Sample records for laryngological society marburg

  1. Microdebrider complications in laryngologic and airway surgery.

    PubMed

    Howell, Rebecca J; Solowski, Nancy L; Belafsky, Peter C; Courey, Mark C; Merati, Albert L; Rosen, Clark A; Weinberger, Paul M; Postma, Gregory N

    2014-11-01

    There is a paucity of experience in the published literature documenting complications of powered surgical instruments in laryngologic surgery. Our objective was to ascertain the nature of these complications from expert opinion and review of the literature, and to recommend strategies to decrease major complications. Review of the literature and an e-mail survey. A literature review of microdebrider complications in laryngologic surgery was conducted using PubMed and Ovid (1985 to 2013), along with an analysis of a confidential e-mail survey of various surgeons in selected high-volume laryngologic centers. Powered instrumentation is frequently used in the operating room for larynx and airway surgery. The microdebrider can improve efficiency, lower costs, and shorten operative times. However, use of the microdebrider has the potential for serious complications in the larynx and airway. Great care must be taken when utilizing the microdebrider in laryngologic surgery. Significant complications including major vocal fold scar, airway compromise, severe hemorrhage, and unintentional tissue loss have occurred. The microdebrider is a popular and valuable tool for the otolaryngologist. A thorough knowledge of the instrument and its potential complications will improve surgical outcomes and may prevent complications. Awareness of the risks and surgeon experience with use of the microdebrider will allow the surgeon to successfully utilize this device in a safe and effective manner. 5. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

  2. Perceptions of the laryngology Match: A survey of program directors and recent trainees.

    PubMed

    Formeister, Eric J; Courey, Mark S; Yung, Katherine C

    2017-12-01

    Evaluate program director and recent trainee perceptions of the advantages and disadvantages of the laryngology Match. Web-based survey study. A Web-based survey study was distributed to program directors and recent laryngology trainees to evaluate perceptions of the laryngology Match. A 15-item questionnaire with free-form, Likert, and multiple selection answers was emailed to 115 recent/current trainees and 22 laryngology directors. Fifty-nine percent (13/22) of the program directors and 47% (54/115) of the recent trainees responded to the survey. There were significant increases in the number of programs applied to, interview offers received, and interviews attended by laryngology trainees who applied after adoption of the Match compared to those who applied prior to the Match. Seventy-one percent (22/31) of applicants after 2012 participated in the Match; those who did not accepted positions outside of the Match. Ninety-five percent (21/22) who applied through the Match successfully matched. Two-thirds of recent trainees and three-quarters of directors believe the Match process primarily benefits the applicant. The number of candidates interviewed per program approximately doubled from three to six after institution of the Match. Overall, both program directors and recent or current laryngology trainees have a positive perception of the laryngology match process. The Match process increased the number of applicants and interviews per year, which both directors and trainees believe increases an applicant's chance at successfully matching. NA. Laryngoscope, 127:2818-2822, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

  3. Transcriptional Profiling of the Immune Response to Marburg Virus Infection.

    PubMed

    Connor, John H; Yen, Judy; Caballero, Ignacio S; Garamszegi, Sara; Malhotra, Shikha; Lin, Kenny; Hensley, Lisa; Goff, Arthur J

    2015-10-01

    circulating in the blood of infected primates respond following exposure to Marburg virus. Our results show that there are three discernible stages of response to infection that correlate with presymptomatic, early, and late symptomatic stages of infection, a response format similar to that seen following challenge with other hemorrhagic fever viruses. In contrast to the ability of the virus to block innate immune signaling in vitro, the earliest and most sustained response is an interferon-like response. Our analysis also identifies a number of cytokines that are transcriptionally upregulated during late stages of infection and suggest that there is a Th2-skewed response to infection. When correlated with companion data describing the animal model from which our samples were collected, our results suggest that the innate immune response may contribute to overall pathogenesis. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  4. A cost and time analysis of laryngology procedures in the endoscopy suite versus the operating room.

    PubMed

    Hillel, Alexander T; Ochsner, Matthew C; Johns, Michael M; Klein, Adam M

    2016-06-01

    To assess the costs, charges, reimbursement, and efficiency of performing awake laryngology procedures in an endoscopy suite (ES) compared with like procedures performed in the operating room (OR). Retrospective review of billing records. Cost, charges, and reimbursements for the hospital, surgeon, and anesthesiologist were compared between ES injection laryngoplasty and laser excision procedures and matched case controls in the OR. Time spent in 1) the preoperative unit, 2) the operating or endoscopy suite, and 3) recovery unit were compared between OR and ES procedures. Hospital expenses were significantly less for ES procedures when compared to OR procedures. Reimbursement was similar for ES and OR injection laryngoplasty, though greater for OR laser excisions. Net balance (reimbursement-expenses) was greater for ES procedures. A predictive model of payer costs over a 3-year period showed similar costs for ES and OR laser procedures and reduced costs for ES compared to OR injection laryngoplasty. Times spent preoperatively and the procedure were significantly less for ES procedures. For individual laryngology procedures, the ES reduces time and costs compared to the OR, increasing otolaryngologist and hospital efficiency. This reveals cost and time savings of ES injection laryngoplasty, which occurs at a similar frequency as OR injection laryngoplasty. Given the increased frequency for ES laser procedures, total costs are similar for ES and OR laser excision of papilloma, which usually require repeated procedures. When regulated office space is unavailable, endoscopy rooms represent an alternative setting for unsedated laryngology procedures. NA Laryngoscope, 126:1385-1389, 2016. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

  5. 21 CFR 874.4490 - Argon laser for otology, rhinology, and laryngology.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Argon laser for otology, rhinology, and laryngology. 874.4490 Section 874.4490 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... Argon laser for otology, rhinology, and laryngology. (a) Identification. The argon laser device for use...

  6. 21 CFR 874.4490 - Argon laser for otology, rhinology, and laryngology.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Argon laser for otology, rhinology, and laryngology. 874.4490 Section 874.4490 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... Argon laser for otology, rhinology, and laryngology. (a) Identification. The argon laser device for use...

  7. Forty-five years of Marburg virus research.

    PubMed

    Brauburger, Kristina; Hume, Adam J; Mühlberger, Elke; Olejnik, Judith

    2012-10-01

    In 1967, the first reported filovirus hemorrhagic fever outbreak took place in Germany and the former Yugoslavia. The causative agent that was identified during this outbreak, Marburg virus, is one of the most deadly human pathogens. This article provides a comprehensive overview of our current knowledge about Marburg virus disease ranging from ecology to pathogenesis and molecular biology.

  8. Forty-Five Years of Marburg Virus Research

    PubMed Central

    Brauburger, Kristina; Hume, Adam J.; Mühlberger, Elke; Olejnik, Judith

    2012-01-01

    In 1967, the first reported filovirus hemorrhagic fever outbreak took place in Germany and the former Yugoslavia. The causative agent that was identified during this outbreak, Marburg virus, is one of the most deadly human pathogens. This article provides a comprehensive overview of our current knowledge about Marburg virus disease ranging from ecology to pathogenesis and molecular biology. PMID:23202446

  9. [Marburg and Ebola hemorrhagic fevers--pathogens, epidemiology and therapy].

    PubMed

    Stock, Ingo

    2014-09-01

    Marburg and Ebola hemorrhagic fevers are severe, systemic viral diseases affecting humans and non-human primates. They are characterized by multiple symptoms such as hemorrhages, fever, headache, muscle and abdominal pain, chills, sore throat, nausea, vomiting and diarrhea. Elevated liver-associated enzyme levels and coagulopathy are also associated with these diseases. Marburg and Ebola hemorrhagic fevers are caused by (Lake victoria) Marburg virus and different species of Ebola viruses, respectively. They are enveloped, single-stranded RNA viruses and belong to the family of filoviridae. Case fatality rates of filovirus disease outbreaks are among the highest reported for any human pathogen, ranging from 25 to 90% or more. Outbreaks of Marburg and Ebola hemorrhagic fever occur in certain regions of equatorial Africa at irregular intervals. Since 2000, the number of outbreaks has increased. In 2014, the biggest outbreak of a filovirus-induced hemorrhagic fever that has been documented so far occurred from March to July 2014 in Guinea, Sierra Leone, Liberia and Nigeria. The outbreak was caused by a new variant of Zaire Ebola-Virus, affected more than 2600 people (stated 20 August) and was associated with case-fatality rates of up to 67% (Guinea). Treatment of Marburg and Ebola hemorrhagic fevers is symptomatic and supportive, licensed antiviral agents are currently not available. Recently, BCX4430, a promising synthetic adenosine analogue with high in vitro and in vivo activity against filoviruses and other RNA viruses, has been described. BCX4430 inhibits viral RNA polymerase activity and protects cynomolgus macaques from Marburg virus infection when administered as late as 48 hours after infection. Nucleic acid-based products, recombinant vaccines and antibodies appear to be less suitable for the treatment of Marburg and Ebola hemorrhagic fevers.

  10. Ebola and marburg hemorrhagic fever.

    PubMed

    Hartman, Amy L; Towner, Jonathan S; Nichol, Stuart T

    2010-03-01

    Ebola and Marburg viruses cause a severe viral hemorrhagic fever disease mainly in Sub-Saharan Africa. Although outbreaks are sporadic, there is the potential for filoviruses to spread to other continents unintentionally because of air travel or intentionally because of bioterrorism. This article discusses the natural history, epidemiology, and clinical presentation of patients infected with Ebola and Marburg viruses. Clinicians in the United States should be aware of the symptoms of these viral infections in humans and know the appropriate procedures for contacting local, state, and national reference laboratories in the event of a suspected case of filoviral hemorrhagic fever. 2010 Elsevier Inc. All rights reserved.

  11. A hamster model for Marburg virus infection accurately recapitulates Marburg hemorrhagic fever

    PubMed Central

    Marzi, Andrea; Banadyga, Logan; Haddock, Elaine; Thomas, Tina; Shen, Kui; Horne, Eva J.; Scott, Dana P.; Feldmann, Heinz; Ebihara, Hideki

    2016-01-01

    Marburg virus (MARV), a close relative of Ebola virus, is the causative agent of a severe human disease known as Marburg hemorrhagic fever (MHF). No licensed vaccine or therapeutic exists to treat MHF, and MARV is therefore classified as a Tier 1 select agent and a category A bioterrorism agent. In order to develop countermeasures against this severe disease, animal models that accurately recapitulate human disease are required. Here we describe the development of a novel, uniformly lethal Syrian golden hamster model of MHF using a hamster-adapted MARV variant Angola. Remarkably, this model displayed almost all of the clinical features of MHF seen in humans and non-human primates, including coagulation abnormalities, hemorrhagic manifestations, petechial rash, and a severely dysregulated immune response. This MHF hamster model represents a powerful tool for further dissecting MARV pathogenesis and accelerating the development of effective medical countermeasures against human MHF. PMID:27976688

  12. A hamster model for Marburg virus infection accurately recapitulates Marburg hemorrhagic fever.

    PubMed

    Marzi, Andrea; Banadyga, Logan; Haddock, Elaine; Thomas, Tina; Shen, Kui; Horne, Eva J; Scott, Dana P; Feldmann, Heinz; Ebihara, Hideki

    2016-12-15

    Marburg virus (MARV), a close relative of Ebola virus, is the causative agent of a severe human disease known as Marburg hemorrhagic fever (MHF). No licensed vaccine or therapeutic exists to treat MHF, and MARV is therefore classified as a Tier 1 select agent and a category A bioterrorism agent. In order to develop countermeasures against this severe disease, animal models that accurately recapitulate human disease are required. Here we describe the development of a novel, uniformly lethal Syrian golden hamster model of MHF using a hamster-adapted MARV variant Angola. Remarkably, this model displayed almost all of the clinical features of MHF seen in humans and non-human primates, including coagulation abnormalities, hemorrhagic manifestations, petechial rash, and a severely dysregulated immune response. This MHF hamster model represents a powerful tool for further dissecting MARV pathogenesis and accelerating the development of effective medical countermeasures against human MHF.

  13. Characteristics of Filoviridae: Marburg and Ebola Viruses

    NASA Astrophysics Data System (ADS)

    Beer, Brigitte; Kurth, Reinhard; Bukreyev, Alexander

    Filoviruses are enveloped, nonsegmented negative-stranded RNA viruses. The two species, Marburg and Ebola virus, are serologically, biochemically, and genetically distinct. Marburg virus was first isolated during an outbreak in Europe in 1967, and Ebola virus emerged in 1976 as the causative agent of two simultaneous outbreaks in southern Sudan and northern Zaire. Although the main route of infection is known to be person-to-person transmission by intimate contact, the natural reservoir for filoviruses still remains a mystery.

  14. Isolated Case of Marburg Virus Disease, Kampala, Uganda, 2014.

    PubMed

    Nyakarahuka, Luke; Ojwang, Joseph; Tumusiime, Alex; Balinandi, Stephen; Whitmer, Shannon; Kyazze, Simon; Kasozi, Sam; Wetaka, Milton; Makumbi, Issa; Dahlke, Melissa; Borchert, Jeff; Lutwama, Julius; Ströher, Ute; Rollin, Pierre E; Nichol, Stuart T; Shoemaker, Trevor R

    2017-06-01

    In September 2014, a single fatal case of Marburg virus was identified in a healthcare worker in Kampala, Uganda. The source of infection was not identified, and no secondary cases were identified. We describe the rapid identification, laboratory diagnosis, and case investigation of the third Marburg virus outbreak in Uganda.

  15. [Ebola and Marburg viruses: the humans strike back].

    PubMed

    Alazard-Dany, Nathalie; Ottmann Terrangle, Michèle; Volchkov, Viktor

    2006-04-01

    Ebola and Marburg viruses are the causative agents of rapidly progressive hemorrhagic fevers with high mortality rates. Pre- or post-exposure treatments against the diseases are currently not available for human use. In the field, establishment of strict quarantine measures preventing further virus transmission are still the only way to fight the infections. However, our knowledge of Ebola and Marburg viruses has markedly increased as a result of two recent discoveries discussed in this review. Chandran et al. have elucidated the mechanism by which Ebola GP is converted to a fusion-active form. Infectivity of Ebola virus was shown to be dependent on the cleavage of GP by cellular endosomal proteases, cathepsin B and L, thus opening new therapeutic approaches options. As for Jones SM et al., they have successfully vaccinated monkeys with recombinant vesicular stomatitis virus expressing Ebola or Marburg virus surface glycoprotein GP, a promising vaccine approach.

  16. Studies of Reservoir Hosts for Marburg Virus

    PubMed Central

    Smit, Sheilagh B.; Rollin, Pierre E.; Formenty, Pierre; Leman, Patricia A.; Kemp, Alan; Burt, Felicity J.; Grobbelaar, Antoinette A.; Croft, Janice; Bausch, Daniel G.; Zeller, Hervé; Leirs, Herwig; Braack, L.E.O.; Libande, Modeste L.; Zaki, Sherif; Nichol, Stuart T.; Ksiazek, Thomas G.; Paweska, Janusz T.

    2007-01-01

    To determine reservoir hosts for Marburg virus (MARV), we examined the fauna of a mine in northeastern Democratic Republic of the Congo. The mine was associated with a protracted outbreak of Marburg hemorrhagic fever during 1998–2000. We found MARV nucleic acid in 12 bats, comprising 3.0%–3.6% of 2 species of insectivorous bat and 1 species of fruit bat. We found antibody to the virus in the serum of 9.7% of 1 of the insectivorous species and in 20.5% of the fruit bat species, but attempts to isolate virus were unsuccessful. PMID:18258034

  17. Crystal Structure of the Marburg Virus VP35 Oligomerization Domain.

    PubMed

    Bruhn, Jessica F; Kirchdoerfer, Robert N; Urata, Sarah M; Li, Sheng; Tickle, Ian J; Bricogne, Gérard; Saphire, Erica Ollmann

    2017-01-15

    Marburg virus (MARV) is a highly pathogenic filovirus that is classified in a genus distinct from that of Ebola virus (EBOV) (genera Marburgvirus and Ebolavirus, respectively). Both viruses produce a multifunctional protein termed VP35, which acts as a polymerase cofactor, a viral protein chaperone, and an antagonist of the innate immune response. VP35 contains a central oligomerization domain with a predicted coiled-coil motif. This domain has been shown to be essential for RNA polymerase function. Here we present crystal structures of the MARV VP35 oligomerization domain. These structures and accompanying biophysical characterization suggest that MARV VP35 is a trimer. In contrast, EBOV VP35 is likely a tetramer in solution. Differences in the oligomeric state of this protein may explain mechanistic differences in replication and immune evasion observed for MARV and EBOV. Marburg virus can cause severe disease, with up to 90% human lethality. Its genome is concise, only producing seven proteins. One of the proteins, VP35, is essential for replication of the viral genome and for evasion of host immune responses. VP35 oligomerizes (self-assembles) in order to function, yet the structure by which it assembles has not been visualized. Here we present two crystal structures of this oligomerization domain. In both structures, three copies of VP35 twist about each other to form a coiled coil. This trimeric assembly is in contrast to tetrameric predictions for VP35 of Ebola virus and to known structures of homologous proteins in the measles, mumps, and Nipah viruses. Distinct oligomeric states of the Marburg and Ebola virus VP35 proteins may explain differences between them in polymerase function and immune evasion. These findings may provide a more accurate understanding of the mechanisms governing VP35's functions and inform the design of therapeutics. Copyright © 2017 American Society for Microbiology.

