Frontal Lobe.

    Science.gov (United States)

    Berto, Stefano; Perdomo-Sabogal, Alvaro; Gerighausen, Daniel; Qin, Jing; Nowick, Katja

    2016-01-01

    Cognitive abilities, such as memory, learning, language, problem solving, and planning, involve the frontal lobe and other brain areas. Not much is known yet about the molecular basis of cognitive abilities, but it seems clear that cognitive abilities are determined by the interplay of many genes. One approach for analyzing the genetic networks involved in cognitive functions is to study the coexpression networks of genes with known importance for proper cognitive functions, such as genes that have been associated with cognitive disorders like intellectual disability (ID) or autism spectrum disorders (ASD). Because many of these genes are gene regulatory factors (GRFs) we aimed to provide insights into the gene regulatory networks active in the human frontal lobe. Using genome wide human frontal lobe expression data from 10 independent data sets, we first derived 10 individual coexpression networks for all GRFs including their potential target genes. We observed a high level of variability among these 10 independently derived networks, pointing out that relying on results from a single study can only provide limited biological insights. To instead focus on the most confident information from these 10 networks we developed a method for integrating such independently derived networks into a consensus network. This consensus network revealed robust GRF interactions that are conserved across the frontal lobes of different healthy human individuals. Within this network, we detected a strong central module that is enriched for 166 GRFs known to be involved in brain development and/or cognitive disorders. Interestingly, several hubs of the consensus network encode for GRFs that have not yet been associated with brain functions. Their central role in the network suggests them as excellent new candidates for playing an essential role in the regulatory network of the human frontal lobe, which should be investigated in future studies.

  19. Computer simulation of leadership, consensus decision making and collective behaviour in humans.

    Science.gov (United States)

    Wu, Song; Sun, Quanbin

    2014-01-01

    The aim of this study is to evaluate the reliability of a crowd simulation model developed by the authors by reproducing Dyer et al.'s experiments (published in Philosophical Transactions in 2009) on human leadership and consensus decision making in a computer-based environment. The theoretical crowd model of the simulation environment is presented, and its results are compared and analysed against Dyer et al.'s original experiments. It is concluded that the simulation results are largely consistent with the experiments, which demonstrates the reliability of the crowd model. Furthermore, the simulation data also reveals several additional new findings, namely: 1) the phenomena of sacrificing accuracy to reach a quicker consensus decision found in ants colonies was also discovered in the simulation; 2) the ability of reaching consensus in groups has a direct impact on the time and accuracy of arriving at the target position; 3) the positions of the informed individuals or leaders in the crowd could have significant impact on the overall crowd movement; and 4) the simulation also confirmed Dyer et al.'s anecdotal evidence of the proportion of the leadership in large crowds and its effect on crowd movement. The potential applications of these findings are highlighted in the final discussion of this paper.

  20. Computer simulation of leadership, consensus decision making and collective behaviour in humans.

    Directory of Open Access Journals (Sweden)

    Song Wu

    Full Text Available The aim of this study is to evaluate the reliability of a crowd simulation model developed by the authors by reproducing Dyer et al.'s experiments (published in Philosophical Transactions in 2009 on human leadership and consensus decision making in a computer-based environment. The theoretical crowd model of the simulation environment is presented, and its results are compared and analysed against Dyer et al.'s original experiments. It is concluded that the simulation results are largely consistent with the experiments, which demonstrates the reliability of the crowd model. Furthermore, the simulation data also reveals several additional new findings, namely: 1 the phenomena of sacrificing accuracy to reach a quicker consensus decision found in ants colonies was also discovered in the simulation; 2 the ability of reaching consensus in groups has a direct impact on the time and accuracy of arriving at the target position; 3 the positions of the informed individuals or leaders in the crowd could have significant impact on the overall crowd movement; and 4 the simulation also confirmed Dyer et al.'s anecdotal evidence of the proportion of the leadership in large crowds and its effect on crowd movement. The potential applications of these findings are highlighted in the final discussion of this paper.

  1. Biomedicine and international human rights law: in search of a global consensus.

    Science.gov (United States)

    Andorno, Roberto

    2002-01-01

    Global challenges raised by biomedical advances require global responses. Some international organizations have made significant efforts over the last few years to establish common standards that can be regarded as the beginning of an international biomedical law. One of the main features of this new legal discipline is the integration of its principles into a human rights framework. This strategy seems the most appropriate, given the role of "universal ethics" that human rights play in our world of philosophical pluralism. In addition to the general standards that are gradually being established, a widespread consensus exists on the urgency of preventing two specific procedures: human germ-line interventions and human reproductive cloning. PMID:12571724

  2. Consensus comparative analysis of human embryonic stem cell-derived cardiomyocytes.

    Directory of Open Access Journals (Sweden)

    Shaohong Zhang

    Full Text Available Global transcriptional analyses have been performed with human embryonic stem cells (hESC derived cardiomyocytes (CMs to identify molecules and pathways important for human CM differentiation, but variations in culture and profiling conditions have led to greatly divergent results among different studies. Consensus investigation to identify genes and gene sets enriched in multiple studies is important for revealing differential gene expression intrinsic to human CM differentiation independent of the above variables, but reliable methods of conducting such comparison are lacking. We examined differential gene expression between hESC and hESC-CMs from multiple microarray studies. For single gene analysis, we identified genes that were expressed at increased levels in hESC-CMs in seven datasets and which have not been previously highlighted. For gene set analysis, we developed a new algorithm, consensus comparative analysis (CSSCMP, capable of evaluating enrichment of gene sets from heterogeneous data sources. Based on both theoretical analysis and experimental validation, CSSCMP is more efficient and less susceptible to experimental variations than traditional methods. We applied CSSCMP to hESC-CM microarray data and revealed novel gene set enrichment (e.g., glucocorticoid stimulus, and also identified genes that might mediate this response. Our results provide important molecular information intrinsic to hESC-CM differentiation. Data and Matlab codes can be downloaded from S1 Data.

  3. A novel combinatory paradigm for chronic hepatitis C treatment using liver-targeted carrier erythrocytes co-encapsulated with interferon alpha-2b, ribavirin and boceprevir

    Directory of Open Access Journals (Sweden)

    Mahshid Foroozesh

    2010-10-01

    Full Text Available "nDespite outstanding developments in medical knowledge and technologies, Hepatitis C virus (HCV affecting almost 180 million people worldwide, is still described as "a serious global health crisis" and its standard of care (combination therapy with pegylated interferon alpha and ribavirin is just effective in at most 50% of all patients. This suboptimal efficacy and apparent side effects underscore the need for "new anti-HCV agents", "novel combination strategies" and "smart delivery systems". As a response to the urgent need for new anti-HCV drugs, specifically targeted antiviral therapy agents for HCV (STAT-C has gained many interests these years. Considering the obligation of multidrug therapy in HCV infection and the results of clinical trials, STAT-C will probably supplement interferon/ribavirin combination. Boceprevir as a HCV protease inhibitor is among the most widely studied STAT-C compounds with promising results in clinical trials. Thus, its combination with current double therapy paradigm would be an alternative combination strategy in the treatment of hepatitis C. On the other hand, drug carriers has now evoked much attentions as new trends to increase the efficacy of available therapies by protecting the therapeutic agents from unwanted reactions and/or targeting them directly to their site of action. Carrier erythrocytes are among the most widely studied cellular and particulate carriers suitable for targeted delivery of various drugs to reticuloendothelial system organs like liver, but, with no report about their application for HCV-targeted therapy. Since the majority of recent efforts are focused on new agents' discovery/development and alternative combinations and no reports are available on targeted delivery of double and/or triple drug combinations directly to the liver, an idea has been raised that combination of all 3 approaches mentioned earlier (a completely combinatory paradigm addressing all 3 mentioned needs by

  4. In vivo assessment of the antiproliferative properties of interferon-alpha during immunotherapy: Ki-67 (MIB-1) in patients with metastatic renal cell carcinoma (mRCC)

    DEFF Research Database (Denmark)

    Donskov, Frede; Marcussen, Niels; Hokland, M.

    2004-01-01

    The aim of the present study was to investigate the in vivo antiproliferative effect of interferon alpha (IFN-alpha) in patients with metastatic renal cell carcinoma (mRCC). Core needle biopsies of metastatic and/or the primary kidney cancer were obtained before interleukin-2 (IL-2)- and IFN......-alpha-based immunotherapy in 34 patients and repeated after 5 weeks in 25 patients. Tumour proliferation was assessed by use of the anti-Ki-67 antibody MIB-1 and evaluated in multiple, random systematic sampled fields of vision. Ki-67 labelling index (LI) at baseline was median 13.6% (range 1.2-85.0) and median 10.......016). Baseline or change in Ki-67 LI did not correlate to survival. These data suggest that IFN-alpha in vivo has only modest effect on tumour proliferation in patients with mRCC. Tumour Ki-67 (MIB-1) reactivity after 1 month of immunotherapy appears to be a significant predictor of patient survival....

  5. Expression of interferon-alpha and Mx1 protein in pigs acutely infected with porcine reproductive and respiratory syndrome virus (PRRSV).

    Science.gov (United States)

    Chung, H-K; Lee, J-H; Kim, S-H; Chae, C

    2004-05-01

    The expression of mRNA encoding interferon-alpha (IFN-alpha) and Mx1 protein was studied, by reverse transcription-polymerase chain reaction and by in-situ hybridization with a non-radioactive digoxigenin-labelled cDNA probe, in formalin-fixed, paraffin wax-embedded lung tissue from pigs experimentally infected with a Korean isolate (North American genotype) of porcine reproductive and respiratory syndrome virus (PRRSV). The animals were examined over a period of 10 days after intranasal inoculation. IFN-alpha and Mx1 protein was detected in the lung at 1 day post inoculation (dpi), the number of positive cells increasing at 7dpi, and rapidly decreasing thereafter. Hybridization signals for IFN-alpha and Mx1 protein were usually associated with inflammation, and in particular with macrophages. Expression of IFN-alpha and Mx1 protein was negative in non-lesional lung of PRRSV-infected pigs and in normal lung from control pigs. There was a good statistical correlation between the number of cells positive for mRNA encoding IFN-alpha and Mx1 protein in the infected lungs (r = 0.95, PMx1 protein plays a role in the early host defence against PRRSV infection.

  6. Enhanced immunogenicity of multiple-epitopes of foot-and-mouth disease virus fused with porcine interferon alpha in mice and protective efficacy in guinea pigs and swine.

    Science.gov (United States)

    Du, Yijun; Li, Yufeng; He, Hairong; Qi, Jing; Jiang, Wenming; Wang, Xinglong; Tang, Bo; Cao, Jun; Wang, Xianwei; Jiang, Ping

    2008-04-01

    Foot-and-mouth disease (FMD) is a highly contagious and economically devastating vesicular disease of cloven-hoofed animals. In this study, three amino acid residues 21-60, 141-160 and 200-213 from VP1 protein of FMDV were selected as multiple-epitopes (VPe), and a recombinant adenovirus expressing the multiple-epitopes fused with porcine interferon alpha (rAd-pIFN alpha-VPe) was constructed. Six groups of female BALB/c mice (18 mice per group) were inoculated subcutaneously (s.c.) twice at 2-week intervals with the recombinant adenoviruses and the immune responses were examined. Following this the protective efficacy of rAd-pIFN alpha-VPe was examined in guinea pigs and swine. The results showed that both FMDV-specific humoral and cell-mediated immune responses could be induced by rAd-VPe and increased when rAd-pIFN alpha is included in this regime in mice model. Moreover, the levels of the immune responses in the group inoculated with rAd-pIFN alpha-VPe were significantly higher than the group inoculated with rAd-VPe plus rAd-pIFN alpha. All guinea pigs and swine vaccinated with rAd-pIFN alpha-VPe were completely protected from viral challenge. It demonstrated that recombinant adenovirus rAd-pIFN alpha-VPe might be an attractive candidate vaccine for preventing FMDV infection.

  7. Simultaneous detection, typing and quantitation of oncogenic human papillomavirus by multiplex consensus real-time PCR.

    Science.gov (United States)

    Jenkins, Andrew; Allum, Anne-Gry; Strand, Linda; Aakre, Randi Kersten

    2013-02-01

    A consensus multiplex real-time PCR test (PT13-RT) for the oncogenic human papillomavirus (HPV) types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 66 is described. The test targets the L1 gene. Analytical sensitivity is between 4 and 400 GU (genomic units) in the presence of 500 ng of human DNA, corresponding to 75,000 human cells. HPV types are grouped into multiplex groups of 3 or 4 resulting in the use of 4 wells per sample and permitting up to 24 samples per run (including controls) in a standard 96-well real-time PCR instrument. False negative results are avoided by (a) measuring sample DNA concentration to control that sufficient cellular material is present and (b) including HPV type 6 as a homologous internal control in order to detect PCR inhibition or competition from other (non-oncogenic) HPV types. Analysis time from refrigerator to report is 8 h, including 2.5 h hands-on time. Relative to the HC2 test, the sensitivity and specificity were respectively 98% and 83%, the lower specificity being attributable to the higher analytical sensitivity of PT13-RT. To assess type determination comparison was made with a reversed line-blot test. Type concordance was high (κ=0.79) with discrepancies occurring mostly in multiple-positive samples. Copyright © 2012 Elsevier B.V. All rights reserved.

  8. Human Performance Optimization Metrics: Consensus Findings, Gaps, and Recommendations for Future Research.

    Science.gov (United States)

    Nindl, Bradley C; Jaffin, Dianna P; Dretsch, Michael N; Cheuvront, Samuel N; Wesensten, Nancy J; Kent, Michael L; Grunberg, Neil E; Pierce, Joseph R; Barry, Erin S; Scott, Jonathan M; Young, Andrew J; OʼConnor, Francis G; Deuster, Patricia A

    2015-11-01

    Human performance optimization (HPO) is defined as "the process of applying knowledge, skills and emerging technologies to improve and preserve the capabilities of military members, and organizations to execute essential tasks." The lack of consensus for operationally relevant and standardized metrics that meet joint military requirements has been identified as the single most important gap for research and application of HPO. In 2013, the Consortium for Health and Military Performance hosted a meeting to develop a toolkit of standardized HPO metrics for use in military and civilian research, and potentially for field applications by commanders, units, and organizations. Performance was considered from a holistic perspective as being influenced by various behaviors and barriers. To accomplish the goal of developing a standardized toolkit, key metrics were identified and evaluated across a spectrum of domains that contribute to HPO: physical performance, nutritional status, psychological status, cognitive performance, environmental challenges, sleep, and pain. These domains were chosen based on relevant data with regard to performance enhancers and degraders. The specific objectives at this meeting were to (a) identify and evaluate current metrics for assessing human performance within selected domains; (b) prioritize metrics within each domain to establish a human performance assessment toolkit; and (c) identify scientific gaps and the needed research to more effectively assess human performance across domains. This article provides of a summary of 150 total HPO metrics across multiple domains that can be used as a starting point-the beginning of an HPO toolkit: physical fitness (29 metrics), nutrition (24 metrics), psychological status (36 metrics), cognitive performance (35 metrics), environment (12 metrics), sleep (9 metrics), and pain (5 metrics). These metrics can be particularly valuable as the military emphasizes a renewed interest in Human Dimension efforts

  9. Recombinant interferon-alpha2b poly(lactic-co-glycolic acid) microspheres: pharmacokinetics.pharmacodynamics study in rhesus monkeys following intramuscular administration

    Institute of Scientific and Technical Information of China (English)

    Yong-ming ZHANG; Fan YANG; Yi-qun YANG; Feng-lan SONG; An-long XU

    2008-01-01

    Aim: Investigation into pharmacokinetic-pharmacodynamic properties of interferon-alpha (IFN-α)2b-loaded poly(lactic-co-glycolic acid) (PLGA) microspheres (MS) in rhesus monkey primates. Method: IFN-α2b was loaded with biodegradable PLGA with 3 inherent viscosities using a double emulsion and solvent evaporation method. The particle size, surface morphology, and in vitro release profiles were investigated. Two groups of rhesus monkeys (n=3) were injected intramuscularly with either 3 MIU/kg commercial IFN-a2b lyophilized powder or IFN-α2b-loaded PLGA microspheres (inherent viscosity of 0.89 dL/g). In vitro release was determined by Lowry protein assay. The serum IFN and neopterin levels were determined by the enzyme-linked immunosorbent assay (ELISA) method to evaluate biological activity of the microspheres in rhesus monkeys. Results: The IFN-α2b microspheres with 3 inherent viscosities (0.39, 0.89, and 1.13 dL/g) were entirely spherical and had a smooth surface. The average diameter of each type was 45.55, 81.23, and 110.25 μm, respectively. The in vitro release was 30 d. The pharmacokinetic-pharmacodynamic properties between the IFN-α2b microspheres and IFN-α2b lyophilized powder were significantly different (P<0.05). Conclusion: The drug residence time for the IFN-α2b of the PLGA microsphere with an inherent viscosity of 0.89 dL/g in plasma significantly increased and had a longer time of biological effects in rhesus monkeys following intramuscular administration.

  10. Effect of Interferon-alpha in systemic lupus erthematosus (SLE) serum on the differentiation and maturation of dendritic cells derived from CD34+ hematopoietic precursor cells

    Institute of Scientific and Technical Information of China (English)

    Rong Zhang; Meifen Xing; Weiwen Wang; Xiaofan Yang; Xiaohui Ji

    2009-01-01

    Objective: To study the effect of interferon-alpha IFN-a in the serum of SLE patients on the differentiation and maturation of dendritic cells (DCs) derived from CD34+ hematopoietic precursor cells (HPCs). Methods: Serum samples from SLE patients and normal controls were collected and the concentration of IFN-a detected by ELISA. CD34+HPCs were purified from cord blood by a magnetic cell sorting system (MACS), and cultured to differentiate to DCs. Normal serum, normal serum with exogenous IFN-α, SLE serum with raised levels of IFN-α, or SLE serum with anti-IFN-α neutralizing antibody was added to the culture medium. The phenotype of DCs was analyzed by flow cytometry (FCM) and the capacity of DCs to stimulate allogenic T lymphocyte proliferation was evaluated in a mixed lymphocyte reaction by the Cell Counting Kit-8. Cytokine production was assessed by ELISA. Results: Serum levels of IFN-a were significantly higher in SLE patients than in normal controls and this correlated positively with disease activity. Cultured in SLE serum with raised levels of IFN-α, CD34+HPCs could differentiate into DCs that expressed higher levels of HLA-DR, CD80 and CD86, and showed an enhanced allogenic T-cell stimulatory capacity, while producing lower levels of IL-12 and higher amounts of IL-10 compared with those DCs cultured in normal serum. Conclusion: Increased levels of IFN-a in SLE serum promotes the differentiation and maturation of DCs derived from CD34+ HPCs and could contribute to the pathogenesis of SLE.

  11. Detecting the replication of the hepatitis B virus using the ImmunoMax technique following treatment with interferon-alpha in children with chronic hepatitis.

    Science.gov (United States)

    Kasprzak, Aldona; Wysocki, Jacek; Zabel, Maciej; Surdyk-Zasada, Joanna

    2002-01-01

    Children with HBV in Poland are treated with preparations of interferon-alpha (IFN-alpha). The continuing lack of complete response to this type of anti-viral therapy remains to be explained. The application of cell biology techniques to identify the viral components in situ makes it possible to clarify the association between the distribution of the virus and morphological injury to the liver, the immune response of the host, and clinical symptoms in the natural course of infection. Our study was intended to evaluate HBV expression in liver biopsies taken an average of two years after completion of IFN-a therapy in 10 children with serological markers of persistent HBV infection. For the immunocytochemical detection of HBcAg and for the hybridocytochemical detection of HBV-DNA, the avidin-biotin-peroxidase (ABC) technique was employed, as well as classical in situ hybridization, both additionally amplified using the ImmunoMax technique. HBcAg and HBV-DNA levels were estimated using a semiquantitative technique. Our study demonstrated persistent active replication of HBV in the liver in all examined children. A mixed pattern of HBcAg localization prevailed (noted in cell nuclei, cytoplasm and cell membranes) with a somewhat lower proportion of involved cells and a more evident membrane localization of HBcAg, as compared to results obtained before treatment. HBV-DNA was observed in the cytoplasm of a fraction of hepatocytes similar to that noted before therapy. The ImmunoMax technique was found to be highly suitable for in situ monitoring of HBV replication after termination of IFN-a treatment. Children with focal distribution of HBcAg and HBV-DNA have the potential for earlier eradication of the virus from their livers.

  12. Evaluation of the effects of omega-3 & interferon alpha-2b administration on partial bladder outlet obstruction in a rat model

    Science.gov (United States)

    Firat, Fatih; Uluocak, Nihat; Erdemir, Fikret; Atilgan, Dogan; Markoc, Fatma; Parlaktas, Bekir Suha; Yasar, Adem

    2016-01-01

    Background & objectives: In bladder outlet obstruction-induced rat models, the transforming growth factor-beta (TGF-β) and collagen ratios have been shown to be increased. Increased TGF-β leads to fibrosis. In this study, the effect of omega-3 and interferon alpha-2b (IFN α-2b) was investigated on oxidative stress, inflammation and fibrosis in bladder structure in a partial bladder outlet obstruction (PBOO) rat model. Methods: A total of 35 male Wistar albino rats, weighing 300-350 g, were used in the study. The rats were randomly divided into five groups. At the end of the experimental period, bladders were harvested from all the rats, and pathological analysis of the rat bladder tissues was performed. In addition, investigations were carried out with enzymatic and non-enzymatic antioxidant systems to study the antioxidant properties of omega-3 fatty acid and IFN alpha-2b. Results: Increased bladder weight in the PBOO group, in comparison to the control group, was decreased by the administration of omega-3 and IFN α-2b (P=0.002). Significantly higher superoxide dismutase (SOD) levels were detected in group 2 in comparison to the control group. It was also detected that serum SOD, glutathione peroxidase and nitric oxide (NO) levels were significantly higher in group 2 when compared to the control group (P<0.05). In the pathologic evaluation, group 2 showed significantly increased inflammation and fibrosis compared to the control group. Omega-3 treatment significantly decreased inflammation. It was shown that IFN α-2b application partially decreased inflammation. Interpretation & conclusions: The results of the present study showed that in addition to the standard primary approaches to prevent the damage to the upper urinary tract secondary to PBOO, omega-3 fatty acid and IFN α-2b could be beneficial as adjunct treatment in clinical practice. However, this needs to be further investigated with prospective, randomized clinical trials with larger sample sizes

  13. Impaired interferon-alpha production by plasmacytoid dendritic cells after cord blood transplantation in children: implication for post-transplantation toll-like receptor ligand-based immunotherapy.

    Science.gov (United States)

    Charrier, Emily; Cordeiro, Paulo; Brito, Rose-Marie; Harnois, Michaël; Mezziani, Samira; Herblot, Sabine; Le Deist, Françoise; Duval, Michel

    2014-10-01

    Plasmacytoid dendritic cells (pDCs) initiate both innate and adaptive immune responses, making them attractive targets for post-transplantation immunotherapy, particularly after cord blood transplantation (CBT). Toll-like receptor (TLR) agonists are currently studied for pDC stimulation in various clinical settings. Their efficacy depends on pDC number and functionality, which are unknown after CBT. We performed a longitudinal study of pDC reconstitution in children who underwent bone marrow transplantation (BMT) and single-unit CBT. Both CBT and unrelated BMT patients received antithymocyte globulin as part of their graft-versus-host disease prophylaxis regimen. pDC blood counts were higher in CBT patients than in healthy volunteers from 2 to 9 months after transplantation, whereas they remained lower in BMT patients. We showed that cord blood progenitors gave rise in vitro to a 500-fold increase in functional pDCs over bone marrow counterparts. Upon stimulation with a TLR agonist, pDCs from both CBT and BMT recipients upregulated T cell costimulatory molecules, whereas interferon-alpha (IFN-α) production was impaired for 9 months after CBT. TLR agonist treatment is thus not expected to induce IFN-α production by pDCs after CBT, limiting its immunotherapeutic potential. Fortunately, in vitro production of large amounts of functional pDCs from cord blood progenitors paves the way for the post-transplantation adoptive transfer of pDCs. Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  14. Molecular stress response in the CNS of mice after systemic exposureto interferon-alpha, ionizing radiation and ketamine

    Energy Technology Data Exchange (ETDEWEB)

    Lowe, Xiu R.; Marchetti, Francesco; Lu, Xiaochen; Wyrobek, Andrew J.

    2009-03-03

    We previously showed that the expression of troponin T1 (Tnnt 1) was induced in the central nervous system (CNS) of adultmice 30 min after treatment with ketamine, a glutamate N-methyl-D-aspartic acid (NMDA) receptor antagonist. We hypothesized that Tnnt 1 expression may be an early molecular biomarker of stress response in the CNS of mice. To further evaluate this hypothesis, we investigated the regional expression of Tnnt 1 in the mouse brain using RNA in situ hybridization 4 h after systemic exposure to interferon-a (IFN-a) and gamma ionizing radiation, both of which have be associated with wide ranges of neuropsychiatric complications. Adult B6C3F1 male mice were treated with either human IFN-a (a single i.p. injection at 1 x 105 IU/kg) or whole body gamma-radiation (10 cGy or 2 Gy). Patterns of Tnnt 1 transcript expression were compared in various CNS regions after IFN-a, radiation and ketamine treatments (previous study). Tnnt 1 expression was consistently induced in pyramidal neurons of cerebral cortex and hippocampus after all treatment regimens including 10 cGy of ionizing radiation. Regional expression of Tnnt 1 was induced in Purkinje cells of cerebellum after ionizing radiation and ketamine treatment; but not after IFN-a treatment. None of the three treatments induced Tnnt 1 expression in glial cells. The patterns of Tnnt 1 expression in pyramidal neurons of cerebral cortex andhippocampus, which are both known to play important roles in cognitive function, memory and emotion, suggest that the expression of Tnnt 1 may be an early molecular biomarker of induced CNS stress.

  15. Heterosubtypic protection against pathogenic human and avian influenza viruses via in vivo electroporation of synthetic consensus DNA antigens.

    Directory of Open Access Journals (Sweden)

    Dominick J Laddy

    Full Text Available BACKGROUND: The persistent evolution of highly pathogenic avian influenza (HPAI highlights the need for novel vaccination techniques that can quickly and effectively respond to emerging viral threats. We evaluated the use of optimized consensus influenza antigens to provide broad protection against divergent strains of H5N1 influenza in three animal models of mice, ferrets, and non-human primates. We also evaluated the use of in vivo electroporation to deliver these vaccines to overcome the immunogenicity barrier encountered in larger animal models of vaccination. METHODS AND FINDINGS: Mice, ferrets and non-human primates were immunized with consensus plasmids expressing H5 hemagglutinin (pH5HA, N1 neuraminidase (pN1NA, and nucleoprotein antigen (pNP. Dramatic IFN-gamma-based cellular immune responses to both H5 and NP, largely dependent upon CD8+ T cells were seen in mice. Hemaggutination inhibition titers classically associated with protection (>1:40 were seen in all species. Responses in both ferrets and macaques demonstrate the ability of synthetic consensus antigens to induce antibodies capable of inhibiting divergent strains of the H5N1 subtype, and studies in the mouse and ferret demonstrate the ability of synthetic consensus vaccines to induce protection even in the absence of such neutralizing antibodies. After challenge, protection from morbidity and mortality was seen in mice and ferrets, with significant reductions in viral shedding and disease progression seen in vaccinated animals. CONCLUSIONS: By combining several consensus influenza antigens with in vivo electroporation, we demonstrate that these antigens induce both protective cellular and humoral immune responses in mice, ferrets and non-human primates. We also demonstrate the ability of these antigens to protect from both morbidity and mortality in a ferret model of HPAI, in both the presence and absence of neutralizing antibody, which will be critical in responding to the

  16. [Consensus statement on the clinical management of human immunodeficiency virus-associated neurocognitive disorders].

    Science.gov (United States)

    Podzamczer Palter, Daniel; Muñoz-Moreno, José A; Alcolea Rodríguez, Daniel; Alonso Villaverde, Carlos; Antela López, Antonio; Blanch Andreu, Jordi; Casado Osorio, José Luis; Galindo Puerto, M José; Garolera i Freixa, Maite; Locutura Rupérez, Jaime; Lleó Bisa, Albert; Prats París, Anna; Pérez-Valero, Ignacio; Portilla Sogorb, Joaquín; Rovira Cañellas, Alex; Téllez Molina, M Jesús; Tiraboschi, Juan Manuel; Vergara Moragues, Esperanza; Arribas López, José Ramón; Goenaga Sánchez, Miguel Ángel; de León-Naranjo, Fernando Lozano; Martínez Chamorro, Esteban; Polo Rodríguez, Rosa; Muñoz-Moreno, José A; Podzamczer, Daniel

    2014-01-01

    To develop a consensus document containing clinical recommendations for the management of human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND). We assembled a panel of experts appointed by GeSIDA and the Secretariat of the National AIDS Plan (PNS), including internal medicine physicians with expertise in the field of HIV, neuropsychologists, neurologists and neuroradiologists. Scientific information was reviewed to October 2012 in publications and conference papers. In support of the recommendations using two levels of evidence: the strength of the recommendation in the opinion of the experts (A, B, C) and the level of empirical evidence (I, II, III), two levels based on the criteria of the Infectious Disease Society of America, already used in previous documents GeSIDA/SPNS. Multiple recommendations for the clinical management of these disorders are provided, including two graphics algorithms, considering both the diagnostic and possible therapeutic strategies. Neurocognitive disorders associated with HIV infection is currently highly prevalent, are associated with a decreased quality of life and daily activities, and given the possibility of occurrence of an increase in the coming years, there is a need to adequately manage these disorders, from a diagnostic as well as therapeutic point of view, and always from a multidisciplinary perspective. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  17. Phase III trial of postoperative cisplatin, interferon alpha-2b, and 5-FU combined with external radiation treatment versus 5-FU alone for patients with resected pancreatic adenocarcinoma – CapRI: study protocol [ISRCTN62866759

    Directory of Open Access Journals (Sweden)

    Schmitz-Winnenthal H

    2005-04-01

    Full Text Available Abstract After surgical intervention with curative intention in specialised centres the five-year survival of patients with carcinoma of the exocrine pancreas is only 15%. The ESPAC-1 trial showed an increased five-year survival of 21% achieved with adjuvant chemotherapy. Investigators from the Virginia Mason Clinic have reported a 5-year survival rate of 55% in a phase II trial evaluating adjuvant chemotherapy, immunotherapy and external-beam radiation. Design The CapRI study is an open, controlled, prospective, randomised multi-centre phase III trial. Patients in study arm A will be treated as outpatients with 5-Fluorouracil; Cisplatin and 3 million units Interferon alpha-2b for 5 1/2 weeks combined with external beam radiation. After chemo-radiation the patients receive continuous 5-FU infusions for two more cycles. Patients in study arm B will be treated as outpatients with intravenous bolus injections of folinic acid, followed by intravenous bolus injections of 5-FU given on 5 consecutive days every 28 days for 6 cycles. A total of 110 patients with specimen-proven R0 or R1 resected pancreatic adenocarcinoma will be enrolled. An interim analysis for patient safety reasons will be done one year after start of recruitment. Evaluation of the primary endpoint will be performed two years after the last patients' enrolment. Discussion The aim of this study is to evaluate the overall survival period attained by chemo-radiotherapy including interferon alpha 2b administration with adjuvant chemotherapy. The influence of interferon alpha on the effectiveness of the patients' chemoradiation regimen, the toxicity, the disease-free interval and the quality of life are analysed. Different factors are tested in terms of their potential role as predictive markers.

  18. An Observational, Multicenter, Cohort Study Evaluating the Antiviral Efficacy and Safety in Korean Patients With Chronic Hepatitis B Receiving Pegylated Interferon-alpha 2a (Pegasys)

    Science.gov (United States)

    Chon, Young Eun; Kim, Dong Joon; Kim, Sang Gyune; Kim, In Hee; Bae, Si Hyun; Hwang, Seong Gyu; Heo, Jeong; Jang, Jeong Won; Lee, Byung Seok; Kim, Hyung Joon; Jun, Dae Won; Kim, Kang Mo; Chung, Woo Jin; Choi, Moon Seok; Jang, Jae Young; Yim, Hyung Joon; Tak, Won Young; Yoon, Ki Tae; Park, Jun Yong; Han, Kwang-Hyub; Suk, Ki Tae; Lee, Hyun Woong; Jang, Byoung Kuk; Ahn, Sang Hoon

    2016-01-01

    Abstract Currently, limited data are available regarding the efficacy and safety of pegylated interferon alpha-2a (PEG-IFN α-2a) in Korean patients with chronic hepatitis B (CHB), in whom hepatitis B virus (HBV) genotype C is the most common type. We collected data from 439 patients (HBeAg positive, n = 349; HBeAg negative, n = 90) with CHB who were treated with PEG-IFN α-2a as a first-line therapy from 18 institutions. Treatment responses at the end of treatment (ET) and at 6 months posttreatment (PT6) were compared between the patients who were treated for 24 weeks versus 48 weeks, and adverse events (AEs) were evaluated. In HBeAg-positive patients, those who received PEG-IFN α-2a for 48 weeks showed significantly higher HBV DNA suppression (HBV DNA < 2000 IU/mL) than those who were treated for 24 weeks (48 weeks vs 24 weeks; at ET, 44.4% vs 36.7%, P = 0.035; at PT6, 35.9% vs 13.3%, P = 0.035). The HBeAg seroconversion rate at ET was 18.1% in 48-week treatment group, which is significantly higher than the 2.2% (P < 0.001) that was seen in 24-week treatment group. This finding also continued at PT6 (29.0% vs 10.0%, P < 0.001). Following 48 weeks of treatment in HBeAg-negative patients, HBV DNA suppression at ET was higher than in HBeAg-positive patients (87.8% vs 44.4%). AEs were typical of those associated with PEG-IFN α-2a. In naïve Korean HBeAg-positive CHB patients treated with PEG-IFN α-2a, higher rates of HBV DNA suppression and HBeAg seroconversion were achieved in the 48-week treatment group than in the 24-week treatment group without additional risk of AEs. PMID:27057828

  19. An Observational, Multicenter, Cohort Study Evaluating the Antiviral Efficacy and Safety in Korean Patients With Chronic Hepatitis B Receiving Pegylated Interferon-alpha 2a (Pegasys): TRACES Study.

    Science.gov (United States)

    Chon, Young Eun; Kim, Dong Joon; Kim, Sang Gyune; Kim, In Hee; Bae, Si Hyun; Hwang, Seong Gyu; Heo, Jeong; Jang, Jeong Won; Lee, Byung Seok; Kim, Hyung Joon; Jun, Dae Won; Kim, Kang Mo; Chung, Woo Jin; Choi, Moon Seok; Jang, Jae Young; Yim, Hyung Joon; Tak, Won Young; Yoon, Ki Tae; Park, Jun Yong; Han, Kwang-Hyub; Suk, Ki Tae; Lee, Hyun Woong; Jang, Byoung Kuk; Ahn, Sang Hoon

    2016-04-01

    Currently, limited data are available regarding the efficacy and safety of pegylated interferon alpha-2a (PEG-IFN α-2a) in Korean patients with chronic hepatitis B (CHB), in whom hepatitis B virus (HBV) genotype C is the most common type.We collected data from 439 patients (HBeAg positive, n = 349; HBeAg negative, n = 90) with CHB who were treated with PEG-IFN α-2a as a first-line therapy from 18 institutions. Treatment responses at the end of treatment (ET) and at 6 months posttreatment (PT6) were compared between the patients who were treated for 24 weeks versus 48 weeks, and adverse events (AEs) were evaluated.In HBeAg-positive patients, those who received PEG-IFN α-2a for 48 weeks showed significantly higher HBV DNA suppression (HBV DNA < 2000 IU/mL) than those who were treated for 24 weeks (48 weeks vs 24 weeks; at ET, 44.4% vs 36.7%, P = 0.035; at PT6, 35.9% vs 13.3%, P = 0.035). The HBeAg seroconversion rate at ET was 18.1% in 48-week treatment group, which is significantly higher than the 2.2% (P < 0.001) that was seen in 24-week treatment group. This finding also continued at PT6 (29.0% vs 10.0%, P < 0.001). Following 48 weeks of treatment in HBeAg-negative patients, HBV DNA suppression at ET was higher than in HBeAg-positive patients (87.8% vs 44.4%). AEs were typical of those associated with PEG-IFN α-2a.In naïve Korean HBeAg-positive CHB patients treated with PEG-IFN α-2a, higher rates of HBV DNA suppression and HBeAg seroconversion were achieved in the 48-week treatment group than in the 24-week treatment group without additional risk of AEs.

  20. Functional polymorphisms in the interleukin-6 and serotonin transporter genes, and depression and fatigue induced by interferon-alpha and ribavirin treatment.

    LENUS (Irish Health Repository)

    Bull, S J

    2009-12-01

    Depression and fatigue are frequent side effects of interferon-alpha (IFN-alpha) treatment, and there is compelling evidence that the inflammatory response system (including interleukin-6, IL-6) and the serotonergic system is important in the pathophysiology of such symptoms. Functional polymorphisms in the promoter region of the IL-6 gene (rs1800795) and serotonin transporter gene (5-HTTLPR) have been identified as regulating these systems. The present study aimed to determine if these polymorphisms were associated with the development of depression and fatigue during IFN-alpha and ribavirin treatment. Ninety-eight Caucasian patients receiving pegylated IFN-alpha and ribavirin treatment for chronic hepatitis C virus at King\\'s College Hospital, London, and Emory University Hospital, Atlanta, participated in this prospective cohort study. Symptoms of depression and fatigue were measured before treatment and at weeks 4, 8, 12 and 24 during treatment. The \\'low IL-6\\' synthesizing genotype (CC) was associated with significantly fewer symptoms of depression (effect size = 0.7 at week 24; F = 9.4, d.f. = 436, P = 0.002). The \\'high transcription\\' serotonin transporter (5-HTT) genotype (LL) was also associated with significantly fewer symptoms of depression, but with a much smaller effect (effect size = 0.2 at week 24; F = 4.5, d.f. = 436, P = 0.03). Neither polymorphisms were associated with symptoms of fatigue (IL-6: F = 1.2, d.f. = 430, P = 0.2; 5-HTT: F = 0.5, d.f. = 430, P = 0.5). The smaller effects of the 5-HTT polymorphism on depression may be explained by an interaction between the genes (F = 5.0, d.f. = 434, P = 0.02): the \\'protective\\' effect of the 5-HTTLPR polymorphism was evident only in the presence of the \\'low IL-6\\' genotype (F = 5.4, d.f. = 64, P = 0.02), not in the presence of the \\'high IL-6\\' genotype (F = 2.2, d.f. = 369, P = 0.1). The association between the IL-6 polymorphism and reduced risk of depressive symptoms confirms the role

  1. Expression of interferon-alpha/beta receptor protein in liver of patients with hepatitis C virus-related chronic liver disease

    Institute of Scientific and Technical Information of China (English)

    Xiang-Wei Meng; Bao-Rong Chi; Li-Gang Chen; Ling-Ling Zhang; Yan Zhuang; Hai-Yan Huang; Xun Sun

    2005-01-01

    AIM: To study the expression of interferon-alpha/beta (IFN-α/β) receptor protein in liver of patients with hepatitis C virus (HCV)-related chronic liver disease and its clinical significance.METHODS: A total of 181 patients with HCV-related chronic liver disease included 56 with HCV-related liver cirrhosis (LC) and 125 with chronic hepatitis C (CHC).CHC patients were treated with five megaunits of interferon-α1b six times weekly for the first 2 weeks and then every other day for 22 wk. The patients were divided into interferon (IFN) treatment-responsive and nonresponsive groups, but 36 patients lost follow-up shortly after receiving the treatment. The expression of IFN-α/β receptor (IFN-α/βR) protein in liver of all patients was determined with immunofluorescence.RESULTS: In liver of patients with HCV-related chronic liver disease, the expression of IFN-α/βR protein in liver cell membrane was stronger than that in cytoplasm and more obvious in the surroundings of portal vein than in the surroundings of central vein. Moreover, it was poorly distributed in hepatic Iobules. The weak positive, positive and strong positive expression of IFN-α/βR were 40% (50/125), 28% (35/125), 32% (40/125), respectively in CHC group, and 91.1% (51/56), 5.35% (3/56), and 3.56% (2/56), respectively in LC group. The positive and strong positive rates were higher in CHC group than in LC group (P<0.01). In IFN treatment responsive group, 27.8% (10/36) showed weak positive expression; 72.2% (26/36)showed positive or strong positive expression. In the nonresponsive group, 71.7% (38/53) showed weak positive expression; 28.3% (15/53) showed positive or strong positive expression. The expression of IFN-α/βR protein in liver was more obvious in IFN treatment responsive group than in non-responsive group.CONCLUSION: Expression of IFN-α/βR protein in liver of patients with HCV-related chronic liver disease is likely involved in the response to IFN treatment.

  2. A campaign to convey the scientific consensus about human-caused climate change: rationale, formative research, and campaign overview. (Invited)

    Science.gov (United States)

    Maibach, E.; Leiserowitz, A.; Gould, R.

    2013-12-01

    Large numbers of Americans mistakenly believe that there is disagreement among the experts about the reality of climate change. For example, in our nationally representative survey conducted in April 2013, only 42% of respondents reported 'most scientists think global warming is happening;' conversely, 33% reported 'there is a lot of disagreement among scientists about whether or not global warming is happening,' and an additional 20% responded they 'don't know enough to say.' Our research has also shown that this common misperception is highly consequential: people who misunderstand the scientific consensus are less convinced that climate change is occurring, is human-caused, serious, and solvable; they are also less likely to support societal responses to address the problem. In this paper, we will present the results of a series of randomized controlled message experiments conducted to determine the most effective means of conveying the extent of the scientific consensus about human-caused climate change. The variables tested include quantitative vs. qualitative consensus descriptions, more vs. less precise descriptions, contextualizing metaphors, graphical representations, and explanations regarding why people may have developed a misperception. The findings from this formative research are being used to create a communication campaign that will be launched in fall 2013 by a leading American scientific society prior to the AGU Annual Meeting. A full description of the campaign will be presented.

  3. Reaching Consensus on Antarctic Tourism Regulation - Calibrating the Human-Nature Relationship?

    NARCIS (Netherlands)

    Bastmeijer, C.J.; Lamers, M.A.J.

    2013-01-01

    The states that jointly manage Antarctica were not yet able to reach consensus on a number of specific Antarctic tourism management issues. While recognizing that many factors influence the international decision-making process, this chapter aims to explore one rarely discussed philosophical factor

  4. Reaching consensus on Antarctic tourism regulation : Calibrating the human-nature relationship?

    NARCIS (Netherlands)

    Bastmeijer, Kees; Lamers, Machiel

    2012-01-01

    The states that jointly manage Antarctica were not yet able to reach consensus on a number of specific management issues relating to Antarctic tourism. While recognizing that many factors influence the international decision-making process, this publication aims to explore one rarely discussed philo

  5. II Brazilian Consensus on the use of human immunoglobulin in patients with primary immunodeficiencies.

    Science.gov (United States)

    Goudouris, Ekaterini Simões; Rego Silva, Almerinda Maria do; Ouricuri, Aluce Loureiro; Grumach, Anete Sevciovic; Condino-Neto, Antonio; Costa-Carvalho, Beatriz Tavares; Prando, Carolina Cardoso; Kokron, Cristina Maria; Vasconcelos, Dewton de Moraes; Tavares, Fabíola Scancetti; Silva Segundo, Gesmar Rodrigues; Barreto, Irma Cecília; Dorna, Mayra de Barros; Barros, Myrthes Anna; Forte, Wilma Carvalho Neves

    2017-01-01

    In the last few years, new primary immunodeficiencies and genetic defects have been described. Recently, immunoglobulin products with improved compositions and for subcutaneous use have become available in Brazil. In order to guide physicians on the use of human immunoglobulin to treat primary immunodeficiencies, based on a narrative literature review and their professional experience, the members of the Primary Immunodeficiency Group of the Brazilian Society of Allergy and Immunology prepared an updated document of the 1st Brazilian Consensus, published in 2010. The document presents new knowledge about the indications and efficacy of immunoglobulin therapy in primary immunodeficiencies, relevant production-related aspects, mode of use (routes of administration, pharmacokinetics, doses and intervals), adverse events (major, prevention, treatment and reporting), patient monitoring, presentations available and how to have access to this therapeutic resource in Brazil. RESUMO Nos últimos anos, novas imunodeficiências primárias e defeitos genéticos têm sido descritos. Recentemente, produtos de imunoglobulina, com aprimoramento em sua composição e para uso por via subcutânea, tornaram-se disponíveis em nosso meio. Com o objetivo de orientar o médico no uso da imunoglobulina humana para o tratamento das imunodeficiências primárias, os membros do Grupo de Assessoria em Imunodeficiências da Associação Brasileira de Alergia e Imunologia produziram um documento que teve por base uma revisão narrativa da literatura e sua experiência profissional, atualizando o I Consenso Brasileiro publicado em 2010. Apresentam-se novos conhecimentos sobre indicações e eficácia do tratamento com imunoglobulina nas imunodeficiências primárias, aspectos relevantes sobre a produção, forma de utilização (vias de administração, farmacocinética, doses e intervalos), efeitos adversos (principais efeitos, prevenção, tratamento e notificação), monitorização do

  6. Emergence of occult minority genotype 2b hepatitis C infection in an HIV-1-co-infected patient treated for genotype 5a HCV infection with 48 weeks of pegylated-interferon-alpha 2b and ribavirin.

    Science.gov (United States)

    Buckton, A J; Kulasegaram, R; Ngui, S L; Fisher, M; James, R; Rangarajan, S; Teo, C G

    2007-09-01

    An HIV-1/hepatitis C virus (HCV) co-infected patient with haemophilia received a 48-week course of pegylated interferon-alpha-2b and ribavirin therapy for genotype 5a HCV infection. Virological response was achieved at week 24. At the end of treatment, HCV RNA in serum was detected and identified to belong to genotype 2b, rather than genotype 5a. A sensitive method for identifying minority HCV genotypes in pre-treatment serum showed genotype 2b HCV carriage prior to treatment. Sequencing the interferon sensitivity-determining region of the HCV NS5A gene obtained from pre-, intra- and post-treatment sera revealed emergence of quasispecies bearing R-->K and M-->A/T mutations at codons 2222 and 2223, respectively. Occult presence of minority HCV subpopulations and their acquisition of mutations following therapy can result in poor treatment outcome.

  7. Quantitative mass spectrometry analysis reveals similar substrate consensus motif for human Mps1 kinase and Plk1.

    Directory of Open Access Journals (Sweden)

    Zhen Dou

    Full Text Available BACKGROUND: Members of the Mps1 kinase family play an essential and evolutionarily conserved role in the spindle assembly checkpoint (SAC, a surveillance mechanism that ensures accurate chromosome segregation during mitosis. Human Mps1 (hMps1 is highly phosphorylated during mitosis and many phosphorylation sites have been identified. However, the upstream kinases responsible for these phosphorylations are not presently known. METHODOLOGY/PRINCIPAL FINDINGS: Here, we identify 29 in vivo phosphorylation sites in hMps1. While in vivo analyses indicate that Aurora B and hMps1 activity are required for mitotic hyper-phosphorylation of hMps1, in vitro kinase assays show that Cdk1, MAPK, Plk1 and hMps1 itself can directly phosphorylate hMps1. Although Aurora B poorly phosphorylates hMps1 in vitro, it positively regulates the localization of Mps1 to kinetochores in vivo. Most importantly, quantitative mass spectrometry analysis demonstrates that at least 12 sites within hMps1 can be attributed to autophosphorylation. Remarkably, these hMps1 autophosphorylation sites closely resemble the consensus motif of Plk1, demonstrating that these two mitotic kinases share a similar substrate consensus. CONCLUSIONS/SIGNIFICANCE: hMps1 kinase is regulated by Aurora B kinase and its autophosphorylation. Analysis on hMps1 autophosphorylation sites demonstrates that hMps1 has a substrate preference similar to Plk1 kinase.

  8. A PILOT AND FEASIBILITY CLINICAL TRIAL EVALUATING IMMUNO-GENE THERAPY OF MALIGNANT PLEURAL MESOTHELIOMA (MPM) USING INTRAPLEURAL DELIVERY OF ADENOVIRUS- INTERFERON-ALPHA (Ad.hIFN-α2b) IN COMBINATION WITH HIGH-DOSE CELECOXIB AND SYSTEMIC CHEMOTHERAPY

    Science.gov (United States)

    Sterman, Daniel H; Alley, Evan; Stevenson, James; Friedberg, Joseph; Metzger, Susan; Recio, Adri; Moon, Edmund; Haas, Andrew R; Vachani, Anil; Katz, Sharyn I; Sun, Jing; Heitjan, Daniel F; Hwang, Wei-Ting; Litzky, Leslie; Yearley, Jennifer H; Tan, Kay See; Papasavvas, Emmanouil; Kennedy, Paul; Montaner, Luis J.; Cengel, Keith; Simone, Charles B; Culligan, Melissa; Langer, Corey J; Albelda, Steven M

    2016-01-01

    Purpose “In situ vaccination” using immuno-gene therapy has the ability to induce polyclonal anti-tumor responses directed by the patient’s immune system. Experimental Design Patients with unresectable MPM received two intrapleural doses of a replication-defective adenoviral vector containing the human interferon-alpha2b gene (Ad.IFN) concomitant with a 14-day course of celecoxib followed by chemotherapy. Primary outcomes were safety, toxicity, and objective response rate; secondary outcomes included progression-free and overall survival. Bio-correlates on blood and tumor were measured. Results Forty subjects were treated: 18 received first-line pemetrexed-based chemotherapy, 22 received second-line chemotherapy with pemetrexed (n=7) or gemcitabine (n=15). Treatment was generally well tolerated. The overall response rate was 25% and the disease control rate was 88%. Median overall survival (MOS) for all patients with epithelial histology was 21 months versus 7 months for patients with non-epithelial histology. MOS in the first-line cohort was 12.5 months, while MOS for the second-line cohort was 21.5 months, with 32% of patients alive at 2 years. No biologic parameters were found to correlate with response, including numbers of activated blood T cells or NK cells, regulatory T cells in blood, peak levels of interferon-α in blood or pleural fluid, induction of anti-tumor antibodies, nor an immune-gene signature in pretreatment biopsies. Conclusions The combination of intrapleural Ad.IFN, celecoxib, and chemotherapy proved safe in patients with MPM. Overall survival rate was significantly higher than historical controls in the second-line group. Results of this study support proceeding with a multi-center randomized clinical trial of chemo-immunogene therapy versus standard chemotherapy alone. PMID:26968202

  9. [Consensus statement on metabolic disorders and cardiovascular risks in patients with human immunodeficiency virus].

    Science.gov (United States)

    Polo Rodríguez, Rosa; Galindo Puerto, María José; Dueñas, Carlos; Gómez Candela, Carmen; Estrada, Vicente; Villar, Noemí G P; Locutura, Jaime; Mariño, Ana; Pascua, Javier; Palacios, Rosario; von Wichmman, Miguel Ángel; Álvarez, Julia; Asensi, Victor; Lopez Aldeguer, José; Lozano, Fernando; Negredo, Eugenia; Ortega, Enrique; Pedrol, Enric; Gutiérrez, Félix; Sanz Sanz, Jesús; Martínez Chamorro, Esteban

    2015-01-01

    This consensus document is an update of metabolic disorders and cardiovascular risk (CVR) guidelines for HIV-infected patients. This document has been approved by an expert panel of GEAM, SPNS and GESIDA after reviewing the results of efficacy and safety of clinical trials, cohort and pharmacokinetic studies published in biomedical journals (PubMed and Embase) or presented in medical scientific meetings. Recommendation strength and the evidence in which they are supported are based on the GRADE system. A healthy lifestyle is recommended, no smoking and at least 30min of aerobic exercise daily. In diabetic patients the same treatment as non-HIV infected patients is recommended. HIV patients with dyslipidemia should be considered as high CVR, thus its therapeutic objective is an LDL less than 100mg/dL. The antihypertensive of ACE inhibitors and ARAII families are better tolerated and have a lower risk of interactions. In HIV-patients with diabetes or metabolic syndrome and elevated transaminases with no defined etiology, the recommended is to rule out a hepatic steatosis Recommendations for action in hormone alterations are also updated. These new guidelines update previous recommendations regarding all those metabolic disorders involved in CVR. Hormone changes and their management and the impact of metabolic disorders on the liver are also included. Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  10. Human Dignity and the Commercial Appropriation of Personality: Towards a Cosmopolitan Consensus in Publicity Rights?

    Directory of Open Access Journals (Sweden)

    Olaf Weber

    2004-03-01

    Full Text Available This article is concerned with the commercial appropriation of human personality and its regulation in different legal systems. Where accepted, so called “publicity rights” allow for the exclusive commercial exercise of a persona’s publicity values. A tradable worth can be found in many personal characteristics such as voice, signature or pseudonym. Predominantly, however, it accrues to one’s name and likeness. It is argued that such potential rights are inherent in every human being.

  11. Consensus conferences

    DEFF Research Database (Denmark)

    Nielsen, Annika Porsborg; Lassen, Jesper

    Our results point to significant national variation both in terms of the perceived aim of consensus conferences, expectations to conference outcomes, conceptions of the roles of lay people and experts, and in terms of the way in which the role of public deliberation is interpreted. Interestingly...

  12. Alpha-interferon induces enhanced expression of HLA-ABC antigens and beta-2-microglobulin in vivo and in vitro in various subsets of human lymphoid cells

    DEFF Research Database (Denmark)

    Nissen, Mogens Holst; Larsen, J K; Plesner, T

    1987-01-01

    The effect of cloned alpha-interferon (alpha-IFN) on the in vitro and in vivo expression of HLA-ABC antigens and beta-2-microglobulin (beta-2-m) on subpopulations of human lymphoid cells was studied by flow cytometry. Mononuclear cells isolated from patients and cell cultures were labelled...

  13. Plastics, the environment and human health: current consensus and future trends

    OpenAIRE

    Richard C. Thompson; Moore, Charles J.; Frederick S Vom Saal; Swan, Shanna H.

    2009-01-01

    Plastics have transformed everyday life; usage is increasing and annual production is likely to exceed 300 million tonnes by 2010. In this concluding paper to the Theme Issue on Plastics, the Environment and Human Health, we synthesize current understanding of the benefits and concerns surrounding the use of plastics and look to future priorities, challenges and opportunities. It is evident that plastics bring many societal benefits and offer future technological and medical advances. However...

  14. Plastics, the environment and human health: current consensus and future trends

    OpenAIRE

    Thompson, Richard C.; Moore, Charles J.; vom Saal, Frederick S.; Swan, Shanna H.

    2009-01-01

    Plastics have transformed everyday life; usage is increasing and annual production is likely to exceed 300 million tonnes by 2010. In this concluding paper to the Theme Issue on Plastics, the Environment and Human Health, we synthesize current understanding of the benefits and concerns surrounding the use of plastics and look to future priorities, challenges and opportunities. It is evident that plastics bring many societal benefits and offer future technological and medical advances. However...

  15. The relevance of the rat lung response to particle overload for human risk assessment: a workshop consensus report.

    Science.gov (United States)

    2000-01-01

    On 23-24 March 1998, the International Life Sciences Institute (ILSI) Risk Science Institute convened a workshop entitled "Relevance of the Rat Lung Response to Particle Overload for Human Risk Assessment." The workshop addressed the numerous study reports of lung tumors in rats resulting from chronic inhalation exposures to poorly soluble, nonfibrous particles of low acute toxicity and not directly genotoxic. These poorly soluble particles, indicated by the acronym PSPs (e.g., carbon black, coal dust, diesel soot, nonasbestiform talc, and titanium dioxide), elicit tumors in rats when deposition overwhelms the clearance mechanisms of the lung resulting in a condition referred to as "overload." These PSPs have been shown not to induce tumors in mice and hamsters, and the available data in humans are consistently negative. The objectives were twofold: (1) to provide guidance for risk assessment on the interpretation of neoplastic and nonneoplastic responses of the rat lung to PSPs; and (2) to identify important data gaps in our understanding of the lung responses of rats and other species to PSPs. Utilizing the five critical reviews of relevant literature that follow herein and the combined expertise and experience of the 30 workshop participants, a number of questions were addressed. The consensus views of the workshop participants are presented in this report. Because it is still not known with certainty whether high lung burdens of PSPs can lead to lung cancer in humans via mechanisms similar to those of the rat, in the absence of mechanistic data to the contrary it must be assumed that the rat model can identify potential carcinogenic hazards to humans. Since the apparent responsiveness of the rat model at overload is dependent on coexistent chronic active inflammation and cell proliferation, at lower lung doses where chronic active inflammation and cell proliferation are not present, no lung cancer hazard is anticipated.

  16. Consensus standards for introductory e-learning courses in human participants research ethics.

    Science.gov (United States)

    Williams, John R; Sprumont, Dominique; Hirtle, Marie; Adebamowo, Clement; Braunschweiger, Paul; Bull, Susan; Burri, Christian; Czarkowski, Marek; Fan, Chien Te; Franck, Caroline; Gefenas, Eugenjius; Geissbuhler, Antoine; Klingmann, Ingrid; Kouyaté, Bocar; Kraehenbhul, Jean-Pierre; Kruger, Mariana; Moodley, Keymanthri; Ntoumi, Francine; Nyirenda, Thomas; Pym, Alexander; Silverman, Henry; Tenorio, Sara

    2014-06-01

    This paper reports the results of a workshop held in January 2013 to begin the process of establishing standards for e-learning programmes in the ethics of research involving human participants that could serve as the basis of their evaluation by individuals and groups who want to use, recommend or accredit such programmes. The standards that were drafted at the workshop cover the following topics: designer/provider qualifications, learning goals, learning objectives, content, methods, assessment of participants and assessment of the course. The authors invite comments on the draft standards and eventual endorsement of a final version by all stakeholders.

  17. Persistence of BCR/ABL mRNA-expressing bone-marrow cells in patients with chronic myelogenous leukemia in complete cytogenetic remission induced by interferon-alpha therapy.

    Science.gov (United States)

    Eberlé, F; Toiron, Y; Camerlo, J; Lafage, M; Sainty, D; Arnoulet, C; Raineri, V; Gabert, J; Maraninchi, D; Mannoni, P

    1995-06-01

    Complete hematologic and cytogenetic responses can be obtained with interferon-alpha (IFN-alpha) in 15-25% of the patients with chronic myelogenous leukemia (CML). In these patients, reverse-transcription polymerase chain reaction (RT-PCR) can be used to evaluate minimal residual disease. We studied 12 patients who remained Philadelphia-negative for a median period of 21 months on IFN-alpha therapy. Using RT-PCR, the specific transcript was found in all bone marrow (BM) samples. Ten patients still exhibiting a persistent residual clone remained in cytogenetic remission for a median period of 14 months. As we observed a dissociation between bcr-abl expression in BM and peripheral blood (PB) cells, and given the known fluctuations of the bcr-abl PCR results, we suggest that PB negative results should be confirmed on BM specimens. Alternatively, it remains to be demonstrated whether longitudinal monitoring of residual disease would benefit from quantitative PCR or double fluorescence in situ hybridization.

  18. Effects of Smoking on Pegylated Interferon alpha 2a and First Generation Protease Inhibitor-based Antiviral Therapy in Naïve Patients Infected with Hepatitis C Virus Genotype 1.

    Science.gov (United States)

    Zimmermann, Tim; Hueppe, Dietrich; Mauss, Stefan; Buggisch, Peter; Pfeiffer-Vornkahl, Heike; Grimm, Daniel; Galle, Peter R; Alshuth, Ulrich

    2016-03-01

    Smoking has multiple effects on factors influencing hepatitis C and antiviral therapy, including lipid metabolism, fibrosis, platelet count and adherence aspects. The aim of this analysis was to determine the impact of smoking on hepatitis C virus antiviral therapy. Data of two cohorts of an observational multicenter study including therapy-naïve patients infected with genotype 1 hepatitis C virus (HCV) treated with dual antiviral therapy (n=7,796) with pegylated interferon alpha 2a in combination with ribavirin, or triple antiviral therapy (n=1,122) containing telaprevir or boceprevir, were analysed. In the univariate matched pair analysis of dual antiviral therapy patients (n=584), smoking was significantly associated with lower sustained viral response rates (p=0.026, OR 0.69 CI: 0.50 - 0.96). The effect of smoking on sustained viral response remained significant (p=0.028, OR 0.67 CI: 0.47 - 0.96) in the multivariate analysis when adjusting for all other baseline parameters with a significant association in the univariate analysis, i.e. diabetes, fibrosis, body mass index, transaminases and baseline viral load. Under protease inhibitors the influence of smoking on virological response did not arise. Smoking has a negative impact on antiviral therapy in naïve patients infected with HCV genotype 1 independently of age, gender, history of drug use or alcoholic liver disease. The effects of smoking might be overcome by the new antiviral agents.

  19. Tamoxifen vs Tamoxifen plus 13-cis-retinoic acid vs Tamoxifen plus Interferon alpha-2a as first-line endocrine treatments in advanced breast cancer: updated results of a phase II, prospective, randomised multicentre trial.

    Science.gov (United States)

    Chiesa, Matteo Dalla; Passalacqua, Rodolfo; Michiara, Maria; Franciosi, Vittorio; Di Costanzo, Francesco; Bisagni, Giancarlo; Camisa, Roberta; Buti, Sebastiano; Tomasello, Gianluca; Cocconi, Giorgio

    2007-12-01

    To demonstrate the efficacy of 13-cis-retinoic acid (RA) or Interferon alpha-2a (IFN alpha-2a) with Tamoxifen (TAM) in the treatment of advanced breast cancer. Ninety-nine postmenopausal patients with advanced breast cancer, and a positive or unknown estrogen (ER) or progesterone (PgR) receptor status, were randomised to receive TAM 20 mg/m2/day orally (arm A), or TAM plus RA 1 mg/kg/day orally (arm B), or TAM plus IFN alpha-2a 3 MU thrice a week intramuscular (arm C). The three treatment groups were well balanced in terms of the main prognostic factors. Response was evaluable in 32 of the patients in arm A, 32 in arm B, and 30 in arm C. Intention-to-treat analysis showed no significant difference of response rate in the three arms (44% vs 38% vs 42%). After an eight years median follow-up, there was no significant between-group difference in median overall survival: 47.4 vs 38.2 vs 45.1 months. Side effects were negligible in arm A, but cutaneous (39%) and mucosal (62%) toxicities were frequent in arm B, and flu-like syndrome and/or myalgia (46%) in arm C. The administration of RA or IFN alpha-2a does not add anything to the therapeutic effects of TAM.

  20. Distinct myeloid suppressor cell subsets correlate with plasma IL-6 and IL-10 and reduced interferon-alpha signaling in CD4⁺ T cells from patients with GI malignancy.

    Science.gov (United States)

    Mundy-Bosse, Bethany L; Young, Gregory S; Bauer, Todd; Binkley, Elaine; Bloomston, Mark; Bill, Matthew A; Bekaii-Saab, Tanios; Carson, William E; Lesinski, Gregory B

    2011-09-01

    Interferon-alpha (IFN-α) promotes anti-tumor immunity through its actions on immune cells. We hypothesized that elevated percentages of myeloid-derived suppressor cells (MDSC) and increased pro-inflammatory cytokines in peripheral blood would be associated with impaired response to IFN-α in patients with gastrointestinal (GI) malignancies. This study evaluated relationships between plasma IL-6, IL-10, circulating MDSC subsets, and IFN-α-induced signal transduction in 40 patients with GI malignancies. Plasma IL-6 and IL-10 were significantly higher in patients versus normal donors. CD33(+)HLADR(-)CD11b(+)CD15(+) and CD33(+)HLADR(-/low)CD14(+) MDSC subsets were also elevated in patients versus normal donors (P normal donors. Exploratory multivariable Cox proportional hazards models revealed that an increased percentage of the CD33(+)HLADR(-)CD15(-) MDSC subset was associated with reduced overall survival (P = 0.049), while an increased percentage of the CD33(+)HLADR(-/low)CD14(+) subset was associated with greater overall survival (P = 0.033). These data provide evidence for a unique relationship between specific cytokines, MDSC subsets, and IFN-α responsiveness in patients with GI malignancies.

  1. Bell’s palsy during interferon alpha 2a treatment in a case with Behçet uveitis [v1; ref status: indexed, http://f1000r.es/27j

    Directory of Open Access Journals (Sweden)

    Fatime Nilüfer Yalçindağ

    2013-11-01

    Full Text Available Purpose: To present a case who developed Bell’s palsy while using interferon alpha 2a for Behçet uveitis. Methods: A patient with Behçet disease presented with decreased vision in his right eye. Ophthalmic examination, fundus fluorescein angiography and optical coherence tomography were performed. After developing facial paralysis while on interferon therapy, the patient was referred to our neurology service for differential diagnosis and treatment. Results: Examination of right eye revealed panuveitis with branch retinal vein occlusion, so high dose steroids were prescribed. In three days there was no improvement in terms of vitreous inflammation and so steroids were replaced with interferon. At the seventh month, patient experienced a facial paralysis. After eliminating other causes, including viral infections, trauma, cold exposure and neurological evaluation with cranial MRI, the patient was diagnosed to have Bell’s palsy by a neurologist. Interferon was replaced with mycophenolate mofetil and the Bell’s palsy was treated with oral steroids. Conclusion: It is important to be alert to both common and rare complications while treating with interferon.

  2. Why Consensus?

    Directory of Open Access Journals (Sweden)

    Francesca Polletta

    2016-05-01

    Full Text Available Activists have long justified their egalitarian organizational forms in prefigurative terms. Making decisions by consensus, decentralizing organization, and rotating leadership serves to model the radically democratic society that activists hope to bring into being. Our comparison of consensus-based decision-making in three historical periods, however, shows that activists have understood the purposes of prefiguration in very different ways. Whereas radical pacifists in the 1940s saw their cooperative organizations as sustaining movement stalwarts in a period of political repression, new left activists in the 1960s imagined that their radically democratic practices would be adopted by ever-widening circles. Along with the political conditions in which they have operated, activists’ distinctive understandings of equality have also shaped the way they have made decisions. Our interviews with 30 leftist activists today reveal a view of decision-making as a place to work through inequalities that are informal, unacknowledged, and pervasive.

  3. Plastics, the environment and human health: current consensus and future trends.

    Science.gov (United States)

    Thompson, Richard C; Moore, Charles J; vom Saal, Frederick S; Swan, Shanna H

    2009-07-27

    Plastics have transformed everyday life; usage is increasing and annual production is likely to exceed 300 million tonnes by 2010. In this concluding paper to the Theme Issue on Plastics, the Environment and Human Health, we synthesize current understanding of the benefits and concerns surrounding the use of plastics and look to future priorities, challenges and opportunities. It is evident that plastics bring many societal benefits and offer future technological and medical advances. However, concerns about usage and disposal are diverse and include accumulation of waste in landfills and in natural habitats, physical problems for wildlife resulting from ingestion or entanglement in plastic, the leaching of chemicals from plastic products and the potential for plastics to transfer chemicals to wildlife and humans. However, perhaps the most important overriding concern, which is implicit throughout this volume, is that our current usage is not sustainable. Around 4 per cent of world oil production is used as a feedstock to make plastics and a similar amount is used as energy in the process. Yet over a third of current production is used to make items of packaging, which are then rapidly discarded. Given our declining reserves of fossil fuels, and finite capacity for disposal of waste to landfill, this linear use of hydrocarbons, via packaging and other short-lived applications of plastic, is simply not sustainable. There are solutions, including material reduction, design for end-of-life recyclability, increased recycling capacity, development of bio-based feedstocks, strategies to reduce littering, the application of green chemistry life-cycle analyses and revised risk assessment approaches. Such measures will be most effective through the combined actions of the public, industry, scientists and policymakers. There is some urgency, as the quantity of plastics produced in the first 10 years of the current century is likely to approach the quantity produced in the

  4. Plastics, the environment and human health: current consensus and future trends

    Science.gov (United States)

    Thompson, Richard C.; Moore, Charles J.; vom Saal, Frederick S.; Swan, Shanna H.

    2009-01-01

    Plastics have transformed everyday life; usage is increasing and annual production is likely to exceed 300 million tonnes by 2010. In this concluding paper to the Theme Issue on Plastics, the Environment and Human Health, we synthesize current understanding of the benefits and concerns surrounding the use of plastics and look to future priorities, challenges and opportunities. It is evident that plastics bring many societal benefits and offer future technological and medical advances. However, concerns about usage and disposal are diverse and include accumulation of waste in landfills and in natural habitats, physical problems for wildlife resulting from ingestion or entanglement in plastic, the leaching of chemicals from plastic products and the potential for plastics to transfer chemicals to wildlife and humans. However, perhaps the most important overriding concern, which is implicit throughout this volume, is that our current usage is not sustainable. Around 4 per cent of world oil production is used as a feedstock to make plastics and a similar amount is used as energy in the process. Yet over a third of current production is used to make items of packaging, which are then rapidly discarded. Given our declining reserves of fossil fuels, and finite capacity for disposal of waste to landfill, this linear use of hydrocarbons, via packaging and other short-lived applications of plastic, is simply not sustainable. There are solutions, including material reduction, design for end-of-life recyclability, increased recycling capacity, development of bio-based feedstocks, strategies to reduce littering, the application of green chemistry life-cycle analyses and revised risk assessment approaches. Such measures will be most effective through the combined actions of the public, industry, scientists and policymakers. There is some urgency, as the quantity of plastics produced in the first 10 years of the current century is likely to approach the quantity produced in the

  5. [Consensus statement: recommendations for the management of metabolic bone disease in human immunodeficiency virus patients].

    Science.gov (United States)

    Martínez, Esteban; Jódar Gimeno, Esteban; Reyes García, Rebeca; Carpintero, Pedro; Casado, José Luis; Del Pino Montes, Javier; Domingo Pedrol, Pere; Estrada, Vicente; Maalouf, Jorge; Negredo, Eugenia; Ocampo, Antonio; Muñoz-Torres, Manuel

    2014-04-01

    To provide practical recommendations for the evaluation and treatment of metabolic bone disease in human immunodeficiency virus (HIV) patients. Members of scientific societies related to bone metabolism and HIV: Grupo de Estudio de Sida (GeSIDA), Sociedad Española de Endocrinología y Nutrición (SEEN), Sociedad Española de Investigación Ósea y del Metabolismo Mineral (SEIOMM), and Sociedad Española de Fractura Osteoporótica (SEFRAOS). A systematic search was carried out in PubMed, and papers in English and Spanish with a publication date before 28 May 2013 were included. Recommendations were formulated according to GRADE system (Grading of Recommendations, Assessment, Development, and Evaluation) setting both their strength and the quality of supporting evidence. Working groups were established for each major part, and the final resulting document was later discussed in a face-to-face meeting. All the authors reviewed the final written document and agreed with its content. The document provides evidence-based practical recommendations on the detection and treatment of bone disease in HIV-infected patients. Copyright © 2013 Elsevier España, S.L. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  6. Astrocyte-targeted expression of interleukin-3 and interferon-alpha causes region-specific changes in metallothionein expression in the brain

    DEFF Research Database (Denmark)

    Giralt, M; Carrasco, J; Penkowa, M;

    2001-01-01

    Transgenic mice expressing IL-3 and IFN-alpha under the regulatory control of the GFAP gene promoter (GFAP-IL3 and GFAP-IFNalpha mice) exhibit a cytokine-specific, late-onset chronic-progressive neurological disorder which resemble many of the features of human diseases such as multiple sclerosis...

  7. Trans-activated interferon-alpha2 delivered to T cells by SV40 inhibits early stages in the HIV-1 replicative cycle.

    Science.gov (United States)

    Cordelier, Pierre; Calarota, Sandra A; Strayer, David S

    2002-10-01

    Several lines of evidence suggest a potential major role for interferon (IFN) in controlling HIV-1 replication. However, this inhibition is moderate and is reversible upon IFN removal. To achieve prolonged high concentrations of IFN at the site of infection, we devised an SV40-based vector, SV[HIVLTR]IFN, to direct the synthesis of human IFN-alpha2, by employing a virus-trans-activated human IFN-alpha2 gene to be transcribed in response to HIV-1 infection. Expression of IFN-alpha2 was confirmed by Northern and Western blotting, in SV[HIVLTR]IFN-transduced, HIV-1-challenged human lymphocyte lines and primary human lymphocytes. SV[HIVLTR]IFN-transduced cells showed no evidence of HIV-1-related cytophatic effects when challenged with high doses of HIV-1(NL4-3). As measured by supernatant HIV-1 p24 antigen concentration, IFN-alpha2-expressing cell lines and peripheral blood lymphocytes (PBL) were protected from high-dose challenges of HIV-1. rSV40-delivered IFN-alpha2 inhibited gp120 protein synthesis and expression of HIV-1 mRNAs. Finally, Southern analysis revealed that levels of proviral DNA were markedly reduced in SV[HIVLTR]IFN-transduced cells compared to control cultures. IFN-alpha2 expression driven by HIVLTR delivered by an rSV40 vector thus strongly inhibits HIV-1 replication, probably by blocking a preintegration step in HIV-1 infection. Targeted expression of IFN-alpha2 delivered by SV40 can thus repress HIV-1 replication, and may be a useful approach to HIV-1 treatment.

  8. Intensive Farmaco- Surveillance of Interferon Alpha 2b Recombinant in Multiple Sclerosis. Farmacovigilancia intensiva al interferón alfa 2b recombinante en la esclerosis múltiple.

    Directory of Open Access Journals (Sweden)

    Hailen Bobillo López

    Full Text Available

    Background: The interferon alpha 2b recombinant, produced in Cuba, is used in the treatment of different illnesses, such as the multiple sclerosis. For its commercialization it is needed to know its safety scope. Objective: To assess the adverse reactions of interferon alpha 2b recombinant in the treatment of multiple sclerosis. Method: During the period between 1996 and 2006, 70 clinical histories and data collection notebooks of patients included in the randomized double blind national clinical trial phase IV were revised. This trial was developed in the Clinic of Multiple Sclerosis of the Hospital "Dr. Gustavo Aldereguía Lima" in Cienfuegos. With regard to the total of manifested adverse reactions we analyzed type, length, and use of a given treatment to counteract them, intensity level (light, moderate, serious or lethal and causality level (definitive, probable, possible, conditional or not related. Results: 53 patients out of the total presented 207 adverse reactions to interferon. The most frequent were: fever, migraine, chills, arthralgia, asthenia and myalgia, being most of them moderate collateral effects of definitive character. In 197 patients the outcome was favorable. Conclusion: The use of the interferon alpha 2b

  9. Seguridad de la terapia de interferón alfa 2b recombinante más ribavirina en la hepatitis crónica C Safety of recombinant interferon alpha 2b plus ribavirin in chronic hepatitis C

    Directory of Open Access Journals (Sweden)

    Yoan Antonio Sánchez Rodríguez

    2011-03-01

    main cause of chronic hepatitis, hepatic cirrhosis, hepatocarcinoma and liver transplantation worldwide. OBJECTIVE: to identify the side effects of a combined therapy of recombinant interpheron alpha 2b plus ribavirin during the treatment and up to 8 weeks afterwards, as well as the main effects related to temporary or definitive withdrawal. METHODS: a pharmacological surveillance study was performed in which 122 patients with chronic hepatitis C, who had been seen at the Institute of Gastroenterology from May 2001 to May 2006, were included. Recombinant interferon alpha 2b (3 million units administered 3 times a week plus ribavirin (1 000 or 1 200 mg daily depending on the body weight was the therapy used for 48 weeks. RESULTS: of the total number of cases, 88.5 % had side effects; 79.5 % of which corresponded to pseudocold syndrome followed by hematological, neuropsychiatric and gastrointestinal manifestations, and other less frequent ailments. In the studied group, 6.6% had to interrupt their treatment temporarily due to some side effect different from anemia whereas 4 patients gave up the study, three affected by severe hemolytic anemia and one with uncontrollable hyperthyroidism. CONCLUSIONS: the combined therapy of recombinant interferon alpha 2b plus ribavirin proved to be safe; the most frequent side effect was pseudocold syndrome in the majority of cases. The hematological manifestations that made the patients to give up the study led to recommend a strict follow-up of hemoglobin levels and thorough diagnosis and treatment of the main side effects found in other systems and associated to this combined therapy.

  10. Vaccination of renal cell cancer patients with modified vaccinia Ankara delivering the tumor antigen 5T4 (TroVax) alone or administered in combination with interferon-alpha (IFN-alpha): a phase 2 trial.

    Science.gov (United States)

    Amato, Robert J; Shingler, William; Goonewardena, Madusha; de Belin, Jackie; Naylor, Stuart; Jac, Jaroslaw; Willis, James; Saxena, Somyata; Hernandez-McClain, Joan; Harrop, Richard

    2009-09-01

    Attenuated vaccinia virus, modified vaccinia Ankara (MVA) has been engineered to deliver the tumor antigen 5T4 (TroVax). MVA-5T4 has been evaluated in an open-label phase 2 trial in metastatic renal cell cancer patients in which the vaccine was administered alone or in combination with interferon-alpha-2b (IFN-alpha). The safety, immunologic, and clinical efficacy of MVA-5T4 with or without IFN-alpha was determined. Twenty-eight patients with metastatic renal cell cancer were treated with MVA-5T4 alone (13) or plus IFN-alpha (15). The 5T4-specific cellular and humoral responses were monitored throughout the study. Clinical responses were assessed by measuring changes in tumor burden by computed tomography or magnetic resonance imaging scan. MVA-5T4 was well tolerated with no serious adverse event attributed to vaccination. Of 23 intent-to-treat patients tested for immune responses postvaccination, 22 (96%) mounted 5T4-specific antibody and/or cellular responses. One patient treated with MVA-5T4 plus IFN-alpha showed a partial response for >7 months, whereas an additional 14 patients (7 receiving MVA-5T4 plus IFN and 7 receiving MVA-5T4 alone) showed periods of disease stabilization ranging from 1.73 to 9.60 months. Median progression free survival and overall survival for all intent-to-treat patients was 3.8 months (range: 1 to 11.47 mo) and 12.1 months (range: 1 to 27 mo), respectively. MVA-5T4 administered alone or in combination with IFN-alpha was well tolerated in all patients. Despite the high frequency of 5T4-specific immune responses, it is not possible to conclude that patients are receiving clinical benefit. The results are encouraging and warrant further investigation.

  11. Fluorescence imaging analysis of upstream regulators and downstream targets of STAT3 in melanoma precursor lesions obtained from patients before and after systemic low-dose interferon-alpha treatment.

    Science.gov (United States)

    Smith, Amanda Pfaff; Kirkwood, John M; Edington, Howard D; Jukic, Drazen M; Farkas, Daniel L; Becker, Dorothea

    2003-01-01

    Atypical nevi are the precursors and risk markers of melanoma. Apart from persistently monitoring these nevocytic lesions and resecting them at the earliest signs of clinical changes, there is as yet no systemic clinical treatment available to interfere with their progression to melanoma. To explore clinical treatments that might interfere with and possibly prevent atypical nevus progression, a previous study documented that 3 months systemic low-dose interferon-alpha (IFN-alpha) treatment of patients with a clinical history of melanoma and numerous atypical nevi, led to inactivation of the STAT1 and STAT3 transcription factors in atypical nevi. Based upon this finding, we initiated a second study to determine whether systemic low-dose IFN-alpha treatment also impairs the expression of upstream regulators and downstream targets of STAT1 and STAT3 in atypical nevi. Using cyanine dye-conjugated antibodies, fluorescence imaging analysis revealed expression of JAK2, JNK1, AKT1, NF-kappa B, and IFN-alpha/beta receptor in benign and atypical nevi, and early- and advanced-stage melanomas. To determine possible changes in the level of expression of these molecules in atypical nevi, excised before and after 3 months of systemic low-dose IFN-alpha treatment, newly designed optical imaging software was used to quantitate the captured fluorescent hybridization signals on a cell-by-cell basis and across an entire nevus section. The results of this analysis did not provide evidence that systemic low-dose IFN-alpha treatment alters the level of expression of upstream regulators or downstream targets of STAT1 and STAT3.

  12. Expression of intracellular interferon-alpha confers antiviral properties in transfected bovine fetal fibroblasts and does not affect the full development of SCNT embryos.

    Directory of Open Access Journals (Sweden)

    Dawei Yu

    Full Text Available Foot-and-mouth disease, one of the most significant diseases of dairy herds, has substantial effects on farm economics, and currently, disease control measures are limited. In this study, we constructed a vector with a human interferon-α (hIFN-α (without secretory signal sequence gene cassette containing the immediate early promoter of human cytomegalovirus. Stably transfected bovine fetal fibroblasts were obtained by G418 selection, and hIFN-α transgenic embryos were produced by somatic cell nuclear transfer (SCNT. Forty-six transgenic embryos were transplanted into surrogate cows, and five cows (10.9% became pregnant. Two male cloned calves were born. Expression of hIFN-α was detected in transfected bovine fetal fibroblasts, transgenic SCNT embryos, and different tissues from a transgenic SCNT calf at two days old. In transfected bovine fetal fibroblasts, expression of intracellular IFN-α induced resistance to vesicular stomatitis virus infection, increased apoptosis, and induced the expression of double-stranded RNA-activated protein kinase gene (PKR and the 2'-5'-oligoadenylate synthetase gene (2'-5' OAS, which are IFN-inducible genes with antiviral activity. Analysis by qRT-PCR showed that the mRNA expression levels of PKR, 2'-5' OAS, and P53 were significantly increased in wild-type bovine fetal fibroblasts stimulated with extracellular recombinant human IFN-α-2b, showing that intracellular IFN-α induces biological functions similar to extracellular IFN-α. In conclusion, expression of intracellular hIFN-α conferred antiviral properties in transfected bovine fetal fibroblasts and did not significantly affect the full development of SCNT embryos. Thus, IFN-α transgenic technology may provide a revolutionary way to achieve elite breeding of livestock.

  13. Recommendations for the Clinical Management of Hepatitis C in Iran: A Consensus-Based National Guideline

    Science.gov (United States)

    Alavian, Seyed Moayed; Hajarizadeh, Behzad; Bagheri Lankarani, Kamran; Sharafi, Heidar; Ebrahimi Daryani, Nasser; Merat, Shahin; Mohraz, Minoo; Mardani, Masoud; Fattahi, Mohamad Reza; Poustchi, Hossein; Nikbin, Mehri; Nabavi, Mahmood; Adibi, Peyman; Ziaee, Masood; Behnava, Bita; Rezaee-Zavareh, Mohammad Saeid; Colombo, Massimo; Massoumi, Hatef; Bizri, Abdul Rahman; Eghtesad, Bijan; Amiri, Majid; Namvar, Ali; Hesamizadeh, Khashayar; Malekzadeh, Reza

    2016-01-01

    Context Hepatitis C virus (HCV) infection is a major public health issue worldwide, including Iran. The new direct-acting antiviral agents (DAAs) with high efficacy have changed the landscape of HCV treatment. This guideline provides updated recommendations for clinical management of HCV infection in Iran. Evidence Acquisition The recommendations of this guideline are based on international and national scientific evidences and consensus-based expert opinion. Scientific evidences were collected through a systematic review of studies that evaluated efficacy and safety of DAA regimens, using PubMed, Scopus and Web of Science. Expert opinion was based on the consensus of Iran Hepatitis Scientific Board (IHSB) in the 3rd national consensus on management of Hepatitis C in Iran, held on 22nd of July 2016. Results Pegylated Interferon alpha (PegIFN), Ribavirin (RBV), Sofosbuvir (SOF), Ledipasvir (LDV) and Daclatasvir (DCV) are currently available in Iran. Pre-treatment assessments include HCV RNA level, HCV genotype and resistance testing, assessment of liver fibrosis, and underlying diseases. In HCV genotype 1 and 4, DCV/SOF and LDV/SOF are recommended. In HCV genotype 2, SOF plus RBV and in HCV genotype 3, DCV/SOF is recommended. Additional care for underlying diseases should be considered. Conclusions Affordable new HCV treatment regimens are available in Iran, providing an opportunity for HCV elimination. Recommendations provided in this current national guideline can facilitate evidence-based management of HCV infection. PMID:27799966

  14. Recommendations for the Clinical Management of Hepatitis C in Iran: A Consensus-Based National Guideline

    Directory of Open Access Journals (Sweden)

    Alavian

    2016-08-01

    Full Text Available Context Hepatitis C virus (HCV infection is a major public health issue worldwide, including Iran. The new direct-acting antiviral agents (DAAs with high efficacy have changed the landscape of HCV treatment. This guideline provides updated recommendations for clinical management of HCV infection in Iran. Evidence Acquisition The recommendations of this guideline are based on international and national scientific evidences and consensus-based expert opinion. Scientific evidences were collected through a systematic review of studies that evaluated efficacy and safety of DAA regimens, using PubMed, Scopus and Web of Science. Expert opinion was based on the consensus of Iran Hepatitis Scientific Board (IHSB in the 3rd national consensus on management of Hepatitis C in Iran, held on 22nd of July 2016. Results Pegylated Interferon alpha (PegIFN, Ribavirin (RBV, Sofosbuvir (SOF, Ledipasvir (LDV and Daclatasvir (DCV are currently available in Iran. Pre-treatment assessments include HCV RNA level, HCV genotype and resistance testing, assessment of liver fibrosis, and underlying diseases. In HCV genotype 1 and 4, DCV/SOF and LDV/SOF are recommended. In HCV genotype 2, SOF plus RBV and in HCV genotype 3, DCV/SOF is recommended. Additional care for underlying diseases should be considered. Conclusions Affordable new HCV treatment regimens are available in Iran, providing an opportunity for HCV elimination. Recommendations provided in this current national guideline can facilitate evidence-based management of HCV infection.

  15. Low doses of subcutaneous interleukin-2 plus interferon-alpha do not induce thyroid function alterations in advanced renal cell carcinoma patients.

    Science.gov (United States)

    Sartore-Bianchi, Andrea; Soriani, Alessandra; Mattioni, Raffaella; Vaglio, Augusto; Buzio, Carlo; Porta, Camillo

    2004-10-01

    The incidence of thyroid function changes among renal cell carcinoma (RCC) patients treated with high-dose IL-2 plus IFN-alpha ranges from 9 to 59%, independently of the administration route (i.v. or s.c.) of IL-2. Although several studies demonstrated a correlation between high-dose IL-2/IFN-alpha regimens and autoimmune thyroid disease, only very limited data are available when low doses of IL-2 plus IFN-alpha are used. We prospectively studied thyroid function in 52 patients with metastatic RCC undergoing immunotherapy with low-dose IL-2 + IFN-alpha. All patients received treatment cycles consisting of both s.c. IL-2 and i.m. IFN-alpha for 4 consecutive weeks; cycles were repeated at 4-month intervals in all patients, irrespectively of their response. Thyroid stimulating hormone (TSH), 3,3',5-triiodo-L-thyronine (T3), thyroxine (T4), human anti-thyroglobulin antibodies (hTg-Ab) and human anti-thyroid peroxidase antibodies (hTPO-Ab) were assayed in all patients before and after each of the first 3 cycles. None of the patients showed clinical signs of dysthyroidism, nor required replacement or suppressive treatment on thyroid function; specifically, no statistically significant differences were found when the median pre- and post-treatment TSH, T3, T4, hTg-Ab and hTPO-Ab levels of each cycle were compared. The median TSH values after the 3 cycles were, respectively, 1.06 [Inter Quartile Range (IQR) 0.58-1.51], 1.21 (IQR 0.58-1.51) and 1.05 micro U/ml (IQR 0.67-1.73). As for thyroid hormones, median values after each of the 3 cycles were: 1.38 (IQR 1.19-1.50), 1.46 (IQR 1.17-1.66) and 1.36 (IQR 1.16-1.46) ng/ml for T3, and 8.74 (IQR 7.26-9.45), 8.67 (IQR 7.12-9.18) and 8.40 (IQR 7.12-9.33) micro g/dl for T4. These data show that a regimen of low-dose IL-2 plus IFN-alpha does not seem to affect thyroid function, neither inducing signs or symptoms of dysthyroidism, nor by causing major biochemical changes in TSH and thyroid hormone levels, or an increase in thyroid

  16. Consensus on context-specific strategies for reducing the stigma of human immunodeficiency virus/acquired immunodeficiency syndrome in Zambézia Province, Mozambique.

    Science.gov (United States)

    Mukolo, Abraham; Torres, Isabel; Bechtel, Ruth M; Sidat, Mohsin; Vergara, Alfredo E

    2013-01-01

    Stigma has been implicated in poor outcomes of human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) care. Reducing stigma is important for HIV prevention and long-term treatment success. Although stigma reduction interventions are conducted in Mozambique, little is known about the current nature of stigma and the efficacy and effectiveness of stigma reduction initiatives. We describe action research to generate consensus on critical characteristics of HIV stigma and anti-stigma interventions in Zambézia Province, Mozambique. Qualitative data gathering methods, including in-depth key-informant interviews, community interviews and consensus group sessions, were utilized. Delphi methods and the strategic options development analysis technique were used to synthesize qualitative data. Key findings are that stigma enacted by the general public might be declining in tandem with the HIV/AIDS epidemic in Mozambique, but there is likely excessive residual fear of HIV disease and community attitudes that sustain high levels of perceived stigma. HIV-positive women accessing maternal and child health services appear to shoulder a disproportionate burden of stigma. Unintentional biases among healthcare providers are currently the critical frontier of stigmatization, but there are few interventions designed to address them. Culturally sensitive psychotherapies are needed to address psychological distress associated with internalized stigma and these interventions should complement current supports for voluntary counseling and testing. While advantageous for defining stakeholder priorities for stigma reduction efforts, confirmatory quantitative studies of these consensus positions are needed before the launch of specific interventions.

  17. Universal quantitative kinase assay based on diagonal SCX chromatography and stable isotope dimethyl labeling provides high-definition kinase consensus motifs for PKA and human Mps1.

    Science.gov (United States)

    Hennrich, Marco L; Marino, Fabio; Groenewold, Vincent; Kops, Geert J P L; Mohammed, Shabaz; Heck, Albert J R

    2013-05-01

    In order to understand cellular signaling, a clear understanding of kinase-substrate relationships is essential. Some of these relationships are defined by consensus recognition motifs present in substrates making them amendable for phosphorylation by designated kinases. Here, we explore a method that is based on two sequential steps of strong cation exchange chromatography combined with differential stable isotope labeling, to define kinase consensus motifs with high accuracy. We demonstrate the value of our method by evaluating the motifs of two very distinct kinases: cAMP regulated protein kinase A (PKA) and human monopolar spindle 1 (Mps1) kinase, also known as TTK. PKA is a well-studied basophilic kinase with a relatively well-defined motif and numerous known substrates in vitro and in vivo. Mps1, a kinase involved in chromosome segregation, has been less well characterized. Its substrate specificity is unclear and here we show that Mps1 is an acidophilic kinase with a striking tendency for phosphorylation of threonines. The final outcomes of our work are high-definition kinase consensus motifs for PKA and Mps1. Our generic method, which makes use of proteolytic cell lysates as a source for peptide-substrate libraries, can be implemented for any kinase present in the kinome.

  18. Consensus on context-specific strategies for reducing the stigma of human immunodeficiency virus/acquired immunodeficiency syndrome in Zambézia Province, Mozambique

    Science.gov (United States)

    Mukolo, Abraham; Torres, Isabel; Bechtel, Ruth M.; Sidat, Mohsin; Vergara, Alfredo E.

    2014-01-01

    Stigma has been implicated in poor outcomes of human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) care. Reducing stigma is important for HIV prevention and long-term treatment success. Although stigma reduction interventions are conducted in Mozambique, little is known about the current nature of stigma and the efficacy and effectiveness of stigma reduction initiatives. We describe action research to generate consensus on critical characteristics of HIV stigma and anti-stigma interventions in Zambézia Province, Mozambique. Qualitative data gathering methods, including indepth key-informant interviews, community interviews and consensus group sessions, were utilized. Delphi methods and the strategic options development analysis technique were used to synthesize qualitative data. Key findings are that stigma enacted by the general public might be declining in tandem with the HIV/AIDS epidemic in Mozambique, but there is likely excessive residual fear of HIV disease and community attitudes that sustain high levels of perceived stigma. HIV-positive women accessing maternal and child health services appear to shoulder a disproportionate burden of stigma. Unintentional biases among healthcare providers are currently the critical frontier of stigmatization, but there are few interventions designed to address them. Culturally sensitive psychotherapies are needed to address psychological distress associated with internalized stigma and these interventions should complement current supports for voluntary counseling and testing. While advantageous for defining stakeholder priorities for stigma reduction efforts, confirmatory quantitative studies of these consensus positions are needed before the launch of specific interventions. PMID:24527744

  19. Chicken interferon alpha pretreatment reduces virus replication of pandemic H1N1 and H5N9 avian influenza viruses in lung cell cultures from different avian species

    Directory of Open Access Journals (Sweden)

    Yang Hanchun

    2011-09-01

    Full Text Available Abstract Background Type I interferons, including interferon alpha (IFN-α, represent one of the first lines of innate immune defense against influenza virus infection. Following natural infection of chickens with avian influenza virus (AIV, transcription of IFN-α is quickly up regulated along with multiple other immune-related genes. Chicken IFN-α up regulates a number of important anti-viral response genes and has been demonstrated to be an important cytokine to establish anti-viral immunity. However, the mechanisms by which interferon inhibit virus replication in avian species remains unknown as does the biological activity of chicken interferon in other avian species. Methods In these studies, we assessed the protective potential of exogenous chicken IFN-α applied to chicken, duck, and turkey primary lung cell cultures prior to infection with the pandemic H1N1 virus (A/turkey/Virginia/SEP-4/2009 and an established avian H5N9 virus (A/turkey/Wisconsin/1968. Growth kinetics and induction of select immune response genes, including IFN-α and myxovirus-resistance gene I (Mx, as well as proinflammatory cytokines (IL-1β and IL-6, were measured in response to chicken IFN-α and viral infection over time. Results Results demonstrate that pretreatment with chicken IFN-α before AIV infection significantly reduced virus replication in both chicken-and turkey-origin lung cells and to a lesser degree the duck-origin cells. Virus growth was reduced by approximately 200-fold in chicken and turkey cells and 30-fold in duck cells after 48 hours of incubation. Interferon treatment also significantly decreased the interferon and proinflammatory response during viral infection. In general, infection with the H1N1 virus resulted in an attenuated interferon and proinflammatory response in these cell lines, compared to the H5N9 virus. Conclusions Taken together, these studies show that chicken IFN-α reduces virus replication, lower host innate immune

  20. Treatment Extension of Pegylated Interferon Alpha and Ribavirin Does Not Improve SVR in Patients with Genotypes 2/3 without Rapid Virological Response (OPTEX Trial: A Prospective, Randomized, Two-Arm, Multicentre Phase IV Clinical Trial.

    Directory of Open Access Journals (Sweden)

    Benjamin Heidrich

    Full Text Available Although sofosbuvir has been approved for patients with genotypes 2/3 (G2/3, many parts of the world still consider pegylated Interferon alpha (P and ribavirin (R as standard of care for G2/3. Patients with rapid virological response (RVR show response rates >80%. However, SVR (sustained virological response in non-RVR patients is not satisfactory. Longer treatment duration may be required but evidence from prospective trials are lacking. A total of 1006 chronic HCV genotype 2/3 patients treated with P/R were recruited into a German HepNet multicenter screening registry. Of those, only 226 patients were still HCV RNA positive at week 4 (non-RVR. Non-RVR patients with ongoing response after 24 weeks P-2b/R qualified for OPTEX, a randomized trial investigating treatment extension of additional 24 weeks (total 48 weeks, Group A or additional 12 weeks (total 36 weeks, group B of 1.5 μg/kg P-2b and 800-1400 mg R. Due to the low number of patients without RVR, the number of 150 anticipated study patients was not met and only 99 non-RVR patients (n=50 Group A, n=49 Group B could be enrolled into the OPTEX trial. Baseline factors did not differ between groups. Sixteen patients had G2 and 83 patients G3. Based on the ITT (intention-to-treat analysis, 68% [55%; 81%] in Group A and 57% [43%; 71%] in Group B achieved SVR (p= 0.31. The primary endpoint of better SVR rates in Group A compared to a historical control group (SVR 70% was not met. In conclusion, approximately 23% of G2/3 patients did not achieve RVR in a real world setting. However, subsequent recruitment in a treatment-extension study was difficult. Prolonged therapy beyond 24 weeks did not result in higher SVR compared to a historical control group.ClinicalTrials.gov NCT00803309.

  1. Polineuropatia desmielinizante inflamatória crônica pós-tratamento com interferon peguilado alfa 2b em um paciente co-infectado HIV/HCV: relato de caso Chronic inflammatory demyelinating polyneuropathy after treatment with pegylated interferon alpha 2b in a patient with HIV/HCV coinfection: case report

    Directory of Open Access Journals (Sweden)

    Bil Randerson Bassetti

    2010-02-01

    Full Text Available A polineuropatia desmielinizante inflamatória cônica possui forte associação com a infecção pelo HIV e HCV. Uma rara associação entre PDIC e o tratamento da hepatite C com interferon peguilado alfa foi descrita recentemente. Nós descrevemos o primeiro caso de polineuropatia desmielinizante inflamatória crônica em um paciente branco, sexo masculino infectado por HIV e HCV associado a interferon peguilado alfa 2b. O paciente recuperou-se completamente após o uso de imunoglobulina hiperimune endovenosa. Infectologistas e hapatologistas devem estar atentos à esta rara e grave associação, que exige imediata descontinuação da droga e tratamento precoce.Chronic inflammatory demyelinating polyneuropathy has a strong association with HIV and HCV infection. A rare association between chronic inflammatory demyelinating polyneuropathy and hepatitis C treatment with pegylated interferon alpha was described recently. We described the first case of chronic inflammatory demyelinating polyneuropathy associated with pegylated interferon alpha 2b in a white man infected with HIV and HCV. The patient recovered completely with the use of intravenous hyperimmune immunoglobulin. Infectologists and hepatologists should be alert regarding this rare and serious association, which requires immediately drug discontinuation and early treatment.

  2. A consensus for occupational health management of healthcare workers infected with human immunodeficiency virus, hepatitis B virus, and / or hepatitis C virus.

    Science.gov (United States)

    Ishimaru, Tomohiro; Wada, Koji; Smith, Derek R

    2017-05-25

    Occupational health management plays an important role in the prevention of provider-to-patient transmission in healthcare workers infected with human immunodeficiency virus (HIV), hepatitis B virus (HBV), and/or hepatitis C virus (HCV). Therefore, the Japan Society for Occupational Health's Research Group on Occupational Health for Health Care Workers has proposed a consensus for the management of healthcare workers infected with HIV, HBV, and/or HCV based on recent evidence for each concerned group. The consensus recommends that: (1) employers in medical institutions should establish a policy of respecting the human rights of healthcare workers, management strategies for occupational blood exposure, and occupational health consultation; (2) occupational health staff should appropriately assess the risk of provider-to-patient transmission of HIV, HBV, and/or HCV infection and rearrange their tasks if necessary. When conducting risk assessment, occupational health staff should obtain informed consent and then cooperate with the physician in charge as well as infection control experts in the workplace; (3) healthcare workers infected with HIV, HBV, and/or HCV should disclose their employment to their treating physician and consult with their doctor regarding the need for special considerations at work; and (4) supervisors and colleagues in medical institutions should correctly understand the risks of HIV, HBV, and HCV infection and should not engage in any behavior that leads to discrimination against colleagues infected with HIV, HBV, and/or HCV.

  3. It Ain't (Just) the Heat, It's the Humanity: Increasing Public Understanding of Scientific Consensus and Its Role in Climate Literacy

    Science.gov (United States)

    Jacobs, P.; Cook, J.; Nuccitelli, D.

    2014-12-01

    An overwhelming scientific consensus exists on the issue of anthropogenic climate change. Unfortunately, public perception of expert agreement remains low- only around 1 in 10 Americans correctly estimates the actual level of consensus on the topic. Moreover, several recent studies have demonstrated the pivotal role that perceived consensus plays in the public's acceptance of key scientific facts about environmental problems, as well as their willingness to support policy to address them. This "consensus gap", between the high level of scientific agreement vs. the public's perception of it, has led to calls for increased consensus messaging. However this call has been challenged by a number of different groups: climate "skeptics" in denial about the existence and validity of the consensus; some social science researchers and journalists who believe that such messages will be ineffective or counterproductive; and even some scientists and science advocates who downplay the value of consensus in science generally. All of these concerns can be addressed by effectively communicating the role of consensus within science to the public, as well as the conditions under which consensus is likely to be correct. Here, we demonstrate that the scientific consensus on anthropogenic climate change satisfies these conditions, and discuss past examples of purported consensus that failed or succeeded to satisfy them as well. We conclude by discussing the way in which scientific consensus is interpreted by the public, and how consensus messaging can improve climate literacy.

  4. Conjunctival papilloma caused by human papillomavirus type 11 treated with systemic interferon in a five-year-old boy.

    Science.gov (United States)

    Okan, Gökhan; Ayan, Inci; Karslioğlu, Safak; Altiok, Ender; Yenmiş, Güven; Vural, Gürcan

    2010-01-01

    Conjunctival papilloma is a benign tumor of the conjunctival mucosa. In childhood, papilloma represents 7-10% of conjunctival tumors. Human papillomavirus (HPV)-6 and HPV-11 are the major HPV types responsible for conjunctival lesions. A five-year-old boy with a two-year history of conjunctival papilloma caused by HPV type 11 treated with systemic interferon alpha is reported and the literature is reviewed.

  5. On consensus biomarker selection

    Directory of Open Access Journals (Sweden)

    Gambin Anna

    2007-05-01

    Full Text Available Abstract Background Recent development of mass spectrometry technology enabled the analysis of complex peptide mixtures. A lot of effort is currently devoted to the identification of biomarkers in human body fluids like serum or plasma, based on which new diagnostic tests for different diseases could be constructed. Various biomarker selection procedures have been exploited in recent studies. It has been noted that they often lead to different biomarker lists and as a consequence, the patient classification may also vary. Results Here we propose a new approach to the biomarker selection problem: to apply several competing feature ranking procedures and compute a consensus list of features based on their outcomes. We validate our methods on two proteomic datasets for the diagnosis of ovarian and prostate cancer. Conclusion The proposed methodology can improve the classification results and at the same time provide a unified biomarker list for further biological examinations and interpretation.