  18. Re-Evaluation of Open Partial Horizontal Laryngectomies at Our Institution According to the New Classification Recommended by the European Laryngological Society.

    PubMed

    Bozkurt, Gülpembe; Ünsal, Özlem; Coşkun, Berna Uslu

    2016-06-01

    The aim of this study was to re-evaluate the open partial horizontal laryngectomies (OPHLs) performed at our institution in terms of the new classification of the European Laryngological Society and compare the differences with the new classification system. A retrospective analysis of 45 patients diagnosed with T1b, T2, and T3 laryngeal carcinoma who were treated with OPHLs in our department between 2010 and 2016 were conducted. All supraglottic laryngectomies (31 operations) were classified as OPHL Type 1. Among these, 11 operations required a resection of an additional structure including arytenoid (ARY) in five operations, piriform sinus (PIR) in four operations, the base of tongue (BOT) in one surgery, and ARY + PIR in one patient. Five supracricoid laryngectomies with cricohyoidoepiglottopexy (CHEP), five supracricoid laryngectomies with cricohyoidopexy (CHP), and four near-total laryngectomy operations constituted Type 2 OPHL (7 operations) and Type 3 OPHL (7 operations). Among these operations, two were classified into Type 2b OPHL and four into Type 3b OPHL as the superior margin of incision included epiglottis. We consider that, this new classification, because it allows understanding the content of the surgery from the related title, will be useful in comparing different series and techniques.

  19. Distribution of Marburg virus in Africa: An evolutionary approach.

    PubMed

    Zehender, Gianguglielmo; Sorrentino, Chiara; Veo, Carla; Fiaschi, Lisa; Gioffrè, Sonia; Ebranati, Erika; Tanzi, Elisabetta; Ciccozzi, Massimo; Lai, Alessia; Galli, Massimo

    2016-10-01

    The aim of this study was to investigate the origin and geographical dispersion of Marburg virus, the first member of the Filoviridae family to be discovered. Seventy-three complete genome sequences of Marburg virus isolated from animals and humans were retrieved from public databases and analysed using a Bayesian phylogeographical framework. The phylogenetic tree of the Marburg virus data set showed two significant evolutionary lineages: Ravn virus (RAVV) and Marburg virus (MARV). MARV divided into two main clades; clade A included isolates from Uganda (five from the European epidemic in 1967), Kenya (1980) and Angola (from the epidemic of 2004-2005); clade B included most of the isolates obtained during the 1999-2000 epidemic in the Democratic Republic of the Congo (DRC) and a group of Ugandan isolates obtained in 2007-2009. The estimated mean evolutionary rate of the whole genome was 3.3×10(-4) substitutions/site/year (credibility interval 2.0-4.8). The MARV strain had a mean root time of the most recent common ancestor of 177.9years ago (YA) (95% highest posterior density 87-284), thus indicating that it probably originated in the mid-XIX century, whereas the RAVV strain had a later origin dating back to a mean 33.8 YA. The most probable location of the MARV ancestor was Uganda (state posterior probability, spp=0.41), whereas that of the RAVV ancestor was Kenya (spp=0.71). There were significant migration rates from Uganda to the DRC (Bayes Factor, BF=42.0) and in the opposite direction (BF=5.7). Our data suggest that Uganda may have been the cradle of Marburg virus in Africa. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. [Multiplex real-time PCR method for rapid detection of Marburg virus and Ebola virus].

    PubMed

    Yang, Yu; Bai, Lin; Hu, Kong-Xin; Yang, Zhi-Hong; Hu, Jian-Ping; Wang, Jing

    2012-08-01

    Marburg virus and Ebola virus are acute infections with high case fatality rates. A rapid, sensitive detection method was established to detect Marburg virus and Ebola virus by multiplex real-time fluorescence quantitative PCR. Designing primers and Taqman probes from highly conserved sequences of Marburg virus and Ebola virus through whole genome sequences alignment, Taqman probes labeled by FAM and Texas Red, the sensitivity of the multiplex real-time quantitative PCR assay was optimized by evaluating the different concentrations of primers and Probes. We have developed a real-time PCR method with the sensitivity of 30.5 copies/microl for Marburg virus positive plasmid and 28.6 copies/microl for Ebola virus positive plasmids, Japanese encephalitis virus, Yellow fever virus, Dengue virus were using to examine the specificity. The Multiplex real-time PCR assays provide a sensitive, reliable and efficient method to detect Marburg virus and Ebola virus simultaneously.

  1. Isolation of genetically diverse Marburg viruses from Egyptian fruit bats.

    PubMed

    Towner, Jonathan S; Amman, Brian R; Sealy, Tara K; Carroll, Serena A Reeder; Comer, James A; Kemp, Alan; Swanepoel, Robert; Paddock, Christopher D; Balinandi, Stephen; Khristova, Marina L; Formenty, Pierre B H; Albarino, Cesar G; Miller, David M; Reed, Zachary D; Kayiwa, John T; Mills, James N; Cannon, Deborah L; Greer, Patricia W; Byaruhanga, Emmanuel; Farnon, Eileen C; Atimnedi, Patrick; Okware, Samuel; Katongole-Mbidde, Edward; Downing, Robert; Tappero, Jordan W; Zaki, Sherif R; Ksiazek, Thomas G; Nichol, Stuart T; Rollin, Pierre E

    2009-07-01

    In July and September 2007, miners working in Kitaka Cave, Uganda, were diagnosed with Marburg hemorrhagic fever. The likely source of infection in the cave was Egyptian fruit bats (Rousettus aegyptiacus) based on detection of Marburg virus RNA in 31/611 (5.1%) bats, virus-specific antibody in bat sera, and isolation of genetically diverse virus from bat tissues. The virus isolates were collected nine months apart, demonstrating long-term virus circulation. The bat colony was estimated to be over 100,000 animals using mark and re-capture methods, predicting the presence of over 5,000 virus-infected bats. The genetically diverse virus genome sequences from bats and miners closely matched. These data indicate common Egyptian fruit bats can represent a major natural reservoir and source of Marburg virus with potential for spillover into humans.

  2. Crystal Structure of Marburg Virus VP40 Reveals a Broad, Basic Patch for Matrix Assembly and a Requirement of the N-Terminal Domain for Immunosuppression.

    PubMed

    Oda, Shun-Ichiro; Noda, Takeshi; Wijesinghe, Kaveesha J; Halfmann, Peter; Bornholdt, Zachary A; Abelson, Dafna M; Armbrust, Tammy; Stahelin, Robert V; Kawaoka, Yoshihiro; Saphire, Erica Ollmann

    2016-02-15

    Marburg virus (MARV), a member of the filovirus family, causes severe hemorrhagic fever with up to 90% lethality. MARV matrix protein VP40 is essential for assembly and release of newly copied viruses and also suppresses immune signaling in the infected cell. Here we report the crystal structure of MARV VP40. We found that MARV VP40 forms a dimer in solution, mediated by N-terminal domains, and that formation of this dimer is essential for budding of virus-like particles. We also found the N-terminal domain to be necessary and sufficient for immune antagonism. The C-terminal domains of MARV VP40 are dispensable for immunosuppression but are required for virus assembly. The C-terminal domains are only 16% identical to those of Ebola virus, differ in structure from those of Ebola virus, and form a distinct broad and flat cationic surface that likely interacts with the cell membrane during virus assembly. Marburg virus, a cousin of Ebola virus, causes severe hemorrhagic fever, with up to 90% lethality seen in recent outbreaks. Molecular structures and visual images of the proteins of Marburg virus are essential for the development of antiviral drugs. One key protein in the Marburg virus life cycle is VP40, which both assembles the virus and suppresses the immune system. Here we provide the molecular structure of Marburg virus VP40, illustrate differences from VP40 of Ebola virus, and reveal surfaces by which Marburg VP40 assembles progeny and suppresses immune function. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  3. Multidistrict Outbreak of Marburg Virus Disease-Uganda, 2012.

    PubMed

    Knust, Barbara; Schafer, Ilana J; Wamala, Joseph; Nyakarahuka, Luke; Okot, Charles; Shoemaker, Trevor; Dodd, Kimberly; Gibbons, Aridth; Balinandi, Stephen; Tumusiime, Alex; Campbell, Shelley; Newman, Edmund; Lasry, Estrella; DeClerck, Hilde; Boum, Yap; Makumbi, Issa; Bosa, Henry Kyobe; Mbonye, Anthony; Aceng, Jane Ruth; Nichol, Stuart T; Ströher, Ute; Rollin, Pierre E

    2015-10-01

    In October 2012, a cluster of illnesses and deaths was reported in Uganda and was confirmed to be an outbreak of Marburg virus disease (MVD). Patients meeting the case criteria were interviewed using a standard investigation form, and blood specimens were tested for evidence of acute or recent Marburg virus infection by reverse transcription-polymerase chain reaction (RT-PCR) and antibody enzyme-linked immunosorbent assay. The total count of confirmed and probable MVD cases was 26, of which 15 (58%) were fatal. Four of 15 laboratory-confirmed cases (27%) were fatal. Case patients were located in 4 different districts in Uganda, although all chains of transmission originated in Ibanda District, and the earliest case detected had an onset in July 2012. No zoonotic exposures were identified. Symptoms significantly associated with being a MVD case included hiccups, anorexia, fatigue, vomiting, sore throat, and difficulty swallowing. Contact with a case patient and attending a funeral were also significantly associated with being a case. Average RT-PCR cycle threshold values for fatal cases during the acute phase of illness were significantly lower than those for nonfatal cases. Following the institution of contact tracing, active case surveillance, care of patients with isolation precautions, community mobilization, and rapid diagnostic testing, the outbreak was successfully contained 14 days after its initial detection. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  4. Human Survivors of Disease Outbreaks Caused by Ebola or Marburg Virus Exhibit Cross-Reactive and Long-Lived Antibody Responses.

    PubMed

    Natesan, Mohan; Jensen, Stig M; Keasey, Sarah L; Kamata, Teddy; Kuehne, Ana I; Stonier, Spencer W; Lutwama, Julius Julian; Lobel, Leslie; Dye, John M; Ulrich, Robert G

    2016-08-01

    A detailed understanding of serological immune responses to Ebola and Marburg virus infections will facilitate the development of effective diagnostic methods, therapeutics, and vaccines. We examined antibodies from Ebola or Marburg survivors 1 to 14 years after recovery from disease, by using a microarray that displayed recombinant nucleoprotein (NP), viral protein 40 (VP40), envelope glycoprotein (GP), and inactivated whole virions from six species of filoviruses. All three outbreak cohorts exhibited significant antibody responses to antigens from the original infecting species and a pattern of additional filoviruses that varied by outbreak. NP was the most cross-reactive antigen, while GP was the most specific. Antibodies from survivors of infections by Marburg marburgvirus (MARV) species were least cross-reactive, while those from survivors of infections by Sudan virus (SUDV) species exhibited the highest cross-reactivity. Based on results revealed by the protein microarray, persistent levels of antibodies to GP, NP, and VP40 were maintained for up to 14 years after infection, and survival of infection caused by one species imparted cross-reactive antibody responses to other filoviruses. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  5. Isolation of Genetically Diverse Marburg Viruses from Egyptian Fruit Bats

    PubMed Central

    Towner, Jonathan S.; Amman, Brian R.; Sealy, Tara K.; Carroll, Serena A. Reeder; Comer, James A.; Kemp, Alan; Swanepoel, Robert; Paddock, Christopher D.; Balinandi, Stephen; Khristova, Marina L.; Formenty, Pierre B. H.; Albarino, Cesar G.; Miller, David M.; Reed, Zachary D.; Kayiwa, John T.; Mills, James N.; Cannon, Deborah L.; Greer, Patricia W.; Byaruhanga, Emmanuel; Farnon, Eileen C.; Atimnedi, Patrick; Okware, Samuel; Katongole-Mbidde, Edward; Downing, Robert; Tappero, Jordan W.; Zaki, Sherif R.; Ksiazek, Thomas G.; Nichol, Stuart T.; Rollin, Pierre E.

    2009-01-01

    In July and September 2007, miners working in Kitaka Cave, Uganda, were diagnosed with Marburg hemorrhagic fever. The likely source of infection in the cave was Egyptian fruit bats (Rousettus aegyptiacus) based on detection of Marburg virus RNA in 31/611 (5.1%) bats, virus-specific antibody in bat sera, and isolation of genetically diverse virus from bat tissues. The virus isolates were collected nine months apart, demonstrating long-term virus circulation. The bat colony was estimated to be over 100,000 animals using mark and re-capture methods, predicting the presence of over 5,000 virus-infected bats. The genetically diverse virus genome sequences from bats and miners closely matched. These data indicate common Egyptian fruit bats can represent a major natural reservoir and source of Marburg virus with potential for spillover into humans. PMID:19649327

  6. Development and Characterization of a Mouse Model for Marburg Hemorrhagic Fever

    DTIC Science & Technology

    2009-07-01

    Microbiology. All Rights Reserved. Development and Characterization of a Mouse Model for Marburg Hemorrhagic Fever Kelly L. Warfield,* Steven B...mouse model has hampered an understanding of the pathogenesis and immunity of Marburg hemorrhagic fever (MHF), the disease caused by marburgvirus (MARV...cause severe hemorrhagic fevers in humans and non- human primates (27). The incubation time is estimated to be 3 to 21 days, with human case fatality

  7. Knowledge and attitude towards Ebola and Marburg virus diseases in Uganda using quantitative and participatory epidemiology techniques

    PubMed Central

    Skjerve, Eystein; Nabadda, Daisy; Sitali, Doreen Chilolo; Mumba, Chisoni; Mwiine, Frank N.; Lutwama, Julius J.; Balinandi, Stephen; Shoemaker, Trevor; Kankya, Clovice

    2017-01-01

    Background Uganda has reported five (5) Ebola virus disease outbreaks and three (3) Marburg virus disease outbreaks from 2000 to 2016. Peoples’ knowledge and attitude towards Ebola and Marburg virus disease impact on control and prevention measures especially during outbreaks. We describe knowledge and attitude towards Ebola and Marburg virus outbreaks in two affected communities in Uganda to inform future outbreak responses and help in the design of health education and communication messages. Methods The study was a community survey done in Luweero, Ibanda and Kamwenge districts that have experienced outbreaks of Ebola and Marburg virus diseases. Quantitative data were collected using a structured questionnaire and triangulated with qualitative participatory epidemiology techniques to gain a communities’ knowledge and attitude towards Ebola and Marburg virus disease. Results Out of 740 respondents, 48.5% (359/740) were categorized as being knowledgeable about Ebola and Marburg virus diseases, whereas 60.5% (448/740) were having a positive attitude towards control and prevention of Ebola and Marburg virus diseases. The mean knowledge and attitude percentage scores were 54.3 (SD = 23.5, 95%CI = 52.6–56.0) and 69.9 (SD = 16.9, 95%CI = 68.9–71.1) respectively. People educated beyond primary school were more likely to be knowledgeable about Ebola and Marburg virus disease than those who did not attain any formal education (OR = 3.6, 95%CI = 2.1–6.1). Qualitative data revealed that communities describe Ebola and Marburg virus diseases as very severe diseases with no cure and they believe the diseases spread so fast. Respondents reported fear and stigma suffered by survivors, their families and the broader community due to these diseases. Conclusion Communities in Uganda affected by filovirus outbreaks have moderate knowledge about these diseases and have a positive attitude towards practices to prevent and control Ebola and Marburg viral diseases. The public

  8. Knowledge and attitude towards Ebola and Marburg virus diseases in Uganda using quantitative and participatory epidemiology techniques.