  6. Immunofunctional assay of human growth hormone (hGH) in serum: A possible consensus for quantitative hGH measurement

    OpenAIRE

    Strasburger, Christian J.; Wu, Zida; Pflaum, Claus-Dieter; Dressendörfer, Regina A.

    1996-01-01

    Confirmation of the diagnosis of GH deficiency in adults and children involves provocative testing for human (h) GH. Different commercially available immunoassays yield largely discrepant results in the measurement of GH levels in human serum. These discrepancies result in doubtful relevance of cut-off levels proposed for GH provocative testing. We have developed an immunofunctional assay method that allows quantitation of only those GH forms in circulation that possess both binding sites of ...

  7. [Consensus statement on assistance to women with human immunodeficiency virus infection in the health care sector. National AIDS Plan (PNS) and AIDS Study Group (GeSIDA)].

    Science.gov (United States)

    2014-02-01

    To develop a consensus document on clinical recommendations for the health care of women with human immunodeficiency virus (HIV) infection. We assembled a panel of experts appointed by the Secretariat of the National AIDS Plan and GeSIDA that included internal medicine physicians with expertise in the field of HIV infection, gynecologists, pediatricians and psychologists, and two panel members acting as coordinators. Scientific information was reviewed in publications and conference reports up to October 2012. In keeping with the criteria of the Infectious Disease Society of America, two levels of evidence were applied to support the proposed recommendations: the strength of the recommendation according to expert opinion (A, B, C), and the level of empirical evidence (i, ii, iii), already used in previous documents from SPNS/GeSIDA. We provide multiple recommendations for the clinical management of women with HIV infection, considering both the diagnostic and possible therapeutic strategies. The consensus recommends gender mainstreaming in health care, and promoting training for healthcare professionals in order to avoid gender bias. With currently available data it seems that the effectiveness of the treatment is the same in both men and women, there being no limitation as to the use of any antiretroviral for this reason. Women have more treatments suspended for reasons other than virological failure, thus they require better monitoring. This document presents recommendations for addressing women with HIV infection. This must be multidisciplinary, taking into account the differences that can be found in the diagnosis, disease development, and treatment between men and women. Copyright © 2012 Elsevier España, S.L. All rights reserved.

  8. USEtox: The UNEP-SETAC consensus model for life-cycle impacts on human health and ecosystems

    DEFF Research Database (Denmark)

    Hauschild, Michael Zwicky; McKone, Tom; Huijbregts, Mark A.J.

    2007-01-01

    Life cycle impact assessment (LCIA) characterizes emissions for the life-cycle assessment (LCA) of a product by translating these emissions into their potential impacts on human health, ecosystems, global climate and other resources. This process requires substance-specific characterization factors...

  9. Consensus theoretic classification methods

    Science.gov (United States)

    Benediktsson, Jon A.; Swain, Philip H.

    1992-01-01

    Consensus theory is adopted as a means of classifying geographic data from multiple sources. The foundations and usefulness of different consensus theoretic methods are discussed in conjunction with pattern recognition. Weight selections for different data sources are considered and modeling of non-Gaussian data is investigated. The application of consensus theory in pattern recognition is tested on two data sets: 1) multisource remote sensing and geographic data and 2) very-high-dimensional remote sensing data. The results obtained using consensus theoretic methods are found to compare favorably with those obtained using well-known pattern recognition methods. The consensus theoretic methods can be applied in cases where the Gaussian maximum likelihood method cannot. Also, the consensus theoretic methods are computationally less demanding than the Gaussian maximum likelihood method and provide a means for weighting data sources differently.

  10. Model-based consensus

    NARCIS (Netherlands)

    M. Boumans

    2014-01-01

    The aim of the rational-consensus method is to produce "rational consensus", that is, "mathematical aggregation", by weighing the performance of each expert on the basis of his or her knowledge and ability to judge relevant uncertainties. The measurement of the performance of the experts is based on

  11. The Limits of Consensus.

    Science.gov (United States)

    Poster, John B.

    Dynamics in the education policy arena suggest that, despite two generations of researchers extolling democratic leadership styles and consensus building over autocratic techniques, wide participation in policymaking and the broadest possible consensus are not always productive: American society has not yet agreed on what schools should…

  12. [Human single chain antibodies directed to tumor necrosis factor].

    Science.gov (United States)

    Vikhrova, M A; Batanova, T A; Lebedev, L R; Shingarova, L N; Frank, L A; Kirpichnikov, M P; Tikunova, N V

    2011-01-01

    Six unique phage antibodies to human TNF have been selected from a combinatorial library of human single chain fragment variable. ELISA and Western-blotting was used to study selected phage antibodies binding with TNF. The specificity of selected antibodies was determined by binding with interferon alpha and gamma, bovine serum albumin, ovalbumin and ubiquitin. Two antibodies, sA1 and sB3, were converted into a soluble single-chain antibody form and their affinity was 2.5 and 13.7 nM respectively.

  13. Analysis on efficacy and predictive factor of interferon alpha-2b in treatment of HBeAg-positive chronic hepatitis B%干扰素α-2b治疗HBeAg阳性慢性乙肝疗效及其预测因素分析

    Institute of Scientific and Technical Information of China (English)

    李海军; 杨新英; 康富标; 李东; 孙殿兴

    2011-01-01

    Objective To evaluate the efficacy and the predictive factor in the treatment of HBeAg-positive chronic hepatitis B with ordinary interferon alpha-2b. Methods Select patients with HBeAg-positive chronic hepatitis B of our hospitals in recent years has not been admitted to the appheation of anfiviral drugs, giving interferon alpha-2b 48 weeks of antiviral treatment, follow-up 24 weeks, to evaluate the efficacy and the predictive factor. Results In this study, the sustained response rate was 23.28%, HBeAg serum conversion rate was 34.48%, and sustained response group HBeAg serum conversion rate was 63.04%. Gender, whether they are mother-to-child transmission are irrelevant with antiviral effect. Baseline HBV-DNA, ALT, AST, TBIL, GGT level are related to anfiviral effect. Baseline HBV-DNA, ALT, CGT level can be used as predictors of anfiviral effect of ordinary interferon alpha-2b to treat HBeAg-posifive chronic hepatitis B. Conclusion Ordinary interferon could be used as a safe and effective drug in the treatment of HBeAg-positive chronic hepatitis B. Sustained response can get higher HBeAg serum conversion rate. According baseline HBV-DNA level and liver function choose the right patient is the key to improving response rates.%目的 观察普通干扰素治疗HBeAg阳性慢性乙肝的临床效果及其预测因素.方法 选择近年收治的未应用过抗病毒药物的HBeAg阳性慢性乙肝患者,给予普通干扰素抗病毒治疗48周,随访24周,观察其临床疗效及其预测因素.结果 持续应答率为23.28%,HBeAg血清转换率为34.48%,持续应答组HBeAg血清转换率为63.04%.性别、是否母婴传播与抗病毒效果无关,基线HBV-DNA、ALT、AST、TBIL、GGT水平与抗病毒效果相关.基线HBV-DNA、ALT、GGT水平可以作为普通干扰素治疗HBeAg阳性慢性乙肝患者抗病毒效果的预测因素.结论 普通干扰素治疗HBeAg阳性慢性乙肝疗效确切.持续应答的患者能够获得较高的HBeAg血清转

  14. Pragmatism and Political Pluralism - Consensus and Pluralism

    Directory of Open Access Journals (Sweden)

    Michele Marsonet

    2015-07-01

    In our day the German philosopher Jürgen Habermas has in a way revived these Peircean insights, putting forward an influential theory to the effect that consensus indeed plays a key role in human praxis, so that the primary task of philosophy is to foster it by eliminating the disagreement which we constantly have to face in the course of our daily life. In his “communicative theory of consensus,” furthermore, he claims that human communication rests on an implicit commitment to a sort of “ideal speech situation” which is the normative foundation of agreement in linguistic matters. Consequently, the quest for consensus is a constitutive feature of our nature of (rational human beings: rationality and consensus are tied together. A very strong consequence derives from Habermas’ premises: were we to abandon the search for consensus we would lose rationality, too, and this makes us understand that he views the pursuit of consensus as a regulative principle (rather than as a merely practical objective. Rescher opposes both Peirce’s eschatological view and Habermas’ regulative and idealized one.

  15. Expression of Canine Interferon Alpha in Silkworm-baculovirus Expression System and the Antiviral Activity Assay%犬α干扰素在家蚕杆状病毒表达系统中的表达及其抗病毒活性的测定

    Institute of Scientific and Technical Information of China (English)

    李皓洋; 胡小元; 易咏竹; 杨鑫; 张志芳; 李轶女

    2015-01-01

    犬α干扰素(CaIFNα)在犬病防治过程中应用广泛。旨在开发一种高效的CaIFNα表达方法。首先按家蚕密码子的偏好性对GenBank中的一个CaIFNα基因进行了优化与合成,将其克隆到杆状病毒转移载体pVL1393中,并与亲本病毒BmBacmid共转染家蚕细胞进行细胞内重组。得到的重组病毒用于感染家蚕幼虫,收集发病幼虫的蚕血淋巴用于CaIFNα检测。采用细胞病变抑制法在MDCK-VSV*GFP系统中测定其抗病毒活性。结果显示家蚕表达的CaIFNα能有效抑制VSV*GFP在细胞内的复制,其抗病毒活性不低于1.78×106U/mL。%Canine interferon alpha(CaIFNα)was widely used in the prophylaxis and cure of canine diseases. The purpose of this study is to develop an efficient method to express CaIFNα. A canine interferon alpha gene in GenBank was optimized according to the codon bias of silkworm and synthesized, and then cloned into the baculovirus transfer vector pVL1393 to construct the recombinant plasmid pVL-CaIFNα. The pVL-CaIFNα was co-transfected with the BmBacmid DNA into silkworm cells and afterin vivo recombination. The recombinant virus was gathered and used to infect silkworm larvae. The hemolymph of infected larvae was collected for antiviral activity assay. The antiviral activity of expressed CaIFNα was examined on Madin-Darby canine kidney cells infected with the vesicular stomatitis virus expressing green fluorescent protein(VSV*GFP). The result showed that CaIFNα expressed in silkworm can inhibit the multiplication of VSV*GFP and the antiviral activity was about 1.78×106U/mL.

  16. Practical Techniques for Achieving Consensus.

    Science.gov (United States)

    Kline, John A.

    Consensus is important in the making of a policy decision. If a decision is reached without consensus, morale and unit satisfaction may both suffer. With genuine consensus, a unit tends to willingly support and implement the new policy. After analyzing how observed small groups had actually reached consensus, the following ten techniques were…

  17. Universal Quantitative Kinase Assay Based on Diagonal SCX Chromatography and Stable Isotope Dimethyl Labeling Provides High-definition Kinase Consensus Motifs for PKA and Human Mps1

    NARCIS (Netherlands)

    Hennrich, Marco L.; Marino, Fabio; Groenewold, Vincent; Kops, Geert J. P. L.; Mohammed, Shabaz; Heck, Albert J. R.

    2013-01-01

    In order to understand cellular signaling, a clear understanding of kinase-substrate relationships is essential. Some of these relationships are defined by consensus recognition motifs present in substrates making them amendable for phosphorylation by designated kinases. Here, we explore a method th

  18. Universal quantitative kinase assay based on diagonal SCX chromatography and stable isotope dimethyl labeling provides high-definition kinase consensus motifs for PKA and human Mps1

    NARCIS (Netherlands)

    Hennrich, M.L.; Marino, F.; Groenewold, V.; Kops, G.J.P.L.; Mohammed, S.; Heck, A.J.R.

    2013-01-01

    In order to understand cellular signaling, a clear understanding of kinase–substrate relationships is essential. Some of these relationships are defined by consensus recognition motifs present in substrates making them amendable for phosphorylation by designated kinases. Here, we explore a method th

  19. [GESIDA/National AIDS Plan: Consensus document on antiretroviral therapy in adults infected by the human immunodeficiency virus (Updated January 2015)].

    Science.gov (United States)

    2015-10-01

    This consensus document is an update of combined antiretroviral therapy (cART) guidelines and recommendations for HIV-1 infected adult patients. To formulate these recommendations, a panel composed of members of the AIDS Study Group and the AIDS National Plan (GeSIDA/Plan Nacional sobre el Sida) reviewed the efficacy and safety advances in clinical trials, and cohort and pharmacokinetic studies published in medical journals (PubMed and Embase) or presented in medical scientific meetings. The strength of the recommendations, and the evidence that supports them, are based on modified criteria of the Infectious Diseases Society of America. In this update, cART is recommended for all patients infected by type 1 human immunodeficiency virus (HIV-1). The strength and level of the recommendation depends on the CD4+T-lymphocyte count, the presence of opportunistic diseases or comorbid conditions, age, and prevention of transmission of HIV. The objective of cART is to achieve an undetectable plasma viral load. Initial cART should always comprise a combination of 3 drugs, including 2 nucleoside reverse transcriptase inhibitors, and a third drug from a different family. Three out of the ten recommended regimes are regarded as preferential (all of them with an integrase inhibitor as the third drug), and the other seven (based on a non-nucleoside reverse transcriptase inhibitor, a ritonavir-boosted protease inhibitor, or an integrase inhibitor) as alternatives. This update presents the causes and criteria for switching cART in patients with undetectable plasma viral load, and in cases of virological failure where rescue cART should comprise 3 (or at least 2) drugs that are fully active against the virus. An update is also provided for the specific criteria for cART in special situations (acute infection, HIV-2 infection, and pregnancy) and with comorbid conditions (tuberculosis or other opportunistic infections, kidney disease, liver disease, and cancer). These new guidelines

  20. [GeSIDA/National AIDS Plan: Consensus document on antiretroviral therapy in adults infected by the human immunodeficiency virus (Updated January 2014)].

    Science.gov (United States)

    2014-01-01

    This consensus document is an update of combined antiretroviral therapy (cART) guidelines for HIV-1 infected adult patients. To formulate these recommendations a panel composed of members of the Grupo de Estudio de Sida and the Plan Nacional sobre el Sida reviewed the efficacy and safety advances in clinical trials, cohort and pharmacokinetic studies published in medical journals (PubMed and Embase) or presented in medical scientific meetings. Recommendations strength and the evidence in which they are supported are based on modified criteria of the Infectious Diseases Society of America. In this update, antiretroviral therapy (ART) is recommended for all patients infected by type 1 human immunodeficiency virus (HIV-1). The strength and grade of the recommendation varies with the clinical circumstances: CDC stage B or C disease (A-I), asymptomatic patients (depending on the CD4+ T-lymphocyte count: 500 cells/μL, B-III), comorbid conditions (HIV nephropathy, chronic hepatitis caused by HBV or HCV, age >55years, high cardiovascular risk, neurocognitive disorders, and cancer, A-II), and prevention of transmission of HIV (mother-to-child or heterosexual, A-I; men who have sex with men, A-III). The objective of ART is to achieve an undetectable plasma viral load. Initial ART should always comprise a combination of 3 drugs, including 2 nucleoside reverse transcriptase inhibitors and a third drug from a different family (non-nucleoside reverse transcriptase inhibitor, protease inhibitor, or integrase inhibitor). Some of the possible initial regimens have been considered alternatives. This update presents the causes and criteria for switching ART in patients with undetectable plasma viral load and in cases of virological failure where rescue ART should comprise 2 or 3 drugs that are fully active against the virus. An update is also provided for the specific criteria for ART in special situations (acute infection, HIV-2 infection, and pregnancy) and with comorbid

  1. Human genomic library screened with 17-base oligonucleotide probes yields a novel interferon gene.

    OpenAIRE

    Torczynski, R M; Fuke, M; Bollon, A P

    1984-01-01

    A method is presented that has permitted a human genomic library to be screened for low-copy genes using 17-base synthetic oligonucleotides as probes. Parallel screening with two different 17-base probes permitted the unambiguous identification of clones containing interferon-alpha (IFN-alpha) genes. The isolated human IFN-alpha genes were sequenced, and one appears to be IFN-alpha L; the other is one not previously described, which we have designated IFN-alpha WA. The IFN-alpha WA sequence d...

  2. The Consensus: Another View.

    Science.gov (United States)

    Brown, H. Douglas

    1984-01-01

    Comments on the seven points of consensus presented in "A Theoretical Basis for Teaching the Receptive Skills" by Stephen Krashen, et al., particularly on the terminology that is derived from Krashen's other writings. Offers eight statements which reflect in more general terms an interpretation of Krashen's theories for language teachers…

  3. Model-based consensus

    NARCIS (Netherlands)

    Boumans, Marcel

    2014-01-01

    The aim of the rational-consensus method is to produce “rational consensus”, that is, “mathematical aggregation”, by weighing the performance of each expert on the basis of his or her knowledge and ability to judge relevant uncertainties. The measurement of the performance of the experts is based on

  4. A Delphic consensus assessment

    DEFF Research Database (Denmark)

    Oberg, Kjell; Krenning, Eric; Sundin, Anders

    2016-01-01

    and pancreastatin); monoanalyte measurements; and lack sensitivity, specificity and predictive capacity. None of them meet the NIH metrics for clinical usage. A multinational, multidisciplinary Delphi consensus meeting of NEN experts (n = 33) assessed current imaging strategies and biomarkers in NEN management...

  5. Making Consensus Tractable

    CERN Document Server

    Mossel, Elchanan

    2010-01-01

    The process of consensus voting has many distinct advantages: it fosters discussion and participation, empowers minorities and independent thinkers, and is more likely, after a decision has been made, to secure the participants' support for the chosen course of action. The disadvantage of consensus decision making is, of course, the difficulty of reaching consensus. While this challenge is largely overcome in many theoretical settings such as Aumann's ``agree to disagree'' result, a hitherto unsolved difficulty is the lack of a framework offering rational (i.e., Bayesian) consensus decision making that can be performed using simple and efficient calculations. We propose a model featuring two possible states of the world and a finite number of individuals. The group has to come to a binary decision, where the merit of each of the two possible courses of action depends on the state of the world. Each member of the group has a private and independent signal at his or her disposal, giving some indication as to wh...

  6. [AIDS Study Group/Spanish AIDS Plan consensus document on antiretroviral therapy in adults with human immunodeficiency virus infection (updated January 2010)].

    Science.gov (United States)

    2010-01-01

    This consensus document is an update of antiretroviral therapy recommendations for adult patients with human immunodeficiency virus infection. To formulate these recommendations a panel made up of members of the Grupo de Estudio de Sida (Gesida, AIDS Study Group) and the Plan Nacional sobre el Sida (PNS, Spanish AIDS Plan) reviewed the advances in the current understanding of the pathophysiology of human immunodeficiency virus (HIV) infection, the efficacy and safety of clinical trials, and cohort and pharmacokinetic studies published in biomedical journals or presented at scientific meetings. Three levels of evidence were defined according to the data source: randomized studies (level A), cohort or case-control studies (level B), and expert opinion (level C). The decision to recommend, consider or not to recommend ART was established in each situation. Currently, the treatment of choice for chronic HIV infection is the combination of three drugs of two different classes, including 2 nucleosides or nucleotide analogs (NRTI) plus 1 non-nucleoside (NNRTI) or 1 boosted protease inhibitor (PI/r), but other combinations are possible. Initiation of ART is recommended in patients with symptomatic HIV infection. In asymptomatic patients, initiation of ART is recommended on the basis of CD4 lymphocyte counts, plasma viral load and patient co-morbidities, as follows: 1) therapy should be started in patients with CD4 counts below 350 cells/microl; 2) When CD4 counts are between 350 and 500 cells/microl, therapy should be started in case of cirrhosis, chronic hepatitis C, high cardiovascular risk, HIV nephropathy, HIV viral load above 100,000 copies/ml, proportion of CD4 cells under 14%, and in people aged over 55; 3) Therapy should be deferred when CD4 are above 500 cells/microl, but could be considered if any of previous considerations concurs. Treatment should be initiated in case of hepatitis B requiring treatment and should be considered for reduce sexual transmission

  7. Use of recombinant adenovirus vectored consensus IFN-α to avert severe arenavirus infection.

    Directory of Open Access Journals (Sweden)

    Brian B Gowen

    Full Text Available Several arenaviruses can cause viral hemorrhagic fever, a severe disease with case-fatality rates in hospitalized individuals ranging from 15-30%. Because of limited prophylaxis and treatment options, new medical countermeasures are needed for these viruses classified by the National Institutes of Allergy and Infectious Diseases (NIAID as top priority biodefense Category A pathogens. Recombinant consensus interferon alpha (cIFN-α is a licensed protein with broad clinical appeal. However, while cIFN-α has great therapeutic value, its utility for biodefense applications is hindered by its short in vivo half-life, mode and frequency of administration, and costly production. To address these limitations, we describe the use of DEF201, a replication-deficient adenovirus vector that drives the expression of cIFN-α, for pre- and post-exposure prophylaxis of acute arenaviral infection modeled in hamsters. Intranasal administration of DEF201 24 h prior to challenge with Pichindé virus (PICV was highly effective at protecting animals from mortality and preventing viral replication and liver-associated disease. A significant protective effect was still observed with a single dosing of DEF201 given two weeks prior to PICV challenge. DEF201 was also efficacious when administered as a treatment 24 to 48 h post-virus exposure. The protective effect of DEF201 was largely attributed to the expression of cIFN-α, as dosing with a control empty vector adenovirus did not protect hamsters from lethal PICV challenge. Effective countermeasures that are highly stable, easily administered, and elicit long lasting protective immunity are much needed for arena and other viral infections. The DEF201 technology has the potential to address all of these issues and may serve as a broad-spectrum antiviral to enhance host defense against a number of viral pathogens.

  8. A New Foreign Policy Consensus?

    Science.gov (United States)

    Melanson, Richard A.

    1990-01-01

    Discusses the achievements of Reagan's foreign policy. Explores the question: Did Reagan reconstruct a domestic foreign policy consensus? Concludes that no consensus was reached. Analyzes Reagan's political beliefs, including his antinuclear sentiments, and examines relations between Reagan and Congress. (RW)

  9. Achieving diagnosis by consensus

    LENUS (Irish Health Repository)

    Kane, Bridget

    2009-08-01

    This paper provides an analysis of the collaborative work conducted at a multidisciplinary medical team meeting, where a patient’s definitive diagnosis is agreed, by consensus. The features that distinguish this process of diagnostic work by consensus are examined in depth. The current use of technology to support this collaborative activity is described, and experienced deficiencies are identified. Emphasis is placed on the visual and perceptual difficulty for individual specialities in making interpretations, and on how, through collaboration in discussion, definitive diagnosis is actually achieved. The challenge for providing adequate support for the multidisciplinary team at their meeting is outlined, given the multifaceted nature of the setting, i.e. patient management, educational, organizational and social functions, that need to be satisfied.

  10. Spanish Consensus Statement

    Science.gov (United States)

    Rey, Guillermo Álvarez; Cuesta, Jordi Ardevol; Loureda, Rafael Arriaza; España, Fernando Ávila; Matas, Ramón Balius; Pazos, Fernando Baró; de Dios Beas Jiménez, Juan; Rosell, Jorge Candel; Fernandez, César Cobián; Ros, Francisco Esparza; Colmenero, Josefina Espejo; de Prado, Jorge Fernández; Cota, Juan José García; González, Jose Ignacio Garrido; Santander, Manuela González; Munilla, Miguel Ángel Herrador; Ruiz, Francisco Ivorra; Díaz, Fernando Jiménez; Marqueta, Pedro Manonelles; Fernandez, Antonio Maestro; Benito, Juan José Muñoz; Vilás, Ramón Olivé; Teres, Xavier Peirau; Amaro, José Peña; Roque, Juan Pérez San; Parenteu, Christophe Ramírez; Serna, Juan Ribas; Álvarez, Mikel Sánchez; Marchori, Carlos Sanchez; Soto, Miguel del Valle; Alonso, José María Villalón; García, Pedro Guillen; de la Iglesia, Nicolas Hugo; Alcorocho, Juan Manuel Lopez

    2016-01-01

    On the 21st of March, 2015, experts met at Clínica CEMTRO in Madrid, Spain, under the patronage of The Spanish Society for Sports Traumatology (SETRADE), The Spanish Federation of Sports Medicine (FEMEDE), The Spanish Association of Medical Services for Football Clubs (AEMEF), and The Spanish Association of Medical Services for Basketball Clubs (AEMB) with the aim of establishing a round table that would allow specialists to consider the most appropriate current general actions to be taken when treating muscle tears in sport, based on proven scientific data described in the medical literature. Each expert received a questionnaire prior to the aforementioned meeting comprising a set of questions concerning therapeutic indications generally applied in the different stages present during muscle repair. The present Consensus Document is the result of the answers to the questionnaire and resulting discussion and consensus over which are the best current indications in the treatment of muscle tears in sport. Avoiding immobilization, not taking nonsteroidal anti-inflammatory drugs (NSAIDs) randomly, fostering early mobilization, increasing vascularization of injured, site and regulating inflammatory mechanisms—without inhibiting these from the early stages of the recovery period—all stood out as main points of the Consensus Document. Additionally, there is controversy concerning cell stimulation techniques and the use of growth factors or cell inhibitors. The decision concerning discharge was unanimous, as was the criteria considered when it came to performing sport techniques without pain. PMID:27213161

  11. Achieving consensus in environmental programs

    Energy Technology Data Exchange (ETDEWEB)

    Kurstedt, Jr., H. A.; Jones, R. M.; Walker, J. A.; Middleman, L. I.

    1989-01-01

    In this paper, we describe a new research effort on consensus tied to the Environmental Restoration Program (ERP) within the US Department of Energy's Office of Defense Waste and Transportation Management (DWTM). We define consensus and explain why consensus decisions are not merely desirable but necessary in furthering ERP activities. As examples of our planned applied research, we first discuss Nominal Group Technique as a representative consensus-generating tool, and we conclude by describing the consensus-related mission of the Waste Management Review Group, established at Virginia Tech to conduct independent, third-party review of DWTM/ERP plans and activities. 10 refs.

  12. [First Argentine consensus guidelines for in vitro antimicrobial susceptibility testing of clinically relevant anaerobic bacteria in humans/ Anaerobic Subcommittee of the Asociación Argentina de Microbiología].

    Science.gov (United States)

    Legaria, María C; Bianchini, Hebe M; Castello, Liliana; Carloni, Graciela; Di Martino, Ana; Fernández Canigia, Liliana; Litterio, Mirta; Rollet, Raquel; Rossetti, Adelaida; Predari, Silvia C

    2011-01-01

    Through time, anaerobic bacteria have shown good susceptibility to clinically useful antianaerobic agents. Nevertheless, the antimicrobial resistance profile of most of the anaerobic species related to severe infections in humans has been modified in the last years and different kinds of resistance to the most active agents have emerged, making their effectiveness less predictable. With the aim of finding an answer and for the purpose of facilitating the detection of anaerobic antimicrobial resistance, the Anaerobic Subcommittee of the Asociación Argentina de Microbiología developed the First Argentine consensus guidelines for in vitro antimicrobial susceptibility testing of clinically relevant anaerobic bacteria in humans. This document resulted from the compatibilization of the Clinical and Laboratory Standards Institute recommendations, the international literature and the work and experience of the Subcommittee. The Consensus document provides a brief taxonomy review, and exposes why and when anaerobic antimicrobial susceptibility tests should be conducted, and which antimicrobial agents can be used according to the species involved. The recommendations on how to perform, read and interpret in vitro anaerobic antimicrobial susceptibility tests with each method are exposed. Finally, the antibiotic susceptibility profile, the classification of antibiotics according to their in vitro activities, the natural and acquired mechanisms of resistance, the emerging resistance and the regional antibiotic resistance profile of clinically relevant anaerobic species are shown.

  13. Mutant U5A cells are complemented by an interferon-alpha beta receptor subunit generated by alternative processing of a new member of a cytokine receptor gene cluster.

    Science.gov (United States)

    Lutfalla, G; Holland, S J; Cinato, E; Monneron, D; Reboul, J; Rogers, N C; Smith, J M; Stark, G R; Gardiner, K; Mogensen, K E

    1995-10-16

    The cellular receptor for the alpha/beta interferons contains at least two components that interact with interferon. The ifnar1 component is well characterized and a putative ifnar2 cDNA has recently been identified. We have cloned the gene for ifnar2 and show that it produces four different transcripts encoding three different polypeptides that are generated by exon skipping, alternative splicing and differential use of polyadenylation sites. One polypeptide is likely to be secreted and two are transmembrane proteins with identical extracellular and transmembrane domains but divergent cytoplasmic tails of 67 and 251 amino acids. A mutant cell line U5A, completely defective in IFN-alpha beta binding and response, has been isolated and characterized. Expression in U5A cells of the polypeptide with the long cytoplasmic domain reconstitutes a functional receptor that restores normal interferon binding, activation of the JAK/STAT signal transduction pathway, interferon-inducible gene expression and antiviral response. The IFNAR2 gene maps at 0.5 kb from the CRFB4 gene, establishing that together IFNAR2, CRFB4, IFNAR1 and AF1 form a cluster of class II cytokine receptor genes on human chromosome 21.

  14. Microscopic enteritis: Bucharest consensus.

    Science.gov (United States)

    Rostami, Kamran; Aldulaimi, David; Holmes, Geoffrey; Johnson, Matt W; Robert, Marie; Srivastava, Amitabh; Fléjou, Jean-François; Sanders, David S; Volta, Umberto; Derakhshan, Mohammad H; Going, James J; Becheanu, Gabriel; Catassi, Carlo; Danciu, Mihai; Materacki, Luke; Ghafarzadegan, Kamran; Ishaq, Sauid; Rostami-Nejad, Mohammad; Peña, A Salvador; Bassotti, Gabrio; Marsh, Michael N; Villanacci, Vincenzo

    2015-03-07

    Microscopic enteritis (ME) is an inflammatory condition of the small bowel that leads to gastrointestinal symptoms, nutrient and micronutrient deficiency. It is characterised by microscopic or sub-microscopic abnormalities such as microvillus changes and enterocytic alterations in the absence of definite macroscopic changes using standard modern endoscopy. This work recognises a need to characterize disorders with microscopic and submicroscopic features, currently regarded as functional or non-specific entities, to obtain further understanding of their clinical relevance. The consensus working party reviewed statements about the aetiology, diagnosis and symptoms associated with ME and proposes an algorithm for its investigation and treatment. Following the 5(th) International Course in Digestive Pathology in Bucharest in November 2012, an international group of 21 interested pathologists and gastroenterologists formed a working party with a view to formulating a consensus statement on ME. A five-step agreement scale (from strong agreement to strong disagreement) was used to score 21 statements, independently. There was strong agreement on all statements about ME histology (95%-100%). Statements concerning diagnosis achieved 85% to 100% agreement. A statement on the management of ME elicited agreement from the lowest rate (60%) up to 100%. The remaining two categories showed general agreement between experts on clinical presentation (75%-95%) and pathogenesis (80%-90%) of ME. There was strong agreement on the histological definition of ME. Weaker agreement on management indicates a need for further investigations, better definitions and clinical trials to produce quality guidelines for management. This ME consensus is a step toward greater recognition of a significant entity affecting symptomatic patients previously labelled as non-specific or functional enteropathy.

  15. Continuity and consensus

    DEFF Research Database (Denmark)

    Abrahamson, Peter

    2010-01-01

    maternal leave. These changes can be explained as adjustments to post-industrial conditions within a political culture relying on class compromises and a broad consensus informed by expert advice coming from civil servants and ad hoc policy commissions. The paper concludes that changes in Danish family......In Danish family policy, changes initiated by the present conservative-liberal government differ little from those proposed by the opposition. Recent changes are minor, but significant ones occurred in the 1960s, when childcare was universalized, and in the 1980s, when parental leave substituted...

  16. Modulation of gene expression in a human cell line caused by poliovirus, vaccinia virus and interferon

    Directory of Open Access Journals (Sweden)

    Hoddevik Gunnar

    2007-03-01

    Full Text Available Abstract Background The project was initiated to describe the response of a human embryonic fibroblast cell line to the replication of two different viruses, and, more specifically, to look for candidate genes involved in viral defense. For this purpose, the cells were synchronously infected with poliovirus in the absence or presence of interferon-alpha, or with vaccinia virus, a virus that is not inhibited by interferon. By comparing the changes in transcriptosome due to these different challenges, it should be possible to suggest genes that might be involved in defense. Results The viral titers were sufficient to yield productive infection in a majority of the cells. The cells were harvested in triplicate at various time-points, and the transcriptosome compared with mock infected cells using oligo-based, global 35 k microarrays. While there was very limited similarities in the response to the different viruses, a large proportion of the genes up-regulated by interferon-alpha were also up-regulated by poliovirus. Interferon-alpha inhibited poliovirus replication, but there were no signs of any interferons being induced by poliovirus. The observations suggest that the cells do launch an antiviral response to poliovirus in the absence of interferon. Analyses of the data led to a list of candidate antiviral genes. Functional information was limited, or absent, for most of the candidate genes. Conclusion The data are relevant for our understanding of how the cells respond to poliovirus and vaccinia virus infection. More annotations, and more microarray studies with related viruses, are required in order to narrow the list of putative defence-related genes.

  17. A Randomized Multicentre Phase II Trial Comparing Adjuvant Therapy in Patients with Interferon Alpha-2b and 5-FU Alone or in Combination with Either External Radiation Treatment and Cisplatin (CapRI or Radiation alone regarding Event-Free Survival – CapRI-2

    Directory of Open Access Journals (Sweden)

    Friess Helmut

    2009-05-01

    Full Text Available Abstract Background The 5-year survival of patients with resected pancreatic adenocarcinoma is still unsatisfying. The ESPAC-1 and the CONKO 001 trial proofed that adjuvant chemotherapy improves 5-year survival significantly from approximately 14% to 21%. In parallel, investigators from the Virginia Mason Clinic reported a 5-year survival rate of 55% in a phase II trial evaluating a combination of adjuvant chemotherapy, immunotherapy and external beam radiation (CapRI-scheme. Two other groups confirmed in phase II trials these results to a certain extent. However, these groups reported severe gastrointestinal toxicity (up to 93% grade 3 or 4 toxicity. In a randomized controlled phase III trial, called CapRI, 110 patients were enrolled from 2004 to 2007 in Germany and Italy to check for reproducibility. Interestingly, much less gastrointestinal toxicity was observed. However, dose-reduction due to haematological side effects had to be performed in nearly all patients. First clinical results are expected for the end of 2009. Methods/Design CapRI-2 is an open, controlled, prospective, randomized, multicentre phase II trial with three parallel arms. A de-escalation of the CapRI-scheme will be tested in two different modifications. Patients in study arm A will be treated as outpatients with the complete CapRI-scheme consisting of cisplatin, Interferon alpha-2b and external beam radiation and three cycles of 5-fluorouracil continuous infusion. In study arm B the first de-escalation will be realised by omitting cisplatin. Next, patients in study arm C will additionally not receive external beam radiation. A total of 135 patients with pathologically confirmed R0 or R1 resected pancreatic adenocarcinoma are planned to be enrolled. Primary endpoint is the comparison of the treatment groups with respect to six-month event-free-survival. An event is defined as grade 3 or grade 4 toxicity, objective tumour recurrence, or death. Discussion The aim of this

  18. 猪α干扰素基因经密码子改造在毕赤酵母菌中的高效分泌表达%High Performance Secreted Expression of Porcine Interferon Alpha Gene in Pichia pastoris by Codon Change

    Institute of Scientific and Technical Information of China (English)

    刘健; 陈瑞爱; 刘珊珊; 朱杰仪; 唐明森; 罗满林

    2011-01-01

    根据毕赤酵母Pichia pastoris表达系统对于密码子的偏嗜性,将去除信号肽的猪α干扰素(PoIFN-α)基因重新设计改造并合成一段新的核苷酸序列,置于毕赤酵母菌α因子分泌信号的DNA序列后,构建成pPICZαC-PoIFN-α分泌型重组表达载体,电转化进入野生型毕赤酵母菌X-33中,经ZeocinTM抗性筛选后获得大量多拷贝重组子,SDSPAGE和Wester-blot分析结果表明,所获得的重组子能够分泌表达出相对分子质量约为19 000的PoIFN-α特异蛋白,其有效蛋白表达量较高达54.105 mg/L.经Vero-VSV系统测定,PoIFN-α效价达到5.87×107 U/L.试验将PoIFN-α成熟肽全基因密码子进行改造,并实现了其在毕赤酵母菌表达系统中的高效分泌表达.%According to the codon metatropism of Pichia pastoris, the porcine interferon alpha (PoIFN-α)gene, in which the sequence encoding signal peptide was replaced by that of the α-factor of Saccharomyces cerevisiae,was cloned into P. pastoris expression vector pPICZαC. The recombinant plasmid pPICZαCPoIFN-α was then transformed into P. pastoris X-33 cells by electroporation, and stable multicopy recombinant P. pastris strains were selected by ZeocinTM resistance. A great quantity of multiple-inserted recombinants were obtained. SDS-PAGE and Western-blot assays of culture broth from a methanol-induced expression strain demonstrated that recombinant PoIFN-α, about 19 000 proteins,were secreted into the culture medium at the concentration of 54. 105 mg/L. The potency of PoIFN-α was up to 5.87 × 107 U/L by Vero-VSV systems measurement. This experiment changed the sequence coding of PoIFN-α by the codon metatropism of P. pastoris and the results proved that this change was feasible.

  19. Conflict or Consensus?

    DEFF Research Database (Denmark)

    Agger, Annika; Poulsen, Birgitte

    forms of institutional design of citizen participation processes, less attention has been paid to the role of public administrators, and their role in facilitating processes of citizen participation. Public administrators have to work with diverse groups of citizens with diverging, and often conflicting......, interests. However, many public administrators have not been adequately exposed to the rationales of conflicts and the skills in resolving conflicts. The aim of this paper is to analyse the different types of conflicts that public administrators experience in formal processes of citizen involvement. Whereas...... the literature of deliberative democracy claims that consensus is most often the result of rational deliberative processes, the claim of this paper is that conflicts is more likely a natural and integrated part of such deliberative acts. Conflicts are, thus, seen as inevitable. Also conflicts may function...

  20. Interferon-alpha in the treatment of multiple myeloma

    DEFF Research Database (Denmark)

    Khoo, T.L.; Joshua, D.; Gibson, J.

    2011-01-01

    Interferons are soluble proteins produced naturally by cells in response to viruses. It has both anti-proliferative and immunomodulating properties and is one of the first examples of a biological response modifier use to treat the hematological malignancy multiple myeloma. Interferon has been used...... in this clinical practice for over thirty years. However, despite considerable efforts, numerous clinical trials and two large meta-analysis, its exact role in the management of multiple myeloma still remains unclear. Its role in the treatment of multiple myeloma has been as a single induction agent, a co...... of multiple myeloma or will interferon be resigned to the history books remains to be seen....

  1. Increased sensitivity to interferon-alpha in psoriatic T cells

    DEFF Research Database (Denmark)

    Eriksen, Karsten Wessel; Lovato, Paola; Skov, Lone

    2005-01-01

    disease characterized by CD8(+)-infiltrating T cells. In this study, we therefore investigate IFN-alpha signaling in T cells isolated from involved skin of psoriatic patients. We show that psoriatic T cells have increased and prolonged responses to IFN-alpha, on the level of signal transducers......Psoriasis is a chronic inflammatory skin disease characterized by abnormal epidermal proliferation. Several studies have shown that skin-infiltrating activated T cells and cytokines play a pivotal role during the initiation and maintenance of the disease. Interferon (IFN)-alpha plays an important...... role in host defense against infections, but recent data have also implicated IFN-alpha in psoriasis. Thus, IFN-alpha induces or aggravates psoriasis in some patients, and mice lacking a transcriptional attenuator of IFN-alpha/beta signaling spontaneously develop a psoriasis-like inflammatory skin...

  2. Renal failure after treatment with interferon alpha 2b

    NARCIS (Netherlands)

    Roeloffzen, WWH; Hospers, GAP; De Vries, EGE; Navis, GJ

    2002-01-01

    Although there has been considerable experience with interferons in the treatment of malignancy and viral illnesses, acute renal failure as a side-effect of interferon treatment has rarely been reported. We present the case of a patient who developed acute on chronic renal failure 16 months after

  3. Renal failure after treatment with interferon alpha 2b

    NARCIS (Netherlands)

    Roeloffzen, WWH; Hospers, GAP; De Vries, EGE; Navis, GJ

    2002-01-01

    Although there has been considerable experience with interferons in the treatment of malignancy and viral illnesses, acute renal failure as a side-effect of interferon treatment has rarely been reported. We present the case of a patient who developed acute on chronic renal failure 16 months after th

  4. [National consensus document by GESIDA/National Aids Plan on antiretroviral treatment in adults infected by the human immunodeficiency virus (January 2011 update)].

    Science.gov (United States)

    2011-03-01

    The update of these adult antiretroviral treatment (cART) recommendations has been carried out by consensus of a panel consisting of members of the Grupo de Estudio de Sida (Gesida, AIDS Study Group) and the Plan Nacional sobre el Sida (PNS, Spanish AIDS Plan) who have reviewed the antiretroviral efficacy and safety advances in clinical trials, cohort and pharmacokinetic studies published in medical journals (PubMed and Embase), or presented in medical scientific meetings. Three levels of evidence were defined according to the data source: randomized studies (level A), cohort or case-control studies (level B), and expert opinion (level C). The decision to recommend, consider or not to recommend antiretroviral treatment (ART) was established by consensus in each situation. The current treatment of choice for HIV infection is the combination of three drugs. Combined ART is recommended in patients with symptomatic HIV infection, and guidelines on this treatment in patients with an opportunistic type C infection are included. In asymptomatic patients, initiation of ART is recommended on the basis of CD4 lymphocyte counts, plasma viral load and patient co-morbidities, as follows: a) therapy should be started in patients with CD4 counts 100,000 copies/ mL, proportion of CD4 cells 55 years, and in cases of discordant serological sexual couples in order to reduce transmission. cART should include 2 reverse transcriptase inhibitor nucleoside analogues (AN) and a non-analogue reverse transcriptase inhibitor (NN) or 2 AN and a ritonavir boosted protease inhibitor (PI/ r), but other combinations are possible. The panel has consensually selected and prioritized some drug combinations, some of them co-formulated. The objective of cART is to achieve an undetectable viral load. Adherence to therapy plays an essential role in maintaining antiviral response. Therapeutic options are limited after cART failures, but undetectable viral load maybe possible with resistance genotypic

  5. A multi-centre investigation towards reaching a consensus on the immunohistochemical detection of ERbeta in archival formalin-fixed paraffin embedded human breast tissue.

    Science.gov (United States)

    Carder, Pauline J; Murphy, Claire E; Dervan, Peter; Kennedy, Maria; McCann, Amanda; Saunders, Philippa T K; Shaaban, Abeer M; Foster, Christopher S; Witton, Caroline J; Bartlett, John M S; Walker, Rosemary A; Speirs, Valerie

    2005-08-01

    Estrogen receptor (ER) alpha is a well-established independent prognostic factor in breast cancer whose presence determines the clinical implications of adjuvant endocrine therapy. A second receptor, ERb has been described, and a number of studies have examined its expression in breast tissue. However elucidation of the role played by ERb has been hampered by published immunohistochemical studies employing a variety of protocols and scoring systems such that inter-laboratory comparisons are difficult. Here we present a multi-centre study designed to critically evaluate inter-laboratory differences in methodology. Six UK and Irish centres participated in this study. A small series of breast cancers were stained using centre-specific laboratory protocols and scored using both centrespecific and standard scoring protocols. There was generally poor agreement as to what constituted a positive or negative case when centre-specific scoring systems were used with less than half of all cases in agreement. Concordance was improved when a standard scoring system was used but varied according to threshold for positivity employed and primary antibody. Our results emphasise the need for further studies addressing the role of ERb to be based on a wider consensus on criteria for positivity. Ideally this should be based on calibration against clinical outcome.

  6. Political Consensus and Fiscal Outcomes

    DEFF Research Database (Denmark)

    Houlberg, Kurt; Holm Pedersen, Lene

    2015-01-01

    It is becoming difficult to maintain consensus in a period of economic austerity, and this possibly challenges the ability of democratic institutions to take decisions on tough economic questions. In order to find out how political consensus influences fiscal outcomes, this article sets out...

  7. Attitude extremity, consensus and diagnosticity

    NARCIS (Netherlands)

    van der Pligt, J.; Ester, P.; van der Linden, J.

    1983-01-01

    Studied the effects of attitude extremity on perceived consensus and willingness to ascribe trait terms to others with either pro- or antinuclear attitudes. 611 Ss rated their attitudes toward nuclear energy on a 5-point scale. Results show that attitude extremity affected consensus estimates. Trait

  8. Main: ANAERO5CONSENSUS [PLACE

    Lifescience Database Archive (English)

    Full Text Available ANAERO5CONSENSUS S000481 05-November-2005 (last modified) kehi One of 16 motifs fou...ty et al., 2005); Arbitrary named ANAERO5CONSENSUS by the PLACEdb curator; See also S000477, S000478, S00047

  9. Main: ANAERO3CONSENSUS [PLACE

    Lifescience Database Archive (English)

    Full Text Available ANAERO3CONSENSUS S000479 05-November-2005 (last modified) kehi One of 16 motifs fou...ty et al., 2005); Arbitrary named ANAERO3CONSENSUS by the PLACEdb curator; See also S000477, S000478, S00048

  10. Main: ANAERO4CONSENSUS [PLACE

    Lifescience Database Archive (English)

    Full Text Available ANAERO4CONSENSUS S000480 05-November-2005 (last modified) kehi One of 16 motifs fou...ty et al., 2005); Arbitrary named ANAERO4CONSENSUS by the PLACEdb curator; See also S000477, S000478, S00047

  11. Main: ANAERO2CONSENSUS [PLACE

    Lifescience Database Archive (English)

    Full Text Available ANAERO2CONSENSUS S000478 05-November-2005 (last modified) kehi One of 16 motifs fou...ty et al., 2005); Arbitrary named ANAERO2CONSENSUS by the PLACEdb curator; See also S000477, S000479, S00048

  12. Main: ANAERO1CONSENSUS [PLACE

    Lifescience Database Archive (English)

    Full Text Available ANAERO1CONSENSUS S000477 05-November-2005 (last modified) kehi One of 16 motifs fou...ty et al., 2005); Arbitrary named ANAERO1CONSENSUS by the PLACEdb curator; See also S000478, S000479, S00048

  13. Consensus Convolutional Sparse Coding

    KAUST Repository

    Choudhury, Biswarup

    2017-04-11

    Convolutional sparse coding (CSC) is a promising direction for unsupervised learning in computer vision. In contrast to recent supervised methods, CSC allows for convolutional image representations to be learned that are equally useful for high-level vision tasks and low-level image reconstruction and can be applied to a wide range of tasks without problem-specific retraining. Due to their extreme memory requirements, however, existing CSC solvers have so far been limited to low-dimensional problems and datasets using a handful of low-resolution example images at a time. In this paper, we propose a new approach to solving CSC as a consensus optimization problem, which lifts these limitations. By learning CSC features from large-scale image datasets for the first time, we achieve significant quality improvements in a number of imaging tasks. Moreover, the proposed method enables new applications in high dimensional feature learning that has been intractable using existing CSC methods. This is demonstrated for a variety of reconstruction problems across diverse problem domains, including 3D multispectral demosaickingand 4D light field view synthesis.

  14. Between consensus and contestation.

    Science.gov (United States)

    Weale, Albert

    2016-08-15

    Purpose - Noting that discussions of public participation and priority setting typically presuppose certain political theories of democracy, the purpose of this paper is to discuss two theories: the consensual and the agonistic. The distinction is illuminating when considering the difference between institutionalized public participation and contestatory participation. Design/methodology/approach - The approach is a theoretical reconstruction of two ways of thinking about public participation in relation to priority setting in health care, drawing on the work of Habermas, a deliberative theorist, and Mouffe, a theorist of agonism. Findings - The different theoretical approaches can be associated with different ways of understanding priority setting. In particular, agonistic democratic theory would understand priority setting as system of inclusions and exclusions rather than the determination of a consensus of social values, which is the typical deliberative way of thinking about the issues. Originality/value - The paper shows the value of drawing out explicitly the tacit assumptions of practices of political participation in order to reveal their scope and limitations. It suggests that making such theoretical presuppositions explicit has value for health services management in recognizing these implicit choices.

  15. Stillbirth Classification-Developing an International Consensus for Research Executive Summary of a National Institute of Child Health and Human Development Workshop

    National Research Council Canada - National Science Library

    Reddy, Uma M; Goldenberg, Robert; Silver, Robert; Smith, Gordon C. S; Pauli, Richard M; Wapner, Ronald J; Gardosi, Jason; Pinar, Halit; Grafe, Marjorie; Kupferminc, Michael; Varli, Ingela Hulthen; Erwich, Jan Jaap H. M; Fretts, Ruth C; Willinger, Marian

    2009-01-01

    .... The Eunice Kennedy Shriver National Institute of Child Health and Human Development held a workshop from October 22-24, 2007, to review the pathophysiology of conditions underlying stillbirth to define causes of death...

  16. [Consensus Statement by GeSIDA/National AIDS Plan Secretariat on antiretroviral treatment in adults infected by the human immunodeficiency virus (Updated January 2013)].

    Science.gov (United States)

    2013-11-01

    This consensus document is an update of combined antiretroviral therapy (cART) guidelines for HIV-1 infected adult patients. To formulate these recommendations a panel composed of members of the GeSIDA/National AIDS Plan Secretariat (Grupo de Estudio de Sida and the Secretaría del Plan Nacional sobre el Sida) reviewed the efficacy and safety advances in clinical trials, cohort and pharmacokinetic studies published in medical journals (PubMed and Embase) or presented in medical scientific meetings. The strength of the recommendations and the evidence which support them are based on a modification of the criteria of Infectious Diseases Society of America. cART is recommended in patients with symptoms of HIV infection, in pregnant women, in serodiscordant couples with high risk of transmission, in hepatitisB co-infection requiring treatment, and in HIV nephropathy. cART is recommended in asymptomatic patients if CD4 is 500cells/μl cART should be considered in the case of chronic hepatitisC, cirrhosis, high cardiovascular risk, plasma viral load >100.000 copies/ml, proportion of CD4 cells 55years. The objective of cART is to achieve an undetectable viral load. The first cART should include 2 reverse transcriptase inhibitors (RTI) nucleoside analogs and a third drug (a non-analog RTI, a ritonavir boosted protease inhibitor, or an integrase inhibitor). The panel has consensually selected some drug combinations, for the first cART and specific criteria for cART in acute HIV infection, in tuberculosis and other HIV related opportunistic infections, for the women and in pregnancy, in hepatitisB or C co-infection, in HIV-2 infection, and in post-exposure prophylaxis. These new guidelines update previous recommendations related to first cART (when to begin and what drugs should be used), how to monitor, and what to do in case of viral failure or adverse drug reactions. cART specific criteria in comorbid patients and special situations are similarly updated. Copyright

  17. Is There a Consensus on Consensus Methodology? Descriptions and Recommendations for Future Consensus Research.

    Science.gov (United States)

    Waggoner, Jane; Carline, Jan D; Durning, Steven J

    2016-05-01

    The authors of this article reviewed the methodology of three common consensus methods: nominal group process, consensus development panels, and the Delphi technique. The authors set out to determine how a majority of researchers are conducting these studies, how they are analyzing results, and subsequently the manner in which they are reporting their findings. The authors conclude with a set of guidelines and suggestions designed to aid researchers who choose to use the consensus methodology in their work.Overall, researchers need to describe their inclusion criteria. In addition to this, on the basis of the current literature the authors found that a panel size of 5 to 11 members was most beneficial across all consensus methods described. Lastly, the authors agreed that the statistical analyses done in consensus method studies should be as rigorous as possible and that the predetermined definition of consensus must be included in the ultimate manuscript. More specific recommendations are given for each of the three consensus methods described in the article.