    PubMed

    Nyakarahuka, Luke; Skjerve, Eystein; Nabadda, Daisy; Sitali, Doreen Chilolo; Mumba, Chisoni; Mwiine, Frank N; Lutwama, Julius J; Balinandi, Stephen; Shoemaker, Trevor; Kankya, Clovice

    2017-09-01

    Uganda has reported five (5) Ebola virus disease outbreaks and three (3) Marburg virus disease outbreaks from 2000 to 2016. Peoples' knowledge and attitude towards Ebola and Marburg virus disease impact on control and prevention measures especially during outbreaks. We describe knowledge and attitude towards Ebola and Marburg virus outbreaks in two affected communities in Uganda to inform future outbreak responses and help in the design of health education and communication messages. The study was a community survey done in Luweero, Ibanda and Kamwenge districts that have experienced outbreaks of Ebola and Marburg virus diseases. Quantitative data were collected using a structured questionnaire and triangulated with qualitative participatory epidemiology techniques to gain a communities' knowledge and attitude towards Ebola and Marburg virus disease. Out of 740 respondents, 48.5% (359/740) were categorized as being knowledgeable about Ebola and Marburg virus diseases, whereas 60.5% (448/740) were having a positive attitude towards control and prevention of Ebola and Marburg virus diseases. The mean knowledge and attitude percentage scores were 54.3 (SD = 23.5, 95%CI = 52.6-56.0) and 69.9 (SD = 16.9, 95%CI = 68.9-71.1) respectively. People educated beyond primary school were more likely to be knowledgeable about Ebola and Marburg virus disease than those who did not attain any formal education (OR = 3.6, 95%CI = 2.1-6.1). Qualitative data revealed that communities describe Ebola and Marburg virus diseases as very severe diseases with no cure and they believe the diseases spread so fast. Respondents reported fear and stigma suffered by survivors, their families and the broader community due to these diseases. Communities in Uganda affected by filovirus outbreaks have moderate knowledge about these diseases and have a positive attitude towards practices to prevent and control Ebola and Marburg viral diseases. The public health sector should enhance this community

  9. Establishment and characterization of a lethal mouse model for the Angola strain of Marburg virus.

    PubMed

    Qiu, Xiangguo; Wong, Gary; Audet, Jonathan; Cutts, Todd; Niu, Yulian; Booth, Stephanie; Kobinger, Gary P

    2014-11-01

    Marburg viruses. With a 90% fatality rate, it is similar to Ebola virus, which makes it one of the most lethal viruses known to humans. There are currently no approved interventions for Marburg virus, in part because a small-animal model that is vulnerable to MARV/Ang infection is not available to screen and test potential vaccines and therapeutics in a quick and economical manner. To address this need, we have adapted MARV/Ang so that it causes illness in mice resulting in death. The signs of disease in these mice are reminiscent of wild-type MARV/Ang infections in humans and nonhuman primates. We believe that this will be of help in accelerating the development of life-saving measures against Marburg virus infections. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  10. Recombinant vesicular stomatitis virus-based vaccines against Ebola and Marburg virus infections.

    PubMed

    Geisbert, Thomas W; Feldmann, Heinz

    2011-11-01

    The filoviruses, Marburg virus and Ebola virus, cause severe hemorrhagic fever with a high mortality rate in humans and nonhuman primates. Among the most-promising filovirus vaccines under development is a system based on recombinant vesicular stomatitis virus (rVSV) that expresses a single filovirus glycoprotein (GP) in place of the VSV glycoprotein (G). Importantly, a single injection of blended rVSV-based filovirus vaccines was shown to completely protect nonhuman primates against Marburg virus and 3 different species of Ebola virus. These rVSV-based vaccines have also shown utility when administered as a postexposure treatment against filovirus infections, and a rVSV-based Ebola virus vaccine was recently used to treat a potential laboratory exposure. Here, we review the history of rVSV-based vaccines and pivotal animal studies showing their utility in combating Ebola and Marburg virus infections.

  11. Recombinant Vesicular Stomatitis Virus–Based Vaccines Against Ebola and Marburg Virus Infections

    PubMed Central

    Feldmann, Heinz

    2011-01-01

    The filoviruses, Marburg virus and Ebola virus, cause severe hemorrhagic fever with a high mortality rate in humans and nonhuman primates. Among the most-promising filovirus vaccines under development is a system based on recombinant vesicular stomatitis virus (rVSV) that expresses a single filovirus glycoprotein (GP) in place of the VSV glycoprotein (G). Importantly, a single injection of blended rVSV-based filovirus vaccines was shown to completely protect nonhuman primates against Marburg virus and 3 different species of Ebola virus. These rVSV-based vaccines have also shown utility when administered as a postexposure treatment against filovirus infections, and a rVSV-based Ebola virus vaccine was recently used to treat a potential laboratory exposure. Here, we review the history of rVSV-based vaccines and pivotal animal studies showing their utility in combating Ebola and Marburg virus infections. PMID:21987744

  12. The Disappearing Fourth Wall: John Marburger, Science Policy, and the SSC

    NASA Astrophysics Data System (ADS)

    Crease, Robert

    2015-04-01

    John H. Marburger (1941-2011) was a skilled science administrator who had a fresh and unique approach to science policy and science leadership. His posthumously published book Science Policy up Close contains recollections of key science policy episodes in which he participated or observed closely. One was the administration of the Superconducting Supercollider (SSC); Marburger was Chairman of the Universities Research Association, the group charged with managing the SSC, from 1988-1994. Many accounts of the SSC saga attribute its demise to a combination of transitory factors: poor management, rising cost estimates, the collapse of the Soviet Union and thus of the Cold War threat, complaints by ``small science'' that the SSC's ``big science'' was consuming their budget, Congress's desire to cut spending, unwarranted contract regulations imposed by the Department of Energy (DOE) in response to environmental lapses at nuclear weapons laboratories, and so forth. Marburger tells a subtler story whose implications for science policy are more significant and far-reaching. The story involves changes in the attitude of the government towards large scientific projects that reach back to management reforms introduced by the administration of Presidents Johnson, Nixon, and Carter in the 1960s and 1970s. This experience impressed Marburger with the inevitability of public oversight of large scientific projects, and with the need for planners of such projects to establish and make public a cost and schedule tracking system that would model the project's progress and expenditures.

  13. Experimental respiratory Marburg virus haemorrhagic fever infection in the common marmoset (Callithrix jacchus)

    PubMed Central

    Smither, Sophie J; Nelson, Michelle; Eastaugh, Lin; Laws, Thomas R; Taylor, Christopher; Smith, Simon A; Salguero, Francisco J; Lever, Mark S

    2013-01-01

    Marburg virus causes a highly infectious and lethal haemorrhagic fever in primates and may be exploited as a potential biothreat pathogen. To combat the infection and threat of Marburg haemorrhagic fever, there is a need to develop and license appropriate medical countermeasures. To determine whether the common marmoset (Callithrix jacchus) would be an appropriate model to assess therapies against Marburg haemorrhagic fever, initial susceptibility, lethality and pathogenesis studies were performed. Low doses of virus, between 4 and 28 TCID50, were sufficient to cause a lethal, reproducible infection. Animals became febrile between days 5 and 6, maintaining a high fever before succumbing to disease between 8 and 11 days postchallenge. Typical signs of Marburg virus infection were observed including haemorrhaging and a transient rash. In pathogenesis studies, virus was isolated from the animals’ lungs from day 3 postchallenge and from the liver, spleen and blood from day 5 postchallenge. Early signs of histopathology were apparent in the kidney and liver from day 3. The most striking features were observed in animals exhibiting severe clinical signs, which included high viral titres in all organs, with the highest levels in the blood, increased levels in liver function enzymes and blood clotting times, decreased levels in platelets, multifocal moderate-to-severe hepatitis and perivascular oedema. PMID:23441639

  14. Phylogenetic assessment of filoviruses: how many lineages of Marburg virus?

    PubMed Central

    Peterson, A Townsend; Holder, Mark T

    2012-01-01

    Filoviruses have to date been considered as consisting of one diverse genus (Ebola viruses) and one undifferentiated genus (Marburg virus). We reconsider this idea by means of detailed phylogenetic analyses of sequence data available for the Filoviridae: using coalescent simulations, we ascertain that two Marburg isolates (termed the “RAVN” strain) represent a quite-distinct lineage that should be considered in studies of biogeography and host associations, and may merit recognition at the level of species. In contrast, filovirus isolates recently obtained from bat tissues are not distinct from previously known strains, and should be considered as drawn from the same population. Implications for understanding the transmission geography and host associations of these viruses are discussed. PMID:22957185

  15. Comparison of the Pathogenesis of the Angola and Ravn Strains of Marburg Virus in the Outbred Guinea Pig Model.

    PubMed

    Cross, Robert W; Fenton, Karla A; Geisbert, Joan B; Ebihara, Hideki; Mire, Chad E; Geisbert, Thomas W

    2015-10-01

    Phylogenetic comparisons of known Marburg virus (MARV) strains reveal 2 distinct genetic lineages: Ravn and the Lake Victoria Marburg complex (eg, Musoke, Popp, and Angola strains). Nucleotide variances of >20% between Ravn and other MARV genomes suggest that differing virulence between lineages may accompany this genetic divergence. To date, there exists limited systematic experimental evidence of pathogenic differences between MARV strains. Uniformly lethal outbred guinea pig models of MARV-Angola (MARV-Ang) and MARV-Ravn (MARV-Rav) were developed by serial adaptation. Changes in genomic sequence, weight, temperature, histopathologic findings, immunohistochemical findings, hematologic profiles, circulating biochemical enzyme levels, coagulation parameters, viremia levels, cytokine levels, eicanosoid levels, and nitric oxide production were compared between strains. MARV-Rav infection resulted in delayed increases in circulating inflammatory and prothrombotic elements, notably lower viremia levels, less severe histologic alterations, and a delay in mean time to death, compared with MARV-Ang infection. Both strains produced more marked coagulation abnormalities than previously seen in MARV-infected mice or inbred guinea pigs. Although both strains exhibit great similarity to pathogenic markers of human and nonhuman primate MARV infection, these data highlight several key differences in pathogenicity that may serve to guide the choice of strain and model used for development of vaccines or therapeutics for Marburg hemorrhagic fever. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  16. Calculation of incubation period and serial interval from multiple outbreaks of Marburg virus disease.

    PubMed

    Pavlin, Boris I

    2014-12-13

    Marburg viruses have been responsible for a number of outbreaks throughout sub-Saharan Africa, as well as a number of laboratory infections. Despite many years of experience with the viruses, little is known about several important epidemiologic parameters relating to the development of Marburg virus disease. The analysis uses pooled data from all Marburg cases between 1967 and 2008 to develop estimates for the incubation period and the clinical onset serial interval (COSI). Data were obtained from original outbreak investigation forms (n=406) and from published data (n=45). Incubation periods were calculated for person-to-person exposure, for laboratory-acquired infections, and for presumed zoonotic exposures. Similar analysis was conducted for COSI, using only cases with unambiguous person-to-person transmission where both the primary and the secondary case patients had well-defined illness onsets. Seventy-six cases were retained for the incubation period analysis. Incubation periods ranged from a minimum of 2 days in the case of two laboratory workers to a maximum of at least 26 days for a person-to-person household transmission. Thirty-eight cases were retained for COSI analysis. The median COSI was 11 days, with an interquartile range of 8 to 15. This study extends the maximum known incubation period of Marburg virus disease to 26 days. The analysis was severely hampered by a lack of completeness in epidemiologic data. It is necessary to prioritize obtaining more accurate epidemiologic data in future outbreaks; greater use of COSI may facilitate an improved understanding of outbreak dynamics in Marburg and other diseases.

  17. Oral shedding of Marburg virus in experimentally infected Egyptian fruit bats (Rousettus aegyptiacus).

    PubMed

    Amman, Brian R; Jones, Megan E B; Sealy, Tara K; Uebelhoer, Luke S; Schuh, Amy J; Bird, Brian H; Coleman-McCray, JoAnn D; Martin, Brock E; Nichol, Stuart T; Towner, Jonathan S

    2015-01-01

    Marburg virus (Marburg marburgvirus; MARV) causes sporadic outbreaks of Marburg hemorrhagic fever (MHF) in Africa. The Egyptian fruit bat (Rousettus aegyptiacus) has been identified as a natural reservoir based most-recently on the repeated isolation of MARV directly from bats caught at two locations in southwestern Uganda where miners and tourists separately contracted MHF from 2007-08. Despite learning much about the ecology of MARV through extensive field investigations, there remained unanswered questions such as determining the primary routes of virus shedding and the severity of disease, if any, caused by MARV in infected bats. To answer these questions and others, we experimentally infected captive-bred R. aegyptiacus with MARV under high (biosafety level 4) containment. These experiments have shown infection profiles consistent with R. aegyptiacus being a bona fide natural reservoir host for MARV and demonstrated routes of viral shedding capable of infecting humans and other animals.

  18. Marburg Virus Reverse Genetics Systems.

    PubMed

    Schmidt, Kristina Maria; Mühlberger, Elke

    2016-06-22

    The highly pathogenic Marburg virus (MARV) is a member of the Filoviridae family and belongs to the group of nonsegmented negative-strand RNA viruses. Reverse genetics systems established for MARV have been used to study various aspects of the viral replication cycle, analyze host responses, image viral infection, and screen for antivirals. This article provides an overview of the currently established MARV reverse genetic systems based on minigenomes, infectious virus-like particles and full-length clones, and the research that has been conducted using these systems.

  19. Experimental respiratory Marburg virus haemorrhagic fever infection in the common marmoset (Callithrix jacchus).

    PubMed

    Smither, Sophie J; Nelson, Michelle; Eastaugh, Lin; Laws, Thomas R; Taylor, Christopher; Smith, Simon A; Salguero, Francisco J; Lever, Mark S

    2013-04-01

    Marburg virus causes a highly infectious and lethal haemorrhagic fever in primates and may be exploited as a potential biothreat pathogen. To combat the infection and threat of Marburg haemorrhagic fever, there is a need to develop and license appropriate medical countermeasures. To determine whether the common marmoset (Callithrix jacchus) would be an appropriate model to assess therapies against Marburg haemorrhagic fever, initial susceptibility, lethality and pathogenesis studies were performed. Low doses of virus, between 4 and 28 TCID50 , were sufficient to cause a lethal, reproducible infection. Animals became febrile between days 5 and 6, maintaining a high fever before succumbing to disease between 8 and 11 days postchallenge. Typical signs of Marburg virus infection were observed including haemorrhaging and a transient rash. In pathogenesis studies, virus was isolated from the animals' lungs from day 3 postchallenge and from the liver, spleen and blood from day 5 postchallenge. Early signs of histopathology were apparent in the kidney and liver from day 3. The most striking features were observed in animals exhibiting severe clinical signs, which included high viral titres in all organs, with the highest levels in the blood, increased levels in liver function enzymes and blood clotting times, decreased levels in platelets, multifocal moderate-to-severe hepatitis and perivascular oedema. © 2013 Crown copyright. International Journal of Experimental Pathology © 2013 International Journal of Experimental Pathology.

  20. [Ebola and Marburg hemorrhagic fever viruses: update on filoviruses].

    PubMed

    Leroy, E; Baize, S; Gonzalez, J P

    2011-04-01

    The Ebola and Marburg viruses are the sole members of the Filoviridae family of viruses. They are characterized by a long filamentous form that is unique in the viral world. Filoviruses are among the most virulent pathogens currently known to infect humans. They cause fulminating disease characterized by acute fever followed by generalized hemorrhagic syndrome that is associated with 90% mortality in the most severe forms. Epidemic outbreaks of Marburg and Ebola viruses have taken a heavy toll on human life in Central Africa and devastated large ape populations in Gabon and Republic of Congo. Since their discovery in 1967 (Marburg) and 1976 (Ebola), more than 2,300 cases and 1,670 deaths have been reported. These numbers pale in comparison with the burden caused by malnutrition or other infectious disease scourges in Africa such as malaria, cholera, AIDS, dengue or tuberculosis. However, due to their extremely high lethality, association with multifocal hemorrhaging and specificity to the African continent, these hemorrhagic fever viruses have given rise to great interest on the part not only of the international scientific community but also of the general public because of their perceived potential as biological weapons. Much research has been performed on these viruses and major progress has been made in knowledge of their ecology, epidemiology and physiopathology and in development of vaccine candidates and therapeutic schemes. The purpose of this review is to present the main developments in these particular fields in the last decade.

  1. Lessons learned during active epidemiological surveillance of Ebola and Marburg viral hemorrhagic fever epidemics in Africa.

    PubMed

    Allaranga, Yokouide; Kone, Mamadou Lamine; Formenty, Pierre; Libama, Francois; Boumandouki, Paul; Woodfill, Celia J I; Sow, Idrissa; Duale, Sambe; Alemu, Wondimagegnehu; Yada, Adamou

    2010-03-01

    To review epidemiological surveillance approaches used during Ebola and Marburg hemorrhagic fever epidemics in Africa in the past fifteen years. Overall, 26 hemorrhagic epidemic outbreaks have been registered in 12 countries; 18 caused by the Ebola virus and eight by the Marburg virus. About 2551 cases have been reported, among which 268 were health workers (9,3%). Based on articles and epidemic management reports, this review analyses surveillance approaches, route of introduction of the virus into the population (urban and rural), the collaboration between the human health sector and the wildlife sector and factors that have affected epidemic management. Several factors affecting the epidemiological surveillance during Ebola and Marburg viruses hemorrhagic epidemics have been observed. During epidemics in rural settings, outbreak investigations have shown multiple introductions of the virus into the human population through wildlife. In contrast, during epidemics in urban settings a single introduction of the virus in the community was responsible for the epidemic. Active surveillance is key to containing outbreaks of Ebola and Marburg viruses Collaboration with those in charge of the conservation of wildlife is essential for the early detection of viral hemorrhagic fever epidemics. Hemorrhagic fever epidemics caused by Ebola and Marburg viruses are occurring more and more frequently in Sub-Saharan Africa and only an adapted epidemiological surveillance system will allow for early detection and effective response.

  2. Marburg Virus Reverse Genetics Systems

    PubMed Central

    Schmidt, Kristina Maria; Mühlberger, Elke

    2016-01-01

    The highly pathogenic Marburg virus (MARV) is a member of the Filoviridae family and belongs to the group of nonsegmented negative-strand RNA viruses. Reverse genetics systems established for MARV have been used to study various aspects of the viral replication cycle, analyze host responses, image viral infection, and screen for antivirals. This article provides an overview of the currently established MARV reverse genetic systems based on minigenomes, infectious virus-like particles and full-length clones, and the research that has been conducted using these systems. PMID:27338448

  3. Protective mAbs and Cross-Reactive mAbs Raised by Immunization with Engineered Marburg Virus GPs.

    PubMed

    Fusco, Marnie L; Hashiguchi, Takao; Cassan, Robyn; Biggins, Julia E; Murin, Charles D; Warfield, Kelly L; Li, Sheng; Holtsberg, Frederick W; Shulenin, Sergey; Vu, Hong; Olinger, Gene G; Kim, Do H; Whaley, Kevin J; Zeitlin, Larry; Ward, Andrew B; Nykiforuk, Cory; Aman, M Javad; Berry, Jody D; Berry, Jody; Saphire, Erica Ollmann

    2015-06-01

    The filoviruses, which include the marburg- and ebolaviruses, have caused multiple outbreaks among humans this decade. Antibodies against the filovirus surface glycoprotein (GP) have been shown to provide life-saving therapy in nonhuman primates, but such antibodies are generally virus-specific. Many monoclonal antibodies (mAbs) have been described against Ebola virus. In contrast, relatively few have been described against Marburg virus. Here we present ten mAbs elicited by immunization of mice using recombinant mucin-deleted GPs from different Marburg virus (MARV) strains. Surprisingly, two of the mAbs raised against MARV GP also cross-react with the mucin-deleted GP cores of all tested ebolaviruses (Ebola, Sudan, Bundibugyo, Reston), but these epitopes are masked differently by the mucin-like domains themselves. The most efficacious mAbs in this panel were found to recognize a novel "wing" feature on the GP2 subunit that is unique to Marburg and does not exist in Ebola. Two of these anti-wing antibodies confer 90 and 100% protection, respectively, one hour post-exposure in mice challenged with MARV.

  4. Vaccine to Confer to Nonhuman Primates Complete Protection Against Multistrain Ebola and Marburg Virus Infections

    DTIC Science & Technology

    2008-01-01

    current filovirus threats in the event of natural hemorrhagic fever outbreak or biological attack. Ebola virus (EBOV) and Marburg virus (MARV) are mem...lethal, causing severe hemorrhagic fever disease in humans and apes with high mortality rates (up to 90%). The recent description of massive gorilla...threats in the event of natural hemorrhagic fever outbreak or biological attack. 15. SUBJECT TERMS filovirus, Ebola, Marburg, adenovirus-based vaccine

  5. Infection and Activation of Monocytes by Marburg and Ebola Viruses

    PubMed Central

    Ströher, Ute; West, Elmar; Bugany, Harald; Klenk, Hans-Dieter; Schnittler, Hans-Joachim; Feldmann, Heinz

    2001-01-01

    In this study we investigated the effects of Marburg virus and Ebola virus (species Zaire and Reston) infections on freshly isolated suspended monocytes in comparison to adherent macrophages under culture conditions. Our data showed that monocytes are permissive for both filoviruses. As is the case in macrophages, infection resulted in the activation of monocytes which was largely independent of virus replication. The activation was triggered similarly by Marburg and Ebola viruses, species Zaire and Reston, as indicated by the release of the proinflammatory cytokines interleukin-1β (IL-1β), tumor necrosis factor α, and IL-6 as well as the chemokines IL-8 and gro-α. Our data suggest that infected monocytes may play an important role in the spread of filoviruses and in the pathogenesis of filoviral hemorrhagic disease. PMID:11602743

  6. Natural History of Aerosol Exposure with Marburg Virus in Rhesus Macaques

    PubMed Central

    Ewers, Evan C.; Pratt, William D.; Twenhafel, Nancy A.; Shamblin, Joshua; Donnelly, Ginger; Esham, Heather; Wlazlowski, Carly; Johnson, Joshua C.; Botto, Miriam; Hensley, Lisa E.; Goff, Arthur J.

    2016-01-01

    Marburg virus causes severe and often lethal viral disease in humans, and there are currently no Food and Drug Administration (FDA) approved medical countermeasures. The sporadic occurrence of Marburg outbreaks does not allow for evaluation of countermeasures in humans, so therapeutic and vaccine candidates can only be approved through the FDA animal rule—a mechanism requiring well-characterized animal models in which efficacy would be evaluated. Here, we describe a natural history study where rhesus macaques were surgically implanted with telemetry devices and central venous catheters prior to aerosol exposure with Marburg-Angola virus, enabling continuous physiologic monitoring and blood sampling without anesthesia. After a three to four day incubation period, all animals developed fever, viremia, and lymphopenia before developing tachycardia, tachypnea, elevated liver enzymes, decreased liver function, azotemia, elevated D-dimer levels and elevated pro-inflammatory cytokines suggesting a systemic inflammatory response with organ failure. The final, terminal period began with the onset of sustained hypotension, dehydration progressed with signs of major organ hypoperfusion (hyperlactatemia, acute kidney injury, hypothermia), and ended with euthanasia or death. The most significant pathologic findings were marked infection of the respiratory lymphoid tissue with destruction of the tracheobronchial and mediastinal lymph nodes, and severe diffuse infection in the liver, and splenitis. PMID:27043611

  7. Natural History of Aerosol Exposure with Marburg Virus in Rhesus Macaques.

    PubMed

    Ewers, Evan C; Pratt, William D; Twenhafel, Nancy A; Shamblin, Joshua; Donnelly, Ginger; Esham, Heather; Wlazlowski, Carly; Johnson, Joshua C; Botto, Miriam; Hensley, Lisa E; Goff, Arthur J

    2016-03-30

    Marburg virus causes severe and often lethal viral disease in humans, and there are currently no Food and Drug Administration (FDA) approved medical countermeasures. The sporadic occurrence of Marburg outbreaks does not allow for evaluation of countermeasures in humans, so therapeutic and vaccine candidates can only be approved through the FDA animal rule-a mechanism requiring well-characterized animal models in which efficacy would be evaluated. Here, we describe a natural history study where rhesus macaques were surgically implanted with telemetry devices and central venous catheters prior to aerosol exposure with Marburg-Angola virus, enabling continuous physiologic monitoring and blood sampling without anesthesia. After a three to four day incubation period, all animals developed fever, viremia, and lymphopenia before developing tachycardia, tachypnea, elevated liver enzymes, decreased liver function, azotemia, elevated D-dimer levels and elevated pro-inflammatory cytokines suggesting a systemic inflammatory response with organ failure. The final, terminal period began with the onset of sustained hypotension, dehydration progressed with signs of major organ hypoperfusion (hyperlactatemia, acute kidney injury, hypothermia), and ended with euthanasia or death. The most significant pathologic findings were marked infection of the respiratory lymphoid tissue with destruction of the tracheobronchial and mediastinal lymph nodes, and severe diffuse infection in the liver, and splenitis.

  8. Determination of specific antibody responses to the six species of ebola and Marburg viruses by multiplexed protein microarrays.

    PubMed

    Kamata, Teddy; Natesan, Mohan; Warfield, Kelly; Aman, M Javad; Ulrich, Robert G

    2014-12-01

    Infectious hemorrhagic fevers caused by the Marburg and Ebola filoviruses result in human mortality rates of up to 90%, and there are no effective vaccines or therapeutics available for clinical use. The highly infectious and lethal nature of these viruses highlights the need for reliable and sensitive diagnostic methods. We assembled a protein microarray displaying nucleoprotein (NP), virion protein 40 (VP40), and glycoprotein (GP) antigens from isolates representing the six species of filoviruses for use as a surveillance and diagnostic platform. Using the microarrays, we examined serum antibody responses of rhesus macaques vaccinated with trivalent (GP, NP, and VP40) virus-like particles (VLP) prior to infection with the Marburg virus (MARV) (i.e., Marburg marburgvirus) or the Zaire virus (ZEBOV) (i.e., Zaire ebolavirus). The microarray-based assay detected a significant increase in antigen-specific IgG resulting from immunization, while a greater level of antibody responses resulted from challenge of the vaccinated animals with ZEBOV or MARV. Further, while antibody cross-reactivities were observed among NPs and VP40s of Ebola viruses, antibody recognition of GPs was very specific. The performance of mucin-like domain fragments of GP (GP mucin) expressed in Escherichia coli was compared to that of GP ectodomains produced in eukaryotic cells. Based on results with ZEBOV and MARV proteins, antibody recognition of GP mucins that were deficient in posttranslational modifications was comparable to that of the eukaryotic cell-expressed GP ectodomains in assay performance. We conclude that the described protein microarray may translate into a sensitive assay for diagnosis and serological surveillance of infections caused by multiple species of filoviruses. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  9. Prospects for immunisation against Marburg and Ebola viruses.

    PubMed

    Geisbert, Thomas W; Bausch, Daniel G; Feldmann, Heinz

    2010-11-01

    For more than 30 years the filoviruses, Marburg virus and Ebola virus, have been associated with periodic outbreaks of hemorrhagic fever that produce severe and often fatal disease. The filoviruses are endemic primarily in resource-poor regions in Central Africa and are also potential agents of bioterrorism. Although no vaccines or antiviral drugs for Marburg or Ebola are currently available, remarkable progress has been made over the last decade in developing candidate preventive vaccines against filoviruses in nonhuman primate models. Due to the generally remote locations of filovirus outbreaks, a single-injection vaccine is desirable. Among the prospective vaccines that have shown efficacy in nonhuman primate models of filoviral hemorrhagic fever, two candidates, one based on a replication-defective adenovirus serotype 5 and the other on a recombinant VSV (rVSV), were shown to provide complete protection to nonhuman primates when administered as a single injection. The rVSV-based vaccine has also shown utility when administered for postexposure prophylaxis against filovirus infections. A VSV-based Ebola vaccine was recently used to manage a potential laboratory exposure. 2010 John Wiley & Sons, Ltd.

  10. Sequencing ebola and marburg viruses genomes using microarrays.

    PubMed

    Hardick, Justin; Woelfel, Roman; Gardner, Warren; Ibrahim, Sofi

    2016-08-01

    Periodic outbreaks of Ebola and Marburg hemorrhagic fevers have occurred in Africa over the past four decades with case fatality rates reaching as high as 90%. The latest Ebola outbreak in West Africa in 2014 raised concerns that these infections can spread across continents and pose serious health risks. Early and accurate identification of the causative agents is necessary to contain outbreaks. In this report, we describe sequencing-by-hybridization (SBH) technique using high density microarrays to identify Ebola and Marburg viruses. The microarrays were designed to interrogate the sequences of entire viral genomes, and were evaluated with three species of Ebolavirus (Reston, Sudan, and Zaire), and three strains of Marburgvirus (Angola, Musoke, and Ravn). The results showed that the consensus sequences generated with four or more hybridizations had 92.1-98.9% accuracy over 95-99% of the genomes. Additionally, with SBH microarrays it was possible to distinguish between different strains of the Lake Victoria Marburgvirus. J. Med. Virol. 88:1303-1308, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  11. Temporal Characterization of Marburg Virus Angola Infection following Aerosol Challenge in Rhesus Macaques.

    PubMed

    Lin, Kenny L; Twenhafel, Nancy A; Connor, John H; Cashman, Kathleen A; Shamblin, Joshua D; Donnelly, Ginger C; Esham, Heather L; Wlazlowski, Carly B; Johnson, Joshua C; Honko, Anna N; Botto, Miriam A; Yen, Judy; Hensley, Lisa E; Goff, Arthur J

    2015-10-01

    Marburg virus (MARV) infection is a lethal hemorrhagic fever for which no licensed vaccines or therapeutics are available. Development of appropriate medical countermeasures requires a thorough understanding of the interaction between the host and the pathogen and the resulting disease course. In this study, 15 rhesus macaques were sequentially sacrificed following aerosol exposure to the MARV variant Angola, with longitudinal changes in physiology, immunology, and histopathology used to assess disease progression. Immunohistochemical evidence of infection and resulting histopathological changes were identified as early as day 3 postexposure (p.e.). The appearance of fever in infected animals coincided with the detection of serum viremia and plasma viral genomes on day 4 p.e. High (>10(7) PFU/ml) viral loads were detected in all major organs (lung, liver, spleen, kidney, brain, etc.) beginning day 6 p.e. Clinical pathology findings included coagulopathy, leukocytosis, and profound liver destruction as indicated by elevated liver transaminases, azotemia, and hypoalbuminemia. Altered cytokine expression in response to infection included early increases in Th2 cytokines such as interleukin 10 (IL-10) and IL-5 and late-stage increases in Th1 cytokines such as IL-2, IL-15, and granulocyte-macrophage colony-stimulating factor (GM-CSF). This study provides a longitudinal examination of clinical disease of aerosol MARV Angola infection in the rhesus macaque model. In this study, we carefully analyzed the timeline of Marburg virus infection in nonhuman primates in order to provide a well-characterized model of disease progression following aerosol exposure. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  12. Successful treatment of Marburg virus with orally administrated T-705 (Favipiravir) in a mouse model.

    PubMed

    Zhu, Wenjun; Zhang, Zirui; He, Shihua; Wong, Gary; Banadyga, Logan; Qiu, Xiangguo

    2018-03-01

    Filoviruses, such as Marburg and Ebola viruses, cause severe disease in humans with high case fatality rates and are therefore considered biological threat agents. To date, no licensed vaccine or therapeutic exists for their treatment. T-705 (favipiravir) is a pyrazinecarboxamide derivative that has shown broad antiviral activity against a number of viruses and is clinically licenced in Japan to treat influenza. Here we report the efficacy of T-705 against Marburg virus infection in vitro and in vivo. Notably, oral administration of T-705 beginning one or two days post-infection and continuing for eight days resulted in complete survival of mice that had been intraperitoneally infected with mouse-adapted Marburg virus (variant Angola). Moreover, lower doses of T-705 and higher doses administered later during infection (day 3 or 4 post-infection) showed partial efficacy, with at least half the infected mice surviving. Accordingly, we observed reductions in infectious virus particles and virus RNA levels following drug treatment that appeared to correlate with survival. Our findings suggest that T-705 may be an effective therapeutic against Marburg virus and might be especially promising for use in the event of an outbreak, where it could be orally administered quickly and safely even after exposure. Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.