  18. FDA Recognized Consensus Standards

    Data.gov (United States)

    U.S. Department of Health & Human Services — This database consists of those national and international standards recognized by FDA which manufacturers can declare conformity to and is part of the information...

  19. Public Awareness of the Scientific Consensus on Climate

    Directory of Open Access Journals (Sweden)

    Lawrence C. Hamilton

    2016-11-01

    Full Text Available Questions about climate change elicit some of the widest political divisions of any items on recent U.S. surveys. Severe polarization affects even basic questions about the reality of anthropogenic climate change (ACC, or whether most scientists agree that humans are changing the Earth’s climate. Statements about scientific consensus have been contentious among social scientists, with some arguing for consensus awareness as a “gateway cognition” that leads to greater public acceptance of ACC, but others characterizing consensus messaging (deliberate communication about the level of scientific agreement as a counterproductive tactic that exacerbates polarization. A series of statewide surveys, with nationwide benchmarks, repeated questions about the reality of ACC and scientific consensus many times over 2010 to 2016. These data permit tests for change in beliefs and polarization. ACC and consensus beliefs have similar trends and individual background predictors. Both rose gradually by about 10 points over 2010 to 2016, showing no abrupt shifts that might correspond to events such as scientific reports, leadership statements, or weather. Growing awareness of the scientific consensus, whether from deliberate messaging or the cumulative impact of many studies and publicly engaged scientists, provides the most plausible explanation for this rise in both series. In state-level data, the gap between liberal and conservative views on the reality of ACC did not widen over this period, whereas the liberal–conservative gap regarding existence of a scientific consensus narrowed.

  20. Combination with nucleoside/tide analogues for the patients with chronic hepatitis B who had no response to failed to interferon alpha and nucleoside/tide analogue: a 5-year clinical course%多次抗病毒治疗无效的慢性乙型肝炎患者停用抗病毒药物后的联合治疗

    Institute of Scientific and Technical Information of China (English)

    肖扬; 卢成鸿; 江山; 潘华将; 王启亮; 胡侠; 张文静; 郑金莉; 周岳进

    2011-01-01

    目的 对于干扰素治疗无效、核苷类似物耐药后停用抗病毒药物治疗的慢性乙型肝炎患者,探讨其停药的后果及再联合应用核苷类似物长期治疗的必要性.方法 先后用干扰素α-2b、核苷类似物抗病毒治疗均无效的42例慢性乙型肝炎患者,其自动停用抗病毒药物一段时间后,再联用拉米夫定(100 mg/d)(或替比夫定600 mg/d、恩替卡韦0.5 mg/d)与阿德福韦酯(10 mg/d),观察再治疗前后5年患者临床症状体征、生化指标、病毒学、B超半定量肝纤维化积分改变情况.结果 42例患者在抗病毒治疗停止后一段时间内均出现不同程度肝功能损害、生化改变以及肝纤维化积分增加,19%出现肝功能失代偿.而患者采用联合抗病毒治疗后肝功能生化指标正常或好转,病情缓解稳定,生活质量改善,HBV DNA下降>2 log10/mL, 肝纤维化积分下降.结论 慢性乙型肝炎患者干扰素治疗无效、核苷类似物耐药后,停用抗病毒药物会加剧病情进展风险,坚持联合抗病毒治疗可能阻止或延缓病情进展.%Objective To evaluate the clinical risk of patients with chronic hepatitis B(CHB) who stop antiviral therapy and identify the significance of sustained combination therapy with nucleoside/tide analogues. Methods Fortytwo CHB patients treated with invalid interferon alpha and nucleoside/tide analogues were received two kinds of nucleoside/tide analogues (adefovir dipivoxil 10 mg/d and lamivudine 100 mg/d or telbivudine 600 mg/d or entecavir 0.5 mg/d for two years). The risk of stopping antiviral therapy and efficacy of sustained combination with nucleoside/tide analogues were assessed based on the clinical presentation, biochemical response, virology response and ultrasonic semiquantitative scoring for quantitating liver fibrosis for five years. Results After stopping antiviral drugs for a few months ,all of 42 patients were deteriorated in liver function, presenting increased

  1. Consensus classification of human prion disease histotypes allows reliable identification of molecular subtypes: an inter-rater study among surveillance centres in Europe and USA

    Science.gov (United States)

    de Boni, Laura; Saverioni, Daniela; Cohen, Mark L.; Ferrer, Isidro; Gambetti, Pierluigi; Gelpi, Ellen; Giaccone, Giorgio; Hauw, Jean-Jacques; Höftberger, Romana; Ironside, James W.; Jansen, Casper; Kovacs, Gabor G.; Rozemuller, Annemieke; Seilhean, Danielle; Tagliavini, Fabrizio; Giese, Armin

    2013-01-01

    The current classification of human sporadic prion diseases recognizes six major phenotypic subtypes with distinctive clinicopathological features, which largely correlate at the molecular level with the genotype at the polymorphic codon 129 (methionine, M, or valine, V) in the prion protein gene and with the size of the protease-resistant core of the abnormal prion protein, PrPSc (i.e. type 1 migrating at 21 kDa and type 2 at 19 kDa). We previously demonstrated that PrPSc typing by Western blotting is a reliable means of strain typing and disease classification. Limitations of this approach, however, particularly in the interlaboratory setting, are the association of PrPSc types 1 or 2 with more than one clinicopathological phenotype, which precludes definitive case classification if not supported by further analysis, and the difficulty of fully recognizing cases with mixed phenotypic features. In this study, we tested the inter-rater reliability of disease classification based only on histopathological criteria. Slides from 21 cases covering the whole phenotypic spectrum of human sporadic prion diseases, and also including two cases of variant Creutzfeldt–Jakob disease (CJD), were distributed blindly to 13 assessors for classification according to given instructions. The results showed good-to-excellent agreement between assessors in the classification of cases. In particular, there was full agreement (100 %) for the two most common sporadic CJD subtypes and variant CJD, and very high concordance in general for all pure phenotypes and the most common subtype with mixed phenotypic features. The present data fully support the basis for the current classification of sporadic human prion diseases and indicate that, besides molecular PrPSc typing, histopathological analysis permits reliable disease classification with high interlaboratory accuracy. PMID:22744790

  2. Chapel Hill bisphenol A expert panel consensus statement: Integration of mechanisms, effects in animals and potential to impact human health at current levels of exposure

    Science.gov (United States)

    vom Saal, Frederick S.; Akingbemi, Benson T.; Belcher, Scott M.; Birnbaum, Linda S.; Crain, D. Andrew; Eriksen, Marcus; Farabollini, Francesca; Guillette, Louis J.; Hauser, Russ; Heindel, Jerrold J.; Ho, Shuk-Mei; Hunt, Patricia A.; Iguchi, Taisen; Jobling, Susan; Kanno, Jun; Keri, Ruth A.; Knudsen, Karen E.; Laufer, Hans; LeBlanc, Gerald A.; Marcus, Michele; McLachlan, John A.; Myers, John Peterson; Nadal, Angel; Newbold, Retha R.; Olea, Nicolas; Prins, Gail S.; Richter, Catherine A.; Rubin, Beverly S.; Sonnenschein, Carlos; Soto, Ana M.; Talsness, Chris E.; Vandenbergh, John G.; Vanderberg, Laura N.; Walser-Kuntz, Debby R.; Watson, Cheryl S.; Welshons, Wade V.; Wetherill, Yelena; Zoeller, R. Thomas

    2007-01-01

    This document is a summary statement of the outcome from the meeting: “Bisphenol A: An Examination of the Relevance of Ecological, In vitro and Laboratory Animal Studies for Assessing Risks to Human Health” sponsored by both the NIEHS and NIDCR at NIH/DHHS, as well as the US-EPA and Commonweal on the estrogenic environmental chemical bisphenol A (BPA, 2,2-bis(4-hydroxyphenyl)propane; CAS# 80-05-7). The meeting was held in Chapel Hill, NC, 28–30 November 2006 due to concerns about the potential for a relationship between BPA and negative trends in human health that have occurred in recent decades. Examples include increases in abnormal penile/urethra development in males, early sexual maturation in females, an increase in neurobehavioral problems such as attention deficit hyperactivity disorder (ADHD) and autism, an increase in childhood and adult obesity and type 2 diabetes, a regional decrease in sperm count, and an increase in hormonally mediated cancers, such as prostate and breast cancers. Concern has been elevated by published studies reporting a relationship between treatment with “low doses” of BPA and many of theses negative health outcomes in experimental studies in laboratory animals as well as in vitro studies identifying plausible molecular mechanisms that could mediate such effects. Importantly, much evidence suggests that these adverse effects are occurring in animals within the range of exposure to BPA of the typical human living in a developed country, where virtually everyone has measurable blood, tissue and urine levels of BPA that exceed the levels produced by doses used in the “low dose” animal experiments.

  3. Evidence for selection against human lung cancers bearing p53 missense mutations which occur within the HLA A*0201 peptide consensus motif.

    Science.gov (United States)

    Wiedenfeld, E A; Fernandez-Viña, M; Berzofsky, J A; Carbone, D P

    1994-03-01

    Short peptide fragments of intracellular proteins that fit a defined sequence motif bind to the most common human major histocompatibility complex class I molecule, HLA A*0201, and mediate killing by cytotoxic T-cells [D.F. Hunt et al., Science (Washington DC), 255: 1261-1263, 1992; K. Falk et al., Nature (Lond.), 351: 290-296, 1991]. The existence of such a motif allows prediction of whether novel peptides derived from mutant oncoporteins might be presented on the surface of cancer cells bearing that HLA allele. Clinical cancer might develop only when these mutations occur outside a major histocompatibility complex binding motif or in those cells that acquire defects in antigen presentation. Here, we find that missense mutations of p53 from a variety of tumors fall within the HLA A*0201 motif less often than would be expected if the location of mutations and motifs were independent. When we analyzed the HLA subtype of lung cancer cell lines with known p53 missense mutations, we found that all of the mutant oncopeptides predicted to be presentable by HLA A*0201 came from tumors that either did not carry the A*0201 allele or had lost that allele in the process of tumorigenesis. Presentation of mutant oncogene peptides on class I major histocompatibility complex might thus represent a physiologically significant selection pressure in the development of human cancer.

  4. Evolution of human IgH3'EC duplicated structures: both enhancers HS1,2 are polymorphic with variation of transcription factor's consensus sites.

    Science.gov (United States)

    Giambra, Vincenzo; Fruscalzo, Alberto; Giufre', Maria; Martinez-Labarga, Cristina; Favaro, Marco; Rocchi, Mariano; Frezza, Domenico

    2005-02-14

    The enhancer complex regulatory region at the 3' of the immunoglobulin heavy cluster (IgH3'EC) is duplicated in apes along with four constant genes and the region is highly conserved throughout humans. Both human IgH3'ECs consist of three loci high sensitive (HS) to DNAse I with enhancer activity. It is thus possible that the presence of structural divergences between the two IgH3'ECs and of relative polymorphisms correspond to functional regulatory changes. To analyse the polymorphisms of these almost identical regions, it resulted mandatory to identify the presence of divergent sequences, in order to select distinctive primers for specific PCR genomic amplifications. To this aim, we first compared the two entire IgH3'ECs in silicio, utilising the updated GenBank (GB) contigs, then we analysed the two IgH3'ECs by cloning and sequencing amplicons from independent genomes. In silicio analysis showed that several inversions, deletions and short insertions had occurred after the duplication. We analysed in detail, by sequencing specific regions, the polymorphisms occurring in enhancer HS1,2-A (which lies in IgH3'EC-1, 3' to the Calpha-1 gene) and in enhancer HS1,2-B (which lies in IgH3'EC-2, 3' to Calpha-2). Polymorphisms are due to the repetition (occurring one to four times) of a 38-bp sequence present at the 3' of the core of enhancers HS1,2. The structure of both human HS1,2 enhancers has revealed not yet described polymorphic features due to the presence of variable spacer elements separating the 38-bp repetitions and to variable external elements bordering the repetition cluster. We found that one of the external elements gave rise to a divergent allele 3 in the two clusters. The frequency of the different alleles of the two loci varies in the Italian population and allele 3 of both loci are very rare. The analysis of the Callicebus moloch, Gorilla gorilla and Pan troglodytes HS1,2 enhancers showed the transformation from the ancestral structure with the 31- to

  5. Ocular allergy latin american consensus

    Directory of Open Access Journals (Sweden)

    Myrna Serapião dos Santos

    2011-12-01

    Full Text Available PURPOSE: To establish current definition, classification and staging, and to develop diagnosis and treatment recommendations for ocular allergy, by using Delphi approach. METHODS: Ten Latin American experts on ocular allergy participated in a 4-round Delphi panel approach. Four surveys were constructed and answered by panelists. A two-thirds majority was defined as consensus. Definition, classification, staging and diagnosis and treatment recommendations were the main outcomes. RESULTS: "Ocular allergy" was proposed as the general term to describe ocular allergic diseases. Consensus regarding classification was not reached. Signs and symptoms were considered extremely important for the diagnosis. It was consensus that a staging system should be proposed based on the disease severity. Environmental control, avoidance of allergens and the use of artificial tears were recommended as first line treatment. The secondary treatment should include topical anti-histamines, mast cell stabilizers and multi actions drugs. Topical non-steroidal anti-inflammatory and vasoconstrictors were not recommended. Topical corticosteroids were recommended as third line of treatment for the most severe keratoconjunctivitis. Consensus was not reached regarding the use of systemic corticosteroids or immunosuppressant. Surgical approach and unconventional treatments were not recommended as routine. CONCLUSION: The task of creating guidelines for ocular allergies showed to be very complex. Many controversial topics remain unsolved. A larger consensus including experts from different groups around the world may be needed to further improve the current recommendations for several aspects of ocular allergy.

  6. Human small cell lung cancer NYH cells selected for resistance to the bisdioxopiperazine topoisomerase II catalytic inhibitor ICRF-187 demonstrate a functional R162Q mutation in the Walker A consensus ATP binding domain of the alpha isoform

    DEFF Research Database (Denmark)

    Wessel, I; Jensen, L H; Jensen, P B;

    1999-01-01

    -AMSA), which act by stabilizing enzyme-DNA-drug complexes at a stage in which the DNA gate strand is cleaved and the protein is covalently attached to DNA. Human small cell lung cancer NYH cells selected for resistance to ICRF-187 (NYH/187) showed a 25% increase in topoisomerase IIalpha level and no change...... in expression of the beta isoform. Sequencing of the entire topoisomerase IIalpha cDNA from NYH/187 cells demonstrated a homozygous G-->A point mutation at nucleotide 485, leading to a R162Q conversion in the Walker A consensus ATP binding site (residues 161-165 in the alpha isoform), this being the first drug......-selected mutation described at this site. Western blotting after incubation with ICRF-187 showed no depletion of the alpha isoform in NYH/187 cells in contrast to wild-type (wt) cells, whereas equal depletion of the beta isoform was observed in the two sublines. Alkaline elution assay demonstrated a lack...

  7. Executive summary of the GESIDA/National AIDS Plan Consensus Document on Antiretroviral Therapy in Adults Infected by the Human Immunodeficiency Virus (Updated January 2016).

    Science.gov (United States)

    2016-01-01

    In this update, antiretroviral therapy (ART) is recommended for all patients infected by type 1 human immunodeficiency virus (HIV-1). The objective of ART is to achieve an undetectable plasma viral load (PVL). Initial ART should comprise 3 drugs, namely, 2 nucleoside reverse transcriptase inhibitors (NRTI), and 1 drug from another family. Four of the recommended regimens, all of which have an integrase strand transfer inhibitor (INSTI) as the third drug, are considered a preferred regimen; a further 6 regimens, which are based on an INSTI, a non-nucleoside reverse transcriptase inhibitor (NNRTI), or a protease inhibitor boosted with cobicistat or ritonavir (PI/COBI, PI/r), are considered alternatives. The reasons and criteria for switching ART are presented both for patients with an undetectable PVL and for patients who experience virological failure, in which case the rescue regimen should include 3 (or at least 2) drugs that are fully active against HIV. The specific criteria for ART in special situations (acute infection, HIV-2 infection, pregnancy) and comorbid conditions (tuberculosis and other opportunistic infections, kidney disease, liver disease, and cancer) are updated.

  8. Executive summary of the GESIDA/National AIDS Plan Consensus Document on antiretroviral therapy in adults infected by the human immunodeficiency virus (updated January 2015).

    Science.gov (United States)

    Berenguer, Juan; Polo, Rosa; Aldeguer, José López; Lozano, Fernando; Aguirrebengoa, Koldo; Arribas, José Ramón; Blanco, José Ramón; Boix, Vicente; Casado, José Luis; Clotet, Bonaventura; Crespo, Manuel; Domingo, Pere; Estrada, Vicente; García, Federico; Gatell, José María; González-García, Juan; Gutiérrez, Félix; Iribarren, José Antonio; Knobel, Hernando; Llibre, Josep María; Locutura, Jaime; López, Juan Carlos; Miró, José M; Moreno, Santiago; Podzamczer, Daniel; Portilla, Joaquín; Pulido, Federico; Ribera, Esteban; Riera, Melchor; Rubio, Rafael; Santos, Jesús; Sanz-Moreno, José; Sanz, Jesús; Téllez, María Jesús; Tuset, Montserrat; Rivero, Antonio

    2015-10-01

    In this update, antiretroviral therapy (ART) is recommended for all patients infected by type 1 human immunodeficiency virus (HIV-1). The strength and grade of the recommendation vary depending on the CD4+ T-lymphocyte count, the presence of opportunistic infections or comorbid conditions, age, and the efforts to prevent the transmission of HIV. The objective of ART is to achieve an undetectable plasma viral load (PVL). Initial ART should comprise three drugs, namely, two nucleoside reverse transcriptase inhibitors (NRTI) and one drug from another family. Three of the recommended regimens, all of which have an integrase strand transfer inhibitor (INSTI) as the third drug, are considered a preferred regimen; a further seven regimens, which are based on an INSTI, an non-nucleoside reverse transcriptase inhibitor (NNRTI), or a protease inhibitor boosted with ritonavir (PI/r), are considered alternatives. The reasons and criteria for switching ART are presented both for patients with an undetectable PVL and for patients who experience virological failure, in which case the rescue regimen should include three (or at least two) drugs that are fully active against HIV. The specific criteria for ART in special situations (acute infection, HIV-2 infection, pregnancy) and comorbid conditions (tuberculosis and other opportunistic infections, kidney disease, liver disease, and cancer) are updated. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  9. Executive summary of the GeSIDA/National AIDS Plan consensus document on antiretroviral therapy in adults infected by the human immunodeficiency virus (updated January 2014).

    Science.gov (United States)

    Berenguer, Juan; Polo, Rosa; Lozano, Fernando; López Aldeguer, José; Antela, Antonio; Arribas, José Ramón; Asensi, Víctor; Blanco, José Ramón; Clotet, Bonaventura; Domingo, Pere; Galindo, María José; Gatell, José María; González-García, Juan; Iribarren, José Antonio; Locutura, Jaime; López, Juan Carlos; Mallolas, Josep; Martínez, Esteban; Miralles, Celia; Miró, José M; Moreno, Santiago; Palacios, Rosario; Pérez Elías, María Jesús; Pineda, Juan Antonio; Podzamczer, Daniel; Portilla, Joaquín; Pulido, Federico; Ribera, Esteban; Riera, Melchor; Rubio, Rafael; Santos, Jesús; Sanz, Jesús; Tuset, Montserrat; Vidal, Francesc; Rivero, Antonio

    2014-01-01

    In this update, antiretroviral therapy (ART) is recommended for all patients infected by type 1 human immunodeficiency virus (HIV-1). The strength and grade of the recommendation varies with clinical circumstances, number of CD4 cells, comorbid conditions and prevention of transmission of HIV. The objective of ART is to achieve an undetectable plasma viral load. Initial ART should always comprise a combination of 3 drugs, including 2 nucleoside reverse transcriptase inhibitors and a third drug from a different family (non-nucleoside reverse transcriptase inhibitor, protease inhibitor, or integrase inhibitor). This update presents the causes and criteria for switching ART in patients with undetectable plasma viral load and in cases of virological failure. An update is also provided for the specific criteria for ART in special situations (acute infection, HIV-2 infection, and pregnancy) and with comorbid conditions (tuberculosis or other opportunistic infections, kidney disease, liver disease, and cancer). Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  10. Consensus clustering in complex networks

    CERN Document Server

    Lancichinetti, Andrea; 10.1038/srep00336

    2012-01-01

    The community structure of complex networks reveals both their organization and hidden relationships among their constituents. Most community detection methods currently available are not deterministic, and their results typically depend on the specific random seeds, initial conditions and tie-break rules adopted for their execution. Consensus clustering is used in data analysis to generate stable results out of a set of partitions delivered by stochastic methods. Here we show that consensus clustering can be combined with any existing method in a self-consistent way, enhancing considerably both the stability and the accuracy of the resulting partitions. This framework is also particularly suitable to monitor the evolution of community structure in temporal networks. An application of consensus clustering to a large citation network of physics papers demonstrates its capability to keep track of the birth, death and diversification of topics.

  11. Decreased Degradation of Internalized Follicle-Stimulating Hormone Caused by Mutation of Aspartic Acid 6.30550 in a Protein Kinase-CK2 Consensus Sequence in the Third Intracellular Loop of Human Follicle-Stimulating Hormone Receptor1

    Science.gov (United States)

    Kluetzman, Kerri S.; Thomas, Richard M.; Nechamen, Cheryl A.; Dias, James A.

    2011-01-01

    A naturally occurring mutation in follicle-stimulating hormone receptor (FSHR) gene has been reported: an amino acid change to glycine occurs at a conserved aspartic acid 550 (D550, D567, D6.30567). This residue is contained in a protein kinase-CK2 consensus site present in human FSHR (hFSHR) intracellular loop 3 (iL3). Because CK2 has been reported to play a role in trafficking of some receptors, the potential roles for CK2 and D550 in FSHR function were evaluated by generating a D550A mutation in the hFSHR. The hFSHR-D550A binds hormone similarly to WT-hFSHR when expressed in HEK293T cells. Western blot analyses showed lower levels of mature hFSHR-D550A. Maximal cAMP production of both hFSHR-D550A as well as the naturally occurring mutation hFSHR-D550G was diminished, but constitutive activity was not observed. Unexpectedly, when 125I-hFSH bound to hFSHR-D550A or hFSHR-D550G, intracellular accumulation of radiolabeled FSH was observed. Both sucrose and dominant-negative dynamin blocked internalization of radiolabeled FSH and its commensurate intracellular accumulation. Accumulation of radiolabeled FSH in cells transfected with hFSHR-D550A is due to a defect in degradation of hFSH as measured in pulse chase studies, and confocal microscopy imaging revealed that FSH accumulated in large intracellular structures. CK2 kinase activity is not required for proper degradation of internalized FSH because inhibition of CK2 kinase activity in cells expressing hFSHR did not uncouple degradation of internalized radiolabeled FSH. Additionally, the CK2 consensus site in FSHR iL3 is not required for binding because CK2alpha coimmunoprecipitated with hFSHR-D550A. Thus, mutation of D550 uncouples the link between internalization and degradation of hFSH. PMID:21270425

  12. The Copenhagen Consensus Conference 2016

    DEFF Research Database (Denmark)

    Bangsbo, Jens; Krustrup, Peter; Duda, Joan

    2016-01-01

    on the effects of physical activity on children’s and youth’s fitness, health, cognitive functioning, engagement, motivation, psychological well-being and social inclusion, as well as presenting educational and physical activity implementation strategies. The consensus was obtained through an iterative process......From 4 to 7 April 2016, 24 researchers from 8 countries and from a variety of academic disciplines gathered in Snekkersten, Denmark, to reach evidence-based consensus about physical activity in children and youth, that is, individuals between 6 and 18 years. Physical activity is an overarching term...

  13. C3 glomerulopathy: consensus report

    Science.gov (United States)

    Pickering, Matthew C; D'Agati, Vivette D; Nester, Carla M; Smith, Richard J; Haas, Mark; Appel, Gerald B; Alpers, Charles E; Bajema, Ingeborg M; Bedrosian, Camille; Braun, Michael; Doyle, Mittie; Fakhouri, Fadi; Fervenza, Fernando C; Fogo, Agnes B; Frémeaux-Bacchi, Véronique; Gale, Daniel P; Goicoechea de Jorge, Elena; Griffin, Gene; Harris, Claire L; Holers, V Michael; Johnson, Sally; Lavin, Peter J; Medjeral-Thomas, Nicholas; Paul Morgan, B; Nast, Cynthia C; Noel, Laure-Hélène; Peters, D Keith; Rodríguez de Córdoba, Santiago; Servais, Aude; Sethi, Sanjeev; Song, Wen-Chao; Tamburini, Paul; Thurman, Joshua M; Zavros, Michael; Cook, H Terence

    2013-01-01

    C3 glomerulopathy is a recently introduced pathological entity whose original definition was glomerular pathology characterized by C3 accumulation with absent or scanty immunoglobulin deposition. In August 2012, an invited group of experts (comprising the authors of this document) in renal pathology, nephrology, complement biology, and complement therapeutics met to discuss C3 glomerulopathy in the first C3 Glomerulopathy Meeting. The objectives were to reach a consensus on: the definition of C3 glomerulopathy, appropriate complement investigations that should be performed in these patients, and how complement therapeutics should be explored in the condition. This meeting report represents the current consensus view of the group. PMID:24172683

  14. Febrile Seizures: Controversy and Consensus

    Science.gov (United States)

    Doiron, Omer A.

    1983-01-01

    Although febrile convulsions are a relatively common complaint, the approach to their management is far from uniform and highly controversial. This article reviews the consensus statement on febrile convulsions arrived at by the Consensus Development Conference held in 1980 by the National Institutes of Health, together with other literature of interest to family physicians. Guidelines are given for the assessment, diagnosis and emergency treatment of febrile seizures. Epilepsy and atypical febrile convulsions are distinguished from simple febrile seizures. Prognosis, prevention, and the importance of counselling parents are discussed, as well as the controversial issue of prophylactic treatment. PMID:21286583

  15. Clinical recommendations for the use of recombinant human erythropoietin in patients with hepatitis C virus being treated with ribavirin.

    Science.gov (United States)

    Sherman, Morris; Cohen, Lawrence; Cooper, Mary Anne; Elkashab, Magdy; Feinman, Victor; Fletcher, David; Girgrah, Nigel; Heathcote, Jenny; Levstik, Mark; McNaull, William B; Wong, David; Wong, Florence; Yim, Colina

    2006-07-01

    Today, combination antiviral therapy with pegylated interferon-alpha and ribavirin (RBV) allows many patients infected with hepatitis C virus (HCV) to achieve a sustained virological response, which is equivalent to cure. Data also support the clinical benefit of combination antiviral therapy in patients coinfected with HCV and HIV, and in patients who have received a liver transplant. Antiviral therapy with pegylated interferon-alpha and RBV is, however, associated with a high incidence and significant magnitude of anemia. This anemia may have several mechanisms, including bone marrow suppression and hemolysis. In addition, patients coinfected with HIV may have both pre-existing and RBV-associated anemia. Management of anemia in patients with HCV through RBV dose reduction or treatment discontinuation may compromise the effectiveness of treatment, because studies have demonstrated that treatment adherence or maintenance of antiviral therapy dose is an important predictor of sustained virological response. Anemia associated with combination antiviral therapy in patients with HCV is frequently associated with an inadequate or blunted endogenous erythropoietin response. Accumulating evidence now supports the use of recombinant human erythropoietin (rHuEpo) to manage anemia in these patients, with the objective of maintaining the RBV dose, but clinical standards are lacking. The present article reviews the data relevant to the use of rHuEpo in this patient population and proposes a set of clinical practice standards to assist clinicians in selecting patients for rHuEpo and in implementing rHuEpo therapy effectively.

  16. ProMMP-1 PRODUCTION BY CULTIVATED CELLS OF VASCULAR ENDОTHELIUM IN VITRO AND IN A HUMAN BODY

    Directory of Open Access Journals (Sweden)

    N. N. Scliankina

    2011-01-01

    Full Text Available Abstract. Matrix metalloproteinases (MMP are structurally related endopeptidase composed of active sites which include ions Zn2+ and Ca2+. Cultured cells of human blood vessels produce MMP-1, proteolytic effect is aimed at splitting the collagen I and III types, and subsequent vascular remodeling. MMP-1 is synthesized as an inactive zymogen proMMP-1. It was shown that interferon alpha, beta and gamma inhibited production by culture of HUVEC proenzyme MMP-1, which seems to characterize their anti-angiogenic action. The effect of immunomodulators is more difficult to explain: perhaps inhibiting effect of imunofan and, as well as activating effect of cycloferon due to their internal structural peculiarities. The action of interferon alpha, beta and gamma, used as HUVEC before infection with HSV-1, and after it led to decrease in production proMMP-1. Apparently, the antiangiogenic effect of IFN is saved in the case of infection of cultures of vascular endothelium with HSV-1. Scatter in the content of proMMP-1 in the serum of blood donors was 1.625–11.8 ng/ml and in patients with chronic microbial-viral infections was 1.22–21.16 ng/ml. Higher rates of proMMP-1 were in older patients group. To estimate the system of MMP in vitro, and in the body a comprehensive study must be conducted, including proMMP-1, the active form of proenzyme and specific inhibitor of MMP-1.

  17. The Copenhagen Consensus Conference 2016

    DEFF Research Database (Denmark)

    Bangsbo, Jens; Krustrup, Peter; Duda, Joan;

    2016-01-01

    that consists of many structured and unstructured forms within school and out-of-school-time contexts, including organised sport, physical education, outdoor recreation, motor skill development programmes, recess, and active transportation such as biking and walking. This consensus statement presents the accord...

  18. Balancing multiple roles through consensus

    DEFF Research Database (Denmark)

    Oshima, Sae

    2014-01-01

    This study demonstrates how participants in haircutting sessions merge different roles during one of the most sensitive moments of an encounter: requesting and/or making revisions to a new cut. During the process of arriving at a consensus of whether or not changes need to be made to the new cut...

  19. Quantized average consensus with delay

    NARCIS (Netherlands)

    Jafarian, Matin; De Persis, Claudio

    2012-01-01

    Average consensus problem is a special case of cooperative control in which the agents of the network asymptotically converge to the average state (i.e., position) of the network by transferring information via a communication topology. One of the issues of the large scale networks is the cost of co

  20. Population conference: consensus and conflict.

    Science.gov (United States)

    Willson, P D

    1984-01-01

    The United Nations-sponsored International Conference on Population held in Mexico City was both a rejection and an affirmation of a new policy of the Reagan administration. The policy denies international family planning funds to nongovernmental organizations that perform or actively promote abortion as a family planning method in other nations. A compromise statement was accepted urging governments to take appropriate measures to discourage abortion as a family planning method and when possible to provide for the humane treatment and counseling of women ho resorted to abortion. The statement on abortion was 1 of 88 reccomendations approved by the conference. The commitment expressed in the 10-year-old World Population Plan of Action to the rights and responsiblity to all people as reaffirmed. The conference also endorsed family life education and sex education as well as suitable family planning, information and services for adolescents, with due consideration given to the role, rights and obligations of parents. Increased support for international population and family planning programs was urged and World Bank President, Clausen, urged a 4-fold increase in international funding by the year 2000. Most of the conference's recommendations re devoted to the broad range of population policy issues, including morbidity and mortality, international and internal migration, the relationship between population and economic development and the status of women. The purpose of the recommendations is to increase the momentum of international support. The Mexico City conference was characterized by a remarkable degree of consensus about population policies with respect to integration with economic development, the need to respect individual rights and the recognition that all nations have sovereign rights to develop and implement their own population policies. Conflict and controversy arose in the areas of the arms race and the Middle East. The US position on abortion funding

  1. 灌饲干扰素-α2b重组双岐杆菌对柯萨奇B3病毒诱导BLAB/c小鼠心肌炎的影响%Bifidobacterium as an oral delivery carrier of interferon-alpha2b for the treatment of coxsackievirus B3-induced myocarditis in the BALB/c mice

    Institute of Scientific and Technical Information of China (English)

    赖春霞; 刘宝兰; 余世强; 邓丽丽; 邓启文

    2014-01-01

    目的 构建干扰素(IFN)-α2b基因重组双歧杆菌(pBAD-SPIFN转化双歧杆菌),观察重组菌是否对小鼠柯萨奇B3病毒(CVB3)诱导的小鼠心肌炎具有治疗作用.方法 体外扩增前期研究中构建的IFN-α2b重组双岐杆菌.选取BLAB/c小鼠40只,腹腔内注射CVB3感染剂量,2周后形成病毒性心肌炎,将感染的小鼠随机分成IFN、BIFN、B、生理盐水组予以干预:IFN组给予肌肉注射干扰素,BIFN组小鼠予灌饲干扰素-α2b重组双岐杆菌;B组给予灌饲pBAD-gIIIA转化双歧杆菌;生理盐水组给予肌肉注射生理盐水.所有小鼠均在治疗14d后取心脏标本观察心肌组织病理变化,检测心肌病毒滴度,实时荧光定量聚合酶链反应(FQ-PCR)分析Th1细胞因子和IFN-α诱导黏液病毒抗性蛋白1(Mx1)基因转录水平.结果 CVB3诱导的心肌炎小鼠干预治疗2周后,BIFN组小鼠心肌炎症程度(0.16±0.10)较B组及生理盐水组明显减轻(P<0.01);BIFN组心肌的病毒滴度水平(3.03 ±0.02)较B组及生理盐水组显著下降(P <0.01);BIFN组Th1细胞因子和IFN-α诱导基因Mx1基因转录水平(分别为1.48±0.08、3.56±0.02、2.13 ±0.01)较B组及生理盐水组显著升高(P<0.01).结论 灌饲给药IFN-α2b重组双岐杆菌对CVB3病毒诱导的小鼠心肌炎具有较好疗效.%Objective To investigate a novel oral delivery system for interferon-alpha2b using genetically engineered Bifidobacterium longum as the carrier and further evaluate the efficacy of interferon (IFN)-α2b-expressed B.longum on the coxsackie B3 virus (CVB3)-induced myocarditis in mice.Methods IFN-α2b recombinant B.longum was amplified in vivo and subsequently,BLAB/c mice were inoculated intraperitoneally with infectious dose of CVB3 for two weeks to produce the models of CVB3-induced myocarditis.Then,the murine models were divided into four groups.The "BIFN group" was orally administered with IFN-α2b-transformed B.longum for two weeks respectively after the

  2. 75 FR 2551 - NIH Consensus Development Conference: Lactose Intolerance and Health; Notice

    Science.gov (United States)

    2010-01-15

    ... HUMAN SERVICES National Institutes of Health NIH Consensus Development Conference: Lactose Intolerance... Consensus Development Conference: Lactose Intolerance and Health'' to be held February 22-24, 2010, in the..., abdominal pain, and diarrhea. These symptoms of lactose intolerance are caused by intestinal...

  3. 75 FR 3745 - NIH Consensus Development Conference on Vaginal Birth After Cesarean: New Insights; Notice

    Science.gov (United States)

    2010-01-22

    ... HUMAN SERVICES National Institutes of Health NIH Consensus Development Conference on Vaginal Birth After... ``NIH Consensus Development Conference on Vaginal Birth After Cesarean: New Insights'' to be held March... baby through an incision made in the abdominal wall and uterus), many clinicians believed that all...

  4. Energy strategy: Roadmap to consensus

    Energy Technology Data Exchange (ETDEWEB)

    1990-11-01

    The United States lacks a comprehensive approach to policy-making in the energy realm. Today, as in the past, individual constituency groups tend to focus on their particular aspect of the energy challenge. Many employ a decide-announce-defend'' approach to policy-making, setting out to secure a unilateral advantage for themselves. By so doing, they inevitably pit interest against interest. The result is a polarization of constituencies, and shortsighted policies designed to address the issue of the moment. The American Energy Assurance Council (AEAC) is a non-profit organization founded in 1987 for the sole purpose of facilitating progress toward a fair efficient wise, stable, and consensus-based national energy strategy. AEAC does not have a substantive policy agencies. Rather, we are committed to supporting a process whereby the many stakeholders and policy makers concerned with energy-related issues can come together in productive discourse, thereby overcoming ignorance of each other's positions. The Council seeks to act as a facilitative body, providing a safe'' context for inventive and creative thinking. We attempt to build a store of common knowledge, and to build on that store according to mutually agreed-upon groundrules, and employing sophisticated approaches to facilitation and mediation. This report, the National Energy Consensus Experiment (NECE), was an ambitious experiment in consensus-building. We learned a great deal from it, both in terms of substance and process, and we are convinced that it holds important lessons for others who may seek to build consensus in the public policy realm.

  5. Energy strategy: Roadmap to consensus

    Energy Technology Data Exchange (ETDEWEB)

    1990-11-01

    The United States lacks a comprehensive approach to policy-making in the energy realm. Today, as in the past, individual constituency groups tend to focus on their particular aspect of the energy challenge. Many employ a ``decide-announce-defend`` approach to policy-making, setting out to secure a unilateral advantage for themselves. By so doing, they inevitably pit interest against interest. The result is a polarization of constituencies, and shortsighted policies designed to address the issue of the moment. The American Energy Assurance Council (AEAC) is a non-profit organization founded in 1987 for the sole purpose of facilitating progress toward a fair efficient wise, stable, and consensus-based national energy strategy. AEAC does not have a substantive policy agencies. Rather, we are committed to supporting a process whereby the many stakeholders and policy makers concerned with energy-related issues can come together in productive discourse, thereby overcoming ignorance of each other`s positions. The Council seeks to act as a facilitative body, providing a ``safe`` context for inventive and creative thinking. We attempt to build a store of common knowledge, and to build on that store according to mutually agreed-upon groundrules, and employing sophisticated approaches to facilitation and mediation. This report, the National Energy Consensus Experiment (NECE), was an ambitious experiment in consensus-building. We learned a great deal from it, both in terms of substance and process, and we are convinced that it holds important lessons for others who may seek to build consensus in the public policy realm.

  6. [Investigation of human papillomavirus prevalence in women in Eskişehir, Turkey by Pap smear, hybrid capture 2 test and consensus real-time polymerase chain reaction and typing with pyrosequencing method].

    Science.gov (United States)

    Aslan, Ferhat Gürkan; Us, Tercan; Kaşifoğlu, Nilgün; Özalp, Sabit Sinan; Akgün, Yurdanur; Öge, Tufan

    2016-01-01

    Human papillomavirus (HPV) infections have a broad range of clinical spectrum from subclinical or asymptomatic infection to anogenital carcinoma. The detection of HPV-DNA and determination of the risk groups in cervical cancer (CC) screening is very important because CC is considered to be a preventable illness which is the third most common cancer type of women in the world. The aims of this study were to investigate the presence of HPV-DNA in women by two different molecular methods and to compare their results together with the results of cytology, in Eskişehir, Central Anatolia, Turkey. A total of 1081 women aged between 30-65 years, who applied to Eskişehir Early Diagnosis, Screening and Training of Cancer Center (KETEM) for screening were included in the study. Three separate cervical samples were collected simultaneously from the participants for cytologic examination and molecular studies. In the first step of the study, all cervical samples were investigated for the presence of HPV-DNA by Hybrid Capture 2 (HC2; Qiagen, Germany) method. In the second part of the study, consensus real-time polymerase chain reaction (RT-PCR) (Takara Bio Inc., Japan) was performed in 152 samples which included HC2 positive and randomly selected negative samples, and then the HPV genotypes were detected by using a commercial kit based on pyrosequencing method (Diatech Pharmacogenetics S.R.L, Italy). In the first part of the study, HC2 test was found positive in 3% (32/1081) of the women, while in 4.4% (47/1081) Pap smear was positive alone or with HC2 test. Five (0.5%) samples yielded positive results with both of the methods, and four of them were positive for high risk HPV types. Cytology results were negative in 19 out of 23 (23/1081, 2.1%) samples that were reported as high risk HPV by HC2 test. On the other hand, 42 (42/1081, 3.9%) samples that were positive by cytology yielded negative results by HC2 test. In the second part of the study, 32 (21.1%) of 152 selected

  7. Revised genomic consensus for the hypermethylated CpG island region of the human L1 transposon and integration sites of full length L1 elements from recombinant clones made using methylation-tolerant host strains

    DEFF Research Database (Denmark)

    Crowther, P J; Doherty, J P; Linsenmeyer, M E

    1991-01-01

    preferentially from L1 members which have accumulated mutations that have removed sites of methylation. We present a revised consensus from the 5' presumptive control region of these elements. This revised consensus contains a consensus RNA polymerase III promoter which would permit the synthesis of transcripts...... from the 5' end of full length L1 elements. Such potential transcripts are likely to exhibit a high degree of secondary structure. In addition, we have determined the flanking sequences for 6 full length L1 elements. The majority of full length L1 clones show no convincing evidence for target site...... duplication in the insertion site as commonly observed with truncated L1 elements. These data would be consistent with two mechanisms of integration of transposing L1 elements with different mechanisms predominating for full length and truncated elements. Udgivelsesdato: 1991-May-11...

  8. Influence of indomethacin on the effect of interferon alpha-2b combined with low dose cytarabine on chronic myeloid leukemia%吲哚美辛对干扰素α-2b联合小剂量阿糖胞苷治疗慢性粒细胞白血病的影响

    Institute of Scientific and Technical Information of China (English)

    阮力; 向群; 谢爱辉; 周红波; 舒更新

    2012-01-01

    Objective To investigate the influence of indomethacin to the unite treatment effect on chronic phase myeloid leukemia (CML-CP) with interferon alpha-2b (IFNα-2b) and low dose cytarabine (LD-Ara-C).Methods 22 CML-CP patients were randomly divided into two groups.Control groups (10 cases) injected with IFNα-2b (3 million units),injection frequency was q.o.d,the duration of treatment was about 3-18 months,cytarabine (Ara-C) by slowly intravenous driped (30 mg/d).In this treatment schedule,every course of treatment sustained 10 days,and with a 2 weeks interval.During this process,patients in treatment group were treated with hydroxyl urea only when their WBC in peripheral blood exceed 20×109/L,otherwise,discontinue it.Treatment group (12 cases),on the first day of treatment with IFNα-2b and Ara-C,added indomethacin (25 mg) through oral administration,the frequency was t.i.d.During treatment in the two group,the end point of observation was completely hematology ease,at the same time,these indicators in the two groups needed to be compared,the time when WBC begin to fall,the time when WBC fall to normal range,the time when immature cells returned to normal,the time which complete hematological remission and the highest temperature of patients after IFNα-2b was subcutaneous injected.Results The time when WBC begin to fall in treatment group was (4.2±2.7) d,and the time was (5.0±2.5) d in control group (t =0.714,P > 0.05).In treatment group,the time when WBC fall to normal range was(10.0±4.5) d,and the time was (12.0±4.5) d in control group (t =1.036,P > 0.05).The time when immature cells returned to normal in treatment group was (14.2±4.8) d,and the time was (19.0±3.6) d in control group (t =2.609,P < 0.02).The time which complete hematological remission was achieved in control group was (45.8±5.6) d,but it was (53.9±10.5) d in control group (t =2.314,· P < 0.05).Meanwhile,the fever degree after IFNα-2b was subcutaneous injected obviously achieved

  9. [Human papillomaviruses].

    Science.gov (United States)

    Gross, G

    2003-10-01

    Human papillomaviruses (HPV) infect exclusively the basal cells of the skin and of mucosal epithelia adjacent to the skin such as the mouth, the upper respiratory tract, the lower genital tract and the anal canal. HPV does not lead to a viremia. Basically there are three different types of HPV infection: Clinically visible lesions, subclinical HPV infections and latent HPV infections. Distinct HPV types induce morphologically and prognostically different clinical pictures. The most common HPV associated benign tumor of the skin is the common wart. Infections of the urogenitoanal tract with specific HPV-types are recognised as the most frequent sexually transmitted viral infections. So-called "high-risk" HPV-types (HPV16, 18 and others) are regarded by the world health organisation as important risk-factors for the development of genital cancer (mainly cervical cancer), anal cancer and upper respiratory tract cancer in both genders. Antiviral substances with a specific anti-HPV effect are so far unknown. Conventional therapies of benign skin warts and of mucosal warts are mainly nonspecific. They comprise tissue-destroying therapies such as electrocautery, cryotherapy and laser. In addition cytotoxic substances such as podophyllotoxin and systemic therapy with retinoids are in use. Systemically and topically administered immunotherapies represent a new approach for treatment. Both interferons and particularly the recently developed imiquimod, an interferon-alpha and cytokine-inductor lead to better results and are better tolerated then conventional therapies. HPV-specific vaccines have been developed in the last 5 years and will be used in future for prevention and treatment of benign and malignant HPV-associated tumors of the genitoanal tract in both sexes.

  10. Consensus Statement National Consensus Workshop on Management of SAM Children through Medical Nutrition Therapy.

    Science.gov (United States)

    Sachdev, H P S; Kapil, Umesh; Vir, Sheila

    2010-08-01

    Severe acute malnutrition (SAM) is an important preventable and treatable cause of morbidity and mortality in children below five years of age in India. The concerned stakeholders are not in agreement about the role of product based medical nutrition therapy in the management of this condition. In November 2009, a National Consensus Workshop was organized by the Department of Human Nutrition, All India Institute of Medical Sciences, New Delhi in collaboration with the Department of Pediatrics and Clinical Epidemiology, Sitaram Bhartia Institute of Science and Research, New Delhi, and the Sub-specialty Chapter on Nutrition, Indian Academy of Pediatrics. Presentations by eminent national and international scientists, the ensuing discussions, and opinions expressed by the participants provided the basic framework for drafting the consensus statement. The draft of the consensus statement was circulated to all the participants; it underwent two revisions after consideration of their comments. (i) Critically appraise the current global evidence on the utility of Medical Nutrition Therapy (MNT) for the management of SAM in under five children; (ii) Formulate a consensus amongst stakeholders regarding the need to introduce product based MNT for the management of SAM in under five children in India; (iii) Identify research priorities for MNT for the management of SAM in under five children in India; and (iv)Ascertain potential challenges for introducing product based MNT in India, if consensus opinion identifies such a need. Guidelines related to the role of MNT in management of children suffering from SAM are presented. Global and regional data document the effectiveness of MNT using ready-to-use therapeutic foods (RUTF) and locally formulated products. Adequate caution should be exercised to ensure that MNT for SAM does not interfere with measures for the holistic prevention of childhood undernutrition. Indian manufacture of RUTF is feasible, and can be scaled up. Product

  11. Research methods for formal consensus development.

    Science.gov (United States)

    James, Daphne; Warren-Forward, Helen

    2015-01-01

    This paper reviews three research methods for developing consensus. Consensus statements and guidelines are increasingly used to clarify and standardise practice, and inform health policy, when relevant and rigorous evidence is lacking. Clinicians need to evaluate the quality of practice guidelines to determine whether to incorporate them into clinical practice or reject them. Formal methods of developing consensus provide a scientific method that uses expert panel members to evaluate current evidence and expert opinions to produce consensus statements for clinical problems. Online search for relevant literature was conducted in Medline and CINAHL. A literature review of consensus, consensus development and research methods papers published in English in peer-reviewed journals. The three methods of developing consensus discussed are the Delphi technique, nominal group technique and the consensus development conference. The techniques and their respective advantages are described, and examples from the literature are provided. The three methods are compared and a flowchart to assist researchers selecting an appropriate method is included. Online resources with information on the development and evaluation of clinical guidelines are reviewed. This paper will help researchers to select an appropriate research method for developing consensus statements and guidelines. When developing consensus guidelines for clinical practice, researchers should use a formal research method to ensure rigour and credibility.

  12. Genome-wide conserved consensus transcription factor binding motifs are hyper-methylated

    Directory of Open Access Journals (Sweden)

    Down Thomas A

    2010-09-01

    Full Text Available Abstract Background DNA methylation can regulate gene expression by modulating the interaction between DNA and proteins or protein complexes. Conserved consensus motifs exist across the human genome ("predicted transcription factor binding sites": "predicted TFBS" but the large majority of these are proven by chromatin immunoprecipitation and high throughput sequencing (ChIP-seq not to be biological transcription factor binding sites ("empirical TFBS". We hypothesize that DNA methylation at conserved consensus motifs prevents promiscuous or disorderly transcription factor binding. Results Using genome-wide methylation maps of the human heart and sperm, we found that all conserved consensus motifs as well as the subset of those that reside outside CpG islands have an aggregate profile of hyper-methylation. In contrast, empirical TFBS with conserved consensus motifs have a profile of hypo-methylation. 40% of empirical TFBS with conserved consensus motifs resided in CpG islands whereas only 7% of all conserved consensus motifs were in CpG islands. Finally we further identified a minority subset of TF whose profiles are either hypo-methylated or neutral at their respective conserved consensus motifs implicating that these TF may be responsible for establishing or maintaining an un-methylated DNA state, or whose binding is not regulated by DNA methylation. Conclusions Our analysis supports the hypothesis that at least for a subset of TF, empirical binding to conserved consensus motifs genome-wide may be controlled by DNA methylation.

  13. The Mexican consensus on probiotics in gastroenterology.

    Science.gov (United States)

    Valdovinos, M A; Montijo, E; Abreu, A T; Heller, S; González-Garay, A; Bacarreza, D; Bielsa-Fernández, M; Bojórquez-Ramos, M C; Bosques-Padilla, F; Burguete-García, A I; Carmona-Sánchez, R; Consuelo-Sánchez, A; Coss-Adame, E; Chávez-Barrera, J A; de Ariño, M; Flores-Calderón, J; Gómez-Escudero, O; González-Huezo, M S; Icaza-Chávez, M E; Larrosa-Haro, A; Morales-Arámbula, M; Murata, C; Ramírez-Mayans, J A; Remes-Troche, J M; Rizo-Robles, T; Peláez-Luna, M; Toro-Monjaraz, E M; Torre, A; Urquidi-Rivera, M E; Vázquez, R; Yamamoto-Furusho, J K; Guarner, F

    Probiotics are frequently prescribed in clinical practice. Their efficacy in treating gastrointestinal disorders is supported by a significant number of clinical trials. However, the correct prescription of these agents is hampered due to a lack of knowledge of the scientific evidence and to the different presentations and microbial compositions of the probiotics that are currently available. To provide the clinician with a consensus review of probiotics and recommendations for their use in gastroenterology. Controlled clinical trials, meta-analyses, and systematic reviews published up to 2015 were selected, using the MESH terms: probiotics, gastrointestinal diseases, humans, adults, AND children. The Delphi method was employed. Eighteen gastroenterologists treating adult patients and 14 pediatric gastroenterologists formulated statements that were voted on until agreement>70% was reached. The level of evidence based on the GRADE system was evaluated for each statement. Eleven statements on the general concepts of probiotics and 27 statements on the use of probiotics in gastrointestinal diseases in both adults and children were formulated. The consensus group recommends the use of probiotics under the following clinical conditions: the prevention of diarrhea associated with antibiotics, the treatment of acute infectious diarrhea, the prevention of Clostridium difficile infection and necrotizing enterocolitis, the reduction of adverse events from Helicobacter pylori eradication therapy, relief from irritable bowel syndrome symptoms, the treatment of functional constipation in the adult, and the induction and maintenance of remission in patients with ulcerative colitis and pouchitis, and the treatment of covert and overt hepatic encephalopathy. Copyright © 2016 Asociación Mexicana de Gastroenterología. Publicado por Masson Doyma México S.A. All rights reserved.