  13. Sorting of Marburg Virus Surface Protein and Virus Release Take Place at Opposite Surfaces of Infected Polarized Epithelial Cells

    PubMed Central

    Sänger, Christian; Mühlberger, Elke; Ryabchikova, Elena; Kolesnikova, Larissa; Klenk, Hans-Dieter; Becker, Stephan

    2001-01-01

    Marburg virus, a filovirus, causes severe hemorrhagic fever with hitherto poorly understood molecular pathogenesis. We have investigated here the vectorial transport of the surface protein GP of Marburg virus in polarized epithelial cells. To this end, we established an MDCKII cell line that was able to express GP permanently (MDCK-GP). The functional integrity of GP expressed in these cells was analyzed using vesicular stomatitis virus pseudotypes. Further experiments revealed that GP is transported in MDCK-GP cells mainly to the apical membrane and is released exclusively into the culture medium facing the apical membrane. When MDCKII cells were infected with Marburg virus, the majority of GP was also transported to the apical membrane, suggesting that the protein contains an autonomous apical transport signal. Release of infectious progeny virions, however, took place exclusively at the basolateral membrane of the cells. Thus, vectorial budding of Marburg virus is presumably determined by factors other than the surface protein. PMID:11152500

  14. Ethical issues in laryngology: tracheal stenting as palliative care.

    PubMed

    Kazi, Aasif A; Flowers, W Jeffrey; Barrett, Jeanna M; O'Rourke, Ashli K; Postma, Gregory N; Weinberger, Paul M

    2014-07-01

    To improve understanding of aspects of end-of-life care that may not be intuitive to the otolaryngology community. A comprehensive review of the literature was performed by searching Medline, Embase, and Google Scholar databases. Primary manuscripts' bibliographies were reviewed to identify any nonindexed references. Prospective consultation by means of one-on-one interviews was sought from nonotolaryngology key stakeholders in the areas of hospice nursing care and patient advocacy in order to identify pertinent issues. We identified over 1,000 articles published from 1965 to 2013 on the topic of tracheal stents, as well as over 40,000 on hospice/end-of-life care. Three articles focusing specifically on palliative care and airway stenting were identified, of which three were case reports and none were definitive reviews. There are a number of significant issues and concepts unique to hospice care. These are likely unfamiliar to all except for head and neck oncology-specialized otolaryngologists. An example is that hospice care focuses on quality of life rather than prolongation of life (such as curative surgery). Patients with nonoperable tracheal obstruction from malignancy face an unpleasant demise from suffocation. For those patients, stenting can relieve suffering by restoring airway patency. Airway stenting can be a valid palliative care option, even for terminal patients receiving hospice care, when performed to relieve airway obstruction and improve quality of life. End-of-life ethics is an underdeveloped area of otolaryngology that should be explored. © 2013 The American Laryngological, Rhinological and Otological Society, Inc.

  15. Quinoxaline-based inhibitors of Ebola and Marburg VP40 egress.

    PubMed

    Loughran, H Marie; Han, Ziying; Wrobel, Jay E; Decker, Sarah E; Ruthel, Gordon; Freedman, Bruce D; Harty, Ronald N; Reitz, Allen B

    2016-08-01

    We prepared a series of quinoxalin-2-mercapto-acetyl-urea analogs and evaluated them for their ability to inhibit viral egress in our Marburg and Ebola VP40 VLP budding assays in HEK293T cells. We also evaluated selected compounds in our bimolecular complementation assay (BiMC) to detect and visualize a Marburg mVP40-Nedd4 interaction in live mammalian cells. Antiviral activity was assessed for selected compounds using a live recombinant vesicular stomatitis virus (VSV) (M40 virus) that expresses the EBOV VP40 PPxY L-domain. Finally selected compounds were evaluated in several ADME assays to have an early assessment of their drug properties. Our compounds had low nM potency in these assays (e.g., compounds 21, 24, 26, 39), and had good human liver microsome stability, as well as little or no inhibition of P450 3A4. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. [Position paper of the German Society of Oto-Rhino-Laryngology, Head and Neck Surgery and the German Society of Phoniatrics and Pediatric Audiology - current state of clinical and endoscopic diagnostics, evaluation, and therapy of swallowing disorders in children and adults].

    PubMed

    Arens, C; Herrmann, I F; Rohrbach, S; Schwemmle, C; Nawka, T

    2015-03-01

    Position Paper of the German Society of Oto-Rhino-Laryngology, Head and Neck Surgery and the German Society of Phoniatrics and Pediatric Audiology - Current State of Clinical and Endoscopic Diagnostics, Evaluation, and Therapy of Swallowing Disorders in Children and AdultsSwallowing disorders are frequent. The main concern is mortality due to aspiration induced pneumonia and malnutrition. On the other hand quality of life is severely affected. The demographic trend indicates an increase of dysphagia in the future. Neurodegenerative diseases, tumors of the digestive tract and sequelae of tumor treatment in the head and neck region are the main pathologic entities.Predominantly ENT physicians and phoniatrists, are asked for diagnostics and therapy who will coordinate the interdisciplinary treatment according to the endoscopic findings.A differentiated approach in history, diagnostics, and symptom oriented treatment is necessary for the mostly complex disorders. The integration of non-medical personnel such as logopeds (speech language pathologists), physiotherapists, and occupational therapists in planning and executing an effective therapy expands and completes the patient-oriented care. Conservative treatment by these therapists is an important pillar in the treatment. Parts of the specific diagnostics can be taken over by them in close cooperation.In particular an interdisciplinary cooperation with the staff from intensive care medicine is indispensable.The diagnostic procedures of specific endoscopy as described in this position paper are part of the primary and fundamental tasks of ENT specialists and phoniatrists.Endoscopy is a medical service that is basically not delegable. Consequently substitution of the physician is precluded. © Georg Thieme Verlag KG Stuttgart · New York.

  17. Therapeutic treatment of Marburg and Ravn virus infection in nonhuman primates with a human monoclonal antibody.

    PubMed

    Mire, Chad E; Geisbert, Joan B; Borisevich, Viktoriya; Fenton, Karla A; Agans, Krystle N; Flyak, Andrew I; Deer, Daniel J; Steinkellner, Herta; Bohorov, Ognian; Bohorova, Natasha; Goodman, Charles; Hiatt, Andrew; Kim, Do H; Pauly, Michael H; Velasco, Jesus; Whaley, Kevin J; Crowe, James E; Zeitlin, Larry; Geisbert, Thomas W

    2017-04-05

    As observed during the 2013-2016 Ebola virus disease epidemic, containment of filovirus outbreaks is challenging and made more difficult by the lack of approved vaccine or therapeutic options. Marburg and Ravn viruses are highly virulent and cause severe and frequently lethal disease in humans. Monoclonal antibodies (mAbs) are a platform technology in wide use for autoimmune and oncology indications. Previously, we described human mAbs that can protect mice from lethal challenge with Marburg virus. We demonstrate that one of these mAbs, MR191-N, can confer a survival benefit of up to 100% to Marburg or Ravn virus-infected rhesus macaques when treatment is initiated up to 5 days post-inoculation. These findings extend the small but growing body of evidence that mAbs can impart therapeutic benefit during advanced stages of disease with highly virulent viruses and could be useful in epidemic settings. Copyright © 2017, American Association for the Advancement of Science.

  18. Case definition for Ebola and Marburg haemorrhagic fevers: a complex challenge for epidemiologists and clinicians.

    PubMed

    Pittalis, Silvia; Fusco, Francesco Maria; Lanini, Simone; Nisii, Carla; Puro, Vincenzo; Lauria, Francesco Nicola; Ippolito, Giuseppe

    2009-10-01

    Viral haemorrhagic fevers (VHFs) represent a challenge for public health because of their epidemic potential, and their possible use as bioterrorism agents poses particular concern. In 1999 the World Health Organization (WHO) proposed a case definition for VHFs, subsequently adopted by other international institutions with the aim of early detection of initial cases/outbreaks in western countries. We applied this case definition to reports of Ebola and Marburg virus infections to estimate its sensitivity to detect cases of the disease. We analyzed clinical descriptions of 795 reported cases of Ebola haemorrhagic fever: only 58.5% of patients met the proposed case definition. A similar figure was obtained reviewing 169 cases of Marburg diseases, of which only 64.5% were in accordance with the case definition. In conclusion, the WHO case definition for hemorrhagic fevers is too specific and has poor sensitivity both for case finding during Ebola or Marburg outbreaks, and for early detection of suspected cases in western countries. It can lead to a hazardous number of false negatives and its use should be discouraged for early detection of cases.

  19. Evaluation of the Protective Efficacy of Recombinant Vesicular Stomatitis Virus Vectors Against Marburg Hemorrhagic Fever in Nonhuman Primate Models

    DTIC Science & Technology

    2007-01-19

    fever in Nonhuman Primate Models" Date d?JO )oi Date )&*7 Date Dissertation and Abstract Approved: Robert Friedm ,M.D. Department of Pathology Committee...thesis manuscript entitled: "Evaluation of the Protective Efficacy of Recombinant Vesicular Stomatitis Virus Vectors Against Marburg Hemorrhagic fever ...stomatitis virus vectors against Marburg hemorrhagic fever in nonhuman primate models By Kathleen Daddario-DiCaprio Dissertation

  20. Inactivation of Lassa, Marburg, and Ebola viruses by gamma irradiation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Elliott, L.H.; McCormick, J.B.; Johnson, K.M.

    1982-10-01

    Because of the cumbersome conditions experienced in a maximum containment laboratory, methods for inactivating highly pathogenic viruses were investigated. The infectivity of Lassa, Marburg, and Ebola viruses was inactivated without altering the immunological activity after radiation with /sup 60/Co gamma rays. At 4 degrees C, Lassa virus was the most difficult to inactivate with a rate of 5.3 X 10(-6) log 50% tissue culture infective dose per rad of /sup 60/Co radiation, as compared with 6.8 X 10(-6) log 50% tissue culture infective dose per rad for Ebola virus and 8.4 X 10(-6) log 50% tissue culture infective dose permore » rad for Marburg virus. Experimental inactivation curves, as well as curves giving the total radiation needed to inactivate a given concentration of any of the three viruses, are presented. We found this method of inactivation to be superior to UV light or beta-propiolactone inactivation and now routinely use it for preparation of material for protein-chemistry studies or for preparation of immunological reagents.« less

  1. Inactivation of Lassa, Marburg, and Ebola viruses by gamma irradiation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Elliott, L.H.; McCormick, J.B.; Johnson, K.M.

    1982-10-01

    Because of the cumbersome conditions experienced in a maximum containment laboratory, methods for inactivating highly pathogenic viruses were investigated. The infectivity of Lassa, Marburg, and Ebola viruses was inactivated without altering the immunological activity after radiation with /sup 60/CO gamma rays. At 4 degrees C, Lassa virus was the most difficult to inactivate with a rate of 5.3 X 10(-6) log 50% tissue culture infective dose per rad of /sup 60/CO radiation, as compared with 6.8 X 10(-6) log 50% tissue culture infective dose per rad for Ebola virus and 8.4 X 10(-6) log 50% tissue culture infective dose permore » rad for Marburg virus. Experimental inactivation curves, as well as curves giving the total radiation needed to inactivate a given concentration of any of the three viruses, are presented. The authors found this method of inactivation to be superior to UV light or beta-propiolactone inactivation and now routinely use it for preparation of material for protein-chemistry studies or for preparation of immunological reagents.« less

  2. Plasma membrane association facilitates conformational changes in the Marburg virus protein VP40 dimer.

    PubMed

    Bhattarai, Nisha; Gc, Jeevan B; Gerstman, Bernard S; Stahelin, Robert V; Chapagain, Prem P

    2017-04-26

    Filovirus infections cause hemorrhagic fever in humans and non-human primates that often results in high fatality rates. The Marburg virus is a lipid-enveloped virus from the Filoviridae family and is closely related to the Ebola virus. The viral matrix layer underneath the lipid envelope is formed by the matrix protein VP40 (VP40), which is also involved in other functions during the viral life-cycle. As in the Ebola virus VP40 (eVP40), the recently determined X-ray crystal structure of the Marburg virus VP40 (mVP40) features loops containing cationic residues that form a lipid binding basic patch. However, the mVP40 basic patch is significantly flatter with a more extended surface than in eVP40, suggesting the possibility of differences in the plasma membrane interactions and phospholipid specificity between the VP40 dimers. In this paper, we report on molecular dynamics simulations that investigate the roles of various residues and lipid types in PM association as well as the conformational changes of the mVP40 dimer facilitated by membrane association. We compared the structural changes of the mVP40 dimer with the mVP40 dimer in both lipid free and membrane associated conditions. Despite the significant structural differences in the crystal structure, the Marburg VP40 dimer is found to adopt a configuration very similar to the Ebola VP40 dimer after associating with the membrane. This conformational rearrangement upon lipid binding allows Marburg VP40 to localize and stabilize at the membrane surface in a manner similar to the Ebola VP40 dimer. Consideration of the structural information in its lipid-interacting condition may be important in targeting mVP40 for novel drugs to inhibit viral budding from the plasma membrane.

  3. Genetic transformation system in the archaebacterium Methanobacterium thermoautotrophicum Marburg.

    PubMed Central

    Worrell, V E; Nagle, D P; McCarthy, D; Eisenbraun, A

    1988-01-01

    A wild-type strain of Methanobacterium thermoautotrophicum Marburg was transformed by DNA from strains resistant to 5-fluorouracil. Recipient cells were grown without selection on gellan gum (GELRITE) plates with DNA. Drug-resistant cells were recovered by replica plating the resulting colonies onto drug plates. Transformation required high-molecular-weight DNA with appropriate markers and was not observed on agar or in liquid media under a variety of conditions. PMID:3422229

  4. Seasonal pulses of Marburg virus circulation in juvenile Rousettus aegyptiacus bats coincide with periods of increased risk of human infection.

    PubMed

    Amman, Brian R; Carroll, Serena A; Reed, Zachary D; Sealy, Tara K; Balinandi, Stephen; Swanepoel, Robert; Kemp, Alan; Erickson, Bobbie Rae; Comer, James A; Campbell, Shelley; Cannon, Deborah L; Khristova, Marina L; Atimnedi, Patrick; Paddock, Christopher D; Crockett, Rebekah J Kent; Flietstra, Timothy D; Warfield, Kelly L; Unfer, Robert; Katongole-Mbidde, Edward; Downing, Robert; Tappero, Jordan W; Zaki, Sherif R; Rollin, Pierre E; Ksiazek, Thomas G; Nichol, Stuart T; Towner, Jonathan S

    2012-01-01

    Marburg virus (family Filoviridae) causes sporadic outbreaks of severe hemorrhagic disease in sub-Saharan Africa. Bats have been implicated as likely natural reservoir hosts based most recently on an investigation of cases among miners infected in 2007 at the Kitaka mine, Uganda, which contained a large population of Marburg virus-infected Rousettus aegyptiacus fruit bats. Described here is an ecologic investigation of Python Cave, Uganda, where an American and a Dutch tourist acquired Marburg virus infection in December 2007 and July 2008. More than 40,000 R. aegyptiacus were found in the cave and were the sole bat species present. Between August 2008 and November 2009, 1,622 bats were captured and tested for Marburg virus. Q-RT-PCR analysis of bat liver/spleen tissues indicated ~2.5% of the bats were actively infected, seven of which yielded Marburg virus isolates. Moreover, Q-RT-PCR-positive lung, kidney, colon and reproductive tissues were found, consistent with potential for oral, urine, fecal or sexual transmission. The combined data for R. aegyptiacus tested from Python Cave and Kitaka mine indicate low level horizontal transmission throughout the year. However, Q-RT-PCR data show distinct pulses of virus infection in older juvenile bats (~six months of age) that temporarily coincide with the peak twice-yearly birthing seasons. Retrospective analysis of historical human infections suspected to have been the result of discrete spillover events directly from nature found 83% (54/65) events occurred during these seasonal pulses in virus circulation, perhaps demonstrating periods of increased risk of human infection. The discovery of two tags at Python Cave from bats marked at Kitaka mine, together with the close genetic linkages evident between viruses detected in geographically distant locations, are consistent with R. aegyptiacus bats existing as a large meta-population with associated virus circulation over broad geographic ranges. These findings provide a

  5. Seasonal Pulses of Marburg Virus Circulation in Juvenile Rousettus aegyptiacus Bats Coincide with Periods of Increased Risk of Human Infection

    PubMed Central

    Amman, Brian R.; Carroll, Serena A.; Reed, Zachary D.; Sealy, Tara K.; Balinandi, Stephen; Swanepoel, Robert; Kemp, Alan; Erickson, Bobbie Rae; Comer, James A.; Campbell, Shelley; Cannon, Deborah L.; Khristova, Marina L.; Atimnedi, Patrick; Paddock, Christopher D.; Kent Crockett, Rebekah J.; Flietstra, Timothy D.; Warfield, Kelly L.; Unfer, Robert; Katongole-Mbidde, Edward; Downing, Robert; Tappero, Jordan W.; Zaki, Sherif R.; Rollin, Pierre E.; Ksiazek, Thomas G.; Nichol, Stuart T.; Towner, Jonathan S.

    2012-01-01

    Marburg virus (family Filoviridae) causes sporadic outbreaks of severe hemorrhagic disease in sub-Saharan Africa. Bats have been implicated as likely natural reservoir hosts based most recently on an investigation of cases among miners infected in 2007 at the Kitaka mine, Uganda, which contained a large population of Marburg virus-infected Rousettus aegyptiacus fruit bats. Described here is an ecologic investigation of Python Cave, Uganda, where an American and a Dutch tourist acquired Marburg virus infection in December 2007 and July 2008. More than 40,000 R. aegyptiacus were found in the cave and were the sole bat species present. Between August 2008 and November 2009, 1,622 bats were captured and tested for Marburg virus. Q-RT-PCR analysis of bat liver/spleen tissues indicated ∼2.5% of the bats were actively infected, seven of which yielded Marburg virus isolates. Moreover, Q-RT-PCR-positive lung, kidney, colon and reproductive tissues were found, consistent with potential for oral, urine, fecal or sexual transmission. The combined data for R. aegyptiacus tested from Python Cave and Kitaka mine indicate low level horizontal transmission throughout the year. However, Q-RT-PCR data show distinct pulses of virus infection in older juvenile bats (∼six months of age) that temporarily coincide with the peak twice-yearly birthing seasons. Retrospective analysis of historical human infections suspected to have been the result of discrete spillover events directly from nature found 83% (54/65) events occurred during these seasonal pulses in virus circulation, perhaps demonstrating periods of increased risk of human infection. The discovery of two tags at Python Cave from bats marked at Kitaka mine, together with the close genetic linkages evident between viruses detected in geographically distant locations, are consistent with R. aegyptiacus bats existing as a large meta-population with associated virus circulation over broad geographic ranges. These findings provide

  6. Generation and characterization of protective antibodies to Marburg virus.

    PubMed

    Froude, Jeffrey W; Pelat, Thibaut; Miethe, Sebastian; Zak, Samantha E; Wec, Anna Z; Chandran, Kartik; Brannan, Jennifer Mary; Bakken, Russell R; Hust, Michael; Thullier, Philippe; Dye, John M

    Marburg virus (MARV) and Ebola virus (EBOV) have been a source of epidemics and outbreaks for several decades. We present here the generation and characterization of the first protective antibodies specific for wild-type MARV. Non-human primates (NHP), cynomolgus macaques, were immunized with viral-replicon particles expressing the glycoproteins (GP) of MARV (Ci67 isolate). An antibody fragment (single-chain variable fragment, scFv) phage display library was built after four immunogen injections, and screened against the GP 1-649 of MARV. Sequencing of 192 selected clones identified 18 clones with distinct V H and V L sequences. Four of these recombinant antibodies (R4A1, R4B11, R4G2, and R3F6) were produced in the scFv-Fc format for in vivo studies. Mice that were challenged with wild-type Marburg virus (Ci67 isolate) receiving 100 µg of scFv-Fc on days -1, 1 and 3 demonstrated protective efficacies ranging from 75-100%. The amino-acid sequences of the scFv-Fcs are similar to those of their human germline counterparts, sharing an identity ranging between 68 and 100% to human germline immunoglobulin. These results demonstrate for the first time that recombinant antibodies offer protection against wild-type MARV, and suggest they may be promising candidates for further therapeutic development especially due to their human homology.

  7. Management of somatic pain induced by head-and-neck cancer treatment: definition and assessment. Guidelines of the French Oto-Rhino-Laryngology- Head and Neck Surgery Society (SFORL).

    PubMed

    Binczak, M; Navez, M; Perrichon, C; Blanchard, D; Bollet, M; Calmels, P; Couturaud, C; Dreyer, C; Espitalier, F; Testelin, S; Albert, S; Morinière, S

    2014-09-01

    The authors present the guidelines of the French Oto-Rhino-Laryngology- Head and Neck Surgery Society (Société Française d'Oto-rhino-Laryngologie et de Chirurgie de la Face et du Cou [SFORL]) for the management of somatic pain induced by head-and-neck cancer treatment, and in particular the instruments needed for the definition and initial assessment of the various types of pain. A multidisciplinary work group was entrusted with a review of the scientific literature on the above topic. Guidelines were drawn up, based on the articles retrieved and the group members' individual experience. They were then read over by an editorial group independent of the work group. The final version was established in a coordination meeting. The guidelines were graded as A, B, C or expert opinion, by decreasing level of evidence. The priority is to eliminate tumoral recurrence when pain reappears or changes following head-and-neck cancer treatment. Neuropathic pain screening instruments and pain assessment scales should be used to assess pain intensity and treatment efficacy. Functional rehabilitation sessions should be prescribed to reduce musculoskeletal pain and prevent ankylosis and postural disorder. Psychotherapy and mind-body therapy, when available, should be provided in case of chronic pain. In case of recalcitrant complex pain, referral should be made to a multidisciplinary pain structure. The management of somatic pain induced by head-and-neck cancer treatment above all requires identifying and assessing the intensity of the various types of pain involved, their functional impact and their emotional component. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  8. Structural Basis for Marburg Virus Neutralization by a Cross-Reactive Human Antibody

    DOE PAGES

    Hashiguchi, Takao; Fusco, Marnie L.; Bornholdt, Zachary A.; ...

    2015-02-26

    The filoviruses, including Marburg and Ebola, express a single glycoprotein on their surface, termed GP, which is responsible for attachment and entry of target cells. Filovirus GPs differ by up to 70% in protein sequence, and no antibodies are yet described that cross-react among them. Here, we present the 3.6 Å crystal structure of Marburg virus GP in complex with a cross-reactive antibody from a human survivor, and a lower resolution structure of the antibody bound to Ebola virus GP. The antibody, MR78, recognizes a GP1 epitope conserved across the filovirus family, which likely represents the binding site of theirmore » NPC1 receptor. Indeed, MR78 blocks binding of the essential NPC1 domain C. We find that these structures and additional small-angle X-ray scattering of mucin-containing MARV and EBOV GPs suggest why such antibodies were not previously elicited in studies of Ebola virus, and provide critical templates for development of immunotherapeutics and inhibitors of entry.« less

  9. Structural basis for Marburg virus neutralization by a cross-reactive human antibody.

    PubMed

    Hashiguchi, Takao; Fusco, Marnie L; Bornholdt, Zachary A; Lee, Jeffrey E; Flyak, Andrew I; Matsuoka, Rei; Kohda, Daisuke; Yanagi, Yusuke; Hammel, Michal; Crowe, James E; Saphire, Erica Ollmann

    2015-02-26

    The filoviruses, including Marburg and Ebola, express a single glycoprotein on their surface, termed GP, which is responsible for attachment and entry of target cells. Filovirus GPs differ by up to 70% in protein sequence, and no antibodies are yet described that cross-react among them. Here, we present the 3.6 Å crystal structure of Marburg virus GP in complex with a cross-reactive antibody from a human survivor, and a lower resolution structure of the antibody bound to Ebola virus GP. The antibody, MR78, recognizes a GP1 epitope conserved across the filovirus family, which likely represents the binding site of their NPC1 receptor. Indeed, MR78 blocks binding of the essential NPC1 domain C. These structures and additional small-angle X-ray scattering of mucin-containing MARV and EBOV GPs suggest why such antibodies were not previously elicited in studies of Ebola virus, and provide critical templates for development of immunotherapeutics and inhibitors of entry. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Inhibition of Ebola and Marburg Virus Entry by G Protein-Coupled Receptor Antagonists.

    PubMed

    Cheng, Han; Lear-Rooney, Calli M; Johansen, Lisa; Varhegyi, Elizabeth; Chen, Zheng W; Olinger, Gene G; Rong, Lijun

    2015-10-01

    Filoviruses, consisting of Ebola virus (EBOV) and Marburg virus (MARV), are among the most lethal infectious threats to mankind. Infections by these viruses can cause severe hemorrhagic fevers in humans and nonhuman primates with high mortality rates. Since there is currently no vaccine or antiviral therapy approved for humans, there is an urgent need to develop prophylactic and therapeutic options for use during filoviral outbreaks and bioterrorist attacks. One of the ideal targets against filoviral infection and diseases is at the entry step, which is mediated by the filoviral glycoprotein (GP). In this report, we screened a chemical library of small molecules and identified numerous inhibitors, which are known G protein-coupled receptor (GPCR) antagonists targeting different GPCRs, including histamine receptors, 5-HT (serotonin) receptors, muscarinic acetylcholine receptor, and adrenergic receptor. These inhibitors can effectively block replication of both infectious EBOV and MARV, indicating a broad antiviral activity of the GPCR antagonists. The time-of-addition experiment and microscopic studies suggest that GPCR antagonists block filoviral entry at a step following the initial attachment but prior to viral/cell membrane fusion. These results strongly suggest that GPCRs play a critical role in filoviral entry and GPCR antagonists can be developed as an effective anti-EBOV/MARV therapy. Infection of Ebola virus and Marburg virus can cause severe illness in humans with a high mortality rate, and currently there is no FDA-approved vaccine or therapeutic treatment available. The 2013-2015 epidemic in West Africa underscores a lack of our understanding in the infection and pathogenesis of these viruses and the urgency of drug discovery and development. In this study, we have identified numerous inhibitors that are known G protein-coupled receptor (GPCR) antagonists targeting different GPCRs. These inhibitors can effectively block replication of both infectious

  11. How Ebola and Marburg viruses battle the immune system.

    PubMed

    Mohamadzadeh, Mansour; Chen, Lieping; Schmaljohn, Alan L

    2007-07-01

    The filoviruses Ebola and Marburg have emerged in the past decade from relative obscurity to serve now as archetypes for some of the more intriguing and daunting challenges posed by such agents. Public imagination is captured by deadly outbreaks of these viruses and reinforced by the specter of bioterrorism. As research on these agents has accelerated, it has been found increasingly that filoviruses use a combination of familiar and apparently new ways to baffle and battle the immune system. Filoviruses have provided thereby a new lens through which to examine the immune system itself.

  12. The VP40 protein of Marburg virus exhibits impaired budding and increased sensitivity to human tetherin following mouse adaptation.

    PubMed

    Feagins, Alicia R; Basler, Christopher F

    2014-12-01

    determinants associated with filovirus mouse adaptation are poorly understood. Our study demonstrates how genetic changes that accrued during mouse adaptation of the Ravn strain of Marburg virus have impacted the budding function of the viral VP40 matrix protein. Strikingly, we find impairment of mouse-adapted VP40 budding function in human but not mouse cell lines, and we correlate the impairment with an increased sensitivity of VP40 to restriction by human but not mouse tetherin and with changes in VP40 oligomerization. These data suggest that there are functional costs associated with filovirus adaptation to new hosts and implicate tetherin as a filovirus host restriction factor. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  13. Investigation of the Lipid Binding Properties of the Marburg Virus Matrix Protein VP40.

    PubMed

    Wijesinghe, Kaveesha J; Stahelin, Robert V

    2015-12-30

    Marburg virus (MARV), which belongs to the virus family Filoviridae, causes hemorrhagic fever in humans and nonhuman primates that is often fatal. MARV is a lipid-enveloped virus that during the replication process extracts its lipid coat from the plasma membrane of the host cell it infects. MARV carries seven genes, one of which encodes its matrix protein VP40 (mVP40), which regulates the assembly and budding of the virions. Currently, little information is available on mVP40 lipid binding properties. Here, we have investigated the in vitro and cellular mechanisms by which mVP40 associates with lipid membranes. mVP40 associates with anionic membranes in a nonspecific manner that is dependent upon the anionic charge density of the membrane. These results are consistent with recent structural determination of mVP40, which elucidated an mVP40 dimer with a flat and extensive cationic lipid binding interface. Marburg virus (MARV) is a lipid-enveloped filamentous virus from the family Filoviridae. MARV was discovered in 1967, and yet little is known about how its seven genes are used to assemble and form a new viral particle in the host cell it infects. The MARV matrix protein VP40 (mVP40) underlies the inner leaflet of the virus and regulates budding from the host cell plasma membrane. In vitro and cellular assays in this study investigated the mechanism by which mVP40 associates with lipids. The results demonstrate that mVP40 interactions with lipid vesicles or the inner leaflet of the plasma membrane are electrostatic but nonspecific in nature and are dependent on the anionic charge density of the membrane surface. Small molecules that can disrupt lipid trafficking or reduce the anionic charge of the plasma membrane interface may be useful in inhibiting assembly and budding of MARV. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  14. How severe and prevalent are Ebola and Marburg viruses? A systematic review and meta-analysis of the case fatality rates and seroprevalence.

    PubMed

    Nyakarahuka, Luke; Kankya, Clovice; Krontveit, Randi; Mayer, Benjamin; Mwiine, Frank N; Lutwama, Julius; Skjerve, Eystein

    2016-11-25

    Ebola and Marburg virus diseases are said to occur at a low prevalence, but are very severe diseases with high lethalities. The fatality rates reported in different outbreaks ranged from 24-100%. In addition, sero-surveys conducted have shown different seropositivity for both Ebola and Marburg viruses. We aimed to use a meta-analysis approach to estimate the case fatality and seroprevalence rates of these filoviruses, providing vital information for epidemic response and preparedness in countries affected by these diseases. Published literature was retrieved through a search of databases. Articles were included if they reported number of deaths, cases, and seropositivity. We further cross-referenced with ministries of health, WHO and CDC databases. The effect size was proportion represented by case fatality rate (CFR) and seroprevalence. Analysis was done using the metaprop command in STATA. The weighted average CFR of Ebola virus disease was estimated to be 65.0% [95% CI (54.0-76.0%), I 2  = 97.98%] whereas that of Marburg virus disease was 53.8% (26.5-80.0%, I 2  = 88.6%). The overall seroprevalence of Ebola virus was 8.0% (5.0%-11.0%, I 2  = 98.7%), whereas that for Marburg virus was 1.2% (0.5-2.0%, I 2  = 94.8%). The most severe species of ebolavirus was Zaire ebolavirus while Bundibugyo Ebolavirus was the least severe. The pooled CFR and seroprevalence for Ebola and Marburg viruses were found to be lower than usually reported, with species differences despite high heterogeneity between studies. Countries with an improved health surveillance and epidemic response have lower CFR, thereby indicating need for improving early detection and epidemic response in filovirus outbreaks.

  15. Formate auxotroph of Methanobacterium thermoautotrophicum Marburg.

    PubMed Central

    Tanner, R S; McInerney, M J; Nagle, D P

    1989-01-01

    A formate-requiring auxotroph of Methanobacterium thermoautotrophicum Marburg was isolated after hydroxylamine mutagenesis and bacitracin selection. The requirement for formate is unique and specific; combined pools of other volatile fatty acids, amino acids, vitamins, and nitrogen bases did not substitute for formate. Compared with those of the wild type, cell extracts of the formate auxotroph were deficient in formate dehydrogenase activity, but cells of all of the strains examined catalyzed a formate-carbon dioxide exchange activity. All of the strains examined took up a small amount (200 to 260 mumol/liter) of formate (3 mM) added to medium. The results of the study of this novel auxotroph indicate a role for formate in biosynthetic reactions in this methanogen. Moreover, because methanogenesis from H2-CO2 is not impaired in the mutant, free formate is not an intermediate in the reduction of CO2 to CH4. PMID:2687241

  16. A brief history of otorhinolaryngolgy: otology, laryngology and rhinology.

    PubMed

    Nogueira, João Flávio; Hermann, Diego Rodrigo; Américo, Ronaldo dos Reis; Barauna Filho, Iulo Sérgio; Stamm, Aldo Eden Cassol; Pignatari, Shirley Shizuo Nagata

    2007-01-01

    Ears, nose and throat have intrigued humanity since immemorial times. Treatments for the larynx, the nose and the ear and also surgeries were practiced by Greek, Hindu and Byzantine doctors. In the 20th century clinical and surgical innovations were incorporated, thanks to new anesthesia techniques, antibiotics, radiology and new technologies. show the evolution of this science throughout the times, recognizing important persons in otology, rhinology and laryngology. Understanding the evolutions in clinical and surgical anatomy, physiology, treatment modalities, and the personalities that lead to these advances is of great importance for the evolution of medical science. Otorhinolaryngology has a very rich history, with important collaborators and personalities in the history of medicine. The specialty was one of the first to use local anesthesia for procedures, pioneer in treatments with devices that recouped hearing and the use of microscopes in surgeries. Few medical specialties had suffered as many changes and scientific developments in these last decades as Otorhinolaryngology had, with the advantage of incorporating technologies such as endoscopy, radiology, microsurgery and information technology.