  14. Consensus of Hybrid Multi-Agent Systems.

    Science.gov (United States)

    Zheng, Yuanshi; Ma, Jingying; Wang, Long

    2017-01-27

    In this brief, we consider the consensus problem of hybrid multiagent systems. First, the hybrid multiagent system is proposed, which is composed of continuous-time and discrete-time dynamic agents. Then, three kinds of consensus protocols are presented for the hybrid multiagent system. The analysis tool developed in this brief is based on the matrix theory and graph theory. With different restrictions of the sampling period, some necessary and sufficient conditions are established for solving the consensus of the hybrid multiagent system. The consensus states are also obtained under different protocols. Finally, simulation examples are provided to demonstrate the effectiveness of our theoretical results.

  15. Theories about consensus-based conservation.

    Science.gov (United States)

    Leach, William D

    2006-04-01

    "Conservation and the Myth of Consensus" (Peterson et al. 2005) levels several serious indictments against consensus-based approaches to environmental decision making. Namely, the authors argue that consensus processes (1) reinforce apathy and ignorance of conservation issues; (2) legitimize damage to the environment; (3) quash public debate about conservation; (4) solidify the existing balance of power in favor of prodevelopment forces; and (5) block progress toward an ecologically sustainable future. Careful scrutiny of consensus-based approaches is important, especially considering their surging use in conservation policy. In the spirit of advancing the debate further, I review some of the limitations of the essay and its modes of inquiry.

  16. Subclinical hypothyroidism: Controversies to consensus

    Directory of Open Access Journals (Sweden)

    Syed Abbas Raza

    2013-01-01

    Full Text Available Diagnoses of subclinicaal hypothyroidism (SCH is biochemically made, when serum thyroid stimulating hormone (TSH levels is elevated while free thyroid hormone levels are within normal reference range. SCH is diagnosed after excluding all other causes of elevated TSH levels. Symptoms of SCH may vary from being asymptomatic to having mild nonspecific symptoms. The risk of progression to overt hypothyroidism is related to number of factors including initial serum TSH concentration, presence of auto antibodies, family history and presence goiter. Various screening recommendations for thyroid function assessment are in practice. There are still controversies surrounding SCH and associated risk of various cardiovascular diseases (CVDs, pregnancy outcomes, neuropsychiatric issues, metabolic syndrome, and dyslipidemia. Consensus will require more large randomized clinical studies involving various age groups and medical condition, especially in developing countries. All these efforts will definitely improve our understanding of disease and ultimately patient outcomes.

  17. Learning consensus in adversarial environments

    Science.gov (United States)

    Vamvoudakis, Kyriakos G.; García Carrillo, Luis R.; Hespanha, João. P.

    2013-05-01

    This work presents a game theory-based consensus problem for leaderless multi-agent systems in the presence of adversarial inputs that are introducing disturbance to the dynamics. Given the presence of enemy components and the possibility of malicious cyber attacks compromising the security of networked teams, a position agreement must be reached by the networked mobile team based on environmental changes. The problem is addressed under a distributed decision making framework that is robust to possible cyber attacks, which has an advantage over centralized decision making in the sense that a decision maker is not required to access information from all the other decision makers. The proposed framework derives three tuning laws for every agent; one associated with the cost, one associated with the controller, and one with the adversarial input.

  18. Humanitarian war: a new consensus?

    Science.gov (United States)

    Woodward, S L

    2001-12-01

    The NATO bombing operation Allied Force against Yugoslavia in March-June 1999 represents the final disappearance of the narrowing divide between humanitarianism and politics: a war initiated and justified on humanitarian grounds. Although unlikely to be repeated any time soon, the Kosovo case appears to have cemented an ideological shift on the international right and even necessity of sing military force to protect civilians within sovereign states. Rather than humanitarians acknowledging the political context and consequences of their work, however, the case suggests the embrace of humanitarian principles of universality and neutrality by military organisations. This article discusses some consequences of the new consensus: neglect of the political context (both local and foreign) of such operations, interaction between the operational dynamics of relief operations and the logic of war and the political consequences of using the humanitarian legitimation and mission in such cases.

  19. International Consensus on drug allergy.

    Science.gov (United States)

    Demoly, P; Adkinson, N F; Brockow, K; Castells, M; Chiriac, A M; Greenberger, P A; Khan, D A; Lang, D M; Park, H-S; Pichler, W; Sanchez-Borges, M; Shiohara, T; Thong, B Y- H

    2014-04-01

    When drug reactions resembling allergy occur, they are called drug hypersensitivity reactions (DHRs) before showing the evidence of either drug-specific antibodies or T cells. DHRs may be allergic or nonallergic in nature, with drug allergies being immunologically mediated DHRs. These reactions are typically unpredictable. They can be life-threatening, may require or prolong hospitalization, and may necessitate changes in subsequent therapy. Both underdiagnosis (due to under-reporting) and overdiagnosis (due to an overuse of the term ‘allergy’) are common. A definitive diagnosis of such reactions is required in order to institute adequate treatment options and proper preventive measures. Misclassification based solely on the DHR history without further testing may affect treatment options, result in adverse consequences, and lead to the use of more-expensive or less-effective drugs, in contrast to patients who had undergone a complete drug allergy workup. Several guidelines and/or consensus documents on general or specific drug class-induced DHRs are available to support the medical decision process. The use of standardized systematic approaches for the diagnosis and management of DHRs carries the potential to improve outcomes and should thus be disseminated and implemented. Consequently, the International Collaboration in Asthma, Allergy and Immunology (iCAALL), formed by the European Academy of Allergy and Clinical Immunology (EAACI), the American Academy of Allergy, Asthma and Immunology (AAAAI), the American College of Allergy, Asthma and Immunology (ACAAI), and the World Allergy Organization (WAO), has decided to issue an International CONsensus (ICON) on drug allergy. The purpose of this document is to highlight the key messages that are common to many of the existing guidelines, while critically reviewing and commenting on any differences and deficiencies of evidence, thus providing a comprehensive reference document for the diagnosis and management of

  20. [Consensus for the prevention of cervical cancer in Mexico].

    Science.gov (United States)

    Kably Ambe, Alberto; Ruiz Moreno, José Antonio; Ponce, Eduardo Lazcano; Vargas Hernández, Victor Manuel; Aguado Pérez, Rogelio A; Alonso de Ruiz, Patricia

    2011-12-01

    Cervical cancer remains a serious public health problem in the world; that is why the Mexican Federation of Schools of Obstetrics and Gynecology convened the elaboration of a consensus that is devoted this number of Ginecologia y Obstetricia de Mexico. In recent years has strengthened perceptions (public and private) in the need for preventive strategies in the medium and long terms. The development of effective vaccines against the human papilloma virus and the application of new methods of detection from viral DNA (completely automated for personal application) allow some degree of optimism. It is proposed a consensus with general recommendations in two consecutive stages: (a) primary prevention consisting of education for the prevention of cervical cancer and universal immunization and (b) secondary prevention by early detection of infections or injuries that could favor carcinogenesis. The consensus reviewed characteristics of available vaccines in detail and proposes strategies for implementation in Mexican population. Also, check out main methods of early detection of infection (or predisposing lesions) and suggests public and private strategies for implementation. Consensus places particular emphasis on early immunization for female population and correct use of methods for detection of infections or injuries that might cause cervical cancer.

  1. Rectal cancer radiotherapy: Towards European consensus

    Energy Technology Data Exchange (ETDEWEB)

    Valentini, Vincenzo (Cattedra di Radioterapia, Univ. Cattolica S.Cuore, Rome (Italy)), E-mail: vvalentini@rm.unicatt.it; Glimelius, Bengt (Dept. of Oncology, Radiology and Clinical Immunology, Uppsala Univ., Uppsala (Sweden))

    2010-11-15

    Background and purpose. During the first decade of the 21st century several important European randomized studies in rectal cancer have been published. In order to help shape clinical practice based on best scientific evidence, the International Conference on 'Multidisciplinary Rectal Cancer Treatment: Looking for an European Consensus' (EURECA-CC2) was organized. This article summarizes the consensus about imaging and radiotherapy of rectal cancer and gives an update until May 2010. Methods. Consensus was achieved using the Delphi method. Eight chapters were identified: epidemiology, diagnostics, pathology, surgery, radiotherapy and chemotherapy, treatment toxicity and quality of life, follow-up, and research questions. Each chapter was subdivided by topic, and a series of statements were developed. Each committee member commented and voted, sentence by sentence three times. Sentences which did not reach agreement after voting round no 2 were openly debated during the Conference in Perugia (Italy) December 2008. The Executive Committee scored percentage consensus based on three categories: 'large consensus', 'moderate consensus', 'minimum consensus'. Results. The total number of the voted sentences was 207. Of the 207, 86% achieved large consensus, 13% achieved moderate consensus, and only three (1%) resulted in minimum consensus. No statement was disagreed by more than 50% of members. All chapters were voted on by at least 75% of the members, and the majority was voted on by >85%. Considerable progress has been made in staging and treatment, including radiation treatment of rectal cancer. Conclusions. This Consensus Conference represents an expertise opinion process that may help shape future programs, investigational protocols, and guidelines for staging and treatment of rectal cancer throughout Europe. In spite of substantial progress, many research challenges remain

  2. The Importance of Consensus Information in Acceptance of Climate Change (Invited)

    Science.gov (United States)

    Cook, J.; Lewandowsky, S.

    2013-12-01

    In recent years, public perception of the scientific consensus on human-caused global warming has been disturbingly low, in contrast to the overwhelming level of agreement among climate scientists and in peer-reviewed research. The misperception is partly cultural, with a significant link between perceived consensus and political ideology, and partly informational with all cultural groups exhibiting the misperception to varying degrees. This universal 'consensus gap' is in large part due to a persistent and focused misinformation campaign casting doubt on the consensus, dating back as early as the 1980s. Opponents of climate action have long recognized that perception of scientific consensus is linked to support for climate policy, a link only acknowledged by social scientists in the last few years. How do we counter the all-too-effective misinformation campaign? Psychological research tells us that a crucial aspect of effective refutations is an alternative narrative. In this case, an important counter-narrative to the consensus story is the strategy to perpetuate the impression of ongoing scientific debate. I will also present recent research into the effect that consensus information has on climate beliefs of Australians and Americans. For both groups, the consensus message significantly increased beliefs about human-caused global warming and outperformed interventions that feature evidence or scientists' expertise. For the Australian sample, consensus information partially neutralised the biasing influence of ideology. However, for Americans, a backfire effect (reduced climate belief) was observed for a small minority holding strong conservative views. A psychological model employing Bayesian Networks indicates that a key element to the backfire effect is conspiratorial thinking, consistent with other research finding a link between rejection of climate science and conspiratorial ideation. Thus when presented to a general audience, consensus information has an

  3. Strategic consensus mapping : A new method for testing and visualizing strategic consensus within and between teams

    NARCIS (Netherlands)

    Tarakci, M.; Ates, N.Y.; Porck, J.P.; van Knippenberg, D.; Groenen, P.J.F.; de Haas, M.

    2014-01-01

    Research on strategic consensus focuses primarily on the extent of agreement among team members regarding organizational strategy. It does not include elements such as the content of the agreement, between-group consensus, or the significance of differences in consensus (e.g., for evaluating the eff

  4. 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

  5. International veterinary epilepsy task force consensus proposal

    DEFF Research Database (Denmark)

    De Risio, Luisa; Bhatti, Sofie; Muñana, Karen

    2015-01-01

    This article outlines the consensus proposal on diagnosis of epilepsy in dogs by the International Veterinary Epilepsy Task Force. The aim of this consensus proposal is to improve consistency in the diagnosis of epilepsy in the clinical and research settings. The diagnostic approach to the patient...

  6. International Veterinary Epilepsy Task Force consensus proposal

    DEFF Research Database (Denmark)

    Bhatti, Sofie F M; De Risio, Luisa; Muñana, Karen;

    2015-01-01

    with the initial drug is unsatisfactory, and 4) when treatment changes should be considered. In this consensus proposal, an overview is given on the aim of AED treatment, when to start long-term treatment in canine epilepsy and which veterinary AEDs are currently in use for dogs. The consensus proposal for drug...

  7. Veto-Consensus Multiple Kernel Learning

    NARCIS (Netherlands)

    Y. Zhou; N. Hu; C.J. Spanos

    2016-01-01

    We propose Veto-Consensus Multiple Kernel Learning (VCMKL), a novel way of combining multiple kernels such that one class of samples is described by the logical intersection (consensus) of base kernelized decision rules, whereas the other classes by the union (veto) of their complements. The propose

  8. Consensus statement on genetic research in dementia

    DEFF Research Database (Denmark)

    Rikkert, M.G. Olde; der, V van; Burns, A.

    2008-01-01

    In this article, the authors describe how the European Dementia Consensus Network developed a consensus on research ethics in dementia, taking into account the questions posed by the era of genetic research and its new research methods. The consensus process started with a Delphi procedure...... to analyze relevant stakeholders' positions by describing their statements on the possibilities and limitations of research into genetic determinants of Alzheimer disease and to describe and analyze the moral desirability of genetic research on Alzheimer disease. The conclusions drawn from the Delphi...... procedure fuelled the development of the consensus statement, which is presented in this paper. The consensus statement aims to stimulate ethically acceptable research in the field of dementia and the protection of vulnerable elderly patients with dementia from application of inadequate research methods...

  9. [Spanish consensus on infantile haemangioma].

    Science.gov (United States)

    Baselga Torres, Eulalia; Bernabéu Wittel, José; van Esso Arbolave, Diego L; Febrer Bosch, María Isabel; Carrasco Sanz, Ángel; de Lucas Laguna, Raúl; Del Pozo Losada, Jesús; Hernández Martín, Ángela; Jiménez Montañés, Lorenzo; López Gutiérrez, Juan Carlos; Martín-Santiago, Ana; Redondo Bellón, Pedro; Ruíz-Canela Cáceres, Juan; Torrelo Fernández, Antonio; Vera Casaño, Ángel; Vicente Villa, María Asunción

    2016-11-01

    Infantile haemangiomas are benign tumours produced by the proliferation of endothelial cells of blood vessels, with a high incidence in children under the age of one year (4-10%). It is estimated that 12% of them require treatment. This treatment must be administered according to clinical practice guidelines, expert experience, patient characteristics and parent preferences. The consensus process was performed by using scientific evidence on the diagnosis and treatment of infantile haemangiomas, culled from a systematic review of the literature, together with specialist expert opinions. The recommendations issued were validated by the specialists, who also provided their level of agreement. This document contains recommendations on the classification, associations, complications, diagnosis, treatment, and follow-up of patients with infantile haemangioma. It also includes action algorithms, and addresses multidisciplinary management and referral criteria between the different specialities involved in the clinical management of this type of patient. The recommendations and the diagnostic and therapeutic algorithms of infantile haemangiomas contained in this document are a useful tool for the proper management of these patients. Copyright © 2015 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  10. Eliminating health disparities through culturally and linguistically centered integrated health care: consensus statements, recommendations, and key strategies from the field.

    Science.gov (United States)

    Sanchez, Katherine; Chapa, Teresa; Ybarra, Rick; Martinez, Octavio N

    2014-05-01

    This report is the outcome of an expert consensus meeting sponsored by the United States Deparment of Health and Human Services Office of Minority Health, which was convened to formulate consensus statements, provide recommendations and identify key strategies from practice for implementing integrated health and behavioral health care intended to improve health status for underserved populations.

  11. Consensus and Synchronization in Complex Networks

    CERN Document Server

    2013-01-01

    Synchronization in complex networks is one of the most captivating cooperative phenomena in nature and has been shown to be of fundamental importance in such varied circumstances as the continued existence of species, the functioning of heart pacemaker cells, epileptic seizures, neuronal firing in the feline visual cortex and cognitive tasks in humans. E.g. coupled visual and acoustic interactions make fireflies flash, crickets chirp, and an audience clap in unison. On the other hand, in distributed systems and networks, it is often necessary for some or all of the nodes to calculate some function of certain parameters, e.g. sink nodes in sensor networks being tasked with calculating the average measurement value of all the sensors or multi-agent systems in which all agents are required to coordinate their speed and direction. When all nodes calculate the same function of the initial values in the system, they are said to reach consensus. Such concepts - sometimes also called state agreement, rendezvous, and ...

  12. International Veterinary Epilepsy Task Force consensus proposal

    DEFF Research Database (Denmark)

    Bhatti, Sofie F M; De Risio, Luisa; Muñana, Karen

    2015-01-01

    with the initial drug is unsatisfactory, and 4) when treatment changes should be considered. In this consensus proposal, an overview is given on the aim of AED treatment, when to start long-term treatment in canine epilepsy and which veterinary AEDs are currently in use for dogs. The consensus proposal for drug...... treatment protocols, 1) is based on current published evidence-based literature, 2) considers the current legal framework of the cascade regulation for the prescription of veterinary drugs in Europe, and 3) reflects the authors' experience. With this paper it is aimed to provide a consensus...

  13. A Study On Distributed Model Predictive Consensus

    CERN Document Server

    Keviczky, Tamas

    2008-01-01

    We investigate convergence properties of a proposed distributed model predictive control (DMPC) scheme, where agents negotiate to compute an optimal consensus point using an incremental subgradient method based on primal decomposition as described in Johansson et al. [2006, 2007]. The objective of the distributed control strategy is to agree upon and achieve an optimal common output value for a group of agents in the presence of constraints on the agent dynamics using local predictive controllers. Stability analysis using a receding horizon implementation of the distributed optimal consensus scheme is performed. Conditions are given under which convergence can be obtained even if the negotiations do not reach full consensus.

  14. Managing Carious Lesions: Consensus Recommendations on Carious Tissue Removal

    National Research Council Canada - National Science Library

    Schwendicke, F; Frencken, J.E; Bjørndal, L; Maltz, M; Manton, D.J; Ricketts, D; Van Landuyt, K; Banerjee, A; Campus, G; Doméjean, S; Fontana, M; Leal, S; Lo, E; Machiulskiene, V; Schulte, A; Splieth, C; Zandona, A.F; Innes, N.P.T

    2016-01-01

    The International Caries Consensus Collaboration undertook a consensus process and here presents clinical recommendations for carious tissue removal and managing cavitated carious lesions, including...

  15. OGC Consensus: How Successful Standards Are Made

    Directory of Open Access Journals (Sweden)

    Carl Reed

    2015-09-01

    Full Text Available This paper describes the history, background, and current status of the Open Geospatial Consortium (OGC standards development consensus process. The roots of the formation of the OGC lie in the early 1990s when a very strong market requirement for exchanging GIS data content was clearly stated. At that time, each GIS vendor had their own formats for publishing and/or exchanging their GIS data. There was no mechanism or organization that provided a forum for the GIS vendors and GIS data users to collaborate and agree on how to share GIS data. That requirement, along with the vision of a few individuals, led to the formation of the OGC. This paper describes the early development of the consensus process in the OGC, how this process has evolved over time, why consensus is so important for defining open standards that are implemented in the marketplace, and the future of the OGC consensus process.

  16. Consensus document on European brain research.

    Science.gov (United States)

    Olesen, Jes; Baker, Mary G; Freund, Tamas; di Luca, Monica; Mendlewicz, Julien; Ragan, Ian; Westphal, Manfred

    2006-08-01

    countries, greater collaboration between industry, academia and patient organisations, and increased investment in the brain sciences. The EBC was formed in 2002 to bring together scientists, clinicians, the pharmaceutical industry, charities and patient organisations from all over Europe to campaign for these goals. It takes a novel, bottom-up approach to research policy, and in developing this consensus document, it aims to promote a greater and more focused effort in this area, to improve public understanding of the brain sciences and above all, to support brain research as a priority under the European Commission's Seventh Framework Programme (FP7, 2007-2013). The research programme outlined here was first conceived by the EBC board. An outline was sent to all member organisations and a number of individual experts for comments. Following that, a table of contents was developed. The 45 research themes were written by groups of experts from across Europe who represent a wide range of disciplines. Each one contains a proposal for future research on a specific brain-related theme which the EBC believes could form the basis of one or more integrated projects or strategic targeted research projects (STREP) funded under FP7. The EBC has deliberately focused on the major diseases and then described the basic research needed to understand and treat or perhaps even cure those diseases. The programme is therefore constructed "from man to molecule" and not the other way round, with equal importance attached to basic and clinical research. The EBC suggests that each of the proposed integrated projects or STREP should be awarded a budget in the order of Euro 10 to 15 million. In addition, brain research should be treated as an important element of many other parts of FP7, such as the European Research Council and research programmes on information technology and the causes of violence. Any research programme that concerns human behaviour should, by definition, take account of brain

  17. Using Behavioral Consensus To Learn About Social Conventions In Early Childhood

    Directory of Open Access Journals (Sweden)

    Wanying Zhao

    2016-10-01

    Full Text Available Adults make inferences about the conventionality of others’ behaviours based on their prevalence across individuals. Here, we look at whether children use behavioural consensus as a cue to conventionality, and whether this informs which cultural models children choose to learn from. We find that 2- to 5-year old children exhibit increasing sensitivity to behavioural consensus with age, suggesting that like adults, young humans use behavioural consensus to identify social conventions. However, unlike previous studies showing children’s tendencies to prefer and to learn from members of a consensus, the present study suggests that there are contexts in which children prefer and learn from unconventional individuals. The implications of these different preferences are discussed.

  18. Democracy-based consensus in medicine.

    Science.gov (United States)

    Greco, Massimiliano; Zangrillo, Alberto; Mucchetti, Marta; Nobile, Leda; Landoni, Paolo; Bellomo, Rinaldo; Landoni, Giovanni

    2015-04-01

    High-quality evidence and derived guidelines, as typically published in major academic journals, are a major process that shapes physician decision-making worldwide. However, for many aspects of medical practice, there is a lack of High-quality evidence or an overload of somewhat contradictory low-quality information, which makes decision-making a difficult, uncertain, and unpredictable process. When the issues in question are important and evidence limited or controversial, the medical community seeks to establish common ground for "best practice" through consensus conferences and consensus statements or guidelines. Such consensus statements are seen as a useful tool to establish expert agreement, define the boundaries of acceptable practice, provide priorities for the research agenda, and obtain opinions from different countries and healthcare systems. This standard approach, however, can be criticized for being elitist, noninclusive, and poorly representative of the community of clinicians who will have to make decisions about the implementation of such recommendations. Accordingly, the authors propose a new model based on a combination of a local core meeting (detailed review and expert input) followed by a worldwide web-based network assessment (democracy-based consensus). The authors already have applied this approach to develop consensus on all nonsurgical interventions that increase or reduce perioperative mortality in critically ill patients and in those with acute kidney injury. The methodology was based on 5 sequential local and web-based steps. Both a panel of experts and a large number of professionals from all over the world were involved, giving birth to a new type of "democracy-based consensus." This new type of "democracy-based consensus" has the potential to increase grass-root clinician involvement, expand the reach to less-developed countries, provide a more global perspective on proposed interventions, and perhaps more importantly, increase

  19. European consensus statement on leptospirosis in dogs and cats.

    Science.gov (United States)

    Schuller, S; Francey, T; Hartmann, K; Hugonnard, M; Kohn, B; Nally, J E; Sykes, J

    2015-03-01

    Leptospirosis is a zoonotic disease with a worldwide distribution affecting most mammalian species. Clinical leptospirosis is common in dogs but appears to be rare in cats. Both dogs and cats, however, can shed leptospires in the urine. This is problematic as it can lead to exposure of humans. The control of leptospirosis, therefore, is important not only from an animal but also from a public health perspective. The aim of this consensus statement is to raise awareness of leptospirosis and to outline the current knowledge on the epidemiology, clinical features, diagnostic tools, prevention and treatment measures relevant to canine and feline leptospirosis in Europe.

  20. Dynamic Average Consensus and Consensusability of General Linear Multiagent Systems with Random Packet Dropout

    Directory of Open Access Journals (Sweden)

    Wen-Min Zhou

    2013-01-01

    Full Text Available This paper is concerned with the consensus problem of general linear discrete-time multiagent systems (MASs with random packet dropout that happens during information exchange between agents. The packet dropout phenomenon is characterized as being a Bernoulli random process. A distributed consensus protocol with weighted graph is proposed to address the packet dropout phenomenon. Through introducing a new disagreement vector, a new framework is established to solve the consensus problem. Based on the control theory, the perturbation argument, and the matrix theory, the necessary and sufficient condition for MASs to reach mean-square consensus is derived in terms of stability of an array of low-dimensional matrices. Moreover, mean-square consensusable conditions with regard to network topology and agent dynamic structure are also provided. Finally, the effectiveness of the theoretical results is demonstrated through an illustrative example.

  1. Cytokines and immune surveillance in humans

    Science.gov (United States)

    Sonnenfeld, Gerald

    1994-01-01

    Evidence from both human and rodent studies has indicated that alterations in immunological parameters occur after space flight. Among the parameters shown, by us and others, to be affected is the production of interferons. Interferons are a family of cytokines that are antiviral and play a major role in regulating immune responses that control resistance to infection. Alterations in interferon and other cytokine production and activity could result in changes in immunity and a possible compromise of host defenses against both opportunistic and external infections. The purpose of the present study is to explore further the effects of space flight on cyotokines and cytokine-directed immunological function. Among the tests carried out are interferon-alpha production, interferon-gamma production, interleukin-1 and -2 production, signal transduction in neutrophils, signal transduction in monocytes, and monocyte phagocytic activity. The experiments will be performed using peripheral blood obtained from human subjects. It is our intent to eventually carry out these experiments using astronauts as subjects to determine the effects of space flight on cytokine production and activity. However, these subjects are not currently available. Until they become available, we will carry out these experiments using subjects maintained in the bed-rest model for microgravity.

  2. Fastest Distributed Consensus on Petal Networks

    CERN Document Server

    Jafarizadeh, Saber

    2010-01-01

    Providing an analytical solution for the problem of finding Fastest Distributed Consensus (FDC) is one of the challenging problems in the field of sensor networks. Here in this work we present analytical solution for the problem of fastest distributed consensus averaging algorithm by means of stratification and semi-definite programming, for two particular types of Petal networks, namely symmetric and Complete Cored Symmetric (CCS) Petal networks. Our method in this paper is based on convexity of fastest distributed consensus averaging problem, and inductive comparing of the characteristic polynomials initiated by slackness conditions in order to find the optimal weights. Also certain types of leaves are introduced along with their optimal weights which are not achievable by the method used in this work if these leaves are considered individually.

  3. [SECOT consensus on medial femorotibial osteoarthritis].

    Science.gov (United States)

    Moreno, A; Silvestre, A; Carpintero, P

    2013-01-01

    A consensus, prepared by SECOT, is presented on the management of medial knee compartment osteoarthritis, in order to establish clinical criteria and recommendations directed at unifying the criteria in its management, dealing with the factors involved in the pathogenesis of medial femorotibial knee osteoarthritis, the usefulness of diagnostic imaging techniques, and the usefulness of arthroscopy. Conservative and surgical treatments are also analysed. The experts consulted showed a consensus (agreed or disagreed) in 65.8% of the items considered, leaving 14items where no consensus was found, which included the aetiopathogenesis of the osteoarthritis, the value of NMR in degenerative disease, the usefulness of COX-2 and the chondroprotective drugs, as well as on the ideal valgus tibial osteotomy technique. © 2013 SECOT. Published by Elsevier Espana. All rights reserved.

  4. Reaching Consensus by Allowing Moments of Indecision

    Science.gov (United States)

    Svenkeson, A.; Swami, A.

    2015-10-01

    Group decision-making processes often turn into a drawn out and costly battle between two opposing subgroups. Using analytical arguments based on a master equation description of the opinion dynamics occurring in a three-state model of cooperatively interacting units, we show how the capability of a social group to reach consensus can be enhanced when there is an intermediate state for indecisive individuals to pass through. The time spent in the intermediate state must be relatively short compared to that of the two polar states in order to create the beneficial effect. Furthermore, the cooperation between individuals must not be too low, as the benefit to consensus is possible only when the cooperation level exceeds a specific threshold. We also discuss how zealots, agents that remain in one state forever, can affect the consensus among the rest of the population by counteracting the benefit of the intermediate state or making it virtually impossible for an opposition to form.

  5. Overlapping community detection using weighted consensus clustering

    Indian Academy of Sciences (India)

    LINTAO YANG; ZETAI YU; JING QIAN; SHOUYIN LIU

    2016-10-01

    Many overlapping community detection algorithms have been proposed. Most of them are unstable and behave non-deterministically. In this paper, we use weighted consensus clustering for combining multiple base covers obtained by classic non-deterministic algorithms to improve the quality of the results. We first evaluate a reliability measure for each community in all base covers and assign a proportional weight to each one. Then we redefine the consensus matrix that takes into account not only the common membership of nodes, but also the reliability of the communities. Experimental results on both artificial and real-world networks show that our algorithm can find overlapping communities accurately.

  6. On Conditions for Convergence to Consensus

    CERN Document Server

    Lorenz, Jan

    2008-01-01

    A new theorem on conditions for convergence to consensus of a multiagent time-dependent time-discrete dynamical system is presented. The theorem is build up on the notion of averaging maps. We compare this theorem to Moreau's Theorem and his proposed set-valued Lyapunov theory (IEEE Transactions on Automatic Control, vol. 50, no. 2, 2005). We give examples that point out differences of approaches including examples where Moreau's theorem is not applicable but ours is. Further on, we give examples that demonstrate that the theory of convergence to consensus is still not complete.

  7. Consensus and conflict cards for metabolic pathway databases

    Science.gov (United States)

    2013-01-01

    Background The metabolic network of H. sapiens and many other organisms is described in multiple pathway databases. The level of agreement between these descriptions, however, has proven to be low. We can use these different descriptions to our advantage by identifying conflicting information and combining their knowledge into a single, more accurate, and more complete description. This task is, however, far from trivial. Results We introduce the concept of Consensus and Conflict Cards (C2Cards) to provide concise overviews of what the databases do or do not agree on. Each card is centered at a single gene, EC number or reaction. These three complementary perspectives make it possible to distinguish disagreements on the underlying biology of a metabolic process from differences that can be explained by different decisions on how and in what detail to represent knowledge. As a proof-of-concept, we implemented C2CardsHuman, as a web application http://www.molgenis.org/c2cards, covering five human pathway databases. Conclusions C2Cards can contribute to ongoing reconciliation efforts by simplifying the identification of consensus and conflicts between pathway databases and lowering the threshold for experts to contribute. Several case studies illustrate the potential of the C2Cards in identifying disagreements on the underlying biology of a metabolic process. The overviews may also point out controversial biological knowledge that should be subject of further research. Finally, the examples provided emphasize the importance of manual curation and the need for a broad community involvement. PMID:23803311

  8. Introduction: experts and consensus in social science

    NARCIS (Netherlands)

    M. Boumans; C. Martini

    2014-01-01

    The ideals of science as objectivity and consensus are - unsurprisingly - not so easy to attain in scientific practice. Science is ultimately a product of individual scientists with their own personal backgrounds and experiences, and there is no unique methodology to de-personalize and objectify kno

  9. ESMO consensus conference on malignant lymphoma

    DEFF Research Database (Denmark)

    Ladetto, M; Buske, C; Hutchings, M;

    2016-01-01

    into three working groups; each group focused on one of these areas in order to address four clinically relevant questions relating to that topic. All relevant scientific literature, as identified by the experts, was reviewed in advance. During the consensus conference, each working group developed...

  10. 2016 updated MASCC/ESMO consensus recommendations

    DEFF Research Database (Denmark)

    Roila, Fausto; Warr, David; Hesketh, Paul J

    2017-01-01

    PURPOSE: An update of the recommendations for the prophylaxis of acute and delayed emesis induced by moderately emetogenic chemotherapy published after the last MASCC/ESMO antiemetic consensus conference in 2009 has been carried out. METHODS: A systematic literature search using PubMed from Janua...

  11. Beyond the Consensus View: Whole Science

    Science.gov (United States)

    Allchin, Douglas

    2017-01-01

    The "consensus view" on the nature of science (NOS) is now outmoded. To help frame an enduring alternative, one should attend first to the "why" of NOS education. Functional, or civic, scientific literacy is foundational. Acknowledging a need for consumers and citizens to assess the reliability of scientific claims in personal…

  12. Discontinuities and hysteresis in quantized average consensus

    NARCIS (Netherlands)

    Ceragioli, Francesca; Persis, Claudio De; Frasca, Paolo

    2011-01-01

    We consider continuous-time average consensus dynamics in which the agents’ states are communicated through uniform quantizers. Solutions to the resulting system are defined in the Krasowskii sense and are proven to converge to conditions of ‘‘practical consensus’’. To cope with undesired chattering

  13. Distributed Estimation using Bayesian Consensus Filtering

    Science.gov (United States)

    2014-06-06

    performance,” in 48th IEEE Conf. Decision Control, (Shanghai, China), pp. 7036–7042, December 2009. [18] M. H. DeGroot , Probability and Statistics...programming,” Autonomous Robots, vol. 16, pp. 49–79, January 2004. [24] M. H. DeGroot , “Reaching a consensus,” J. Amer. Statistical Assoc., vol. 69

  14. 3rd BRAZILIAN CONSENSUS ON Helicobacter pylori

    Directory of Open Access Journals (Sweden)

    Luiz Gonzaga Coelho

    2013-04-01

    Full Text Available Significant progress has been obtained since the Second Brazilian Consensus Conference on Helicobacter pylori Infection held in 2004, in São Paulo, SP, Brazil, and justify a third meeting to establish updated guidelines on the current management of H. pylori infection. The Third Brazilian Consensus Conference on H pylori Infection was organized by the Brazilian Nucleus for the Study of Helicobacter, a Department of the Brazilian Federation of Gastroenterology and took place on April 12-15, 2011, in Bento Gonçalves, RS, Brazil. Thirty-one delegates coming from the five Brazilian regions and one international guest, including gastroenterologists, pathologists, epidemiologists, and pediatricians undertook the meeting. The participants were allocated in one of the five main topics of the meeting: H pylori, functional dyspepsia and diagnosis; H pylori and gastric cancer; H pylori and other associated disorders; H pylori treatment and retreatment; and, epidemiology of H pylori infection in Brazil. The results of each subgroup were submitted to a final consensus voting to all participants. Relevant data were presented, and the quality of evidence, strength of recommendation, and level of consensus were graded. Seventy per cent and more votes were considered as acceptance for the final statement. This article presents the main recommendations and conclusions to guide Brazilian doctors involved in the management of H pylori infection.

  15. 3rd Brazilian Consensus on Helicobacter pylori.

    Science.gov (United States)

    Coelho, Luiz Gonzaga; Maguinilk, Ismael; Zaterka, Schlioma; Parente, José Miguel; do Carmo Friche Passos, Maria; Moraes-Filho, Joaquim Prado P

    2013-04-01

    Signicant progress has been obtained since the Second Brazilian Consensus Conference on Helicobacter pylori Infection held in 2004, in São Paulo, SP, Brazil, and justify a third meeting to establish updated guidelines on the current management of H. pylori infection. The Third Brazilian Consensus Conference on H pylori Infection was organized by the Brazilian Nucleus for the Study of Helicobacter, a Department of the Brazilian Federation of Gastroenterology and took place on April 12-15, 2011, in Bento Gonçalves, RS, Brazil. Thirty-one delegates coming from the five Brazilian regions and one international guest, including gastroenterologists, pathologists, epidemiologists, and pediatricians undertook the meeting. The participants were allocated in one of the five main topics of the meeting: H pylori, functional dyspepsia and diagnosis; H pylori and gastric cancer; H pylori and other associated disorders; H pylori treatment and retreatment; and, epidemiology of H pylori infection in Brazil. The results of each subgroup were submitted to a final consensus voting to all participants. Relevant data were presented, and the quality of evidence, strength of recommendation, and level of consensus were graded. Seventy per cent and more votes were considered as acceptance for the final statement. This article presents the main recommendations and conclusions to guide Brazilian doctors involved in the management of H pylori infection.

  16. Consensus over peri-implantaire infecties

    NARCIS (Netherlands)

    van Winkelhoff, A J

    2010-01-01

    In 2008, in a workshop of the European Federation on Periodontology, a consensus was reached concerning oral peri-implant infections on the basis of the state of the art in the relevant sciences. Important conclusions were that peri-implant mucositis occurs in 80% of subjects with oral implants, and

  17. The Overreliance of Accreditors on Consensus Standards.

    Science.gov (United States)

    Murray, Frank B.

    2001-01-01

    Argues that the legitimacy of accreditation in teacher education is rooted in political consensus, power, and scholarship. Because these roots are fragile, there is no accepted concept of educational malpractice. The legitimacy of accreditation should be rooted in scholarly evidence that the program has fulfilled the claim that its graduates are…

  18. Judicial Deference Allows European Consensus to Emerge

    DEFF Research Database (Denmark)

    Dothan, Shai

    2017-01-01

    conceived as competing doctrines: the more there is of one, the less there is of another. This paper suggests a novel rationale for the emerging consensus doctrine: the doctrine can allow the ECHR to make good policies by drawing on the independent decision-making of many similar countries. In light of that...

  19. Health Promoting Schools: Consensus, Strategies, and Potential

    Science.gov (United States)

    Macnab, Andrew J.; Gagnon, Faith A.; Stewart, Donald

    2014-01-01

    Purpose: The purpose of this paper is to summarize a consensus statement generated on the current challenges, strategies, and potential of health promoting schools (HPS) at a 2011 colloquium at the Stellenbosch Institute for Advanced Study where 40 people from five continents came together to share their global and regional experience surrounding…

  20. Introduction: experts and consensus in social science

    NARCIS (Netherlands)

    Boumans, M.; Martini, C.; Martini, C.; Boumans, M.

    2014-01-01

    The ideals of science as objectivity and consensus are - unsurprisingly - not so easy to attain in scientific practice. Science is ultimately a product of individual scientists with their own personal backgrounds and experiences, and there is no unique methodology to de-personalize and objectify

  1. Consensus over peri-implantaire infecties

    NARCIS (Netherlands)

    van Winkelhoff, A J

    2010-01-01

    In 2008, in a workshop of the European Federation on Periodontology, a consensus was reached concerning oral peri-implant infections on the basis of the state of the art in the relevant sciences. Important conclusions were that peri-implant mucositis occurs in 80% of subjects with oral implants, and

  2. Adult Asthma Consensus Guidelines Update 2003

    Directory of Open Access Journals (Sweden)

    Catherine Lemière

    2004-01-01

    Full Text Available BACKGROUND: Several sets of Canadian guidelines for the diagnosis and management of asthma have been published over the past 15 years. Since the last revision of the 1999 Canadian Asthma Consensus Report, important new studies have highlighted the need to incorporate new information into the asthma guidelines.

  3. Non-consensus Opinion Models on Complex Networks

    Science.gov (United States)

    Li, Qian; Braunstein, Lidia A.; Wang, Huijuan; Shao, Jia; Stanley, H. Eugene; Havlin, Shlomo

    2013-04-01

    Social dynamic opinion models have been widely studied to understand how interactions among individuals cause opinions to evolve. Most opinion models that utilize spin interaction models usually produce a consensus steady state in which only one opinion exists. Because in reality different opinions usually coexist, we focus on non-consensus opinion models in which above a certain threshold two opinions coexist in a stable relationship. We revisit and extend the non-consensus opinion (NCO) model introduced by Shao et al. (Phys. Rev. Lett. 103:01870, 2009). The NCO model in random networks displays a second order phase transition that belongs to regular mean field percolation and is characterized by the appearance (above a certain threshold) of a large spanning cluster of the minority opinion. We generalize the NCO model by adding a weight factor W to each individual's original opinion when determining their future opinion (NCO W model). We find that as W increases the minority opinion holders tend to form stable clusters with a smaller initial minority fraction than in the NCO model. We also revisit another non-consensus opinion model based on the NCO model, the inflexible contrarian opinion (ICO) model (Li et al. in Phys. Rev. E 84:066101, 2011), which introduces inflexible contrarians to model the competition between two opinions in a steady state. Inflexible contrarians are individuals that never change their original opinion but may influence the opinions of others. To place the inflexible contrarians in the ICO model we use two different strategies, random placement and one in which high-degree nodes are targeted. The inflexible contrarians effectively decrease the size of the largest rival-opinion cluster in both strategies, but the effect is more pronounced under the targeted method. All of the above models have previously been explored in terms of a single network, but human communities are usually interconnected, not isolated. Because opinions propagate not

  4. Human Smuggling

    NARCIS (Netherlands)

    Siegel - Rozenblit, Dina; Zaitch, Damian

    2014-01-01

    Human smuggling is based on a consensus between smuggler, smuggled, and his/her family (which usually guarantees or effectuates payment). However, unauthorized immigrants are violating immigration laws and human smugglers are profiting from enabling illegal immigration. Both human smuggling and its

  5. Expert consensus document: A consensus on the medical treatment of acromegaly.

    Science.gov (United States)

    Giustina, Andrea; Chanson, Philippe; Kleinberg, David; Bronstein, Marcello D; Clemmons, David R; Klibanski, Anne; van der Lely, Aart J; Strasburger, Christian J; Lamberts, Steven W; Ho, Ken K Y; Casanueva, Felipe F; Melmed, Shlomo

    2014-04-01

    In March 2013, the Acromegaly Consensus Group met to revise and update guidelines for the medical treatment of acromegaly. The meeting comprised experts skilled in the medical management of acromegaly. The group considered treatment goals covering biochemical, clinical and tumour volume outcomes, and the place in guidelines of somatostatin receptor ligands, growth hormone receptor antagonists and dopamine agonists, and alternative modalities for treatment including combination therapy and novel treatments. This document represents the conclusions of the workshop consensus.

  6. Consensus Through Conversation How to Achieve High-Commitment Decisions

    CERN Document Server

    Dressler, Larry

    2006-01-01

    Facilitation expert Larry Dressler's Consensus Through Conversation is a guide for the effective facilitation and practice of one of business's most popular - but most widely misunderstood - decision-making models: consensus.

  7. International Multispecialty Consensus on How to Evaluate Ultrasound Competence

    DEFF Research Database (Denmark)

    Tolsgaard, Martin G.; Todsen, Tobias; Sorensen, Jette L.

    2013-01-01

    To achieve international consensus across multiple specialties on a generic ultrasound rating scale using a Delphi technique.......To achieve international consensus across multiple specialties on a generic ultrasound rating scale using a Delphi technique....

  8. Managing Carious Lesions: Consensus Recommendations on Carious Tissue Removal

    NARCIS (Netherlands)

    Schwendicke, F.; Frencken, J.E.; Bjorndal, L.; Maltz, M.; Manton, D.J.; Ricketts, D.; Van Landuyt, K.; Banerjee, A.; Campus, G.; Domejean, S.; Fontana, M.; Leal, S.; Lo, E.; Machiulskiene, V.; Schulte, A.; Splieth, C.; Zandona, A.F.; Innes, N.P.

    2016-01-01

    The International Caries Consensus Collaboration undertook a consensus process and here presents clinical recommendations for carious tissue removal and managing cavitated carious lesions, including restoration, based on texture of demineralized dentine. Dentists should manage the disease dental

  9. International Consensus for ultrasound lesions in gout

    DEFF Research Database (Denmark)

    Gutierrez, Marwin; Schmidt, Wolfgang A; Thiele, Ralf G

    2015-01-01

    elementary lesions. A group of 20 images was displayed twice to evaluate intra-reader reliability. RESULTS: A total of 32 participants responded to the questionnaires. Good agreement (>80%) was obtained for US definitions on DC, tophus, aggregates and erosion in the Delphi exercise after three rounds......OBJECTIVE: To produce consensus-based definitions of the US elementary lesions in gout and to test their reliability in a web-based exercise. METHODS: The process consisted of two steps. In the first step a written Delphi questionnaire was developed from a systematic literature review and expert....... The reliability on images showed inter-reader κ values for DC, tophus, aggregates, erosion findings of 0.98, 0.71, 0.54 and 0.85, respectively. The mean intra-reader κ values were also acceptable: 0.93, 0.78, 0.65 and 0.78, respectively. CONCLUSION: This, the first consensus-based US definition of elementary...

  10. Police suicide research: conflict and consensus.

    Science.gov (United States)

    Violanti, John M

    2008-01-01

    Despite new frontiers in suicide research over the past ten years, police suicide remains a difficult, persistent, and controversial problem. Controversy appears to focus on the accuracy and validity of police suicide rates, but other controversies exist as well. This is likely due to studies that are methodologically flawed, incomplete, or specific to limited geographic areas. The objective of this paper is to review issues related to both conflicts and consensus on police suicide.

  11. Pragmatism and Political Pluralism - Consensus and Pluralism

    OpenAIRE

    Michele Marsonet

    2015-01-01

    A pragmatist thinker like Nicholas Rescher deems the idea that social harmony must be predicated in consensus to be both dangerous and misleading. An essential problem of our time is the creation of political and social institutions that enable people to live together in peaceful and productive ways, despite the presence of not eliminable disagreements about theoretical and practical issues. Such remarks, in turn, strictly recall the “practical” impossibility of settling philosophical dispute...

  12. Sarcopenia: European consensus on definition and diagnosis

    OpenAIRE

    Alfonso J Cruz-Jentoft; Baeyens, Jean Pierre; Jürgen M Bauer; Boirie, Yves; Cederholm, Tommy; Landi, Francesco; Martin, Finbarr C; Michel, Jean-Pierre; Rolland, Yves; Schneider, Stéphane M; Topinková, Eva; Vandewoude, Maurits; Zamboni, Mauro

    2010-01-01

    The European Working Group on Sarcopenia in Older People (EWGSOP) developed a practical clinical definition and consensus diagnostic criteria for age-related sarcopenia. EWGSOP included representatives from four participant organisations, i.e. the European Geriatric Medicine Society, the European Society for Clinical Nutrition and Metabolism, the International Association of Gerontology and Geriatrics—European Region and the International Association of Nutrition and Aging. These organisation...

  13. A Self-Categorization Explanation for Opinion Consensus Perceptions

    Science.gov (United States)

    Zhang, Jinguang; Reid, Scott A.

    2013-01-01

    The public expression of opinions (and related communicative activities) hinges upon the perception of opinion consensus. Current explanations for opinion consensus perceptions typically focus on egocentric and other biases, rather than functional cognitions. Using self-categorization theory we showed that opinion consensus perceptions flow from…

  14. Consensus contact prediction by linear programming.

    Science.gov (United States)

    Gao, Xin; Bu, Dongbo; Li, Shuai Cheng; Li, Ming; Xu, Jinbo

    2007-01-01

    Protein inter-residue contacts are of great use for protein structure determination or prediction. Recent CASP events have shown that a few accurately predicted contacts can help improve both computational efficiency and prediction accuracy of the ab inito folding methods. This paper develops an integer linear programming (ILP) method for consensus-based contact prediction. In contrast to the simple "majority voting" method assuming that all the individual servers are equal and independent, our method evaluates their correlations using the maximum likelihood method and constructs some latent independent servers using the principal component analysis technique. Then, we use an integer linear programming model to assign weights to these latent servers in order to maximize the deviation between the correct contacts and incorrect ones; our consensus prediction server is the weighted combination of these latent servers. In addition to the consensus information, our method also uses server-independent correlated mutation (CM) as one of the prediction features. Experimental results demonstrate that our contact prediction server performs better than the "majority voting" method. The accuracy of our method for the top L/5 contacts on CASP7 targets is 73.41%, which is much higher than previously reported studies. On the 16 free modeling (FM) targets, our method achieves an accuracy of 37.21%.

  15. Studying the existence and attributes of consensus on psychological concepts by a cognitive psychological model

    DEFF Research Database (Denmark)

    Oravecz, Zita; Faust, Katherine; Batchelder, William H.

    2015-01-01

    Psychological research can take a variety of directions while building on theoretical concepts that are commonly shared among the population of researchers. We investigate the question of how agreement or consensus on basic scientific concepts can be measured. Our approach to the problem is based...... on a state-of-the-art cognitive psychometric technique, implemented in the theoretical framework of Cultural Consensus Theory (CCT). With this approach, consensus-based answers for questions exploring shared knowledge can be derived while basic factors of the human decision making process are accounted for...... of the individual, and is typically not a developmental change." The general goal of the paper is to demonstrate the utility of the CCT based approach as a method for investigating what current, working definitions of scientific concepts are....

  16. Interferon alpha as monotherapy or combination therapy for chronic hepatitis B

    NARCIS (Netherlands)

    M. van Zonneveld (Monika)

    2005-01-01

    markdownabstract__Abstract__ The hepatitis B virus (HBV) is a DNA virus that belongs to the group ofhepadnaviridae. The partially double-stranded DNA contains 4 open reading frames, encoding for the envelope (pre-S/ S), core (precore/ core), polymerase and X proteins. The pre-S/S open reading frame

  17. 17β-estradiol protects primary macrophages against HIV infection through induction of interferon-alpha.

    Science.gov (United States)

    Tasker, Carley; Ding, Jian; Schmolke, Mirco; Rivera-Medina, Amariliz; García-Sastre, Adolfo; Chang, Theresa L

    2014-05-01

    Estrogen has been shown to increase resistance to HIV/SIV transmission by increasing the thickness of the genital epithelium. The immunological role of estrogen in HIV infection of primary target cells is less well characterized. We have found that primary macrophages are a target for anti-HIV activity of 17β-estradiol (E2). E2 did not affect surface expression of CD4 and HIV co-receptors nor HIV attachment to monocyte-derived macrophages (MDMs). In addition, E2 treatment blocked infection by a co-receptor-independent HIV-1VSV-G pseudotyped virus. Quantitative polymerase chain reaction analysis of HIV reverse transcribed DNA products indicated that E2 blocked HIV reverse transcription. E2 upregulated gene expression of interferons (IFNs) in MDMs from multiple donors. However, induction of host restriction factors APOBEC3G, APOBEC3F, or SAMHD1 was not consistent, with exception of APOBEC3A. Anti-HIV activity of E2 was abolished in the presence of IFN-α neutralizing antibody, and was absent in bone marrow-derived macrophages from IFN-α receptor deficient mice. Interestingly, HIV overcame E2-mediated HIV inhibition by suppressing induction of IFNs when MDMs were exposed to HIV before E2 treatment. These results offer a new mechanism of E2 on HIV inhibition. Future studies on the interplay between HIV and E2-mediated innate immune responses will likely provide insights relevant for development of effective strategies for HIV prevention.