  17. Tissue and cellular tropism, pathology and pathogenesis of Ebola and Marburg viruses.

    PubMed

    Martines, Roosecelis Brasil; Ng, Dianna L; Greer, Patricia W; Rollin, Pierre E; Zaki, Sherif R

    2015-01-01

    Ebola viruses and Marburg viruses include some of the most virulent and fatal pathogens known to humans. These viruses cause severe haemorrhagic fevers, with case fatality rates in the range 25-90%. The diagnosis of filovirus using formalin-fixed tissues from fatal cases poses a significant challenge. The most characteristic histopathological findings are seen in the liver; however, the findings overlap with many other viral and non-viral haemorrhagic diseases. The need to distinguish filovirus infections from other haemorrhagic fevers, particularly in areas with multiple endemic viral haemorrhagic agents, is of paramount importance. In this review we discuss the current state of knowledge of filovirus infections and their pathogenesis, including histopathological findings, epidemiology, modes of transmission and filovirus entry and spread within host organisms. The pathogenesis of filovirus infections is complex and involves activation of the mononuclear phagocytic system, with release of pro-inflammatory cytokines, chemokines and growth factors, endothelial dysfunction, alterations of the innate and adaptive immune systems, direct organ and endothelial damage from unrestricted viral replication late in infection, and coagulopathy. Although our understanding of the pathogenesis of filovirus infections has rapidly increased in the past few years, many questions remain unanswered. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  18. Lack of Marburg Virus Transmission From Experimentally Infected to Susceptible In-Contact Egyptian Fruit Bats.

    PubMed

    Paweska, Janusz T; Jansen van Vuren, Petrus; Fenton, Karla A; Graves, Kerry; Grobbelaar, Antoinette A; Moolla, Naazneen; Leman, Patricia; Weyer, Jacqueline; Storm, Nadia; McCulloch, Stewart D; Scott, Terence P; Markotter, Wanda; Odendaal, Lieza; Clift, Sarah J; Geisbert, Thomas W; Hale, Martin J; Kemp, Alan

    2015-10-01

    Egyptian fruit bats (Rousettus aegyptiacus) were inoculated subcutaneously (n = 22) with Marburg virus (MARV). No deaths, overt signs of morbidity, or gross lesions was identified, but microscopic pathological changes were seen in the liver of infected bats. The virus was detected in 15 different tissues and plasma but only sporadically in mucosal swab samples, urine, and fecal samples. Neither seroconversion nor viremia could be demonstrated in any of the in-contact susceptible bats (n = 14) up to 42 days after exposure to infected bats. In bats rechallenged (n = 4) on day 48 after infection, there was no viremia, and the virus could not be isolated from any of the tissues tested. This study confirmed that infection profiles are consistent with MARV replication in a reservoir host but failed to demonstrate MARV transmission through direct physical contact or indirectly via air. Bats develop strong protective immunity after infection with MARV. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  19. Ebola virus disease and Marburg disease in pregnancy: a review and management considerations for filovirus infection.

    PubMed

    Bebell, Lisa M; Riley, Laura E

    2015-06-01

    The largest-ever recorded outbreak of viral hemorrhagic fever is ongoing. As a result of the epidemic and rural nature of outbreaks, little is published about the Filovirus infections Ebola virus disease and Marburg disease in pregnancy. This review of viral hemorrhagic fever focusing on Marburg and Ebola uses knowledge of disease in nonpregnant individuals and pregnancy-specific data to inform management for pregnant women. Filovirus infection presentation is similar between pregnant and nonpregnant patients, although infections may be more severe in pregnancy. Although labeled as hemorrhagic fevers, Marburg and Ebola do not commonly cause gross bleeding and should be conceptualized as diseases of high gastrointestinal losses. Early, aggressive supportive care is the mainstay of Filovirus infection management with massive fluid resuscitation as the key management principle. Patients often require 5-10 L or more per day of intravenous or oral fluid to maintain circulating blood volume in the setting of ongoing gastrointestinal loss. Fluid shifts warrant aggressive monitoring and correction of potassium levels and acid-base disturbances to prevent life-threatening arrhythmias and metabolic complications. Regardless of maternal survival, fetal loss rates are nearly 100% in Filovirus infection, likely resulting from unchecked transplacental and hematogenous viral spread. High fetal loss rates support the placenta as a difficult-to-eradicate Filovirus infection reservoir. In conclusion, the management of Filovirus infection in pregnancy should focus on stabilizing the mother with intensive monitoring and aggressive fluid and electrolyte repletion as well as maintaining strict infection control to minimize transmission to others.

  20. Live-cell imaging of Marburg virus-infected cells uncovers actin-dependent transport of nucleocapsids over long distances

    PubMed Central

    Schudt, Gordian; Kolesnikova, Larissa; Dolnik, Olga; Sodeik, Beate; Becker, Stephan

    2013-01-01

    Transport of large viral nucleocapsids from replication centers to assembly sites requires contributions from the host cytoskeleton via cellular adaptor and motor proteins. For the Marburg and Ebola viruses, related viruses that cause severe hemorrhagic fevers, the mechanism of nucleocapsid transport remains poorly understood. Here we developed and used live-cell imaging of fluorescently labeled viral and host proteins to characterize the dynamics and molecular requirements of nucleocapsid transport in Marburg virus-infected cells under biosafety level 4 conditions. The study showed a complex actin-based transport of nucleocapsids over long distances from the viral replication centers to the budding sites. Only after the nucleocapsids had associated with the matrix viral protein VP40 at the plasma membrane were they recruited into filopodia and cotransported with host motor myosin 10 toward the budding sites at the tip or side of the long cellular protrusions. Three different transport modes and velocities were identified: (i) Along actin filaments in the cytosol, nucleocapsids were transported at ∼200 nm/s; (ii) nucleocapsids migrated from one actin filament to another at ∼400 nm/s; and (iii) VP40-associated nucleocapsids moved inside filopodia at 100 nm/s. Unique insights into the spatiotemporal dynamics of nucleocapsids and their interaction with the cytoskeleton and motor proteins can lead to novel classes of antivirals that interfere with the trafficking and subsequent release of the Marburg virus from infected cells. PMID:23940347

  1. Live-cell imaging of Marburg virus-infected cells uncovers actin-dependent transport of nucleocapsids over long distances.

    PubMed

    Schudt, Gordian; Kolesnikova, Larissa; Dolnik, Olga; Sodeik, Beate; Becker, Stephan

    2013-08-27

    Transport of large viral nucleocapsids from replication centers to assembly sites requires contributions from the host cytoskeleton via cellular adaptor and motor proteins. For the Marburg and Ebola viruses, related viruses that cause severe hemorrhagic fevers, the mechanism of nucleocapsid transport remains poorly understood. Here we developed and used live-cell imaging of fluorescently labeled viral and host proteins to characterize the dynamics and molecular requirements of nucleocapsid transport in Marburg virus-infected cells under biosafety level 4 conditions. The study showed a complex actin-based transport of nucleocapsids over long distances from the viral replication centers to the budding sites. Only after the nucleocapsids had associated with the matrix viral protein VP40 at the plasma membrane were they recruited into filopodia and cotransported with host motor myosin 10 toward the budding sites at the tip or side of the long cellular protrusions. Three different transport modes and velocities were identified: (i) Along actin filaments in the cytosol, nucleocapsids were transported at ∼200 nm/s; (ii) nucleocapsids migrated from one actin filament to another at ∼400 nm/s; and (iii) VP40-associated nucleocapsids moved inside filopodia at 100 nm/s. Unique insights into the spatiotemporal dynamics of nucleocapsids and their interaction with the cytoskeleton and motor proteins can lead to novel classes of antivirals that interfere with the trafficking and subsequent release of the Marburg virus from infected cells.

  2. Ebola and Marburg virus vaccines.

    PubMed

    Reynolds, Pierce; Marzi, Andrea

    2017-08-01

    The filoviruses, Ebola virus (EBOV), and Marburg virus (MARV), are among the most pathogenic viruses known to man and the causative agents of viral hemorrhagic fever outbreaks in Africa with case fatality rates of up to 90%. Nearly 30,000 infections were observed in the latest EBOV epidemic in West Africa; previous outbreaks were much smaller, typically only affecting less than a few hundred people. Compared to other diseases such as AIDS or Malaria with millions of cases annually, filovirus hemorrhagic fever (FHF) is one of the neglected infectious diseases. There are no licensed vaccines or therapeutics available to treat EBOV and MARV infections; therefore, these pathogens can only be handled in maximum containment laboratories and are classified as select agents. Under these limitations, a very few laboratories worldwide conducted basic research and countermeasure development for EBOV and MARV since their respective discoveries in 1967 (MARV) and 1976 (EBOV). In this review, we discuss several vaccine platforms against EBOV and MARV, which have been assessed for their protective efficacy in animal models of FHF. The focus is on the most promising approaches, which were accelerated in clinical development (phase I-III trials) during the EBOV epidemic in West Africa.

  3. Large-Scale Screening and Identification of Novel Ebola Virus and Marburg Virus Entry Inhibitors.

    PubMed

    Anantpadma, Manu; Kouznetsova, Jennifer; Wang, Hang; Huang, Ruili; Kolokoltsov, Andrey; Guha, Rajarshi; Lindstrom, Aaron R; Shtanko, Olena; Simeonov, Anton; Maloney, David J; Maury, Wendy; LaCount, Douglas J; Jadhav, Ajit; Davey, Robert A

    2016-08-01

    Filoviruses are highly infectious, and no FDA-approved drug therapy for filovirus infection is available. Most work to find a treatment has involved only a few strains of Ebola virus and testing of relatively small drug libraries or compounds that have shown efficacy against other virus types. Here we report the findings of a high-throughput screening of 319,855 small molecules from the Molecular Libraries Small Molecule Repository library for their activities against Marburg virus and Ebola virus. Nine of the most potent, novel compounds that blocked infection by both viruses were analyzed in detail for their mechanisms of action. The compounds inhibited known key steps in the Ebola virus infection mechanism by blocking either cell surface attachment, macropinocytosis-mediated uptake, or endosomal trafficking. To date, very few specific inhibitors of macropinocytosis have been reported. The 2 novel macropinocytosis inhibitors are more potent inhibitors of Ebola virus infection and less toxic than ethylisopropylamiloride, one commonly accepted macropinocytosis inhibitor. Each compound blocked infection of primary human macrophages, indicating their potential to be developed as new antifiloviral therapies. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  4. Lassa and Marburg viruses elicit distinct host transcriptional responses early after infection.

    PubMed

    Caballero, Ignacio S; Yen, Judy Y; Hensley, Lisa E; Honko, Anna N; Goff, Arthur J; Connor, John H

    2014-11-06

    Lassa virus and Marburg virus are two causative agents of viral hemorrhagic fever. Their diagnosis is difficult because patients infected with either pathogen present similar nonspecific symptoms early after infection. Current diagnostic tests are based on detecting viral proteins or nucleic acids in the blood, but these cannot be found during the early stages of disease, before the virus starts replicating in the blood. Using the transcriptional response of the host during infection can lead to earlier diagnoses compared to those of traditional methods. In this study, we use RNA sequencing to obtain a high-resolution view of the in vivo transcriptional dynamics of peripheral blood mononuclear cells (PBMCs) throughout both types of infection. We report a subset of host mRNAs, including heat-shock proteins like HSPA1B, immunoglobulins like IGJ, and cell adhesion molecules like SIGLEC1, whose differences in expression are strong enough to distinguish Lassa infection from Marburg infection in non-human primates. We have validated these infection-specific expression differences by using microarrays on a larger set of samples, and by quantifying the expression of individual genes using RT-PCR. These results suggest that host transcriptional signatures are correlated with specific viral infections, and that they can be used to identify highly pathogenic viruses during the early stages of disease, before standard detection methods become effective.

  5. Ebola and Marburg Hemorrhagic Fevers: Neglected Tropical Diseases?

    PubMed Central

    MacNeil, Adam; Rollin, Pierre E.

    2012-01-01

    Ebola hemorrhagic fever (EHF) and Marburg hemorrhagic fever (MHF) are rare viral diseases, endemic to central Africa. The overall burden of EHF and MHF is small in comparison to the more common protozoan, helminth, and bacterial diseases typically referred to as neglected tropical diseases (NTDs). However, EHF and MHF outbreaks typically occur in resource-limited settings, and many aspects of these outbreaks are a direct consequence of impoverished conditions. We will discuss aspects of EHF and MHF disease, in comparison to the “classic” NTDs, and examine potential ways forward in the prevention and control of EHF and MHF in sub-Saharan Africa, as well as examine the potential for application of novel vaccines or antiviral drugs for prevention or control of EHF and MHF among populations at highest risk for disease. PMID:22761967

  6. Ebola and Marburg haemorrhagic fever viruses: major scientific advances, but a relatively minor public health threat for Africa.

    PubMed

    Leroy, E M; Gonzalez, J-P; Baize, S

    2011-07-01

    Ebola and Marburg viruses are the only members of the Filoviridae family (order Mononegavirales), a group of viruses characterized by a linear, non-segmented, single-strand negative RNA genome. They are among the most virulent pathogens for humans and great apes, causing acute haemorrhagic fever and death within a matter of days. Since their discovery 50 years ago, filoviruses have caused only a few outbreaks, with 2317 clinical cases and 1671 confirmed deaths, which is negligible compared with the devastation caused by malnutrition and other infectious diseases prevalent in Africa (malaria, cholera, AIDS, dengue, tuberculosis …). Yet considerable human and financial resourses have been devoted to research on these viruses during the past two decades, partly because of their potential use as bioweapons. As a result, our understanding of the ecology, host interactions, and control of these viruses has improved considerably. © 2011 The Authors. Clinical Microbiology and Infection © 2011 European Society of Clinical Microbiology and Infectious Diseases.

  7. Mannose-binding lectin binds to Ebola and Marburg envelope glycoproteins, resulting in blocking of virus interaction with DC-SIGN and complement-mediated virus neutralization.

    PubMed

    Ji, Xin; Olinger, Gene G; Aris, Sheena; Chen, Ying; Gewurz, Henry; Spear, Gregory T

    2005-09-01

    Mannose-binding lectin (MBL), a serum lectin that mediates innate immune functions including activation of the lectin complement pathway, binds to carbohydrates expressed on some viral glycoproteins. In this study, the ability of MBL to bind to virus particles pseudotyped with Ebola and Marburg envelope glycoproteins was evaluated. Virus particles bearing either Ebola (Zaire strain) or Marburg (Musoke strain) envelope glycoproteins bound at significantly higher levels to immobilized MBL compared with virus particles pseudotyped with vesicular stomatitis virus glycoprotein or with no virus glycoprotein. As observed in previous studies, Ebola-pseudotyped virus bound to cells expressing the lectin DC-SIGN (dendritic cell-specific intercellular adhesion molecule 3-grabbing non-integrin). However, pre-incubation of virus with MBL blocked DC-SIGN-mediated binding to cells, suggesting that the two lectins bind at the same or overlapping sites on the Ebola glycoprotein. Neutralization experiments showed that virus pseudotyped with Ebola or Marburg (Musoke) glycoprotein was neutralized by complement, while the Marburg (Ravn strain) glycoprotein-pseudotyped virus was less sensitive to neutralization. Neutralization was partially mediated through the lectin complement pathway, since a complement source deficient in MBL was significantly less effective at neutralizing viruses pseudotyped with filovirus glycoproteins and addition of purified MBL to the MBL-deficient complement increased neutralization. These experiments demonstrated that MBL binds to filovirus envelope glycoproteins resulting in important biological effects and suggest that MBL can interact with filoviruses during infection in humans.

  8. One-Step Reverse Transcription-Polymerase Chain Reaction for Ebola and Marburg Viruses.

    PubMed

    Park, Sun-Whan; Lee, Ye-Ji; Lee, Won-Ja; Jee, Youngmee; Choi, WooYoung

    2016-06-01

    Ebola and Marburg viruses (EBOVs and MARVs, respectively) are causative agents of severe hemorrhagic fever with high mortality rates in humans and nonhuman primates. In 2014, there was a major Ebola outbreak in various countries in West Africa, including Guinea, Liberia, Republic of Sierra Leone, and Nigeria. EBOV and MARV are clinically difficult to diagnose and distinguish from other African epidemic diseases. Therefore, in this study, we aimed to develop a method for rapid identification of the virus to prevent the spread of infection. We established a conventional one-step reverse transcription-polymerase chain reaction (RT-PCR) assay for these pathogens based on the Superscript Reverse Transcriptase-Platinum Taq polymerase enzyme mixture. All assays were thoroughly optimized using in vitro-transcribed RNA. We designed seven primer sets of nucleocapsid protein (NP) genes based on sequences from seven filoviruses, including five EBOVs and two MARVs. To evaluate the sensitivity of the RT-PCR assay for each filovirus, 10-fold serial dilutions of synthetic viral RNA transcripts of EBOV or MARV NP genes were used to assess detection limits of viral RNA copies. The potential for these primers to cross react with other filoviruses was also examined. The results showed that the primers were specific for individual genotype detection in the examined filoviruses. The assay established in this study may facilitate rapid, reliable laboratory diagnosis in suspected cases of Ebola and Marburg hemorrhagic fevers.