  18. Interferon-alpha in the treatment of Philadelphia-negative chronic myeloproliferative neoplasms. Status and perspectives

    DEFF Research Database (Denmark)

    Hasselbalch, Hans Carl; Larsen, Thomas Stauffer; Riley, Caroline Hasselbalch

    2011-01-01

    The Philadelphia-negative chronic myeloproliferative neoplasms encompass essential thrombocythemia (ET), polycythemia vera (PV) and primary myelofibrosis (PMF). A major break-through in the understanding of the pathogenesis of these neoplasms occurred in 2005 by the discovery of the JAK2 V617F mu...

  19. Combination Therapy of Interferon-alpha (PDferon B® and Ribavirin for Chronic Hepatitis C

    Directory of Open Access Journals (Sweden)

    Seyed-Moayed Alavian

    2004-04-01

    Full Text Available Introduction: The addition of ribavirin (RIBA to the standard treatment with interferon(IFN alpha led to an improvement in sustained virologic response (SVR from less than20% with IFN monotherapy to 40-45% in combination therapy. The aim of this study isto assess the therapeutic efficacy and safety of IFN alpha (PDferon B® in combinationwith RIBA on Iranian patients with chronic hepatitis C (CHC.Methods: 48 naive patients aged 18 years or more with CHC were enrolled and treatedwith 3 mega units (MU IFN alpha-2b three times a week plus 800-1000 mg RIBA perday for 48 weeks. Follow-up after therapy was 6 months. The efficacy was evident at theend of treatment and at the end of follow-up in terms of sustained normalization of alanineaminotransferase and sustained serum HCV-RNA loss.Results: The rate of sustained biochemical and virologic response were 68.3% and78%, respectively. Virologic response was 80.9% and 86.4% at weeks 12 and 48 as well.Any patient didn’t have serious complication.Conclusion: Although we had no control group who used standard IFN, our preliminaryfinding showed acceptable and promising response rate of PDferon. On the other hand,it seems that adverse events with PDferon are as like as other standard IFNs.Fax: +98-21-8975730

  20. Pegylated interferon-alpha plus taurine in treatment of rat liver fibrosis

    Institute of Scientific and Technical Information of China (English)

    Ilker Tasci; Cihan Yurdaydin; Hakan Bozkaya; Ozden Uzunalimoglu; Ahmet Turan Isik; Harun M Said; Mehmet Refik Mas; Sevil Atalay Vural; Salih Deveci; Bilgin Comert; Gunay Alcigir; Nuket Mas; Cemal Akay; Mithat Bozdayi

    2007-01-01

    AIM: To investigate the antifibrotic effects of peginterferonalpha 2b and taurine on oxidative stress markers and hepatocellular apoptosis.METHODS: Sixty rats with CCl4-induced liver fibrosis were divided into 4 groups (n=15). Group 1 was left for spontaneous recovery (SR). Groups 2-4 received peginterferon-alpha 2b, taurine, and their combination,respectively, for four weeks. Histological fibrosis scores,histomorphometric analysis, tissue hydroxyproline, tissue MDA, GPx and SOD activities were determined. Activated stellate cells and hepatocellular apoptosis were also evaluated.RESULTS: The degree of fibrosis decreased in all treatment groups compared to spontaneous recovery group. Taurine alone and in combination with peginterferon-alpha 2b reduced oxidative stress markers,but peginterferon-alpha 2b alone did not. Apoptotic hepatocytes and activated stellate cells were higher in groups 2-4 than in group 1. Combined taurine and peginterferon-alpha 2b further reduced fibrosis and increased activated stellate cell apoptosis, but could not improve oxidative stress more than taurine alone.CONCLUSION: Peginterferon-alpha 2b exerts antifibrotic effects on rat liver fibrosis. It seems ineffective against oxidative stress in vivo. Peginterferon-alpha 2b in combination with taurine seems to be an antifibrotic strategy.

  1. Natural interferon alpha/beta-producing cells link innate and adaptive immunity

    National Research Council Canada - National Science Library

    Kadowaki, N; Antonenko, S; Lau, J Y; Liu, Y J

    2000-01-01

    .... However, it is not completely understood how innate immunity controls the initiation of adaptive immunities or how it determines which type of adaptive immunity will be induced to eliminate a given pathogen...

  2. Protection of hepatocytes from cytotoxic T cell mediated killing by interferon-alpha.

    Directory of Open Access Journals (Sweden)

    Christian B Willberg

    Full Text Available BACKGROUND: Cellular immunity plays a key role in determining the outcome of hepatitis C virus (HCV infection, although the majority of infections become persistent. The mechanisms behind persistence are still not clear; however, the primary site of infection, the liver, may be critical. We investigated the ability of CD8+ T-cells (CTL to recognise and kill hepatocytes under cytokine stimulation. METHODS/PRINCIPLE FINDINGS: Resting hepatocytes cell lines expressed low levels of MHC Class I, but remained susceptible to CTL cytotoxicity. IFN-alpha treatment, in vitro, markedly increased hepatocyte MHC Class I expression, however, reduced sensitivity to CTL cytotoxicity. IFN-alpha stimulated hepatocyte lines were still able to present antigen and induce IFN-gamma expression in interacting CTL. Resistance to killing was not due to the inhibition of the FASL/FAS- pathway, as stimulated hepatocytes were still susceptible to FAS-mediated apoptosis. In vitro stimulation with IFN-alpha, or the introduction of a subgenomic HCV replicon into the HepG2 line, upregulated the expression of the granzyme-B inhibitor-proteinase inhibitor 9 (PI-9. PI-9 expression was also observed in liver tissue biopsies from patients with chronic HCV infection. CONCLUSION/SIGNIFICANCE: IFN-alpha induces resistance in hepatocytes to perforin/granzyme mediate CTL killing pathways. One possible mechanism could be through the expression of the PI-9. Hindrance of CTL cytotoxicity could contribute to the chronicity of hepatic viral infections.

  3. Interferon-alpha administration enhances CD8+ T cell activation in HIV infection.

    Directory of Open Access Journals (Sweden)

    Maura Manion

    Full Text Available BACKGROUND: Type I interferons play important roles in innate immune defense. In HIV infection, type I interferons may delay disease progression by inhibiting viral replication while at the same time accelerating disease progression by contributing to chronic immune activation. METHODS: To investigate the effects of type I interferons in HIV-infection, we obtained cryopreserved peripheral blood mononuclear cell samples from 10 subjects who participated in AIDS Clinical Trials Group Study 5192, a trial investigating the activity of systemic administration of IFNα for twelve weeks to patients with untreated HIV infection. Using flow cytometry, we examined changes in cell cycle status and expression of activation antigens by circulating T cells and their maturation subsets before, during and after IFNα treatment. RESULTS: The proportion of CD38+HLA-DR+CD8+ T cells increased from a mean of 11.7% at baseline to 24.1% after twelve weeks of interferon treatment (p = 0.006. These frequencies dropped to an average of 20.1% six weeks after the end of treatment. In contrast to CD8+ T cells, the frequencies of activated CD4+ T cells did not change with administration of type I interferon (mean percentage of CD38+DR+ cells = 2.62% at baseline and 2.17% after 12 weeks of interferon therapy. As plasma HIV levels fell with interferon therapy, this was correlated with a "paradoxical" increase in CD8+ T cell activation (p<0.001. CONCLUSION: Administration of type I interferon increased expression of the activation markers CD38 and HLA DR on CD8+ T cells but not on CD4+ T cells of HIV+ persons. These observations suggest that type I interferons may contribute to the high levels of CD8+ T cell activation that occur during HIV infection.

  4. Interferon-alpha subtype 11 activates NK cells and enables control of retroviral infection.

    Directory of Open Access Journals (Sweden)

    Kathrin Gibbert

    Full Text Available The innate immune response mediated by cells such as natural killer (NK cells is critical for the rapid containment of virus replication and spread during acute infection. Here, we show that subtype 11 of the type I interferon (IFN family greatly potentiates the antiviral activity of NK cells during retroviral infection. Treatment of mice with IFN-α11 during Friend retrovirus infection (FV significantly reduced viral loads and resulted in long-term protection from virus-induced leukemia. The effect of IFN-α11 on NK cells was direct and signaled through the type I IFN receptor. Furthermore, IFN-α11-mediated activation of NK cells enabled cytolytic killing of FV-infected target cells via the exocytosis pathway. Depletion and adoptive transfer experiments illustrated that NK cells played a major role in successful IFN-α11 therapy. Additional experiments with Mouse Cytomegalovirus infections demonstrated that the therapeutic effect of IFN-α11 is not restricted to retroviruses. The type I IFN subtypes 2 and 5, which bind the same receptor as IFN-α11, did not elicit similar antiviral effects. These results demonstrate a unique and subtype-specific activation of NK cells by IFN-α11.

  5. In vivo effects of interferon-alpha and interferon-gamma on lipolysis and ketogenesis.

    Science.gov (United States)

    Memon, R A; Feingold, K R; Moser, A H; Doerrler, W; Grunfeld, C

    1992-10-01

    The host response to infection and cancer produces disturbances in fatty acid (FA) oxidation and ketogenesis. Interferons (IFNs) stimulate lipolysis in cultured adipocytes. Since FA mobilization is a major stimulus for ketogenesis, we studied the effect of IFN alpha and IFN gamma on lipolysis and ketogenesis in intact mice. Both IFNs acutely stimulated lipolysis; however, their effects on ketogenesis differed. INF gamma increased serum and hepatic ketone body levels in parallel to its effect on serum FFA, whereas IFN alpha exerted a biphasic effect on ketogenesis. At low doses, IFN alpha increased serum and hepatic ketone body levels, whereas at higher doses, this ketogenic effect was abolished. To determine the mechanism of the biphasic response, we studied the effect of IFN alpha on hepatic malonyl-coenzyme-A (malonyl-CoA), the first committed intermediate in FA synthesis and an inhibitor of FA oxidation and ketogenesis. At low doses, IFN alpha had no effect on malonyl-CoA; however, higher doses of IFN alpha significantly increased malonyl-CoA levels, which could counterbalance its mobilization of FFA. In contrast, INF gamma had little effect on malonyl-CoA, and hence, the FA oxidation was not opposed. By using phenylisopropyladenosine to block IFN-induced lipolysis, we found that in the absence of increased FA flux, INF gamma did not exert a ketogenic effect. However, when IFN alpha-induced lipolysis was blocked, the higher doses of IFN alpha that raise malonyl-CoA levels were antiketogenic. These data suggest that both IFNs exert a ketogenic effect by stimulating lipolysis, but at higher doses the ketogenic effect of IFN alpha is counteracted by its effect on hepatic FA synthesis.

  6. Interferon alpha as monotherapy or combination therapy for chronic hepatitis B

    NARCIS (Netherlands)

    M. van Zonneveld (Monika)

    2005-01-01

    markdownabstract__Abstract__ The hepatitis B virus (HBV) is a DNA virus that belongs to the group ofhepadnaviridae. The partially double-stranded DNA contains 4 open reading frames, encoding for the envelope (pre-S/ S), core (precore/ core), polymerase and X proteins. The pre-S/S open reading

  7. Increased interferon alpha receptor 2 mRNA levels is associated with renal cell carcinoma metastasis

    Directory of Open Access Journals (Sweden)

    Yamanishi Tomonori

    2007-08-01

    Full Text Available Abstract Background Interferon-α (IFN-α is one of the central agents in immunotherapy for renal cell carcinoma (RCC and binds to the IFN-α receptor (IFNAR. We investigated the role of IFNAR in RCC. Methods We quantified IFNAR mRNA expression in paired tumor and non-tumor samples from the surgical specimens of 103 consecutive patients with RCC using a real-time reverse transcription polymerase chain reaction (RT-PCR, and IFNAR2 protein using Western blotting. Results The absolute level of IFNAR1 and IFNAR2 mRNAs in tumor and non-tumor tissues did not correlate with the malignant and metastatic profiles. The relative yields of the PCR product from the tumor tissue to that from the corresponding non-tumor tissue (T/N for the expression of IFNAR mRNAs were calculated. While the T/N ratio of IFNAR1 did not correlate with any factor, a high T/N ratio of IFNAR2 correlated with poor differentiation (P P P P P Conclusion IFNAR2 is associated with the progression of RCC.

  8. Risk factors for the development of depression in patients with hepatitis C taking interferon-&alpha;

    OpenAIRE

    Smith KJ; Norris S; O'Farrelly C; O'Mara SM

    2011-01-01

    Kimberley J Smith¹, Suzanne Norris², Cliona O'Farrelly³, O'Mara SM¹¹Trinity College Institute of Neuroscience, ²Hepatology Centre, St James's Hospital, Dublin, Ireland; ³Department of Biochemistry and Immunology, Trinity College Dublin, Dublin, IrelandAbstract: Interferon-α, currently used for the treatment of hepatitis C, is associated with a substantially elevated risk of depression. However, no...

  9. Treatment with interferon-alpha delays disease in swine infected with a highly virulent CSFV strain

    Science.gov (United States)

    Classical swine fever (CSF) is an economically significant, highly contagious swine disease. The etiological agent, CSF virus (CSFV), is an enveloped virus with a positive-sense, single-stranded RNA genome, classified as a member of the genus Pestivirus within the family Flaviviridae (Becher et al.,...

  10. Salvage treatment after r-interferon [alpha]-2a in advanced neuroendocrine tumors

    Energy Technology Data Exchange (ETDEWEB)

    Zilembo, N. (Italian Trials in Medical Oncology (I.T.M.O.) Group, Ist. Nazionale per lo Studio et la Cura dei Tumori, Milano (Italy)); Buzzoni, R. (Italian Trials in Medical Oncology (I.T.M.O.) Group, Ist. Nazionale per lo Studio et la Cura dei Tumori, Milano (Italy)); Bajetta, E. (Italian Trials in Medical Oncology (I.T.M.O.) Group, Ist. Nazionale per lo Studio et la Cura dei Tumori, Milano (Italy)); Di Bartolomeo, M. (Italian Trials in Medical Oncology (I.T.M.O.) Group, Ist. Nazionale per lo Studio et la Cura dei Tumori, Milano (Italy)); De Braud, F. (Italian Trials in Medical Oncology (I.T.M.O.) Group, Ist. Nazionale per lo Studio et la Cura dei Tumori, Milano (Italy)); Castellani, R. (Italian Trials in Medical Oncology (I.T.M.O.) Group, Ist. Nazionale per lo Studio et la Cura dei Tumori, Milano (Italy)); Maffioli, L. (Italian Trials in Medical Oncology (I.T.M.O.) Group, Ist. Nazionale per lo Studio et la Cura dei Tumori, Milano (Italy)); Celio, L. (Italian Trials in Medical

    1993-01-01

    The use of interferon (IFN) in neuroendocrine advanced tumors has achieved control of hormonal symptoms but low objective tumor response rate. In patients resistant to, or failing on, IFN a second line treatment may be required. Seventeen patients having received recombinant IFN [alpha]-2a as last treatment entered the study. There were 12 carcinoids, 3 medullary thyroid carcinomas, one Merkel cell carcinoma, and one neuroendocrine pancreatic tumor. Two different treatments were used: one radiometabolic therapy with metaiodobenzylguanidine (MIBG) in 3 patients with high MIBG uptake and one polychemotherapy regimen, including streptozotocin 500 mg/m[sup 2] intravenously days 1, 2, 3 and epirubicin 75 mg/m[sup 2] intravenously day 1, in the remaining 14 patients. Stable disease with relief of symptoms and tumor marker reduction was obtained in two patients receiving MIGB therapy, whereas the third patient had progressive disease. In the chemotherapy group only one partial response was obtained and neither tumor marker reduction nor subjective improvement were seen. Our second-line treatment was not especially effective but may be considered for rapidly progressive and/or symptomatic disease. The radiometabolic therapy appears promising in symptomatic patients with small tumor burden whereas our chemotherapy regimen appears ineffective. (orig.).

  11. Minimal residual disease after long-term interferon-alpha2 treatment

    DEFF Research Database (Denmark)

    Utke Rank, Cecilie; Weis Bjerrum, Ole; Larsen, Thomas Stauffer;

    2016-01-01

    of inducing MRD with low-burden JAK2 V617F, major molecular response (MMR), complete hematological remission (CHR) and complete histomorphological normalization of the bone marrow in a sub-set of patients with ET and PV after long-term treatment (≥ 3.5 years). Furthermore, long-lasting hematological...

  12. 三 干扰素-α(interferon alpha,IFN-α)

    Institute of Scientific and Technical Information of China (English)

    张丽兰

    2007-01-01

    @@ 1概述 干扰素-α历史上曾用名为:B-细胞干扰素(Bcell interferon);血浆沉淀淡黄色表层干扰素(Buffy coat interferon);外源性细胞干扰素(Foreign cellinduced interferon);白细胞干扰素(Leukocyte interferon,LeIFN);淋巴母细胞干扰素(Lymphoblast interferon,LyIFN-alpha);类淋巴母细胞干扰素(Lymphoblastoid interferon,LyIFN-alpha);Namalwa细胞干扰素(Namalwa interferon);pH2-稳定干扰素(pH2-stable interferon);Ⅰ型干扰素(Type-1 interferon);RSV-诱导因子(RSV-induced factor).

  13. Bilateral Retrobulbar Optic Neuropathy in the Setting of Interferon Alpha-2a Therapy

    Directory of Open Access Journals (Sweden)

    Dujon R.W. Fuzzard

    2014-08-01

    Full Text Available The development of biopharmaceutical agents, including the interferons (IFN, offers new treatment options for a wide range of medical conditions. Such advancements, however, have not come without risk to patients. Optic neuropathy in the setting of IFN therapy has been previously documented and is usually attributed to anterior ischaemic optic neuropathy; however, the pathophysiology remains poorly understood. Retrobulbar optic neuropathy associated with IFN treatment has not been described in the medical literature to date. We report the case of a 38-year-old Caucasian female with refractory acute myeloid leukaemia who developed painless bilateral blurred vision within 2 weeks of commencing a course of IFN alpha-2a. Extensive clinical workup demonstrated bilateral retrobulbar optic neuropathy. We report the clinical evaluation of this first documented case and discuss the possible aetiologies of her presentation.

  14. Cytotoxic activity of interferon alpha induced dendritic cells as a biomarker of glioblastoma

    Science.gov (United States)

    Mishinov, S. V.; Stupak, V. V.; Tyrinova, T. V.; Leplina, O. Yu.; Ostanin, A. A.; Chernykh, E. R.

    2016-08-01

    Dendritic cells (DCs) are the most potent antigen presenting cells that can play direct role in anti-tumor immune response as killer cells. DC tumoricidal activity can be stimulated greatly by type I IFN (IFNα and IFNβ). In the present study, we examined cytostatic and cytotoxic activity of monocyte-derived IFNα-induced DCs generated from patients with brain glioma and evaluated the potential use of these parameters in diagnostics of high-grade gliomas. Herein, we demonstrated that patient DCs do not possess the ability to inhibit the growth of tumor HEp-2 cell line but low-grade and high-grade glioma patients do not differ significantly in DC cytostatic activity. However, glioma patient DCs are characterized by reduced cytotoxic activity against HEp-2 cells. The impairment of DC cytotoxic function is observed mainly in glioblastoma patients. The cytotoxic activity of DCs against HEp-2 cells below 9% is an informative marker for glioblastomas.

  15. Interferon Alpha-2a Therapy in Patients with Refractory Behçet Uveitis.

    Science.gov (United States)

    Hasanreisoglu, Murat; Cubuk, Mehmet Ozgur; Ozdek, Sengul; Gurelik, Gokhan; Aktas, Zeynep; Hasanreisoglu, Berati

    2017-02-01

    To report the results of IFNα2a therapy in patients with Behçet uveitis refractory to azathioprine-cyclosporine combination treatment. In a retrospective study, 39 patients treated with either azathioprine-cyclosporine combination treatment (group 1, n = 23) or IFNα2a (group 2, n = 16) with a diagnosis of ocular Behçet disease (BD), were included in the study. Group 2 consisted of patients who did not respond to conventional combination therapy, and were therefore treated with IFNα2a. Clinical response and relapse rates were recorded for each group. The mean number of uveitis attacks/year per patient was 0.8 ± 1.6 in Group 1. In Group 2, a significant decrease in the mean number of uveitis attacks/year per patient was observed after initiation of IFNα2a (2.4 ± 1.8 vs 1.3 ± 2.0) (puveitis attack/year and attack-free intervals, with a partial response to both treatments. IFNα2a therapy is an effective alternative for Behçet uveitis patients where conventional combination therapy fails.

  16. Interferon-alpha in the treatment of Philadelphia-negative chronic myeloproliferative neoplasms. Status and perspectives

    DEFF Research Database (Denmark)

    Hasselbalch, H.C.; Larsen, T.S.; Riley, C.H.

    2011-01-01

    and the hyperproliferative phase of PMF. This paper reviews the history of IFN -in principle IFN-alpha2 -and its present status in the treatment of PV and related diseases. The role of IFN-alpha2 as immune therapy in the future treatment of CMPNs is highlighted and the rationale for the concept of minimal residual disease...

  17. Efficacy of interferon alpha-2b and lamivudine therapy for chronic hepatitis B in children

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    Objective To evaluate the efficacy of interferon (IFN) alpha-2b and lamivudine therapy in children with chronic hepatitis B virus (HBV) infection.Method Ten children who developed chronic hepatitis B infection received IFN alpha-2b 10 million international units (IU)/m2 body surface area, subcutaneously three times a week for six months. IFN+lamivudine therapy began to be used in the cases who were unresponsive to IFN treatment. Results Among 27 HBsAg (+) subjects in this study, interferon treatment was given to 11 subjects who developed chronic hepatitis. One case was excluded from the study due to detection of Herpes type 1 encephalitis. At the end of six months of follow-up, complete response was obtained in three (30%) patients and partial response in four (40%) patients, whereas no response was detected in three (30%) patients. Fifty percent of the cases experienced serological response, 70% biochemical response, and all (100%) had histological response. In three cases started concomitant IFN+lamivudine therapy, HBV-DNA became negative at the second month of treatment. Conclusions IFN-alpha and lamivudine can be used for the treatment of chronic hepatitis B infection in children.

  18. [Social consensus on medical technology policy: ethical issues and citizen participation].

    Science.gov (United States)

    Sato, Hajime

    2004-01-01

    Social consensus is considered to be a necessary condition for a policy to be introduced and implemented effectively. This is the case with the approval, regulation and prohibition of certain advanced medical research and technology, especially when they could invoke moral disputes in society. Public policies on organ transplantation, definition of death, euthanasia, genetic screening and diagnosis, and human stem cell research are recent examples. The concept of consensus, however, is elusive, along with the measures to secure it. Technocratic decision making, as a paternalistic activity frequently led by experts, sometimes poses a challenge to democratic decision making, supposedly based on a well-informed and rational public. It also remains to be proved whether public involvement in policymaking can be a solution to ethical value conflicts in society. From the perspective of policy sciences, this paper first introduces the concept of consensus, especially consensus on moral issues in pluralistic societies, and its implications to public policy, including citizen participation in decision making. Then, it briefly explains the historical background with which social consensus and public involvement have increasingly flourished in the field of technology assessments and technology policy making, including biomedical technology. Next, major institutions, governmental and nongovernmental, involved in the ethical aspects of medical research and technology, are presented along with their efforts for citizen participation. Finally, the paper discusses some of the future agendas on this issue.

  19. Consensus Formation in Science Modeled by Aggregated Bibliographic Coupling

    DEFF Research Database (Denmark)

    Nicolaisen, Jeppe; Frandsen, Tove Faber

    2012-01-01

    Abstract: The level of consensus in science has traditionally been measured by a number of different methods. The variety is important as each method measures different aspects of science and consensus. Citation analytical studies have previously measured the level of consensus using the scientific...... journal as their unit of analysis. To produce a more fine grained citation analysis one needs to study consensus formation on an even more detailed level – i.e. the scientific document or article. To do so, we have developed a new technique that measures consensus by aggregated bibliographic couplings...

  20. International consensus on ANA patterns (ICAP): the bumpy road towards a consensus on reporting ANA results.

    Science.gov (United States)

    Damoiseaux, Jan; von Mühlen, Carlos A; Garcia-De La Torre, Ignacio; Carballo, Orlando Gabriel; de Melo Cruvinel, Wilson; Francescantonio, Paulo Luiz Carvalho; Fritzler, Marvin J; Herold, Manfred; Mimori, Tsuneyo; Satoh, Minoru; Andrade, Luis E C; Chan, Edward K L; Conrad, Karsten

    2016-12-01

    The International Consensus on ANA Patterns (ICAP) was initiated as a workshop aiming to thoroughly discuss and achieve consensus regarding the morphological patterns observed in the indirect immunofluorescence assay on HEp-2 cells. One of the topics discussed at the second ICAP workshop, and addressed in this paper, was the harmonization of reporting ANA test results. This discussion centered on the issue if cytoplasmic and mitotic patterns should be reported as positive or negative. This report outlines the issues that impact on two major different reporting methods. Although it was appreciated by all participants that cytoplasmic and mitotic patterns are clinically relevant, implications for existing diagnostic/classification criteria for ANA-associated diseases in particular hampered a final consensus on this topic. Evidently, a more concerted action of all relevant stakeholders is required. Future ICAP workshops may help to facilitate this action.

  1. Developing consensus criteria for sarcopenia: an update.

    Science.gov (United States)

    McLean, Robert R; Kiel, Douglas P

    2015-04-01

    Sarcopenia, the age-related loss of muscle mass and strength, is a major cause of impaired physical function, which contributes to mobility disability, falls and hospitalizations in older adults. Lower muscle mass and strength are also associated with lower bone mineral density and greater risk for osteoporotic fractures. Thus, identification of sarcopenia could be important for fracture prevention as it may help improve fracture risk assessment, and muscle mass and strength can be improved with exercise, even among the frailest older adults. Unfortunately, there are no consensus diagnostic criteria for sarcopenia. Consequently there is no guidance to help clinicians identify older adults with clinically meaningful low muscle mass or weakness. Further, development of novel sarcopenia therapies is hindered not only due to the difficulty in identifying participants for clinical trials, and but also because there are no validated, clinically appropriate endpoints for assessment of treatment efficacy. There is currently a major push to establish a consensus definition of sarcopenia, and recent work holds promise that this goal may be within reach. This article discusses the evolution of the definition of sarcopenia, and focuses on the latest recommended diagnostic criteria proposed by the Foundation for the National Institutes of Health (FNIH) Sarcopenia Project. While these empirically-based cut-points for clinically important low muscle mass and weakness are a significant step forward for the sarcopenia field, important questions remain to be answered before consensus diagnostic criteria can be definitively established. Ongoing work to refine sarcopenia criteria will further advance the field and bring this important contributor to falls, fractures and disability into the mainstream of clinical care and ultimately lead to better quality of life with aging. © 2015 American Society for Bone and Mineral Research.

  2. The Mexican consensus on probiotics in gastroenterology

    Directory of Open Access Journals (Sweden)

    M.A. Valdovinos

    2017-04-01

    Results and conclusions: Eleven statements on the general concepts of probiotics and 27 statements on the use of probiotics in gastrointestinal diseases in both adults and children were formulated. The consensus group recommends the use of probiotics under the following clinical conditions: the prevention of diarrhea associated with antibiotics, the treatment of acute infectious diarrhea, the prevention of Clostridium difficile infection and necrotizing enterocolitis, the reduction of adverse events from Helicobacter pylori eradication therapy, relief from irritable bowel syndrome symptoms, the treatment of functional constipation in the adult, and the induction and maintenance of remission in patients with ulcerative colitis (UC and pouchitis, and the treatment of covert and overt hepatic encephalopathy.

  3. Consensus Paper: Neuroimmune Mechanisms of Cerebellar Ataxias.

    Science.gov (United States)

    Mitoma, Hiroshi; Adhikari, Keya; Aeschlimann, Daniel; Chattopadhyay, Partha; Hadjivassiliou, Marios; Hampe, Christiane S; Honnorat, Jérôme; Joubert, Bastien; Kakei, Shinji; Lee, Jongho; Manto, Mario; Matsunaga, Akiko; Mizusawa, Hidehiro; Nanri, Kazunori; Shanmugarajah, Priya; Yoneda, Makoto; Yuki, Nobuhiro

    2016-04-01

    In the last few years, a lot of publications suggested that disabling cerebellar ataxias may develop through immune-mediated mechanisms. In this consensus paper, we discuss the clinical features of the main described immune-mediated cerebellar ataxias and address their presumed pathogenesis. Immune-mediated cerebellar ataxias include cerebellar ataxia associated with anti-GAD antibodies, the cerebellar type of Hashimoto's encephalopathy, primary autoimmune cerebellar ataxia, gluten ataxia, Miller Fisher syndrome, ataxia associated with systemic lupus erythematosus, and paraneoplastic cerebellar degeneration. Humoral mechanisms, cell-mediated immunity, inflammation, and vascular injuries contribute to the cerebellar deficits in immune-mediated cerebellar ataxias.

  4. Multiple chemical sensitivity: a 1999 consensus.

    Science.gov (United States)

    1999-01-01

    Consensus criteria for the definition of multiple chemical sensitivity (MCS) were first identified in a 1989 multidisciplinary survey of 89 clinicians and researchers with extensive experience in, but widely differing views of, MCS. A decade later, their top 5 consensus criteria (i.e., defining MCS as [1] a chronic condition [2] with symptoms that recur reproducibly [3] in response to low levels of exposure [4] to multiple unrelated chemicals and [5] improve or resolve when incitants are removed) are still unrefuted in published literature. Along with a 6th criterion that we now propose adding (i.e., requiring that symptoms occur in multiple organ systems), these criteria are all commonly encompassed by research definitions of MCS. Nonetheless, their standardized use in clinical settings is still lacking, long overdue, and greatly needed--especially in light of government studies in the United States, United Kingdom, and Canada that revealed 2-4 times as many cases of chemical sensitivity among Gulf War veterans than undeployed controls. In addition, state health department surveys of civilians in New Mexico and California showed that 2-6%, respectively, already had been diagnosed with MCS and that 16% of the civilians reported an "unusual sensitivity" to common everyday chemicals. Given this high prevalence, as well as the 1994 consensus of the American Lung Association, American Medical Association, U.S. Environmental Protection Agency, and the U.S. Consumer Product Safety Commission that "complaints [of MCS] should not be dismissed as psychogenic, and a thorough workup is essential," we recommend that MCS be formally diagnosed--in addition to any other disorders that may be present--in all cases in which the 6 aforementioned consensus criteria are met and no single other organic disorder (e.g., mastocytosis) can account for all the signs and symptoms associated with chemical exposure. The millions of civilians and tens of thousands of Gulf War veterans who

  5. Wireless sensor networks distributed consensus estimation

    CERN Document Server

    Chen, Cailian; Guan, Xinping

    2014-01-01

    This SpringerBrief evaluates the cooperative effort of sensor nodes to accomplish high-level tasks with sensing, data processing and communication. The metrics of network-wide convergence, unbiasedness, consistency and optimality are discussed through network topology, distributed estimation algorithms and consensus strategy. Systematic analysis reveals that proper deployment of sensor nodes and a small number of low-cost relays (without sensing function) can speed up the information fusion and thus improve the estimation capability of wireless sensor networks (WSNs). This brief also investiga

  6. Local communities obstruct global consensus: Naming game on multi-local-world networks

    CERN Document Server

    Lou, Yang; Fan, Zhengping; Xiang, Luna

    2016-01-01

    Community structure is essential for social communications, where individuals belonging to the same community are much more actively interacting and communicating with each other than those in different communities within the human society. Naming game, on the other hand, is a social communication model that simulates the process of learning a name of an object within a community of humans, where the individuals can reach global consensus on naming an object asymptotically through iterative pair-wise conversations. The underlying communication network indicates the relationships among the individuals. In this paper, three typical topologies of human communication networks, namely random-graph, small-world and scale-free networks, are employed, which are embedded with the multi-local-world community structure, to study the naming game. Simulations show that 1) when the intra-community connections increase while the inter-community connections remain to be unchanged, the convergence to global consensus is slow ...

  7. Global consensus on keratoconus and ectatic diseases.

    Science.gov (United States)

    Gomes, José A P; Tan, Donald; Rapuano, Christopher J; Belin, Michael W; Ambrósio, Renato; Guell, José L; Malecaze, François; Nishida, Kohji; Sangwan, Virender S

    2015-04-01

    Despite extensive knowledge regarding the diagnosis and management of keratoconus and ectatic corneal diseases, many controversies still exist. For that reason, there is a need for current guidelines for the diagnosis and management of these conditions. This project aimed to reach consensus of ophthalmology experts from around the world regarding keratoconus and ectatic diseases, focusing on their definition, concepts, clinical management, and surgical treatments. The Delphi method was followed with 3 questionnaire rounds and was complemented with a face-to-face meeting. Thirty-six panelists were involved and allocated to 1 of 3 panels: definition/diagnosis, nonsurgical management, or surgical treatment. The level of agreement considered for consensus was two thirds. Numerous agreements were generated in definitions, methods of diagnosing, and management of keratoconus and other ectatic diseases. Nonsurgical and surgical treatments for these conditions, including the use of corneal cross-linking and corneal transplantations, were presented in a stepwise approach. A flowchart describing a logical management sequence for keratoconus was created. This project resulted in definitions, statements, and recommendations for the diagnosis and management of keratoconus and other ectatic diseases. It also provides an insight into the current worldwide treatment of these conditions.

  8. Consensus on biomarkers for neuroendocrine tumour disease

    Science.gov (United States)

    Oberg, Kjell; Modlin, Irvin M; De Herder, Wouter; Pavel, Marianne; Klimstra, David; Frilling, Andrea; Metz, David C; Heaney, Anthony; Kwekkeboom, Dik; Strosberg, Jonathan; Meyer, Timothy; Moss, Steven F; Washington, Kay; Wolin, Edward; Liu, Eric; Goldenring, James

    2016-01-01

    Management of neuroendocrine neoplasia represents a clinical challenge because of its late presentation, lack of treatment options, and limitations in present imaging modalities and biomarkers to guide management. Monoanalyte biomarkers have poor sensitivity, specificity, and predictive ability. A National Cancer Institute summit, held in 2007, on neuroendocrine tumours noted biomarker limitations to be a crucial unmet need in the management of neuroendocrine tumours. A multinational consensus meeting of multidisciplinary experts in neuroendocrine tumours assessed the use of current biomarkers and defined the perquisites for novel biomarkers via the Delphi method. Consensus (at >75%) was achieved for 88 (82%) of 107 assessment questions. The panel concluded that circulating multianalyte biomarkers provide the highest sensitivity and specificity necessary for minimum disease detection and that this type of biomarker had sufficient information to predict treatment effectiveness and prognosis. The panel also concluded that no monoanalyte biomarker of neuroendocrine tumours has yet fulfilled these criteria and there is insufficient information to support the clinical use of miRNA or circulating tumour cells as useful prognostic markers for this disease. The panel considered that trials measuring multianalytes (eg, neuroendocrine gene transcripts) should also identify how such information can optimise the management of patients with neuroendocrine tumours. PMID:26370353

  9. International Consensus On (ICON) Pediatric Asthma

    Science.gov (United States)

    Papadopoulos, N. G.; Arakawa, H.; Carlsen, K.-H.; Custovic, A.; Gern, J.; Lemanske, R.; Le Souef, P.; Makela, M.; Roberts, G.; Wong, G.; Zar, H.; Akdis, C. A.; Bacharier, L. B.; Baraldi, E.; van Bever, H. P.; de Blic, J.; Boner, A.; Burks, W.; Casale, T. B.; Castro-Rodriguez, J. A.; Chen, Y. Z.; El-Gamal, Y. M.; Everard, M. L.; Frischer, T.; Geller, M.; Gereda, J.; Goh, D. Y.; Guilbert, T. W.; Hedlin, G.; Heymann, P. W.; Hong, S. J.; Hossny, E. M.; Huang, J. L.; Jackson, D. J.; de Jongste, J. C.; Kalayci, O.; Khaled, N.; Kling, S.; Kuna, P.; Lau, S.; Ledford, D. K.; Lee, S. I.; Liu, A. H.; Lockey, R. F.; Lodrup-Carlsen, K.; Lotvall, J.; Morikawa, A.; Nieto, A.; Paramesh, H.; Pawankar, R.; Pohunek, P.; Pongracic, J.; Price, D.; Robertson, C.; Rosario, N.; Rossenwasser, L. J.; Sly, P. D.; Stein, R.; Stick, S.; Szefler, S.; Taussig, L. M.; Valovirta, E.; Vichyanond, P.; Wallace, D.; Weinberg, E.; Wennergren, G.; Wildhaber, J.; Zeiger, R. S.

    2015-01-01

    Asthma is the most common chronic lower respiratory disease in childhood throughout the world. Several guidelines and/or consensus documents are available to support medical decisions on pediatric asthma. Although there is no doubt that the use of common systematic approaches for management can considerably improve outcomes, dissemination and implementation of these are still major challenges. Consequently, the International Collaboration in Asthma, Allergy and Immunology (iCAALL), recently formed by the EAACI, AAAAI, ACAAI and WAO, has decided to propose an International Consensus on (ICON) Pediatric Asthma. The purpose of this document is to highlight the key messages that are common to many of the existing guidelines, while critically reviewing and commenting on any differences, thus providing a concise reference. The principles of pediatric asthma management are generally accepted. Overall, the treatment goal is disease control. In order to achieve this, patients and their parents should be educated to optimally manage the disease, in collaboration with health care professionals. Identification and avoidance of triggers is also of significant importance. Assessment and monitoring should be performed regularly to re-evaluate and fine-tune treatment. Pharmacotherapy is the cornerstone of treatment. The optimal use of medication can, in most cases, help patients control symptoms and reduce the risk for future morbidity. The management of exacerbations is a major consideration, independent from chronic treatment. There is a trend towards considering phenotype specific treatment choices; however this goal has not yet been achieved. PMID:22702533

  10. Frailty Consensus: A Call to Action

    Science.gov (United States)

    Morley, John E.; Vellas, Bruno; van Kan, G. Abellan; Anker, Stefan D.; Bauer, Juergen M.; Bernabei, Roberto; Cesari, Matteo; Chumlea, W.C.; Doehner, Wolfram; Evans, Jonathan; Fried, Linda P.; Guralnik, Jack M.; Katz, Paul R.; Malmstrom, Theodore K.; McCarter, Roger J.; Gutierrez Robledo, Luis M.; Rockwood, Ken; von Haehling, Stephan; Vandewoude, Maurits F.; Walston, Jeremy

    2014-01-01

    Frailty is a clinical state in which there is an increase in an individual’s vulnerability for developing increased dependency and/or mortality when exposed to a stressor. Frailty can occur as the result of a range of diseases and medical conditions. A consensus group consisting of delegates from 6 major international, European, and US societies created 4 major consensus points on a specific form of frailty: physical frailty. Physical frailty is an important medical syndrome. The group defined physical frailty as “a medical syndrome with multiple causes and contributors that is characterized by diminished strength, endurance, and reduced physiologic function that increases an individual’s vulnerability for developing increased dependency and/or death.”Physical frailty can potentially be prevented or treated with specific modalities, such as exercise, protein-calorie supplementation, vitamin D, and reduction of polypharmacy.Simple, rapid screening tests have been developed and validated, such as the simple FRAIL scale, to allow physicians to objectively recognize frail persons.For the purposes of optimally managing individuals with physical frailty, all persons older than 70 years and all individuals with significant weight loss (≥5%) due to chronic disease should be screened for frailty. PMID:23764209

  11. Dialogic Consensus In Clinical Decision-Making.

    Science.gov (United States)

    Walker, Paul; Lovat, Terry

    2016-12-01

    This paper is predicated on the understanding that clinical encounters between clinicians and patients should be seen primarily as inter-relations among persons and, as such, are necessarily moral encounters. It aims to relocate the discussion to be had in challenging medical decision-making situations, including, for example, as the end of life comes into view, onto a more robust moral philosophical footing than is currently commonplace. In our contemporary era, those making moral decisions must be cognizant of the existence of perspectives other than their own, and be attuned to the demands of inter-subjectivity. Applicable to clinical practice, we propose and justify a Habermasian approach as one useful means of achieving what can be described as dialogic consensus. The Habermasian approach builds around, first, his discourse theory of morality as universalizable to all and, second, communicative action as a cooperative search for truth. It is a concrete way to ground the discourse which must be held in complex medical decision-making situations, in its actual reality. Considerations about the theoretical underpinnings of the application of dialogic consensus to clinical practice, and potential difficulties, are explored.

  12. International consensus on (ICON) pediatric asthma.

    Science.gov (United States)

    Papadopoulos, N G; Arakawa, H; Carlsen, K-H; Custovic, A; Gern, J; Lemanske, R; Le Souef, P; Mäkelä, M; Roberts, G; Wong, G; Zar, H; Akdis, C A; Bacharier, L B; Baraldi, E; van Bever, H P; de Blic, J; Boner, A; Burks, W; Casale, T B; Castro-Rodriguez, J A; Chen, Y Z; El-Gamal, Y M; Everard, M L; Frischer, T; Geller, M; Gereda, J; Goh, D Y; Guilbert, T W; Hedlin, G; Heymann, P W; Hong, S J; Hossny, E M; Huang, J L; Jackson, D J; de Jongste, J C; Kalayci, O; Aït-Khaled, N; Kling, S; Kuna, P; Lau, S; Ledford, D K; Lee, S I; Liu, A H; Lockey, R F; Lødrup-Carlsen, K; Lötvall, J; Morikawa, A; Nieto, A; Paramesh, H; Pawankar, R; Pohunek, P; Pongracic, J; Price, D; Robertson, C; Rosario, N; Rossenwasser, L J; Sly, P D; Stein, R; Stick, S; Szefler, S; Taussig, L M; Valovirta, E; Vichyanond, P; Wallace, D; Weinberg, E; Wennergren, G; Wildhaber, J; Zeiger, R S

    2012-08-01

    Asthma is the most common chronic lower respiratory disease in childhood throughout the world. Several guidelines and/or consensus documents are available to support medical decisions on pediatric asthma. Although there is no doubt that the use of common systematic approaches for management can considerably improve outcomes, dissemination and implementation of these are still major challenges. Consequently, the International Collaboration in Asthma, Allergy and Immunology (iCAALL), recently formed by the EAACI, AAAAI, ACAAI, and WAO, has decided to propose an International Consensus on (ICON) Pediatric Asthma. The purpose of this document is to highlight the key messages that are common to many of the existing guidelines, while critically reviewing and commenting on any differences, thus providing a concise reference. The principles of pediatric asthma management are generally accepted. Overall, the treatment goal is disease control. To achieve this, patients and their parents should be educated to optimally manage the disease, in collaboration with healthcare professionals. Identification and avoidance of triggers is also of significant importance. Assessment and monitoring should be performed regularly to re-evaluate and fine-tune treatment. Pharmacotherapy is the cornerstone of treatment. The optimal use of medication can, in most cases, help patients control symptoms and reduce the risk for future morbidity. The management of exacerbations is a major consideration, independent of chronic treatment. There is a trend toward considering phenotype-specific treatment choices; however, this goal has not yet been achieved.

  13. Consensus in networks of mobile communicating agents

    Science.gov (United States)

    Baronchelli, Andrea; Díaz-Guilera, Albert

    2012-01-01

    Populations of mobile and communicating agents describe a vast array of technological and natural systems, ranging from sensor networks to animal groups. Here, we investigate how a group-level agreement may emerge in the continuously evolving network defined by the local interactions of the moving individuals. We adopt a general scheme of motion in two dimensions and we let the individuals interact through the minimal naming game, a prototypical scheme to investigate social consensus. We distinguish different regimes of convergence determined by the emission range of the agents and by their mobility, and we identify the corresponding scaling behaviors of the consensus time. In the same way, we rationalize also the behavior of the maximum memory used during the convergence process, which determines the minimum cognitive/storage capacity needed by the individuals. Overall, we believe that the simple and general model presented in this paper can represent a helpful reference for a better understanding of the behavior of populations of mobile agents.

  14. Consensus in evolving networks of mobile agents

    Science.gov (United States)

    Baronchelli, Andrea; Díaz-Guilera, Albert

    2012-02-01

    Populations of mobile and communicating agents describe a vast array of technological and natural systems, ranging from sensor networks to animal groups. Here, we investigate how a group-level agreement may emerge in the continuously evolving networks defined by the local interactions of the moving individuals. We adopt a general scheme of motion in two dimensions and we let the individuals interact through the minimal naming game, a prototypical scheme to investigate social consensus. We distinguish different regimes of convergence determined by the emission range of the agents and by their mobility, and we identify the corresponding scaling behaviors of the consensus time. In the same way, we rationalize also the behavior of the maximum memory used during the convergence process, which determines the minimum cognitive/storage capacity needed by the individuals. Overall, we believe that the simple and general model presented in this talk can represent a helpful reference for a better understanding of the behavior of populations of mobile agents.

  15. Consensus Paper: Management of Degenerative Cerebellar Disorders

    Science.gov (United States)

    Ilg, W.; Bastian, A. J.; Boesch, S.; Burciu, R. G.; Celnik, P.; Claaßen, J.; Feil, K.; Kalla, R.; Miyai, I.; Nachbauer, W.; Schöls, L.; Strupp, M.; Synofzik, M.; Teufel, J.

    2015-01-01

    Treatment of motor symptoms of degenerative cerebellar ataxia remains difficult. Yet there are recent developments that are likely to lead to significant improvements in the future. Most desirable would be a causative treatment of the underlying cerebellar disease. This is currently available only for a very small subset of cerebellar ataxias with known metabolic dysfunction. However, increasing knowledge of the pathophysiology of hereditary ataxia should lead to an increasing number of medically sensible drug trials. In this paper, data from recent drug trials in patients with recessive and dominant cerebellar ataxias will be summarized. There is consensus that up to date, no medication has been proven effective. Aminopyridines and acetazolamide are the only exception, which are beneficial in patients with episodic ataxia type 2. Aminopyridines are also effective in a subset of patients presenting with downbeat nystagmus. As such, all authors agreed that the mainstays of treatment of degenerative cerebellar ataxia are currently physiotherapy, occupational therapy, and speech therapy. For many years, well-controlled rehabilitation studies in patients with cerebellar ataxia were lacking. Data of recently published studies show that coordinative training improves motor function in both adult and juvenile patients with cerebellar degeneration. Given the well-known contribution of the cerebellum to motor learning, possible mechanisms underlying improvement will be outlined. There is consensus that evidence-based guidelines for the physiotherapy of degenerative cerebellar ataxia need to be developed. Future developments in physiotherapeutical interventions will be discussed including application of non-invasive brain stimulation. PMID:24222635

  16. Consensus statement on panic disorder from the International Consensus Group on Depression and Anxiety

    NARCIS (Netherlands)

    Ballenger, JC; Lecrubier, Y; Nutt, DJ; Baldwin, DS; den Boer, JA; Kasper, S; Shear, MK

    1998-01-01

    Objective: To provide primary care clinicians with a better understanding of management issues in panic disorder and guide clinical practice with recommendations for appropriate pharmacotherapy. Participants: The 4 members of the International Consensus Group on Depression and Anxiety were James C.

  17. Consensus Coding as a Tool in Visual Appearance Research

    Directory of Open Access Journals (Sweden)

    D R Simmons

    2011-04-01

    Full Text Available A common problem in visual appearance research is how to quantitatively characterise the visual appearance of a region of an image which is categorised by human observers in the same way. An example of this is scarring in medical images (Ayoub et al, 2010, The Cleft-Palate Craniofacial Journal, in press. We have argued that “scarriness” is itself a visual appearance descriptor which summarises the distinctive combination of colour, texture and shape information which allows us to distinguish scarred from non-scarred tissue (Simmons et al, ECVP 2009. Other potential descriptors for other image classes would be “metallic”, “natural”, or “liquid”. Having developed an automatic algorithm to locate scars in medical images, we then tested “ground truth” by asking untrained observers to draw around the region of scarring. The shape and size of the scar on the image was defined by building a contour plot of the agreement between observers' outlines and thresholding at the point above which 50% of the observers agreed: a consensus coding scheme. Based on the variability in the amount of overlap between the scar as defined by the algorithm, and the consensus scar of the observers, we have concluded that the algorithm does not completely capture the putative appearance descriptor “scarriness”. A simultaneous analysis of qualitative descriptions of the scarring by the observers revealed that other image features than those encoded by the algorithm (colour and texture might be important, such as scar boundary shape. This approach to visual appearance research in medical imaging has potential applications in other application areas, such as botany, geology and archaeology.

  18. Consensus on Moving Neighborhood Model of Peterson Graph

    CERN Document Server

    Arendt, Hannah

    2012-01-01

    In this paper, we study the consensus problem of multiple agents on a kind of famous graph, Peterson graph. It is an undirected graph with 10 vertices and 15 edges. Each agent randomly walks on this graph and communicates with each other if and only if they coincide on a node at the same time. We conduct numerical study on the consensus problem in this framework and show that global consensus can be achieved.

  19. Consensus of Heterogeneous Multiagent Systems with Arbitrarily Bounded Communication Delay

    Directory of Open Access Journals (Sweden)

    Xue Li

    2017-01-01

    Full Text Available This paper focuses on the consensus problem of high-order heterogeneous multiagent systems with arbitrarily bounded communication delays. Through the method of nonnegative matrices, we get a sufficient consensus condition for the systems with dynamically changing topology. The results of this paper show, even when there are arbitrarily bounded communication delays in the systems, all agents can reach a consensus no matter whether there are spanning trees for the corresponding communication graphs at any time.

  20. Consensus formation in science modeled by aggregated bibliographic coupling

    DEFF Research Database (Denmark)

    Nicolaisen, Jeppe; Frandsen, Tove Faber

    2012-01-01

    The level of consensus in science has traditionally been measured by a number of different methods. The variety is important as each method measures different aspects of science and consensus. Citation analytical studies have previously measured the level of consensus using the scientific journal...... as their unit of analysis. To produce a more fine grained citation analysis one needs to study consensusformation on an even more detailed level – i.e. the scientific document or article. To do so, we have developed a new technique that measures consensus by aggregatedbibliographiccouplings (ABC) between...

  1. Finite-time consensus of heterogeneous multi-agent systems

    Institute of Scientific and Technical Information of China (English)

    Zhu Ya-Kun; Guan Xin-Ping; Luo Xiao-Yuan

    2013-01-01

    We investigate the finite-time consensus problem for heterogeneous multi-agent systems composed of first-order and second-order agents.A novel continuous nonlinear distributed consensus protocol is constructed,and finite-time consensus criteria are obtained for the heterogeneous multi-agent systems.Compared with the existing results,the stationary and kinetic consensuses of the heterogeneous multi-agent systems can be achieved in a finite time respectively.Moreover,the leader can be a first-order or a second-order integrator agent.Finally,some simulation examples are employed to verify the efficiency of the theoretical results.

  2. Consensus and Stability Analysis of Networked Multiagent Predictive Control Systems.

    Science.gov (United States)

    Liu, Guo-Ping

    2017-04-01

    This paper is concerned with the consensus and stability problem of multiagent control systems via networks with communication delays and data loss. A networked multiagent predictive control scheme is proposed to achieve output consensus and also compensate for the communication delays and data loss actively. The necessary and sufficient conditions of achieving both consensus and stability of the closed-loop networked multiagent control systems are derived. An important result that is obtained is that the consensus and stability of closed-loop networked multiagent predictive control systems are not related to the communication delays and data loss. An example illustrates the performance of the networked multiagent predictive control scheme.

  3. NASA's strategic direction and the need for a national consensus

    National Research Council Canada - National Science Library

    Division on Engineering and Physical Sciences; National Research Council; Committee on NASA's Strategic Direction

    2012-01-01

    ...? After a "comprehensive independent assessment of NASA's strategic direction and agency management", the NRC Committee determined that, only with a national consensus on the agency's future strategic...

  4. Consensus states of local majority rule in stochastic process

    Energy Technology Data Exchange (ETDEWEB)

    Luo, Yu-Pin [Department of Electronic Engineering, National Formosa University, Huwei, 63201, Taiwan (China); Tang, Chia-Wei; Xu, Hong-Yuan [Department of Physics, Chung-Yuan Christian University, Chungli, 32023, Taiwan (China); Wu, Jinn-Wen [Department of Applied Mathematics, Chung-Yuan Christian University, Chungli, 32023, Taiwan (China); Huang, Ming-Chang, E-mail: mchuang@cycu.edu.tw [Center for Theoretical Science and Department of Physics, Chung-Yuan Christian University, Chungli, 32023, Taiwan (China)

    2015-04-03

    A sufficient condition for a network system to reach a consensus state of the local majority rule is shown. The influence of interpersonal environment on the occurrence probability of consensus states for Watts–Strogatz and scale-free networks with random initial states is analyzed by numerical method. We also propose a stochastic local majority rule to study the mean first passage time from a random state to a consensus and the escape rate from a consensus state for systems in a noisy environment. Our numerical results show that there exists a window of fluctuation strengths for which the mean first passage time from a random to a consensus state reduces greatly, and the escape rate of consensus states obeys the Arrhenius equation in the window. - Highlights: • A sufficient condition for reaching a consensus. • The relation between the geometry of networks and the reachability of a consensus. • Stochastic local majority rule. • The mean first-passage time and the escape rate of consensus states.

  5. Integrated consensus-based frameworks for unmanned vehicle routing and targeting assignment

    Science.gov (United States)

    Barnawi, Waleed T.

    Unmanned aerial vehicles (UAVs) are increasingly deployed in complex and dynamic environments to perform multiple tasks cooperatively with other UAVs that contribute to overarching mission effectiveness. Studies by the Department of Defense (DoD) indicate future operations may include anti-access/area-denial (A2AD) environments which limit human teleoperator decision-making and control. This research addresses the problem of decentralized vehicle re-routing and task reassignments through consensus-based UAV decision-making. An Integrated Consensus-Based Framework (ICF) is formulated as a solution to the combined single task assignment problem and vehicle routing problem. The multiple assignment and vehicle routing problem is solved with the Integrated Consensus-Based Bundle Framework (ICBF). The frameworks are hierarchically decomposed into two levels. The bottom layer utilizes the renowned Dijkstra's Algorithm. The top layer addresses task assignment with two methods. The single assignment approach is called the Caravan Auction Algorithm (CarA) Algorithm. This technique extends the Consensus-Based Auction Algorithm (CBAA) to provide awareness for task completion by agents and adopt abandoned tasks. The multiple assignment approach called the Caravan Auction Bundle Algorithm (CarAB) extends the Consensus-Based Bundle Algorithm (CBBA) by providing awareness for lost resources, prioritizing remaining tasks, and adopting abandoned tasks. Research questions are investigated regarding the novelty and performance of the proposed frameworks. Conclusions regarding the research questions will be provided through hypothesis testing. Monte Carlo simulations will provide evidence to support conclusions regarding the research hypotheses for the proposed frameworks. The approach provided in this research addresses current and future military operations for unmanned aerial vehicles. However, the general framework implied by the proposed research is adaptable to any unmanned

  6. Using Network Dynamical Influence to Drive Consensus

    Science.gov (United States)

    Punzo, Giuliano; Young, George F.; MacDonald, Malcolm; Leonard, Naomi E.

    2016-05-01

    Consensus and decision-making are often analysed in the context of networks, with many studies focusing attention on ranking the nodes of a network depending on their relative importance to information routing. Dynamical influence ranks the nodes with respect to their ability to influence the evolution of the associated network dynamical system. In this study it is shown that dynamical influence not only ranks the nodes, but also provides a naturally optimised distribution of effort to steer a network from one state to another. An example is provided where the “steering” refers to the physical change in velocity of self-propelled agents interacting through a network. Distinct from other works on this subject, this study looks at directed and hence more general graphs. The findings are presented with a theoretical angle, without targeting particular applications or networked systems; however, the framework and results offer parallels with biological flocks and swarms and opportunities for design of technological networks.

  7. Consensus control of flexible-joint robots

    Science.gov (United States)

    Avila-Becerril, Sofía; Espinosa-Pérez, Gerardo; Panteley, Elena; Ortega, Romeo

    2015-06-01

    Synchronisation of networks composed by fully actuated robot manipulators has received a lot of attention from the control theory community. Unfortunately, the case of under-actuated robots has not been deeply studied. The aim of this paper is to extend previous results reported by the authors addressing the particular (but of practical interest) case of networks composed by flexible-joint robots. The main feature of the contribution is to consider a change of coordinates, first introduced in Nuno, Ortega, Basanes and Hill, to solve the consensus problem assuming the existence of unknown delays in the communication channels. The extension is twofold, namely: the presentation of a control scheme that, in contrast to the one considered in Avila-Becerril and Espinosa-Perez, does not require knowledge of the initial conditions and the proof that the controller can also be implemented in Cartesian coordinates. The usefulness of the contribution is illustrated through numerical simulations.

  8. Distributed consensus and fault tolerance - Lecture 2

    CERN Document Server

    CERN. Geneva

    2017-01-01

    In a world where clusters with thousands of nodes are becoming commonplace, we are often faced with the task of having them coordinate and share state. As the number of machines goes up, so does the probability that something goes wrong: a node could temporarily lose connectivity, crash because of some race condition, or have its hard drive fail. What are the challenges when designing fault-tolerant distributed systems, where a cluster is able to survive the loss of individual nodes? In this lecture, we will discuss some basics on this topic (consistency models, CAP theorem, failure modes, byzantine faults), detail the raft consensus algorithm, and showcase an interesting example of a highly resilient distributed system, bitcoin.

  9. Distributed consensus and fault tolerance - Lecture 1

    CERN Document Server

    CERN. Geneva

    2017-01-01

    In a world where clusters with thousands of nodes are becoming commonplace, we are often faced with the task of having them coordinate and share state. As the number of machines goes up, so does the probability that something goes wrong: a node could temporarily lose connectivity, crash because of some race condition, or have its hard drive fail. What are the challenges when designing fault-tolerant distributed systems, where a cluster is able to survive the loss of individual nodes? In this lecture, we will discuss some basics on this topic (consistency models, CAP theorem, failure modes, byzantine faults), detail the raft consensus algorithm, and showcase an interesting example of a highly resilient distributed system, bitcoin.

  10. Consensus and new improvements of disability glare

    Directory of Open Access Journals (Sweden)

    Yu-Wei Zheng

    2014-12-01

    Full Text Available Patients with early cataract may have normal visual acuity(VAbut complain that they have problems in driving at night, like seeing things through a veil. This phenomenon is defined as disability glare which maybe caused by growing stray light. Patients with intraocular lens following cataract surgery may complain about glare, halos and shadows in visual field, which are also resulted from dysphotopia. Disability glare is the VA loss due to disturbing luminance in visual field. In other words, it's the retinal contrast sensitivity reduction because of the straylight. This article contains the consensus and new progress of disability glare. It provides solutions according to its effect factors and offers clues for further study.

  11. CONSENSUS STATEMENT ON THE MANAGEMENT OF URTICARIA

    Science.gov (United States)

    Godse, Kiran V; Zawar, Vijay; Krupashankar, DS; Girdhar, Mukesh; Kandhari, Sanjiv; Dhar, Sandipan; Ghosh, Sanjay; Rajagopalan, Murlidhar; Zuberbier, Torsten

    2011-01-01

    This consensus statement was developed by Special Interest Group – Urticaria (IADVL). Urticaria, a heterogeneous group of diseases, often cannot be recognized by its morphology. Due to non-specific and non-affordable diagnosis, management of urticaria, especially chronic urticaria, is very challenging. This guideline includes definition, causes, classification and management of urticaria. Urticaria has a profound impact on the quality of life and causes immense distress to patients, necessitating effective treatment. One approach to manage urticaria is identification and elimination of the underlying cause(s) and/or eliciting trigger(s), while the second one is treatment aimed at providing symptomatic relief. This guideline recommends use of second-generation non-sedating H1 antihistamines as the first-line treatment. The dose can be increased up to four times to meet the expected results. In case patients still do not respond, appropriate treatment options can be selected depending on the cost. PMID:22121259

  12. Consensus document on European brain research

    DEFF Research Database (Denmark)

    Di Luca, Monica; Baker, Mary; Corradetti, Renato

    2011-01-01

    Psychiatric and neurological diseases combined represent a considerable social and economic burden in Europe. A recent study conducted by the European Brain Council (EBC) quantified the 'cost and burden' of major brain diseases in Europe, amounting to €386bn per year. Considering that these costs...... the economic and social challenge posed by management of brain diseases in European countries. To setup a platform for discussion, EBC published in 2006 a Consensus Document on European Brain Research, describing needs and achievements of research in Europe and presenting proposals for future research programs....... Since 2006, European research in neuroscience has advanced tremendously. The present document represents an update elaborated to reflect changes in research priorities and advances in brain research that have taken place since 2006. The same approach and format have been used here as in the previous...

  13. Consensus recommendations for anaesthetic peripheral nerve block.

    Science.gov (United States)

    Santos Lasaosa, S; Cuadrado Pérez, M L; Guerrero Peral, A L; Huerta Villanueva, M; Porta-Etessam, J; Pozo-Rosich, P; Pareja, J A

    2017-06-01

    Anaesthetic block, alone or in combination with other treatments, represents a therapeutic resource for treating different types of headaches. However, there is significant heterogeneity in patterns of use among different professionals. This consensus document has been drafted after a thorough review and analysis of the existing literature and our own clinical experience. The aim of this document is to serve as guidelines for professionals applying anaesthetic blocks. Recommendations are based on the levels of evidence of published studies on migraine, trigeminal autonomic cephalalgias, cervicogenic headache, and pericranial neuralgias. We describe the main technical and formal considerations of the different procedures, the potential adverse reactions, and the recommended approach. Anaesthetic block in patients with headache should always be individualised and based on a thorough medical history, a complete neurological examination, and expert technical execution. Copyright © 2016 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  14. 2003 Canadian Asthma Consensus Guidelines Executive Summary

    Directory of Open Access Journals (Sweden)

    Becker Allan

    2006-03-01

    Full Text Available Abstract Background Guidelines for the diagnosis and management of asthma have been published over the last 15 years; however, there has been little focus on issues relating to asthma in childhood. Since the last revision of the 1999 Canadian Asthma Consensus Report, important new studies, particularly in children, have highlighted the need to incorporate new information into the asthma guidelines. The objectives of this article are to review the literature on asthma published between January 2000 and June 2003 and to evaluate the influence of new evidence on the recommendations made in the 1999 Canadian Asthma Consensus Report and its 2001 update, with a major focus on pediatric issues. Methods The diagnosis of asthma in young children and prevention strategies, pharmacotherapy, inhalation devices, immunotherapy, and asthma education were selected for review by small expert resource groups. The reviews were discussed in June 2003 at a meeting under the auspices of the Canadian Network For Asthma Care and the Canadian Thoracic Society. Data published through December 2004 were subsequently reviewed by the individual expert resource groups. Results This report evaluates early-life prevention strategies and focuses on treatment of asthma in children, emphasizing the importance of early diagnosis and preventive therapy, the benefits of additional therapy, and the essential role of asthma education. Conclusion We generally support previous recommendations and focus on new issues, particularly those relevant to children and their families. This document is a guide for asthma management based on the best available published data and the opinion of health care professionals, including asthma experts and educators.

  15. From social network (centralized vs. decentralized) to collective decision-making (unshared vs. shared consensus).

    Science.gov (United States)

    Sueur, Cédric; Deneubourg, Jean-Louis; Petit, Odile

    2012-01-01

    Relationships we have with our friends, family, or colleagues influence our personal decisions, as well as decisions we make together with others. As in human beings, despotism and egalitarian societies seem to also exist in animals. While studies have shown that social networks constrain many phenomena from amoebae to primates, we still do not know how consensus emerges from the properties of social networks in many biological systems. We created artificial social networks that represent the continuum from centralized to decentralized organization and used an agent-based model to make predictions about the patterns of consensus and collective movements we observed according to the social network. These theoretical results showed that different social networks and especially contrasted ones--star network vs. equal network--led to totally different patterns. Our model showed that, by moving from a centralized network to a decentralized one, the central individual seemed to lose its leadership in the collective movement's decisions. We, therefore, showed a link between the type of social network and the resulting consensus. By comparing our theoretical data with data on five groups of primates, we confirmed that this relationship between social network and consensus also appears to exist in animal societies.

  16. Methodological Quality of Consensus Guidelines in Implant Dentistry

    Science.gov (United States)

    Faggion, Clovis Mariano; Apaza, Karol; Ariza-Fritas, Tania; Málaga, Lilian; Giannakopoulos, Nikolaos Nikitas; Alarcón, Marco Antonio

    2017-01-01

    Background Consensus guidelines are useful to improve clinical decision making. Therefore, the methodological evaluation of these guidelines is of paramount importance. Low quality information may guide to inadequate or harmful clinical decisions. Objective To evaluate the methodological quality of consensus guidelines published in implant dentistry using a validated methodological instrument. Methods The six implant dentistry journals with impact factors were scrutinised for consensus guidelines related to implant dentistry. Two assessors independently selected consensus guidelines, and four assessors independently evaluated their methodological quality using the Appraisal of Guidelines for Research & Evaluation (AGREE) II instrument. Disagreements in the selection and evaluation of guidelines were resolved by consensus. First, the consensus guidelines were analysed alone. Then, systematic reviews conducted to support the guidelines were included in the analysis. Non-parametric statistics for dependent variables (Wilcoxon signed rank test) was used to compare both groups. Results Of 258 initially retrieved articles, 27 consensus guidelines were selected. Median scores in four domains (applicability, rigour of development, stakeholder involvement, and editorial independence), expressed as percentages of maximum possible domain scores, were below 50% (median, 26%, 30.70%, 41.70%, and 41.70%, respectively). The consensus guidelines and consensus guidelines + systematic reviews data sets could be compared for 19 guidelines, and the results showed significant improvements in all domain scores (p < 0.05). Conclusions Methodological improvement of consensus guidelines published in major implant dentistry journals is needed. The findings of the present study may help researchers to better develop consensus guidelines in implant dentistry, which will improve the quality and trust of information needed to make proper clinical decisions. PMID:28107405

  17. Coding ATC Incident Data Using HFACS: Intercoder Consensus

    Directory of Open Access Journals (Sweden)

    Liang Wang

    2011-01-01

    Full Text Available Reliability studies for coding contributing factors of incident reports in high hazard industries are rarely conducted and reported. Although the Human Factors Analysis and Classification System (HFACS appears to have a larger number of such studies completed than most other systems doubt exists as the accuracy and comparability of results between studies due to aspects of methodology and reporting. This paper reports on a trial conducted on HFACS to determine its reliability in the context of military air traffic control (ATC. Two groups participated in the trial: one group comprised of specialists in the field of human factors, and the other group comprised air traffic controllers. All participants were given standardized training via a self-paced workbook and then read 14 incident reports and coded the associated findings. The results show similarly low consensus for both groups of participants. Several reasons for the results are proposed associated with the HFACS model, the context within which incident reporting occurs in real organizations and the conduct of the studies.

  18. Reconciliation of the Washington Consensus with the Beijing Model in Africa

    OpenAIRE

    Asongu, Simplice; Nwachukwu, Jacinta

    2016-01-01

    In this study, we argue that an approach which will reconcile the two opposing camps in Sino-African relations and bring the most progress is a “middle passage” that greases contradictions and offers an accommodative, balanced and pragmatic vision on which Africans can unite. We present a case under which countries can substantially enhance the prospect of development if an African consensus builds on a merger between the Western and Chinese models. We balance national interest with human ri...

  19. Ensemble distribution models in conservation prioritization: from consensus predictions to consensus reserve networks

    Science.gov (United States)

    Meller, Laura; Cabeza, Mar; Pironon, Samuel; Barbet-Massin, Morgane; Maiorano, Luigi; Georges, Damien; Thuiller, Wilfried

    2014-01-01

    Aim Conservation planning exercises increasingly rely on species distributions predicted either from one particular statistical model or, more recently, from an ensemble of models (i.e. ensemble forecasting). However, it has not yet been explored how different ways of summarizing ensemble predictions affect conservation planning outcomes. We evaluate these effects and compare commonplace consensus methods, applied before the conservation prioritization phase, to a novel method that applies consensus after reserve selection. Location Europe. Methods We used an ensemble of predicted distributions of 146 Western Palaearctic bird species in alternative ways: four different consensus methods, as well as distributions discounted with variability, were used to produce inputs for spatial conservation prioritization. In addition, we developed and tested a novel method, in which we built 100 datasets by sampling the ensemble of predicted distributions, ran a conservation prioritization analysis on each of them and averaged the resulting priority ranks. We evaluated the conservation outcome against three controls: (i) a null control, based on random ranking of cells; (2) the reference solution, based on an expert-refined dataset; and (3) the independent solution, based on an independent dataset. Results Networks based on predicted distributions were more representative of rare species than randomly selected networks. Alternative methods to summarize ensemble predictions differed in representativeness of resulting reserve networks. Our novel method resulted in better representation of rare species than pre-selection consensus methods. Main conclusions Retaining information about the variation in the predicted distributions throughout the conservation prioritization seems to provide better results than summarizing the predictions before conservation prioritization. Our results highlight the need to understand and consider model-based uncertainty when using predicted

  20. Consent and consensus-ethical perspectives on obtaining bodies for anatomical dissection.

    Science.gov (United States)

    Winkelmann, Andreas

    2016-01-01

    Biomedical research and education benefit from the use of human cadavers. These are usually acquired from donors who have willed their body to science during their lifetime. This concept of donation through "informed consent" respects the personal autonomy of the donor and the dignity of the dead body (extended from the dignity of the living person). The concept of informed consent is taken from research on living human subjects regulated in the Helsinki Declaration. This transfer to the domain of anatomical donation, however, has several problems. For example, the dead cannot speak for themselves and the ethical status of the human cadaver remains ambiguous. It is therefore suggested that an element of consensus is added to the concept of consent, a consensus between donors, relatives, anatomists, and the wider community. A consensus can give difficult decisions surrounding body donation and dissection a broader basis and can help bridge the gap between donors and families on the one side and anatomists, researchers and students on the other side. This approach can help to establish relationships of trust with local communities, on which body donation programs depend.

  1. Consensus in Directed Networks of Agents With Nonlinear Dynamics

    NARCIS (Netherlands)

    Yu, Wenwu; Chen, Guanrong; Cao, Ming; Qu, Z.

    2011-01-01

    This technical note studies the consensus problem for cooperative agents with nonlinear dynamics in a directed network. Both local and global consensus are defined and investigated. Techniques for studying the synchronization in such complex networks are exploited to establish various sufficient con

  2. 77 FR 24251 - Consensus Standards, Light-Sport Aircraft

    Science.gov (United States)

    2012-04-23

    ... Federal Aviation Administration Consensus Standards, Light-Sport Aircraft AGENCY: Federal Aviation... availability of three new and three revised consensus standards relating to the provisions of the Sport Pilot and Light-Sport Aircraft rule issued July 16, 2004, and effective September 1, 2004....

  3. 78 FR 35085 - Consensus Standards, Light-Sport Aircraft

    Science.gov (United States)

    2013-06-11

    ... Federal Aviation Administration Consensus Standards, Light-Sport Aircraft AGENCY: Federal Aviation... availability of one new and seven revised consensus standards relating to the provisions of the Sport Pilot and Light-Sport Aircraft rule issued July 16, 2004, and effective September 1, 2004. ASTM...

  4. Consensus of Multiagent Systems with Sampled Information and Noisy Measurements

    Directory of Open Access Journals (Sweden)

    Zhao-Jun Tang

    2013-01-01

    Full Text Available We consider consensus problems of first-order multiagent systems with sampled information and noisy measurements. A distributed stochastic approximation type algorithm is employed to attenuate the measurement noises. We provide conditions under which almost sure strong consensus is guaranteed for fixed and switching directed network topologies. Simulation results are provided to illustrate the theoretical results.

  5. Kyoto global consensus report on Helicobacter pylori gastritis

    NARCIS (Netherlands)

    K. Sugano (Kentaro); J. Tack (Jan); E.J. Kuipers (Ernst); D.Y. Graham (David Y.); E. El-Omar; S. Miura (Soichiro); K. Haruma (Ken); M. Asaka (Masahiro); N. Uemura (Naomi); P. Malfertheiner

    2015-01-01

    textabstractObjective To present results of the Kyoto Global Consensus Meeting, which was convened to develop global consensus on (1) classification of chronic gastritis and duodenitis, (2) clinical distinction of dyspepsia caused by Helicobacter pylori from functional dyspepsia, (3) appropriate dia

  6. A consensus on criteria for cure of acromegaly

    NARCIS (Netherlands)

    A. Giustina (Andrea); P. Chanson (Philippe); M.D. Bronstein; A. Klibanski; S.W.J. Lamberts (Steven); F.F. Casanueva; P. Trainer; E. Ghigo (Ezio); K.K.Y. Ho; S. Melmed (Shlomo)

    2010-01-01

    textabstractObjective: The Acromegaly Consensus Group met in April 2009 to revisit the guidelines on criteria for cure as defined in 2000. Participants: Participants included 74 neurosurgeons and endocrinologists with extensive experience of treating acromegaly. Evidence/Consensus Process: Relevant

  7. The Consensus Definition Redefined from a Representational Perspective

    Science.gov (United States)

    Zand Scholten, Annemarie

    2012-01-01

    This paper presents the author's critique to Paul E. Newton's article titled "Clarifying the consensus definition of validity." In his article, Newton not only clarifies but also redefines the consensus definition of validity. In this redefinition he omits the term "construct" and introduces the term "measurement." Both omission and introduction…

  8. Treatment of adrenocorticotropin-dependent cushing's syndrome: A consensus statement

    NARCIS (Netherlands)

    B.M.K. Biller; A. Grossman (Ashley Barry); P.M. Stewart; S. Melmed (Shlomo); X. Bertagna; J. Bertherat (Jerome); M. Buchfelder; A. Colao (Annamaria); A.R. Hermus (Ad); L.J. Hofland (Leo); A. Klibanski; A. Lacroix; J.R. Lindsay; J. Newell-Price; L.K. Nieman; S. Petersenn; N. Sonino; G.K. Stalla (Günter); B. Swearingen; M.L. Vance; J.A.H. Wass (John); M. Boscaro

    2008-01-01

    textabstractObjective: Our objective was to evaluate the published literature and reach a consensus on the treatment of patients with ACTH-dependent Cushing's syndrome, because there is no recent consensus on the management of this rare disorder. Participants: Thirty-two leading endocrinologists,

  9. Treatment of adrenocorticotropin-dependent Cushing's syndrome: a consensus statement.

    NARCIS (Netherlands)

    Grossman, A.B.; Stewart, P.M.; Melmed, S.; Bertagna, X.; Bertherat, J.; Buchfelder, M.; Colao, A.; Hermus, A.R.M.M.; Hofland, L.J.; Klibanski, A.; Lacroix, A.; Lindsay, J.R.; Newell-Price, J.; Nieman, L.K.; Petersenn, S.; Sonino, N.; Stalla, G.K.; Swearingen, B.; Vance, M.L.; Wass, J.A.; Boscaro, M.

    2008-01-01

    OBJECTIVE: Our objective was to evaluate the published literature and reach a consensus on the treatment of patients with ACTH-dependent Cushing's syndrome, because there is no recent consensus on the management of this rare disorder. PARTICIPANTS: Thirty-two leading endocrinologists, clinicians,

  10. A consensus on criteria for cure of acromegaly

    NARCIS (Netherlands)

    A. Giustina (Andrea); P. Chanson (Philippe); M.D. Bronstein; A. Klibanski; S.W.J. Lamberts (Steven); F.F. Casanueva; P. Trainer; E. Ghigo (Ezio); K.K.Y. Ho; S. Melmed (Shlomo)

    2010-01-01

    textabstractObjective: The Acromegaly Consensus Group met in April 2009 to revisit the guidelines on criteria for cure as defined in 2000. Participants: Participants included 74 neurosurgeons and endocrinologists with extensive experience of treating acromegaly. Evidence/Consensus Process: Relevant

  11. Kyoto global consensus report on Helicobacter pylori gastritis

    NARCIS (Netherlands)

    K. Sugano (Kentaro); J. Tack (Jan); E.J. Kuipers (Ernst); D.Y. Graham (David Y.); E. El-Omar; S. Miura (Soichiro); K. Haruma (Ken); M. Asaka (Masahiro); N. Uemura (Naomi); P. Malfertheiner; T. Azuma (Takeshi); F. Bazzoli (Franco); F.K.-L. Chan (Francis Ka-Leung); M. Chen (Minhu); N. Chiba (Naoki); T. Chiba (Tsutomu); L.G. Vas Coelho (Luiz Gonzaga); F. Di Mario (Francesco); K.M. Fock (Kwong Ming); Y. Fukuda (Yasuhiro); R.M. Genta (Robert Maximilian); K.-L. Goh (Khean-Lee); P.H. Katelaris (Peter Harry); M. Kato (Mototsugu); T. Kawai (Takashi); R. Kushima (Ryuji); V. Mahachai (Varocha); T. Matsuhisa (Takeshi); H. Miwa (Hiroto); K. Murakami (Kazunari); C. O'Morain (C.); M. Rugge (Massimo); K. Sato (Kiichi); T. Shimoyama (Tadashi); T. Sugiyama (Toshiro); H. Suzuki (Hidekazu); K. Yagi (Kazuyoshi); M.-S. Wu (Ming-Shiang); M. Ito (Masanori); N. Kim (Nayoung); T. Furuta (Takahisa); F. Mégraud (Francis); A. Shiotani (Akiko); T. Kamada (Tomonori)

    2015-01-01

    textabstractObjective To present results of the Kyoto Global Consensus Meeting, which was convened to develop global consensus on (1) classification of chronic gastritis and duodenitis, (2) clinical distinction of dyspepsia caused by Helicobacter pylori from functional dyspepsia, (3) appropriate

  12. Consensus networks with time-delays over finite fields

    Science.gov (United States)

    Li, Xiuxian; Su, Housheng; Chen, Michael Z. Q.

    2016-05-01

    In this paper, we investigate the consensus problem in networks with time-delays over finite fields. The delays are categorised into three cases: single constant delay, multiple constant delays, and time-varying bounded delays. For all cases, some sufficient and necessary conditions for consensus are derived. Furthermore, assuming that the communication graph is strongly connected, some of the obtained necessary conditions reveal that the conditions for consensus with time-delays over finite fields depend not only on the diagonal entries but also on the off-diagonal entries, something that is intrinsically distinct from the case over real numbers (where having at least one nonzero diagonal entry is a sufficient and necessary condition to guarantee consensus). In addition, it is shown that delayed networks cannot achieve consensus when the interaction graph is a tree if the corresponding delay-free networks cannot reach consensus, which is consistent with the result over real numbers. As for average consensus, we show that it can never be achieved for delayed networks over finite fields, although it indeed can be reached under several conditions for delay-free networks over finite fields. Finally, networks with time-varying delays are discussed and one sufficient condition for consensus is presented by graph-theoretic method.

  13. Randomized Consensus Processing over Random Graphs: Independence and Convergence

    CERN Document Server

    Shi, Guodong

    2011-01-01

    Various consensus algorithms over random networks have been investigated in the literature. In this paper, we focus on the role that randomized individual decision-making plays to consensus seeking under stochastic communications. At each time step, each node will independently choose to follow the consensus algorithm, or to stick to current state by a simple Bernoulli trial with time-dependent success probabilities. This node decision strategy characterizes the random node-failures on a communication networks, or a biased opinion selection in the belief evolution over social networks. Connectivity-independent and arc-independent graphs are defined, respectively, to capture the fundamental nature of random network processes with regard to the convergence of the consensus algorithms. A series of sufficient and/or necessary conditions are given on the success probability sequence for the network to reach a global consensus with probability one under different stochastic connectivity assumptions, by which a comp...

  14. Distributed Consensus over Wireless Sensor Networks Affected by Multipath Fading

    CERN Document Server

    Scutari, Gesualdo

    2008-01-01

    The design of sensor networks capable of reaching a consensus on a globally optimal decision test, without the need for a fusion center, is a problem that has received considerable attention in the last years. Many consensus algorithms have been proposed, with convergence conditions depending on the graph describing the interaction among the nodes. In most works, the graph is undirected and there are no propagation delays. Only recently, the analysis has been extended to consensus algorithms incorporating propagation delays. In this work, we propose a consensus algorithm able to converge to a globally optimal decision statistic, using a wideband wireless network, governed by a fairly simple MAC mechanism, where each link is a multipath, frequency-selective, channel. The main contribution of the paper is to derive necessary and sufficient conditions on the network topology and sufficient conditions on the channel transfer functions guaranteeing the exponential convergence of the consensus algorithm to a global...

  15. DASACT: A decision aiding software for axiomatic consensus theory.

    Science.gov (United States)

    Domenach, Florent; Tayari, Ali

    2016-01-01

    There have been various attempts, solutions, and approaches towards constructing an appropriate consensus tree based on a given set of phylogenetic trees. However, for practitioners, it is not always clear, for a given data set, which of these would create the most relevant consensus tree. In this paper, we introduce an open-source software called DASACT (Decision Aiding Software for Axiomatic Consensus Theory) created to assist practitioners on choosing the most appropriate consensus function. It is based on an exhaustive evaluation of axiomatic properties and consensus functions, which define the knowledge space as a concept lattice. Using a selection of axiomatic properties provided by the user, it is able to aid the user in choosing the most suitable function. DASACT is freely available at http://www.cs.unic.ac.cy/florent/software.htm. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Consensus maps of cloned plant cuticle genes

    Institute of Scientific and Technical Information of China (English)

    Eviatar; Nevo

    2010-01-01

    Plant cuticle,which covers the plant surface,consists of waxes and cutins,and is associated with plant drought,cold,and salt resistance.Hitherto,at least 47 genes participating in the formation of plant cuticle have been cloned from Arabidopsis thaliana,Oryza sativa,Zea mays,Ricinus communis,Brassica napus,and Medicago truncatula;and about 85% of them encode proteins sharing above 50% identities with their rice homologous sequences.These cloned cuticle genes were mapped in silico on different chromosomes of rice and Arabidopsis,respectively.The mapping results revealed that plant cuticle genes were not evenly distributed in both genomes.About 40% of the mapped cuticle genes were located on chromosome 1 in Arabidopsis,while 20% of the mapped cuticle genes were located on chromosome 2 but none on chromosome 12 in rice.Some cloned plant cuticle genes have several rice homologous sequences,which might be produced by chromosomal segment duplication.The consensus map of cloned plant cuticle genes will provide important clues for the selection of candidate genes in a positional cloning of an unknown cuticle gene in plants.

  17. The Delphi Technique: Making Sense of Consensus

    Directory of Open Access Journals (Sweden)

    Chia-Chien Hsu

    2007-08-01

    Full Text Available The Delphi technique is a widely used and accepted method for gathering data from respondents within their domain of expertise. The technique is designed as a group communication process which aims to achieve a convergence of opinion on a specific real-world issue. The Delphi process has been used in various fields of study such as program planning, needs assessment, policy determination, and resource utilization to develop a full range of alternatives, explore or expose underlying assumptions, as well as correlate judgments on a topic spanning a wide range of disciplines. The Delphi technique is well suited as a method for consensus-building by using a series of questionnaires delivered using multiple iterations to collect data from a panel of selected subjects. Subject selection, time frames for conducting and completing a study, the possibility of low response rates, and unintentionally guiding feedback from the respondent group are areas which should be considered when designing and implementing a Delphi study.

  18. National consensus on geriatric immunization 2011.

    Science.gov (United States)

    2012-01-01

    As the growth of elderly population increases, the number of geriatric patients who may demand health care services is also increasing since the elderly are more vulnerable to various conditions of acute illnesses. Upper respiratory tract infections are the leading cause of death and the most significant cause that impairs quality of life in the elderly. Upper respiratory tract infections and influenza are common in the elderly and may develop into pneumonia. Considering the high morbidity and mortality rates related to pneumonia in the elderly, it is important to have prevention strategies. A delay in diagnosis due to non-specific signs and symptoms of pneumonia in the elderly has demanded greater concern on the importance of pneumonia prevention strategies. Influenza and pneumonia impair quality of life in the elderly, resulted in decreased functional status (ADL scores) during infection and recovery period. With increasing antibiotic resistance, the management may be complicated as it may lead to conditions that reduce quality of life and cause high mortality rate. Therefore, immunization is very important as the prevention strategy against influenza and or pneumonia, reducing the incidence as well as the complication. The consensus has been made in order to provide immunization against influenza and pneumonia for elderly population in Indonesia. It is expected that by 2025, about 60% of the elderly in Indonesia would have immunization against influenza and 50% of them would have immunization against pneumonia annually.

  19. Sarcopenia With Limited Mobility: An International Consensus

    Science.gov (United States)

    Morley, John E.; Abbatecola, Angela Marie; Argiles, Josep M.; Baracos, Vickie; Bauer, Juergen; Bhasin, Shalender; Cederholm, Tommy; Stewart Coats, Andrew J.; Cummings, Steven R.; Evans, William J.; Fearon, Kenneth; Ferrucci, Luigi; Fielding, Roger A.; Guralnik, Jack M.; Harris, Tamara B.; Inui, Akio; Kalantar-Zadeh, Kamyar; Kirwan, Bridget-Anne; Mantovani, Giovanni; Muscaritoli, Maurizio; Newman, Anne B.; Rossi-Fanelli, Filippo; Rosano, Giuseppe M. C.; Roubenoff, Ronenn; Schambelan, Morris; Sokol, Gerald H.; Storer, Thomas W.; Vellas, Bruno; von Haehling, Stephan; Yeh, Shing-Shing; Anker, Stefan D.

    2016-01-01

    A consensus conference convened by the Society of Sarcopenia, Cachexia and Wasting Disorders has concluded that “Sarcopenia, ie, reduced muscle mass, with limited mobility” should be considered an important clinical entity and that most older persons should be screened for this condition. “Sarcopenia with limited mobility” is defined as a person with muscle loss whose walking speed is equal to or less than 1 m/s or who walks less than 400 m during a 6-minute walk, and who has a lean appendicular mass corrected for height squared of 2 standard deviations or more below the mean of healthy persons between 20 and 30 years of age of the same ethnic group. The limitation in mobility should not clearly be a result of otherwise defined specific diseases of muscle, peripheral vascular disease with intermittent claudication, central and peripheral nervous system disorders, or cachexia. Clinically significant interventions are defined as an increase in the 6-minute walk of at least 50 meters or an increase of walking speed of at least 0.1 m/s. “A word is not a crystal, transparent and unchanged; it is the skin of a living thought and may vary greatly in color and content according to the circumstances and the time when it is used.”—Oliver Wendell Holmes PMID:21640657

  20. Canadian Asthma Consensus Conference Summary of Recommendations

    Directory of Open Access Journals (Sweden)

    Pierre Ernst

    1996-01-01

    Full Text Available The Asthma Committee of the Canadian Thoracic Society invited a group of Canadian physicians with a particular interest in asthma to meet in Montebello, Quebec, March 9-12, 1995 to arrive at a consensus statement on the optimal approach to the management of asthma in the pediatric and adult ambulatory care settings. The societies and associations represented are listed in the appendix with the names of the contributors to this document. The objectives of the Montebello conference were: 1. To review the current ambulatory care management of asthma in Canada; 2. To develop guidelines with the participation of family physicians and specialists; 3. To develop guidelines which are evidence-based; 4. In creating evidence-based guidelines to focus attention on aspects of asthma management that are currently not supported by randomized controlled trials; 5. To develop strategies that allow for the implementation of rational guidelines at a local level. Recommendations were based on a critical review of the scientific literature by small groups prior to the meeting and are categorized according to the strength of the scientific evidence supporting each recommendation (Table 1.

  1. The role of fanatics in consensus formation

    Science.gov (United States)

    Gündüç, Semra

    2015-08-01

    A model of opinion dynamics with two types of agents as social actors are presented, using the Ising thermodynamic model as the dynamics template. The agents are considered as opportunists which live at sites and interact with the neighbors, or fanatics/missionaries which move from site to site randomly in persuasion of converting agents of opposite opinion with the help of opportunists. Here, the moving agents act as an external influence on the opportunists to convert them to the opposite opinion. It is shown by numerical simulations that such dynamics of opinion formation may explain some details of consensus formation even when one of the opinions are held by a minority. Regardless the distribution of the opinion, different size societies exhibit different opinion formation behavior and time scales. In order to understand general behavior, the scaling relations obtained by comparing opinion formation processes observed in societies with varying population and number of randomly moving agents are studied. For the proposed model two types of scaling relations are observed. In fixed size societies, increasing the number of randomly moving agents give a scaling relation for the time scale of the opinion formation process. The second type of scaling relation is due to the size dependent information propagation in finite but large systems, namely finite-size scaling.

  2. Current Consensus Guidelines for Treatment of Neurocysticercosis

    Science.gov (United States)

    García, Hector H.; Evans, Carlton A. W.; Nash, Theodore E.; Takayanagui, Osvaldo M.; White, A. Clinton; Botero, David; Rajshekhar, Vedantam; Tsang, Victor C. W.; Schantz, Peter M.; Allan, James C.; Flisser, Ana; Correa, Dolores; Sarti, Elsa; Friedland, Jon S.; Martinez, S. Manuel; Gonzalez, Armando E.; Gilman, Robert H.; Del Brutto, Oscar H.

    2002-01-01

    Taenia solium neurocysticercosis is a common cause of epileptic seizures and other neurological morbidity in most developing countries. It is also an increasingly common diagnosis in industrialized countries because of immigration from areas where it is endemic. Its clinical manifestations are highly variable and depend on the number, stage, and size of the lesions and the host's immune response. In part due to this variability, major discrepancies exist in the treatment of neurocysticercosis. A panel of experts in taeniasis/cysticercosis discussed the evidence on treatment of neurocysticercosis for each clinical presentation, and we present the panel's consensus and areas of disagreement. Overall, four general recommendations were made: (i) individualize therapeutic decisions, including whether to use antiparasitic drugs, based on the number, location, and viability of the parasites within the nervous system; (ii) actively manage growing cysticerci either with antiparasitic drugs or surgical excision; (iii) prioritize the management of intracranial hypertension secondary to neurocysticercosis before considering any other form of therapy; and (iv) manage seizures as done for seizures due to other causes of secondary seizures (remote symptomatic seizures) because they are due to an organic focus that has been present for a long time. PMID:12364377

  3. Consensus building on the development of a stress-based indicator for LCA-based impact assessment of water consumption

    NARCIS (Netherlands)

    Boulay, Anne Marie; Bare, Jane; Camillis, De Camillo; Döll, Petra; Gassert, Francis; Gerten, Dieter; Humbert, Sebastien; Inaba, Atsushi; Itsubo, Norihiro; Lemoine, Yann; Margni, Manuele; Motoshita, Masaharu; Núñez, Montse; Pastor, A.V.; Ridoutt, Brad; Schencker, Urs; Shirakawa, Naoki; Vionnet, Samuel; Worbe, Sebastien; Yoshikawa, Sayaka; Pfister, Stephan

    2015-01-01

    Purpose: The WULCA group, active since 2007 on Water Use in LCA, commenced the development of consensus-based indicators in January 2014. This activity is planned to last 2 years and covers human health, ecosystem quality, and a stress-based indicator. This latter encompasses potential

  4. Consensus building on the development of a stress-based indicator for LCA-based impact assessment of water consumption

    NARCIS (Netherlands)

    Boulay, Anne Marie; Bare, Jane; Camillis, De Camillo; Döll, Petra; Gassert, Francis; Gerten, Dieter; Humbert, Sebastien; Inaba, Atsushi; Itsubo, Norihiro; Lemoine, Yann; Margni, Manuele; Motoshita, Masaharu; Núñez, Montse; Pastor, A.V.; Ridoutt, Brad; Schencker, Urs; Shirakawa, Naoki; Vionnet, Samuel; Worbe, Sebastien; Yoshikawa, Sayaka; Pfister, Stephan

    2015-01-01

    Purpose: The WULCA group, active since 2007 on Water Use in LCA, commenced the development of consensus-based indicators in January 2014. This activity is planned to last 2 years and covers human health, ecosystem quality, and a stress-based indicator. This latter encompasses potential deprivatio

  5. Convergence to consensus in heterogeneous groups and the emergence of informal leadership.

    Science.gov (United States)

    Gavrilets, Sergey; Auerbach, Jeremy; van Vugt, Mark

    2016-07-14

    When group cohesion is essential, groups must have efficient strategies in place for consensus decision-making. Recent theoretical work suggests that shared decision-making is often the most efficient way for dealing with both information uncertainty and individual variation in preferences. However, some animal and most human groups make collective decisions through particular individuals, leaders, that have a disproportionate influence on group decision-making. To address this discrepancy between theory and data, we study a simple, but general, model that explicitly focuses on the dynamics of consensus building in groups composed by individuals who are heterogeneous in preferences, certain personality traits (agreeability and persuasiveness), reputation, and social networks. We show that within-group heterogeneity can significantly delay democratic consensus building as well as give rise to the emergence of informal leaders, i.e. individuals with a disproportionately large impact on group decisions. Our results thus imply strong benefits of leadership particularly when groups experience time pressure and significant conflict of interest between members (due to various between-individual differences). Overall, our models shed light on why leadership and decision-making hierarchies are widespread, especially in human groups.

  6. Consensus Paper: The Cerebellum's Role in Movement and Cognition

    Science.gov (United States)

    Koziol, Leonard F.; Budding, Deborah; Andreasen, Nancy; D'Arrigo, Stefano; Bulgheroni, Sara; Imamizu, Hiroshi; Ito, Masao; Manto, Mario; Marvel, Cherie; Parker, Krystal; Pezzulo, Giovanni; Ramnani, Narender; Riva, Daria; Schmahmann, Jeremy; Vandervert, Larry; Yamazaki, Tadashi

    2014-01-01

    While the cerebellum's role in motor function is well recognized, the nature of its concurrent role in cognitive function remains considerably less clear. The current consensus paper gathers diverse views on a variety of important roles played by the cerebellum across a range of cognitive and emotional functions. This paper considers the cerebellum in relation to neurocognitive development, language function, working memory, executive function, and the development of cerebellar internal control models and reflects upon some of the ways in which better understanding the cerebellum's status as a “supervised learning machine” can enrich our ability to understand human function and adaptation. As all contributors agree that the cerebellum plays a role in cognition, there is also an agreement that this conclusion remains highly inferential. Many conclusions about the role of the cerebellum in cognition originate from applying known information about cerebellar contributions to the coordination and quality of movement. These inferences are based on the uniformity of the cerebellum's compositional infrastructure and its apparent modular organization. There is considerable support for this view, based upon observations of patients with pathology within the cerebellum. PMID:23996631

  7. Multipattern Consensus Regions in Multiple Aligned Protein Sequences and Their Segmentation

    Directory of Open Access Journals (Sweden)

    Yan Wang

    2006-08-01

    Full Text Available Decomposing a biological sequence into its functional regions is an important prerequisite to understand the molecule. Using the multiple alignments of the sequences, we evaluate a segmentation based on the type of statistical variation pattern from each of the aligned sites. To describe such a more general pattern, we introduce multipattern consensus regions as segmented regions based on conserved as well as interdependent patterns. Thus the proposed consensus region considers patterns that are statistically significant and extends a local neighborhood. To show its relevance in protein sequence analysis, a cancer suppressor gene called p53 is examined. The results show significant associations between the detected regions and tendency of mutations, location on the 3D structure, and cancer hereditable factors that can be inferred from human twin studies.

  8. Consensus reaching in swarms ruled by a hybrid metric-topological distance

    CERN Document Server

    Shang, Yilun

    2014-01-01

    Recent empirical observations of three-dimensional bird flocks and human crowds have challenged the long-prevailing assumption that a metric interaction distance rules swarming behaviors. In some cases, individual agents are found to be engaged in local information exchanges with a fixed number of neighbors, i.e. a topological interaction. However, complex system dynamics based on pure metric or pure topological distances both face physical inconsistencies in low and high density situations. Here, we propose a hybrid metric-topological interaction distance overcoming these issues and enabling a real-life implementation in artificial robotic swarms. We use network- and graph-theoretic approaches combined with a dynamical model of locally interacting self-propelled particles to study the consensus reaching pro- cess for a swarm ruled by this hybrid interaction distance. Specifically, we establish exactly the probability of reaching consensus in the absence of noise. In addition, simulations of swarms of self-pr...

  9. Adapting oecd aquatic toxicity tests for use with manufactured nanomaterials: key issues and consensus recommendations

    DEFF Research Database (Denmark)

    Petersen, Elijah J.; Diamond, Stephen A.; Kennedy, Alan J.

    2015-01-01

    The unique or enhanced properties of manufactured nanomaterials (MNs) suggest that their use in nano-enabled products will continue to increase. This will result in increased potential for human and environmental exposure to MNs, during manufacturing, use, and disposal of nano-enabled products...... participants that require specific guidance for MN testing: preparation of dispersions, dose metrics, the importance and challenges associated with maintaining and monitoring exposure levels, and the need for reliable methods to quantify MNs in complex media. To facilitate a scientific advance...... in the consistency of nanoecotoxicology test results, we identify and discuss critical considerations where expert consensus recommendations were and were not achieved, and provide specific research recommendations to resolve issues for which consensus was not reached. This process will enable development...

  10. Consensus Making in Requirements Negotiation: the communication perspective

    Directory of Open Access Journals (Sweden)

    Jenny Price

    2005-11-01

    Full Text Available When developing an Information System (IS, organizational goals of various stakeholders are commonly in direct conflict. Furthermore, individuals often rank their private objectives well over their management's directions. Recognising and reconciling all these diverse goals, and reaching agreement among the stakeholders, are prerequisite to establishing project cooperation and collaboration. This paper focuses, in particular, on the negotiation and consensus making during requirements elicitation - the earliest stages of the IS development process. As requirements elicitation involves rich communication between project stakeholders, we therefore explore negotiation and consensus making from the communication perspective. The resulting model assists our understanding of the communication factors that influence the consensus process during requirements negotiation.

  11. Leader-Based Consensus of Heterogeneous Nonlinear Multiagent Systems

    Directory of Open Access Journals (Sweden)

    Tairen Sun

    2014-01-01

    Full Text Available This paper considers the leader-based consensus of heterogeneous multiple agents with nonlinear uncertain systems. Based on the information obtained from the following agents’ neighbors, leader observers are designed by the following agents to estimate the leader’s states and nonlinear dynamics. Then, to achieve leader-based consensus, adaptive distributed controllers are designed for the following agents to track the designed corresponding leader observers. The effectiveness of the leader observers and distributed consensus controllers are illustrated by formal proof and simulation results.

  12. Recent consensus statements in pediatric endocrinology: a selective review.

    Science.gov (United States)

    Klein, Michelle; Sathasivam, Anpalakan; Novoa, Yeray; Rapaport, Robert

    2011-10-01

    Clinical guidelines and consensus statements serve to summarize and organize current knowledge on diverse subjects and provide practical guidelines for proper clinical management. Recommendations should be based on research and evidence derived from appropriate sources. In 2008, more than 20 consensus statements were published in the pediatric literature alone. This article summarizes the salient points of the latest consensus statements jointly developed by multiple endocrine societies including the Lawson Wilkins Society for Pediatric Endocrinology and the European Society for Pediatric Endocrinology. As much as possible, the original intent and language of the statements was respected and paraphrased.

  13. Consensus protocol for multi-agent continuous systems

    Institute of Scientific and Technical Information of China (English)

    Tan Fu-Xiao; Guan Xin-Ping; Liu De-Rong

    2008-01-01

    Based on the algebraic graph theory,the networked multi-agent continuous systems are investigated.Firstly,the digraph(directed graph)represents the topology of a networked system,and then a consensus convergence criterion of system is proposed.Secondly,the issue of stability of multi-agent systems and the consensus convergence problem of information states are all analysed.Furthermore,the Consensus equilibrium point of system is proved to be global and asymptotically reach the convex combination of initial states.Finally,two examples are taken to show the effectiveness of the results obtained in this paper.

  14. Latin American Consensus on Retinal Vein Occlusion

    Directory of Open Access Journals (Sweden)

    Francisco J. Rodriguez

    2016-01-01

    Full Text Available The introduction of anti-VEGF agents has allowed unprecedented progress in the management and treatment of ophthalmologic conditions characterized by an increased vascular permeability and intraocular neovascularization. One of these conditions is retinal vein occlusion (RVO.  RVO is one of the most common causes of reduced vision due to retinal vascular disease. Without timely treatment, macular edema, macular ischemia, neovascularization and other potential sequelae of RVO can lead to photoreceptor cell death and consequently to irreversible vision loss.   Treatments for this indication that have been recently approved by several regulatory agencies throughout the world include: the VEGF inhibitor ranibizumab (Lucentis, Genentech, the VEGF and placental growth factor inhibitor aflibercept (Eylea, Regeneron Pharmaceuticals and Bayer HealthCare, and a slow release intravitreal implant of dexamethasone (Ozurdex, Allergan. In addition bevacizumab (Avastin, Genentech has been used extensively in an off-label manner.   These new treatments allow us to preserve vision for many RVO patients who could not have expected such favorable results just 5 or 6 years ago. However, not every treatment is effective for every patient, and whether one option is superior to another or a combination of options is superior to monotherapy, have yet to be definitively determined.   A growing body of literature with strong evidence supports the use of these new treatments. However, in several instances the literature is not conclusive to support unified management of RVO. This document is a summary analysis on RVO assembled by a group of specialists summoned by the Pan-American Vitreo-Retinal Society (SPRV to participate in this Latin American consensus.

  15. Consensus statement on diabetes in children.

    Science.gov (United States)

    Prasanna Kumar, K M; Dev, N Prabhu; Raman, K V; Desai, Rajnanda; Prasadini, T Geetha; Das, A K; Ramoul, Soraya

    2014-05-01

    While T1DM has been traditionally seen as a minor concern in the larger picture of pediatric ailments, new data reveals that the incidence of T1DM has assumed alarming proportions. It has long been clear that while the disease may be diagnosed at an early age, its impact is not isolated to afflicted children. The direct impact of the disease on the patient is debilitating due to the nature of the disease and lack of proper access to treatment in India. But this impact is further compounded by the utter apathy and often times antipathy, which patients withT1DM have to face. Lack of awareness of the issue in all stakeholders, low access to quality healthcare, patient, physician, and system level barriers to the delivery of optimal diabetes care are some of the factors which hinder successful management of T1DM. The first international consensus meet on diabetes in children was convened with the aim of providing a common platform to all the stakeholders in the management of T1DM, to discuss the academic, administrative and healthcare system related issues. The ultimate aim was to articulate the problems faced by children with diabetes in a way that centralized their position and focused on creating modalities of management sensitive to their needs and aspirations. It was conceptualized to raise a strong voice of advocacy for improving the management of T1DM and ensuring that "No child should die of diabetes". The unique clinical presentations of T1DM coupled with ignorance on the part of the medical community and society in general results in outcomes that are far worse than that seen with T2DM. So there is a need to substantially improve training of HCPs at all levels on this neglected aspect of healthcare.

  16. Management of Neuroblastoma: ICMR Consensus Document.

    Science.gov (United States)

    Bansal, Deepak; Totadri, Sidharth; Chinnaswamy, Girish; Agarwala, Sandeep; Vora, Tushar; Arora, Brijesh; Prasad, Maya; Kapoor, Gauri; Radhakrishnan, Venkatraman; Laskar, Siddharth; Kaur, Tanvir; Rath, G K; Bakhshi, Sameer

    2017-06-01

    Neuroblastoma (NBL) is the most common extra-cranial solid tumor in childhood. High-risk NBL is considered challenging and has one of the least favourable outcomes amongst pediatric cancers. Primary tumor can arise anywhere along the sympathetic chain. Advanced disease at presentation is common. Diagnosis is established by tumor biopsy and elevated urinary catecholamines. Staging is performed using bone marrow and mIBG scan (FDG-PET/bone scan if mIBG unavailable or non-avid). Age, stage, histopathological grading, MYCN amplification and 11q aberration are important prognostic factors utilized in risk stratification. Low-risk disease including Stage 1 and asymptomatic Stage 2 disease has an excellent prognosis with non-mutilating surgery alone. Perinatal adrenal neuroblastoma may be managed with close observation alone. Intermediate-risk disease consisting largely of unresectable/symptomatic Stage 2/3 disease and infants with Stage 4 disease has good outcome with few cycles of chemotherapy followed by surgical resection. Paraspinal neuroblastomas with cord compression are treated emergently, typically with upfront chemotherapy. Asymptomatic Stage 4S disease may be followed closely without treatment. Organ dysfunction and age below 3 mo would warrant chemotherapy in 4S. High-risk disease includes older children with Stage 4 disease and MYCN amplified tumors. High-risk disease has a suboptimal outcome, though the survival is improving with multimodality therapy including autologous stem cell transplant and immunotherapy. Relapse after multimodality therapy is difficult to salvage. Late presentation, lack of transplant facility, malnutrition and treatment abandonment are additional hurdles for survival in India. The review provides a consensus document on management of NBL for developing countries, including India.

  17. Sarcopenia: European consensus on definition and diagnosis

    Science.gov (United States)

    Cruz-Jentoft, Alfonso J.; Baeyens, Jean Pierre; Bauer, Jürgen M.; Boirie, Yves; Cederholm, Tommy; Landi, Francesco; Martin, Finbarr C.; Michel, Jean-Pierre; Rolland, Yves; Schneider, Stéphane M.; Topinková, Eva; Vandewoude, Maurits; Zamboni, Mauro

    2010-01-01

    The European Working Group on Sarcopenia in Older People (EWGSOP) developed a practical clinical definition and consensus diagnostic criteria for age-related sarcopenia. EWGSOP included representatives from four participant organisations, i.e. the European Geriatric Medicine Society, the European Society for Clinical Nutrition and Metabolism, the International Association of Gerontology and Geriatrics—European Region and the International Association of Nutrition and Aging. These organisations endorsed the findings in the final document. The group met and addressed the following questions, using the medical literature to build evidence-based answers: (i) What is sarcopenia? (ii) What parameters define sarcopenia? (iii) What variables reflect these parameters, and what measurement tools and cut-off points can be used? (iv) How does sarcopenia relate to cachexia, frailty and sarcopenic obesity? For the diagnosis of sarcopenia, EWGSOP recommends using the presence of both low muscle mass + low muscle function (strength or performance). EWGSOP variously applies these characteristics to further define conceptual stages as ‘presarcopenia’, ‘sarcopenia’ and ‘severe sarcopenia’. EWGSOP reviewed a wide range of tools that can be used to measure the specific variables of muscle mass, muscle strength and physical performance. Our paper summarises currently available data defining sarcopenia cut-off points by age and gender; suggests an algorithm for sarcopenia case finding in older individuals based on measurements of gait speed, grip strength and muscle mass; and presents a list of suggested primary and secondary outcome domains for research. Once an operational definition of sarcopenia is adopted and included in the mainstream of comprehensive geriatric assessment, the next steps are to define the natural course of sarcopenia and to develop and define effective treatment. PMID:20392703

  18. Consensus statement on diabetes in children

    Directory of Open Access Journals (Sweden)

    K M Prasanna Kumar

    2014-01-01

    Full Text Available While T1DM has been traditionally seen as a minor concern in the larger picture of pediatric ailments, new data reveals that the incidence of T1DM has assumed alarming proportions. It has long been clear that while the disease may be diagnosed at an early age, its impact is not isolated to afflicted children. The direct impact of the disease on the patient is debilitating due to the nature of the disease and lack of proper access to treatment in India. But this impact is further compounded by the utter apathy and often times antipathy, which patients withT1DM have to face. Lack of awareness of the issue in all stakeholders, low access to quality healthcare, patient, physician, and system level barriers to the delivery of optimal diabetes care are some of the factors which hinder successful management of T1DM. The first international consensus meet on diabetes in children was convened with the aim of providing a common platform to all the stakeholders in the management of T1DM, to discuss the academic, administrative and healthcare system related issues. The ultimate aim was to articulate the problems faced by children with diabetes in a way that centralized their position and focused on creating modalities of management sensitive to their needs and aspirations. It was conceptualized to raise a strong voice of advocacy for improving the management of T1DM and ensuring that "No child should die of diabetes". The unique clinical presentations of T1DM coupled with ignorance on the part of the medical community and society in general results in outcomes that are far worse than that seen with T2DM. So there is a need to substantially improve training of HCPs at all levels on this neglected aspect of healthcare.

  19. In control? IQC consensus and statutory regulation.

    Science.gov (United States)

    Lee, Graham R; Fitzgibbon, Maria C; O'Shea, Paula

    2016-06-13

    have provided a template to potentially harmonise IQC practice nationally. Given the central and critical role that IQC practice plays in ensuring the quality of patient results' importance, the authors contend that the time has come for international consensus and statutory regulation regarding the minimally acceptable criteria for its implementation, monitoring and review.

  20. Carotid endarterectomy: current consensus and controversies.

    Science.gov (United States)

    Meerwaldt, Robbert; Hermus, Linda; Reijnen, Michel M P J; Zeebregts, Clark J

    2010-10-01

    Stroke is the third most common cause of mortality, and carotid artery stenosis causes 8% to 29% of all ischemic strokes. Best medical treatment forms the basis of carotid stenosis treatment, and carotid endarterectomy (CEA) has an additional beneficial effect in high-grade stenosis. Carotid angioplasty and stenting (CAS) has challenged CEA as a primary carotid intervention. At present, CEA remains the gold standard, but in the future, CAS techniques will evolve and might become beneficial for subgroups of patients with carotid stenosis. This chapter briefly describes the history of carotid interventions and current consensus and controversies in CEA. In the last two years, several meta-analyses were published on a variety of aspects of best medical treatment, CEA, and CAS. It is still a matter of debate as to whether asymptomatic patients with carotid stenosis should undergo a carotid intervention. Especially because medical treatment has dramatically evolved since the early carotid trials. On the other hand, it is clear that carotid interventions in symptomatic patients with a high-grade stenosis should be performed as early as possible after the initial neurological event in order to achieve optimal stroke risk reduction. In CEA, the use of patching is advocated above primary closure, while the role of selective patching is still unclear. No differences in stroke and mortality rates are observed for routine versus selective shunting, for conventional versus eversion CEA, or for local versus general anesthesia. It is anticipated that in the future, there will be several interesting developments in carotid interventions such as plaque morphology analysis, acute interventions during stroke in progress, and further evolvement of CAS techniques.

  1. Managing Carious Lesions: Consensus Recommendations on Terminology.

    Science.gov (United States)

    Innes, N P T; Frencken, J E; Bjørndal, L; Maltz, M; Manton, D J; Ricketts, D; Van Landuyt, K; Banerjee, A; Campus, G; Doméjean, S; Fontana, M; Leal, S; Lo, E; Machiulskiene, V; Schulte, A; Splieth, C; Zandona, A; Schwendicke, F

    2016-05-01

    Variation in the terminology used to describe clinical management of carious lesions has contributed to a lack of clarity in the scientific literature and beyond. In this article, the International Caries Consensus Collaboration presents 1) issues around terminology, a scoping review of current words used in the literature for caries removal techniques, and 2) agreed terms and definitions, explaining how these were decided.Dental cariesis the name of the disease, and thecarious lesionis the consequence and manifestation of the disease-the signs or symptoms of the disease. The termdental caries managementshould be limited to situations involving control of the disease through preventive and noninvasive means at a patient level, whereascarious lesion managementcontrols the disease symptoms at the tooth level. While it is not possible to directly relate the visual appearance of carious lesions' clinical manifestations to the histopathology, we have based the terminology around the clinical consequences of disease (soft, leathery, firm, and hard dentine). Approaches to carious tissue removal are defined: 1)selective removal of carious tissue-includingselective removal to soft dentineandselective removal to firm dentine; 2)stepwise removal-including stage 1,selective removal to soft dentine, and stage 2,selective removal to firm dentine6 to 12 mo later; and 3)nonselective removal to hard dentine-formerly known ascomplete caries removal(technique no longer recommended). Adoption of these terms, around managing dental caries and its sequelae, will facilitate improved understanding and communication among researchers and within dental educators and the wider clinical dentistry community. © International & American Associations for Dental Research 2016.

  2. Peptide consensus sequence determination for the enhancement of the antimicrobial activity and selectivity of antimicrobial peptides

    Science.gov (United States)

    Almaaytah, Ammar; Ajingi, Ya’u; Abualhaijaa, Ahmad; Tarazi, Shadi; Alshar’i, Nizar; Al-Balas, Qosay

    2017-01-01

    The rise of multidrug-resistant bacteria is causing a serious threat to the world’s human population. Recent reports have identified bacterial strains displaying pan drug resistance against antibiotics and generating fears among medical health specialists that humanity is on the dawn of entering a post-antibiotics era. Global research is currently focused on expanding the lifetime of current antibiotics and the development of new antimicrobial agents to tackle the problem of antimicrobial resistance. In the present study, we designed a novel consensus peptide named “Pepcon” through peptide consensus sequence determination among members of a highly homologous group of scorpion antimicrobial peptides. Members of this group were found to possess moderate antimicrobial activity with significant toxicity against mammalian cells. The aim of our design method was to generate a novel peptide with an enhanced antimicrobial potency and selectivity against microbial rather than mammalian cells. The results of our study revealed that the consensus peptide displayed potent antibacterial activities against a broad range of Gram-positive and Gram-negative bacteria. Our membrane permeation studies displayed that the peptide efficiently induced membrane damage and consequently led to cell death through the process of cell lysis. The microbial DNA binding assay of the peptide was found to be very weak suggesting that the peptide is not targeting the microbial DNA. Pepcon induced minimal cytotoxicity at the antimicrobial concentrations as the hemolytic activity was found to be zero at the minimal inhibitory concentrations (MICs). The results of our study demonstrate that the consensus peptide design strategy is efficient in generating peptides. PMID:28096686

  3. The development of a consensus definition for healthcare improvement science (HIS) in seven European countries: A consensus methods approach

    Science.gov (United States)

    Macrae, Rhoda; Lillo-Crespo, Manuel; Rooney, Kevin D

    2017-01-01

    Abstract Introduction There is a limited body of research in the field of healthcare improvement science (HIS). Quality improvement and ‘change making’ should become an intrinsic part of everyone’s job, every day in all parts of the healthcare system. The lack of theoretical grounding may partly explain the minimal transfer of health research into health policy. Methods This article seeks to present the development of the definition for healthcare improvement science. A consensus method approach was adopted with a two-stage Delphi process, expert panel and consensus group techniques. A total of 18 participants were involved in the expert panel and consensus group, and 153 answers were analysed as a part of the Delphi survey. Participants were researchers, educators and healthcare professionals from Scotland, Slovenia, Spain, Italy, England, Poland, and Romania. Results A high level of consensus was achieved for the broad definition in the 2nd Delphi iteration (86%). The final definition was agreed on by the consensus group: ‘Healthcare improvement science is the generation of knowledge to cultivate change and deliver person-centred care that is safe, effective, efficient, equitable and timely. It improves patient outcomes, health system performance and population health.’ Conclusions The process of developing a consensus definition revealed different understandings of healthcare improvement science between the participants. Having a shared consensus definition of healthcare improvement science is an important step forward, bringing about a common understanding in order to advance the professional education and practice of healthcare improvement science. PMID:28289467

  4. Consensus on Exercise Reporting Template (CERT) : A Modified Delphi Study

    NARCIS (Netherlands)

    Slade, Susan C; Dionne, Clermont E; Underwood, Martin; Buchbinder, Rachelle; Beck, Belinda; Bennell, Kim; Brosseau, Lucie; Costa, Leonardo; Cramp, Fiona; Cup, Edith; Feehan, Lynne; Ferreira, Manuela; Forbes, Scott; Glasziou, Paul; Habets, Bas; Harris, Susan; Hay-Smith, Jean; Hillier, Susan; Hinman, Rana; Holland, Ann; Hondras, Maria; Kelly, George; Kent, Peter; Lauret, Gert-Jan; Long, Audrey; Maher, Chris; Morso, Lars; Osteras, Nina; Peterson, Tom; Quinlivan, Ros; Rees, Karen; Regnaux, Jean-Philippe; Reitberg, Marc; Saunders, Dave; Skoetz, Nicole; Sogaard, Karen; Takken, Tim; van Tulder, Maurits; Voet, Nicoline; Ward, Lesley; White, Claire

    2016-01-01

    BACKGROUND: Exercise interventions are often incompletely described in reports of clinical trials hampering evaluation of results and replication and implementation into practice. OBJECTIVE: To develop a standardized method for reporting exercise programs in clinical trials, the Consensus on Exercis

  5. ESMO-ESGO-ESTRO Consensus Conference on Endometrial Cancer

    Science.gov (United States)

    Colombo, Nicoletta; Creutzberg, Carien; Amant, Frederic; Bosse, Tjalling; González-Martín, Antonio; Ledermann, Jonathan; Marth, Christian; Nout, Remi; Querleu, Denis; Mirza, Mansoor Raza; Sessa, Cristiana

    2016-01-01

    Abstract The first joint European Society for Medical Oncology (ESMO), European SocieTy for Radiotherapy & Oncology (ESTRO) and European Society of Gynaecological Oncology (ESGO) consensus conference on endometrial cancer was held on 11–13 December 2014 in Milan, Italy, and comprised a multidisciplinary panel of 40 leading experts in the management of endometrial cancer. Before the conference, the expert panel prepared three clinically-relevant questions about endometrial cancer relating to the following four areas: prevention and screening, surgery, adjuvant treatment and advanced and recurrent disease. All relevant scientific literature, as identified by the experts, was reviewed in advance. During the consensus conference, the panel developed recommendations for each specific question and a consensus was reached. Results of this consensus conference, together with a summary of evidence supporting each recommendation, are detailed in this article. All participants have approved this final article. PMID:26645990

  6. testing a consensus conference method by discussing the ...

    African Journals Online (AJOL)

    hi-tech

    2000-10-10

    Oct 10, 2000 ... Study participants: Fifteen dentists as representatives of the ... Results: For most types of injuries, consensus on the feasibility of the recommended ..... through the WHO Collaborating Center for Oral Health Planning and.

  7. NIH Blood and Marrow Transplant Late Effects Consensus Conference

    Science.gov (United States)

    This day and a half symposium will bring together experts in blood and marrow transplantation, late effects, and health care delivery to discuss current evidence and knowledge gaps, develop consensus guidelines, and inform future research in the BMT survivor population.

  8. Robust consensus of multi-agent systems with noise

    Institute of Scientific and Technical Information of China (English)

    WANG Lin; LIU ZhiXin

    2009-01-01

    The consensus problem of multi-agent systems has attracted wide attention from researchers in recent years, following the initial work of Jadbabaie et al. on the analysis of a simplified Vicsek model. While the original Vicsek model contains noise effects, almost all the existing theoretical results on consensus problem, however, do not take the noise effects into account. The purpose of this paper is to initiate a study of the consensus problems under noise disturbances. First, the class of multi-agent systems under study is transformed into a general time-varying system with noise. Then, for such a system, the equivalent relationships are established among (ⅰ) robust consensus, (ⅱ) the positivity of the second smallest eigenvalue of a weighted Laplacian matrix, and (ⅲ) the joint connectivity of the associated dynamical neighbor graphs. Finally, this basic equivalence result is shown to be applicable to several classes of concrete multi-agent models with noise.

  9. Taiwanese Dermatological Association consensus for the management of atopic dermatitis

    Directory of Open Access Journals (Sweden)

    Chia-Yu Chu

    2015-12-01

    Conclusion: The consensus provides a comprehensive overview of treatment for AD, with some local and cultural considerations for practitioners in Taiwan, especially the use of wet dressings/wraps, systemic immunomodulatory agents, and complementary therapies.

  10. Network-Based Practical Consensus of Heterogeneous Nonlinear Multiagent Systems.

    Science.gov (United States)

    Ding, Lei; Zheng, Wei Xing

    2016-09-07

    This paper studies network-based practical leader-following consensus problem of heterogeneous multiagent systems with Lipschitz nonlinear dynamics under both fixed and switching topologies. Considering the effect of network-induced delay, a network-based leader-following consensus protocol with heterogeneous gain matrix is proposed for each follower agent. By employing Lyapunov-Krasovskii method, a sufficient condition for designing the network-based consensus controller gain is derived such that the leader-following consensus error exponentially converges to a bounded region under a fixed topology. Correspondingly, the proposed design approach is then extended to the case of switching topology. Two numerical examples with networked Chua's circuits are given to show the efficiency of the design method proposed in this paper.

  11. Degree Fluctuations and the Convergence Time of Consensus Algorithms

    CERN Document Server

    Olshevsky, Alex

    2011-01-01

    We consider a consensus algorithm in which every node in a time-varying undirected connected graph assigns equal weight to each of its neighbors. Under the assumption that the degree of any given node is constant in time, we show that the algorithm achieves consensus within a given accuracy epsilon on n nodes in time O(n^3 log(n/epsilon)). Because there is a direct relation between consensus algorithms in time-varying environments and inhomogeneous random walks, our result also translates into a general statement on such random walks. Moreover, we give simple proofs that the convergence time becomes exponentially large in the number of nodes n under slight relaxations of the above assumptions. We prove that exponential convergence time is possible for consensus algorithms on fixed directed graphs, and we use an example of Cao, Spielman, and Morse to give a simple argument that the same is possible if the constant degrees assumption is even slightly relaxed.

  12. Adaptive neural network consensus based control of robot formations

    Science.gov (United States)

    Guzey, H. M.; Sarangapani, Jagannathan

    2013-05-01

    In this paper, adaptive consensus based formation control scheme is derived for mobile robots in a pre-defined formation when full dynamics of the robots which include inertia, Corolis, and friction vector are considered. It is shown that dynamic uncertainties of robots can make overall formation unstable when traditional consensus scheme is utilized. In order to estimate the affine nonlinear robot dynamics, a NN based adaptive scheme is utilized. In addition to this adaptive feedback control input, an additional control input is introduced based on the consensus approach to make the robots keep their desired formation. Subsequently, the outer consensus loop is redesigned for reduced communication. Lyapunov theory is used to show the stability of overall system. Simulation results are included at the end.

  13. The WULCA consensus characterization model for water scarcity footprints

    OpenAIRE

    Boulay, Anne Marie; BARE Jane; Benini, Lorenzo; Berger, Markus; Lathuillière, Michael J.; Manzardo, Alessandro; Margni, Manuele; MOTOSHITA Masaharu; NÚÑEZ Montserrat; Pastor, Amandine Valerie; Ridoutt, Bradley; Oki, Taikan; Worbe, Sebastien; Pfister, Stephan

    2017-01-01

    Purpose: Life cycle assessment (LCA) has been used to assess freshwater-related impacts according to a new water footprint framework formalized in the ISO 14046 standard. To date, no consensus-based approach exists for applying this standard and results are not always comparable when different scarcity or stress indicators are used for characterization of impacts. This paper presents the outcome of a 2-year consensus building process by the Water Use in Life Cycle Assessment (WULCA), a workin...

  14. Consensus algorithm in smart grid and communication networks

    Science.gov (United States)

    Alfagee, Husain Abdulaziz

    On a daily basis, consensus theory attracts more and more researches from different areas of interest, to apply its techniques to solve technical problems in a way that is faster, more reliable, and even more precise than ever before. A power system network is one of those fields that consensus theory employs extensively. The use of the consensus algorithm to solve the Economic Dispatch and Load Restoration Problems is a good example. Instead of a conventional central controller, some researchers have explored an algorithm to solve the above mentioned problems, in a distribution manner, using the consensus algorithm, which is based on calculation methods, i.e., non estimation methods, for updating the information consensus matrix. Starting from this point of solving these types of problems mentioned, specifically, in a distribution fashion, using the consensus algorithm, we have implemented a new advanced consensus algorithm. It is based on the adaptive estimation techniques, such as the Gradient Algorithm and the Recursive Least Square Algorithm, to solve the same problems. This advanced work was tested on different case studies that had formerly been explored, as seen in references 5, 7, and 18. Three and five generators, or agents, with different topologies, correspond to the Economic Dispatch Problem and the IEEE 16-Bus power system corresponds to the Load Restoration Problem. In all the cases we have studied, the results met our expectations with extreme accuracy, and completely matched the results of the previous researchers. There is little question that this research proves the capability and dependability of using the consensus algorithm, based on the estimation methods as the Gradient Algorithm and the Recursive Least Square Algorithm to solve such power problems.

  15. Consensus of Multiagent Networks with Intermittent Interaction and Directed Topology

    Directory of Open Access Journals (Sweden)

    Li Xiao

    2014-01-01

    Full Text Available Intermittent interaction control is introduced to solve the consensus problem for second-order multiagent networks due to the limited sensing abilities and environmental changes periodically. And, we get some sufficient conditions for the agents to reach consensus with linear protocol from the theoretical findings by using the Lyapunov control approach. Finally, the validity of the theoretical results is validated through the numerical example.

  16. Deriving consensus rankings via multicriteria decision making methodology

    OpenAIRE

    Amy Poh Ai Ling; Mohamad Nasir Saludin; Masao Mukaidono

    2012-01-01

    Purpose - This paper seeks to take a cautionary stance to the impact of the marketing mix on customer satisfaction, via a case study deriving consensus rankings for benchmarking on selected retail stores in Malaysia. Design/methodology/approach - The ELECTRE I model is used in deriving consensus rankings via multicriteria decision making method for benchmarking base on the marketing mix model 4P's. Descriptive analysis is used to analyze best practice among the four marketing tactics. Finding...

  17. A consensus opinion model based on the evolutionary game

    Science.gov (United States)

    Yang, Han-Xin

    2016-08-01

    We propose a consensus opinion model based on the evolutionary game. In our model, both of the two connected agents receive a benefit if they have the same opinion, otherwise they both pay a cost. Agents update their opinions by comparing payoffs with neighbors. The opinion of an agent with higher payoff is more likely to be imitated. We apply this model in scale-free networks with tunable degree distribution. Interestingly, we find that there exists an optimal ratio of cost to benefit, leading to the shortest consensus time. Qualitative analysis is obtained by examining the evolution of the opinion clusters. Moreover, we find that the consensus time decreases as the average degree of the network increases, but increases with the noise introduced to permit irrational choices. The dependence of the consensus time on the network size is found to be a power-law form. For small or larger ratio of cost to benefit, the consensus time decreases as the degree exponent increases. However, for moderate ratio of cost to benefit, the consensus time increases with the degree exponent. Our results may provide new insights into opinion dynamics driven by the evolutionary game theory.

  18. Chinese Consensus on Combination Therapy of Chronic Hepatitis B

    Institute of Scientific and Technical Information of China (English)

    2012-01-01

    In May 2011,editorial boards of Chinese Journal of Experimental and Clinical Infectious Diseases (Electronic Edition),Chinese Journal of Liver Diseases (Electronic Edition) and Infection International (Electronic Edition) organized an expert committee to form an expert consensus on antiviral combination therapy of chronic hepatitis B (CHB).The consensus publication promoted and standardized the combination therapy concept of chronic hepatitis B.Clinical evidence of combination therapy for CHB is incomplete.The concept of combination therapy is gradually extended,from combination of antiviral drugs plus antiviral drugs,to antiviral drugs plus hepatoprotective drugs,and antiviral drugs plus immunomodulatory drugs.Therefore,editorial boards once again asked experts to analyze the new clinical evidence,and form the expert consensus on combination therapy of chronic hepatitis B.The formulation of this consensus is according to the principles of evidence-based medicine.Large number of clinical studies of combination therapy is still in progress.This consensus can not fully answer all the problems encountered in the combination therapy of CHB.With the progress of clinical practice of antiviral therapy,and the accumulation of evidence in combination therapy,the expert committee will update the consensus timely.

  19. The Consensus Project: Survey of the peer-reviewed scientific literature to determine the degree of consensus on anthropogenic climate change

    Science.gov (United States)

    Nuccitelli, D. A.; Cook, J.; Jokimäki, A.; Skuce, A. G.; Green, S. A.; Painting, R.; Morrison, G. W.; Reitano, R.; Richardson, M.; Honeycutt, R.; Winkler, B.; Tamblyn, G.

    2012-12-01

    Prior studies have identified a consensus amongst climate science experts regarding anthropogenic global warming (AGW) as outlined by the Intergovernmental Panel on Climate Change (Oreskes 2004). Despite this evidence, a poll of 1010 American adults (Leiserowitz et al. 2011) revealed that only 15% believed that a large majority (>81%) of climate scientists think that global warming is caused mostly by human activities. This lack of public awareness of the consensus has hindered the implementation of climate policy, in the United States in particular. Using an online abstract classification and rating system in combination with an email survey of the papers' authors, a team of 24 contributors to the weblog Skeptical Science undertook an analysis of 12,465 abstracts published between 1991 and 2011, listed in the Web of Science with the keywords "global warming" and/or "global climate change". Each abstract was reviewed independently at least twice, based on the abstract and the title, with no reference to the authorship. This study represents the single largest survey of peer-reviewed climate research, and the large sample size allows for identification of patterns in climate research over time. Abstracts were classified based on subject focus, using a set of written criteria, as one of "impacts", "methods", "mitigation", "paleoclimate", or "opinion"; and rated according to degree of endorsement or rejection of AGW: three categories each of explicit/implicit endorsement and rejection, and a neutral category. Abstracts that referred to a changing climate but did not assert or reject a linkage to human-produced greenhouse gases were rated "neutral", and this rating proved to be by far the most common, comprising approximately 67% of total abstracts. Endorsement categories made up approximately 33% of all abstracts examined, whereas those rejecting AGW comprised less than 1%. Overall, endorsements outnumbered rejections approximately 50-to-1, consistent with the 97

  20. A Consensus on Mantle Potential Temperatures? (Invited)

    Science.gov (United States)

    Putirka, K. D.

    2009-12-01

    Recent publications may indicate a mounting consensus regarding mantle temperatures - an agreement that can be crucial for improving our understanding of mantle dynamics. To compare temperatures at various localities, McKenzie & Bickle (1988) proposed the concept of a mantle potential temperature (Tp) as a reference; Tp is the temperature the mantle would have at the surface, if it ascended along an adiabat without undergoing melting. Perhaps the most precise method to estimate Tp involves estimating the conditions of partial melting, and then correcting for the heat of fusion. The several sources of error include estimation of: a parental liquid, an equilibrium mantle olivine, the degree of partial melting (F), and the depth at which the parental melt is generated. There is also model error inherent to any thermometer. And when correcting for the heat of fusion we assume that we are correcting up to the convective adiabat, but if the parental melt was generated within the conductive lithosphere, Tp will be low. In any case, if we accept that the highest Tp estimates at Hawaii are of most interest (since magmas generated away from a plume centerline will not reflect the full heat content of a high T source), then in spite of these sources of error, recent estimates, published over a span of 10 months by three independent research groups, indicate considerable convergence. At Hawaii maximum Tp values are: 1600 deg. C by Herzberg & Asimow (2008), ca. 1630 deg. C by Lee et al. (2009; their Fig. 2B), and using two slightly different equation sets, 1687 deg. C by Putirka (2008; Geology) and 1660 deg. C by Putirka (2008; RiMG volume 69), yielding an average of 1644±38oC. Similarly, there is convergence for mean Tp at MORs (accepting that MORs are not isothermal; Klein and Langmuir, 1987): Herzberg & Asimow (2008) and Lee et al. (2009) estimate that Tp is ca. 1350 deg. C, and Putirka (2008; Geology) estimates a Tp of 1396 deg. C; these estimates average to 1365±26o

  1. International consensus principles for ethical wildlife control.

    Science.gov (United States)

    Dubois, Sara; Fenwick, Nicole; Ryan, Erin A; Baker, Liv; Baker, Sandra E; Beausoleil, Ngaio J; Carter, Scott; Cartwright, Barbara; Costa, Federico; Draper, Chris; Griffin, John; Grogan, Adam; Howald, Gregg; Jones, Bidda; Littin, Kate E; Lombard, Amanda T; Mellor, David J; Ramp, Daniel; Schuppli, Catherine A; Fraser, David

    2017-08-01

    Human-wildlife conflicts are commonly addressed by excluding, relocating, or lethally controlling animals with the goal of preserving public health and safety, protecting property, or conserving other valued wildlife. However, declining wildlife populations, a lack of efficacy of control methods in achieving desired outcomes, and changes in how people value animals have triggered widespread acknowledgment of the need for ethical and evidence-based approaches to managing such conflicts. We explored international perspectives on and experiences with human-wildlife conflicts to develop principles for ethical wildlife control. A diverse panel of 20 experts convened at a 2-day workshop and developed the principles through a facilitated engagement process and discussion. They determined that efforts to control wildlife should begin wherever possible by altering the human practices that cause human-wildlife conflict and by developing a culture of coexistence; be justified by evidence that significant harms are being caused to people, property, livelihoods, ecosystems, and/or other animals; have measurable outcome-based objectives that are clear, achievable, monitored, and adaptive; predictably minimize animal welfare harms to the fewest number of animals; be informed by community values as well as scientific, technical, and practical information; be integrated into plans for systematic long-term management; and be based on the specifics of the situation rather than negative labels (pest, overabundant) applied to the target species. We recommend that these principles guide development of international, national, and local standards and control decisions and implementation. © 2017 The Authors. Conservation Biology published by Wiley Periodicals, Inc. on behalf of Society for Conservation Biology.

  2. Restoring balance: a consensus statement on the protection of vulnerable research participants.

    Science.gov (United States)

    DuBois, James M; Beskow, Laura; Campbell, Jean; Dugosh, Karen; Festinger, David; Hartz, Sarah; James, Rosalina; Lidz, Charles

    2012-12-01

    A diverse panel convened in June 2011 to explore a dilemma in human research: some traits may make individuals or communities particularly vulnerable to a variety of harms in research; however, well-intended efforts to protect these vulnerable individuals and communities from harm may actually generate a series of new harms. We have presented a consensus statement forged by the panel through discussion during a 2-day meeting and the article-writing process. We have identified practical problems that sometimes arise in connection with providing additional safeguards for groups labeled as vulnerable and offered recommendations on how we might better balance concerns for protection with concerns for justice and participant autonomy.

  3. Logical Consensus for Distributed and Robust Intrusion Detection

    CERN Document Server

    Fagiolini, Adriano

    2011-01-01

    In this paper we introduce a novel consensus mech- anism where agents of a network are able to share logical values, or Booleans, representing their local opinions on e.g. the presence of an intruder or of a fire within an indoor environment. We first formulate the logical consensus problem, and then we review relevant results in the literature on cellular automata and convergence of finite-state iteration maps. Under suitable joint conditions on the visibility of agents and their communication capability, we provide an algorithm for generating a logical linear consensus system that is globally stable. The solution is optimal in terms of the number of messages to be exchanged and the time needed to reach a consensus. Moreover, to cope with possible sensor failure, we propose a second design approach that produces robust logical nonlinear consensus systems tolerating a given maximum number of faults. Finally, we show applicability of the agreement mechanism to a case study consisting of a distributed Intrusion...

  4. Big cat phylogenies, consensus trees, and computational thinking.

    Science.gov (United States)

    Sul, Seung-Jin; Williams, Tiffani L

    2011-07-01

    Phylogenetics seeks to deduce the pattern of relatedness between organisms by using a phylogeny or evolutionary tree. For a given set of organisms or taxa, there may be many evolutionary trees depicting how these organisms evolved from a common ancestor. As a result, consensus trees are a popular approach for summarizing the shared evolutionary relationships in a group of trees. We examine these consensus techniques by studying how the pantherine lineage of cats (clouded leopard, jaguar, leopard, lion, snow leopard, and tiger) evolved, which is hotly debated. While there are many phylogenetic resources that describe consensus trees, there is very little information, written for biologists, regarding the underlying computational techniques for building them. The pantherine cats provide us with a small, relevant example to explore the computational techniques (such as sorting numbers, hashing functions, and traversing trees) for constructing consensus trees. Our hope is that life scientists enjoy peeking under the computational hood of consensus tree construction and share their positive experiences with others in their community.

  5. First Italian Consensus Conference on VATS lobectomy for NSCLC.

    Science.gov (United States)

    Nosotti, Mario; Droghetti, Andrea; Luzzi, Luca; Solli, Piergiorgio; Crisci, Roberto

    2017-03-24

    Video-assisted thoracoscopic surgery (VATS) lobectomy has become an accepted procedure for the treatment of selected cases of lung cancer. The aim of this project was to establish national practical recommendations for the management of patients suitable for VATS lobectomy. The Scientific Committee of the VATS Lobectomy Group (a branch of the Italian Society of Thoracic Surgery) identified the consensus conference as an appropriate tool for a national debate. The consensus conference was organized following indications of the Italian Department of Health: a panel of experts reviewed the literature, the jury board revised the experts' reports, and the national conference discussed and voted on statements. The strength of recommendation for a statement was classified as weak, fair, or high when the total score ranged between 51% and 67%, 68% and 84%, or 85% and 100%, respectively. Eighty-six Italian thoracic surgeons attended the 1st Italian Consensus Conference on VATS lobectomy in Giulianova, Italy, on October 29-30, 2015. Thirty-three topics were discussed: indications, surgical strategy, perioperative management, and training were the main topics. Consensus was reached on 24 statements that were consequently recommended. The Italian Consensus Conference is the first attempt to discuss VATS lobectomy-related issues in a national scientific community. Such experience determined an improvement in epistemic knowledge among the Italian thoracic surgeons and could be a suggestion for other national communities.

  6. Ethics committees and consensus in the post-totalitarian society.

    Science.gov (United States)

    Glasa, J; Glasova, M

    2001-01-01

    Ethics committees are usually expected to reach and frame their decisions by consensus. In a post-totalitarian society the conception of consensus might somewhat differ from the one present in societies with a long-term, uninterrupted tradition of democratic development. In 1990s, post totalitarian societies of Central and East Europe have been walking difficult paths from the situation, when matters of public interest had been decided almost solely within the structures of a totalitarian power (usually a 'communist' party and by the party dominated governmental or municipal structures) and the political decisions implemented by more or less coercive exercise of that power (while requiring the broadest community attainment--'imposed consensus'); toward societies deciding their fate and matters of public interest via institutions of a modern, pluralistic, parliamentary democracy (subscribing implicitly or even explicitly to consensus, perceived mostly as 'overlapping' or 'procedural'). The paper gives an analysis of evolution of the notion of consensus in the post-totalitarian Slovakia as seen within the frame of the first decade of establishment and work of ethics committees in the institutions of biomedical research and health care. Examples of present challenges for ethics committees' consensual decision making are outlined.

  7. ncRNA consensus secondary structure derivation using grammar strings.

    Science.gov (United States)

    Achawanantakun, Rujira; Sun, Yanni; Takyar, Seyedeh Shohreh

    2011-04-01

    Many noncoding RNAs (ncRNAs) function through both their sequences and secondary structures. Thus, secondary structure derivation is an important issue in today's RNA research. The state-of-the-art structure annotation tools are based on comparative analysis, which derives consensus structure of homologous ncRNAs. Despite promising results from existing ncRNA aligning and consensus structure derivation tools, there is a need for more efficient and accurate ncRNA secondary structure modeling and alignment methods. In this work, we introduce a consensus structure derivation approach based on grammar string, a novel ncRNA secondary structure representation that encodes an ncRNA's sequence and secondary structure in the parameter space of a context-free grammar (CFG) and a full RNA grammar including pseudoknots. Being a string defined on a special alphabet constructed from a grammar, grammar string converts ncRNA alignment into sequence alignment. We derive consensus secondary structures from hundreds of ncRNA families from BraliBase 2.1 and 25 families containing pseudoknots using grammar string alignment. Our experiments have shown that grammar string-based structure derivation competes favorably in consensus structure quality with Murlet and RNASampler. Source code and experimental data are available at http://www.cse.msu.edu/~yannisun/grammar-string.

  8. Optimal Network Design for Consensus Formation: Wisdom of Networked Agents

    Directory of Open Access Journals (Sweden)

    Eugene S. Kitamura

    2014-08-01

    Full Text Available The wisdom of crowds refers to the phenomenon in which the collective knowledge of a community is greater than the knowledge of any individual. This paper proposes a network design for the fastest and slowest consensus formation under average node degree restrictions, which is one aspect of the wisdom of crowds concept. Consensus and synchronization problems are closely related to variety of issues such as collective behavior in nature, the interaction among agents as a matter of the robot control, and building efficient wireless sensor networks. However, designing networks with desirable properties is complex and it may pose a multi-constraint and multi-criterion optimization problem. For the purpose of realizing such efficient network topology, this paper presents an optimization approach to design networks for better consensus formation by focusing on the eigenvalue spectral of Laplacian matrix. In both the fastest and slowest networks presented, consensus is formed among local structures first, then on a global scale. This suggests that both local and global topology influence the networks dynamics. These findings are useful for those who seek to manage efficient consensus and synchronization in a setting that can be modeled as a multi-agent system.

  9. Expert consensus document: The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics.

    Science.gov (United States)

    Gibson, Glenn R; Hutkins, Robert; Sanders, Mary Ellen; Prescott, Susan L; Reimer, Raylene A; Salminen, Seppo J; Scott, Karen; Stanton, Catherine; Swanson, Kelly S; Cani, Patrice D; Verbeke, Kristin; Reid, Gregor

    2017-08-01

    In December 2016, a panel of experts in microbiology, nutrition and clinical research was convened by the International Scientific Association for Probiotics and Prebiotics to review the definition and scope of prebiotics. Consistent with the original embodiment of prebiotics, but aware of the latest scientific and clinical developments, the panel updated the definition of a prebiotic: a substrate that is selectively utilized by host microorganisms conferring a health benefit. This definition expands the concept of prebiotics to possibly include non-carbohydrate substances, applications to body sites other than the gastrointestinal tract, and diverse categories other than food. The requirement for selective microbiota-mediated mechanisms was retained. Beneficial health effects must be documented for a substance to be considered a prebiotic. The consensus definition applies also to prebiotics for use by animals, in which microbiota-focused strategies to maintain health and prevent disease is as relevant as for humans. Ultimately, the goal of this Consensus Statement is to engender appropriate use of the term 'prebiotic' by relevant stakeholders so that consistency and clarity can be achieved in research reports, product marketing and regulatory oversight of the category. To this end, we have reviewed several aspects of prebiotic science including its development, health benefits and legislation.

  10. Does Having More Options Mean Harder to Reach Consensus?

    CERN Document Server

    Wu, Degang

    2016-01-01

    We generalize a binary majority-vote model on adaptive networks to a plurality-vote counterpart. When opinions are uniformly distributed in the population of voters in the initial state, it is found that having more available opinions in the initial state actually accelerate the time to consensus. In particular, we investigate the three-state plurality-vote model. While time to consensus in two state model scales exponentially with population size $N$, for finite-size system, there is a non-zero probability that either the population reaches the consensus state in a time that is very short and independent of $N$ (in the heterophily regime), or in a time that scales exponentially with $N$ but is still much faster than two-state model.

  11. The "Gent" consensus on perforator flap terminology: preliminary definitions.

    Science.gov (United States)

    Blondeel, Phillip N; Van Landuyt, Koen H I; Monstrey, Stan J M; Hamdi, Moustapha; Matton, Guido E; Allen, Robert J; Dupin, Charles; Feller, Axel-Mario; Koshima, Isao; Kostakoglu, Naci; Wei, Fu-Chan

    2003-10-01

    Due to its increasing popularity, more and more articles on the use of perforator flaps have been reported in the literature during the past few years. Because the area of perforator flaps is new and rapidly evolving, there are no definitions and standard rules on terminology and nomenclature, which creates confusion when surgeons try to communicate and compare surgical techniques. This article attempts to represent the opinion of a group of pioneers in the field of perforator flap surgery. This consensus was reached after a terminology consensus meeting held during the Fifth International Course on Perforator Flaps in Gent, Belgium, on September 29, 2001. It stipulates not only the definitions of perforator vessels and perforator flaps but also the correct nomenclature for different perforator flaps. The authors believe that this consensus is a foundation that will stimulate further discussion and encourage further refinements in the future.

  12. Cultural Consensus Theory: Aggregating Continuous Responses in a Finite Interval

    Science.gov (United States)

    Batchelder, William H.; Strashny, Alex; Romney, A. Kimball

    Cultural consensus theory (CCT) consists of cognitive models for aggregating responses of "informants" to test items about some domain of their shared cultural knowledge. This paper develops a CCT model for items requiring bounded numerical responses, e.g. probability estimates, confidence judgments, or similarity judgments. The model assumes that each item generates a latent random representation in each informant, with mean equal to the consensus answer and variance depending jointly on the informant and the location of the consensus answer. The manifest responses may reflect biases of the informants. Markov Chain Monte Carlo (MCMC) methods were used to estimate the model, and simulation studies validated the approach. The model was applied to an existing cross-cultural dataset involving native Japanese and English speakers judging the similarity of emotion terms. The results sharpened earlier studies that showed that both cultures appear to have very similar cognitive representations of emotion terms.

  13. Fastest Distributed Consensus Averaging Problem on Chain of Rhombus Networks

    CERN Document Server

    Jafarizadeh, Saber

    2010-01-01

    Distributed consensus has appeared as one of the most important and primary problems in the context of distributed computation and it has received renewed interest in the field of sensor networks (due to recent advances in wireless communications), where solving fastest distributed consensus averaging problem over networks with different topologies is one of the primary problems in this issue. Here in this work analytical solution for the problem of fastest distributed consensus averaging algorithm over Chain of Rhombus networks is provided, where the solution procedure consists of stratification of associated connectivity graph of the network and semidefinite programming, particularly solving the slackness conditions, where the optimal weights are obtained by inductive comparing of the characteristic polynomials initiated by slackness conditions. Also characteristic polynomial together with its roots corresponding to eigenvalues of weight matrix including SLEM of network is determined inductively. Moreover t...

  14. The importance of assessing and communicating scientific consensus

    Science.gov (United States)

    Maibach, Edward W.; van der Linden, Sander L.

    2016-09-01

    The spread of influential misinformation, such as conspiracy theories about the existence of a secret, large-scale atmospheric spraying program (SLAP), is contributing to the politicization of science. In an important recent study, Shearer et al (2016 Environ. Res. Lett. 11 084011) employ a novel methodology to quantify the expert consensus of popular SLAP assertions. The authors find that 99% (76/77) of surveyed experts have not encountered any evidence that would support the existence of such a program. Here we argue that this finding is important because a growing body of research has shown that the public’s perception of expert consensus on key societal issues acts an important ‘gateway’ to science acceptance. Furthermore, communicating normative agreement among experts, such as the strong scientific consensus against the existence of a SLAP, can help limit the spread of misinformation and promote more effective public decision-making about science and society.

  15. Bipartite Consensus Control of Multiagent Systems on Coopetition Networks

    Directory of Open Access Journals (Sweden)

    Jiangping Hu

    2014-01-01

    Full Text Available Cooperation and competition are two typical interactional relationships in natural and engineering networked systems. Some complex behaviors can emerge through local interactions within the networked systems. This paper focuses on the coexistence of competition and cooperation (i.e., coopetition at the network level and, simultaneously, the collective dynamics on such coopetition networks. The coopetition network is represented by a directed signed graph. The collective dynamics on the coopetition network is described by a multiagent system. We investigate two bipartite consensus strategies for multiagent systems such that all the agents converge to a final state characterized by identical modulus but opposite sign. Under a weak connectivity assumption that the coopetition network has a spanning tree, some sufficient conditions are derived for bipartite consensus of multiagent systems with the help of a structural balance theory. Finally, simulation results are provided to demonstrate the bipartite consensus formation.

  16. Critical phenomena in the spreading of opinion consensus and disagreement

    Directory of Open Access Journals (Sweden)

    Andrés Chacoma

    2014-08-01

    Full Text Available We consider a class of models of opinion formation where the dissemination of individual opinions occurs through the spreading of local consensus and disagreement. We study the emergence of full collective consensus or maximal disagreement in one- and two-dimensional arrays. In both cases, the probability of reaching full consensus exhibits well-defined scaling properties as a function of the system size. Two-dimensional systems, in particular, possess nontrivial exponents and critical points. The dynamical rules of our models, which emphasize the interaction between small groups of agents, should be considered as complementary to the imitation mechanisms of traditional opinion dynamics. Received: 11 March 2014, Accepted: 1 August 2014; Reviewed by: F. Bagnoli, Dipartimento di Fisica ed Astronomia, Universita degli Studi di Firenze, Italy; Edited by: G. Martinez Mekler; DOI: http://dx.doi.org/10.4279/PIP.060003 Cite as: A Chacoma, D H Zanette, Papers in Physics 6, 060003 (2014

  17. Cohesion, consensus and extreme information in opinion dynamics

    CERN Document Server

    Sîrbu, Alina; Servedio, Vito D P; Tria, Francesca

    2013-01-01

    Opinion formation is an important element of social dynamics. It has been widely studied in the last years with tools from physics, mathematics and computer science. Here, a continuous model of opinion dynamics for multiple possible choices is analysed. Its main features are the inclusion of disagreement and possibility of modulating information, both from one and multiple sources. The interest is in identifying the effect of the initial cohesion of the population, the interplay between cohesion and information extremism, and the effect of using multiple sources of information that can influence the system. Final consensus, especially with external information, depends highly on these factors, as numerical simulations show. When no information is present, consensus or segregation is determined by the initial cohesion of the population. Interestingly, when only one source of information is present, consensus can be obtained, in general, only when this is extremely mild, i.e. there is not a single opinion stron...

  18. Suppression of Angiogenesis and Therapy of Human Colon Cancer Liver Metastasis by Systemic Administration of Interferon-α

    Directory of Open Access Journals (Sweden)

    Shutaro Ozawa

    2001-01-01

    Full Text Available The purpose of this study was to determine whether systemic administration of interferon-alpha (IFN-α can inhibit liver metastasis produced in nude mice by human colon cancer cells. KM12L4 (IFN-α-sensitive or KM12L4 IFNR (IFN-α-resistant cells were injected into the spleen of nude mice. Seven days later, the mice were treated with subcutaneous (s.c. injections of IFN-α (70,000 units/week at different dosing schedules (1, 2, or 7 times/week. Significant inhibition of tumor growth, vascularization and expression of basic fibroblast growth factor (bFGF or matrix metal loproteinase9 (MMP-9 mRNA and protein occurred in mice given daily injections of IFN-α. Kinetic analysis of therapy showed that daily s.c. administrations of 10,000 units of IFN-α induced apoptosis in liver metastasis-associated endothelial cells, followed by inhibition of tumor cell division and apoptosis of tumor cells. These data suggest that the antiangiogenic activity of IFN-α-2a depends on frequent administration of the optimal biologic dose.

  19. Kyoto global consensus report on Helicobacter pylori gastritis.

    Science.gov (United States)

    Sugano, Kentaro; Tack, Jan; Kuipers, Ernst J; Graham, David Y; El-Omar, Emad M; Miura, Soichiro; Haruma, Ken; Asaka, Masahiro; Uemura, Naomi; Malfertheiner, Peter

    2015-09-01

    To present results of the Kyoto Global Consensus Meeting, which was convened to develop global consensus on (1) classification of chronic gastritis and duodenitis, (2) clinical distinction of dyspepsia caused by Helicobacter pylori from functional dyspepsia, (3) appropriate diagnostic assessment of gastritis and (4) when, whom and how to treat H. pylori gastritis. Twenty-three clinical questions addressing the above-mentioned four domains were drafted for which expert panels were asked to formulate relevant statements. A Delphi method using an anonymous electronic system was adopted to develop the consensus, the level of which was predefined as ≥80%. Final modifications of clinical questions and consensus were achieved at the face-to-face meeting in Kyoto. All 24 statements for 22 clinical questions after extensive modifications and omission of one clinical question were achieved with a consensus level of >80%. To better organise classification of gastritis and duodenitis based on aetiology, a new classification of gastritis and duodenitis is recommended for the 11th international classification. A new category of H. pylori-associated dyspepsia together with a diagnostic algorithm was proposed. The adoption of grading systems for gastric cancer risk stratification, and modern image-enhancing endoscopy for the diagnosis of gastritis, were recommended. Treatment to eradicate H. pylori infection before preneoplastic changes develop, if feasible, was recommended to minimise the risk of more serious complications of the infection. A global consensus for gastritis was developed for the first time, which will be the basis for an international classification system and for further research on the subject. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  20. ConStruct: Improved construction of RNA consensus structures

    Directory of Open Access Journals (Sweden)

    Steger Gerhard

    2008-04-01

    Full Text Available Abstract Background Aligning homologous non-coding RNAs (ncRNAs correctly in terms of sequence and structure is an unresolved problem, due to both mathematical complexity and imperfect scoring functions. High quality alignments, however, are a prerequisite for most consensus structure prediction approaches, homology searches, and tools for phylogeny inference. Automatically created ncRNA alignments often need manual corrections, yet this manual refinement is tedious and error-prone. Results We present an extended version of CONSTRUCT, a semi-automatic, graphical tool suitable for creating RNA alignments correct in terms of both consensus sequence and consensus structure. To this purpose CONSTRUCT combines sequence alignment, thermodynamic data and various measures of covariation. One important feature is that the user is guided during the alignment correction step by a consensus dotplot, which displays all thermodynamically optimal base pairs and the corresponding covariation. Once the initial alignment is corrected, optimal and suboptimal secondary structures as well as tertiary interaction can be predicted. We demonstrate CONSTRUCT's ability to guide the user in correcting an initial alignment, and show an example for optimal secondary consensus structure prediction on very hard to align SECIS elements. Moreover we use CONSTRUCT to predict tertiary interactions from sequences of the internal ribosome entry site of CrP-like viruses. In addition we show that alignments specifically designed for benchmarking can be easily be optimized using CONSTRUCT, although they share very little sequence identity. Conclusion CONSTRUCT's graphical interface allows for an easy alignment correction based on and guided by predicted and known structural constraints. It combines several algorithms for prediction of secondary consensus structure and even tertiary interactions. The CONSTRUCT package can be downloaded from the URL listed in the Availability and