  9. Crystal Structure of the Marburg Virus VP35 Oligomerization Domain

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Bruhn, Jessica F.; Kirchdoerfer, Robert N.; Urata, Sarah M.

    ABSTRACT Marburg virus (MARV) is a highly pathogenic filovirus that is classified in a genus distinct from that of Ebola virus (EBOV) (generaMarburgvirusandEbolavirus, respectively). Both viruses produce a multifunctional protein termed VP35, which acts as a polymerase cofactor, a viral protein chaperone, and an antagonist of the innate immune response. VP35 contains a central oligomerization domain with a predicted coiled-coil motif. This domain has been shown to be essential for RNA polymerase function. Here we present crystal structures of the MARV VP35 oligomerization domain. These structures and accompanying biophysical characterization suggest that MARV VP35 is a trimer. In contrast, EBOVmore » VP35 is likely a tetramer in solution. Differences in the oligomeric state of this protein may explain mechanistic differences in replication and immune evasion observed for MARV and EBOV. IMPORTANCEMarburg virus can cause severe disease, with up to 90% human lethality. Its genome is concise, only producing seven proteins. One of the proteins, VP35, is essential for replication of the viral genome and for evasion of host immune responses. VP35 oligomerizes (self-assembles) in order to function, yet the structure by which it assembles has not been visualized. Here we present two crystal structures of this oligomerization domain. In both structures, three copies of VP35 twist about each other to form a coiled coil. This trimeric assembly is in contrast to tetrameric predictions for VP35 of Ebola virus and to known structures of homologous proteins in the measles, mumps, and Nipah viruses. Distinct oligomeric states of the Marburg and Ebola virus VP35 proteins may explain differences between them in polymerase function and immune evasion. These findings may provide a more accurate understanding of the mechanisms governing VP35's functions and inform the design of therapeutics.« less

  10. Differential transcriptional responses to Ebola and Marburg virus infection in bat and human cells.

    PubMed

    Hölzer, Martin; Krähling, Verena; Amman, Fabian; Barth, Emanuel; Bernhart, Stephan H; Carmelo, Victor A O; Collatz, Maximilian; Doose, Gero; Eggenhofer, Florian; Ewald, Jan; Fallmann, Jörg; Feldhahn, Lasse M; Fricke, Markus; Gebauer, Juliane; Gruber, Andreas J; Hufsky, Franziska; Indrischek, Henrike; Kanton, Sabina; Linde, Jörg; Mostajo, Nelly; Ochsenreiter, Roman; Riege, Konstantin; Rivarola-Duarte, Lorena; Sahyoun, Abdullah H; Saunders, Sita J; Seemann, Stefan E; Tanzer, Andrea; Vogel, Bertram; Wehner, Stefanie; Wolfinger, Michael T; Backofen, Rolf; Gorodkin, Jan; Grosse, Ivo; Hofacker, Ivo; Hoffmann, Steve; Kaleta, Christoph; Stadler, Peter F; Becker, Stephan; Marz, Manja

    2016-10-07

    The unprecedented outbreak of Ebola in West Africa resulted in over 28,000 cases and 11,000 deaths, underlining the need for a better understanding of the biology of this highly pathogenic virus to develop specific counter strategies. Two filoviruses, the Ebola and Marburg viruses, result in a severe and often fatal infection in humans. However, bats are natural hosts and survive filovirus infections without obvious symptoms. The molecular basis of this striking difference in the response to filovirus infections is not well understood. We report a systematic overview of differentially expressed genes, activity motifs and pathways in human and bat cells infected with the Ebola and Marburg viruses, and we demonstrate that the replication of filoviruses is more rapid in human cells than in bat cells. We also found that the most strongly regulated genes upon filovirus infection are chemokine ligands and transcription factors. We observed a strong induction of the JAK/STAT pathway, of several genes encoding inhibitors of MAP kinases (DUSP genes) and of PPP1R15A, which is involved in ER stress-induced cell death. We used comparative transcriptomics to provide a data resource that can be used to identify cellular responses that might allow bats to survive filovirus infections.

  11. Evasion of interferon responses by Ebola and Marburg viruses.

    PubMed

    Basler, Christopher F; Amarasinghe, Gaya K

    2009-09-01

    The filoviruses, Ebola virus (EBOV) and Marburg virus (MARV), cause frequently lethal viral hemorrhagic fever. These infections induce potent cytokine production, yet these host responses fail to prevent systemic virus replication. Consistent with this, filoviruses have been found to encode proteins VP35 and VP24 that block host interferon (IFN)-alpha/beta production and inhibit signaling downstream of the IFN-alpha/beta and the IFN-gamma receptors, respectively. VP35, which is a component of the viral nucleocapsid complex and plays an essential role in viral RNA synthesis, acts as a pseudosubstrate for the cellular kinases IKK-epsilon and TBK-1, which phosphorylate and activate interferon regulatory factor 3 (IRF-3) and interferon regulatory factor 7 (IRF-7). VP35 also promotes SUMOylation of IRF-7, repressing IFN gene transcription. In addition, VP35 is a dsRNA-binding protein, and mutations that disrupt dsRNA binding impair VP35 IFN-antagonist activity while leaving its RNA replication functions intact. The phenotypes of recombinant EBOV bearing mutant VP35s unable to inhibit IFN-alpha/beta demonstrate that VP35 IFN-antagonist activity is critical for full virulence of these lethal pathogens. The structure of the VP35 dsRNA-binding domain, which has recently become available, is expected to provide insight into how VP35 IFN-antagonist and dsRNA-binding functions are related. The EBOV VP24 protein inhibits IFN signaling through an interaction with select host cell karyopherin-alpha proteins, preventing the nuclear import of otherwise activated STAT1. It remains to be determined to what extent VP24 may also modulate the nuclear import of other host cell factors and to what extent this may influence the outcome of infection. Notably, the Marburg virus VP24 protein does not detectably block STAT1 nuclear import, and, unlike EBOV, MARV infection inhibits STAT1 and STAT2 phosphorylation. Thus, despite their similarities, there are fundamental differences by which

  12. Post-exposure treatments for Ebola and Marburg virus infections.

    PubMed

    Cross, Robert W; Mire, Chad E; Feldmann, Heinz; Geisbert, Thomas W

    2018-06-01

    The filoviruses - Ebola virus and Marburg virus - cause lethal haemorrhagic fever in humans and non-human primates (NHPs). Filoviruses present a global health threat both as naturally acquired diseases and as potential agents of bioterrorism. In the recent 2013-2016 outbreak of Ebola virus, the most promising therapies for post-exposure use with demonstrated efficacy in the gold-standard NHP models of filovirus disease were unable to show statistically significant protection in patients infected with Ebola virus. This Review briefly discusses these failures and what has been learned from these experiences, and summarizes the current status of post-exposure medical countermeasures in development, including antibodies, small interfering RNA and small molecules. We outline how our current knowledge could be applied to the identification of novel interventions and ways to use interventions more effectively.

  13. Determination of Specific Antibody Responses to the Six Species of Ebola and Marburg Viruses by Multiplexed Protein Microarrays

    PubMed Central

    Kamata, Teddy; Natesan, Mohan; Warfield, Kelly; Aman, M. Javad

    2014-01-01

    Infectious hemorrhagic fevers caused by the Marburg and Ebola filoviruses result in human mortality rates of up to 90%, and there are no effective vaccines or therapeutics available for clinical use. The highly infectious and lethal nature of these viruses highlights the need for reliable and sensitive diagnostic methods. We assembled a protein microarray displaying nucleoprotein (NP), virion protein 40 (VP40), and glycoprotein (GP) antigens from isolates representing the six species of filoviruses for use as a surveillance and diagnostic platform. Using the microarrays, we examined serum antibody responses of rhesus macaques vaccinated with trivalent (GP, NP, and VP40) virus-like particles (VLP) prior to infection with the Marburg virus (MARV) (i.e., Marburg marburgvirus) or the Zaire virus (ZEBOV) (i.e., Zaire ebolavirus). The microarray-based assay detected a significant increase in antigen-specific IgG resulting from immunization, while a greater level of antibody responses resulted from challenge of the vaccinated animals with ZEBOV or MARV. Further, while antibody cross-reactivities were observed among NPs and VP40s of Ebola viruses, antibody recognition of GPs was very specific. The performance of mucin-like domain fragments of GP (GP mucin) expressed in Escherichia coli was compared to that of GP ectodomains produced in eukaryotic cells. Based on results with ZEBOV and MARV proteins, antibody recognition of GP mucins that were deficient in posttranslational modifications was comparable to that of the eukaryotic cell-expressed GP ectodomains in assay performance. We conclude that the described protein microarray may translate into a sensitive assay for diagnosis and serological surveillance of infections caused by multiple species of filoviruses. PMID:25230936

  14. The VP35 and VP40 proteins of filoviruses. Homology between Marburg and Ebola viruses.

    PubMed

    Bukreyev, A A; Volchkov, V E; Blinov, V M; Netesov, S V

    1993-05-03

    The fragments of genomic RNA sequences of Marburg (MBG) and Ebola (EBO) viruses are reported. These fragments were found to encode the VP35 and VP40 proteins. The canonic sequences were revealed before and after each open reading frame. It is suggested that these sequences are mRNA extremities and at the same time the regulatory elements for mRNA transcription. Homology between the MBG and EBO proteins was discovered.

  15. Structural and Functional Studies on the Marburg Virus GP2 Fusion Loop.

    PubMed

    Liu, Nina; Tao, Yisong; Brenowitz, Michael D; Girvin, Mark E; Lai, Jonathan R

    2015-10-01

    Marburg virus (MARV) and the ebolaviruses belong to the family Filoviridae (the members of which are filoviruses) that cause severe hemorrhagic fever. Infection requires fusion of the host and viral membranes, a process that occurs in the host cell endosomal compartment and is facilitated by the envelope glycoprotein fusion subunit, GP2. The N-terminal fusion loop (FL) of GP2 is a hydrophobic disulfide-bonded loop that is postulated to insert and disrupt the host endosomal membrane during fusion. Here, we describe the first structural and functional studies of a protein corresponding to the MARV GP2 FL. We found that this protein undergoes a pH-dependent conformational change, as monitored by circular dichroism and nuclear magnetic resonance. Furthermore, we report that, under low pH conditions, the MARV GP2 FL can induce content leakage from liposomes. The general aspects of this pH-dependent structure and lipid-perturbing behavior are consistent with previous reports on Ebola virus GP2 FL. However, nuclear magnetic resonance studies in lipid bicelles and mutational analysis indicate differences in structure exist between MARV and Ebola virus GP2 FL. These results provide new insight into the mechanism of MARV GP2-mediated cell entry. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  16. Filovirus pathogenesis and immune evasion: insights from Ebola virus and Marburg virus.

    PubMed

    Messaoudi, Ilhem; Amarasinghe, Gaya K; Basler, Christopher F

    2015-11-01

    Ebola viruses and Marburg viruses, members of the filovirus family, are zoonotic pathogens that cause severe disease in people, as highlighted by the latest Ebola virus epidemic in West Africa. Filovirus disease is characterized by uncontrolled virus replication and the activation of host responses that contribute to pathogenesis. Underlying these phenomena is the potent suppression of host innate antiviral responses, particularly the type I interferon response, by viral proteins, which allows high levels of viral replication. In this Review, we describe the mechanisms used by filoviruses to block host innate immunity and discuss the links between immune evasion and filovirus pathogenesis.

  17. Mechanism of human antibody-mediated neutralization of Marburg virus.

    PubMed

    Flyak, Andrew I; Ilinykh, Philipp A; Murin, Charles D; Garron, Tania; Shen, Xiaoli; Fusco, Marnie L; Hashiguchi, Takao; Bornholdt, Zachary A; Slaughter, James C; Sapparapu, Gopal; Klages, Curtis; Ksiazek, Thomas G; Ward, Andrew B; Saphire, Erica Ollmann; Bukreyev, Alexander; Crowe, James E

    2015-02-26

    The mechanisms by which neutralizing antibodies inhibit Marburg virus (MARV) are not known. We isolated a panel of neutralizing antibodies from a human MARV survivor that bind to MARV glycoprotein (GP) and compete for binding to a single major antigenic site. Remarkably, several of the antibodies also bind to Ebola virus (EBOV) GP. Single-particle EM structures of antibody-GP complexes reveal that all of the neutralizing antibodies bind to MARV GP at or near the predicted region of the receptor-binding site. The presence of the glycan cap or mucin-like domain blocks binding of neutralizing antibodies to EBOV GP, but not to MARV GP. The data suggest that MARV-neutralizing antibodies inhibit virus by binding to infectious virions at the exposed MARV receptor-binding site, revealing a mechanism of filovirus inhibition. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Filovirus pathogenesis and immune evasion: insights from Ebola virus and Marburg virus

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Messaoudi, Ilhem; Amarasinghe, Gaya K.; Basler, Christopher F.

    Ebola viruses and Marburg viruses, members of the filovirus family, are zoonotic pathogens that cause severe disease in people, as highlighted by the latest Ebola virus epidemic in West Africa. Filovirus disease is characterized by uncontrolled virus replication and the activation of host responses that contribute to pathogenesis. Underlying these phenomena is the potent suppression of host innate antiviral responses, particularly the type I interferon response, by viral proteins, which allows high levels of viral replication. In this Review, we describe the mechanisms used by filoviruses to block host innate immunity and discuss the links between immune evasion and filovirusmore » pathogenesis.« less

  19. Filovirus pathogenesis and immune evasion: insights from Ebola virus and Marburg virus

    PubMed Central

    Messaoudi, Ilhem; Amarasinghe, Gaya K.; Basler, Christopher F.

    2016-01-01

    Ebola viruses and Marburg viruses, members of the filovirus family, are zoonotic pathogens that cause severe disease in people. The Ebola virus epidemic in West Africa, which was first recognized in early 2014, highlights the threat posed by these deadly viruses. Filovirus disease is characterized by uncontrolled virus replication and the activation of damaging host pathways. Underlying these phenomena is the potent suppression of host innate antiviral responses, particularly the type I interferon (IFN) response, which allows high levels of replication. Here we review the mechanisms deployed by filoviruses to block host innate immunity and discuss aspects of virus replication that promote disease. PMID:26439085

  20. Vesicular stomatitis virus-based vaccines protect nonhuman primates against aerosol challenge with Ebola and Marburg viruses.

    PubMed

    Geisbert, Thomas W; Daddario-Dicaprio, Kathleen M; Geisbert, Joan B; Reed, Douglas S; Feldmann, Friederike; Grolla, Allen; Ströher, Ute; Fritz, Elizabeth A; Hensley, Lisa E; Jones, Steven M; Feldmann, Heinz

    2008-12-09

    Considerable progress has been made over the last decade in developing candidate preventive vaccines that can protect nonhuman primates against Ebola and Marburg viruses. A vaccine based on recombinant vesicular stomatitis virus (VSV) seems to be particularly robust as it can also confer protection when administered as a postexposure treatment. While filoviruses are not thought to be transmitted by aerosol in nature the inhalation route is among the most likely portals of entry in the setting of a bioterrorist event. At present, all candidate filoviral vaccines have been evaluated against parenteral challenges but none have been tested against an aerosol exposure. Here, we evaluated our recombinant VSV-based Zaire ebolavirus (ZEBOV) and Marburg virus (MARV) vaccines against aerosol challenge in cynomolgus macaques. All monkeys vaccinated with a VSV vector expressing the glycoprotein of ZEBOV were completely protected against an aerosol exposure of ZEBOV. Likewise, all monkeys vaccinated with a VSV vector expressing the glycoprotein of MARV were completely protected against an aerosol exposure of MARV. All control animals challenged by the aerosol route with either ZEBOV or MARV succumbed. Interestingly, disease in control animals appeared to progress slower than previously seen in macaques exposed to comparable doses by intramuscular injection.

  1. Structural Insight into Nucleoprotein Conformation Change Chaperoned by VP35 Peptide in Marburg Virus.

    PubMed

    Liu, Baocheng; Dong, Shishang; Li, Guobang; Wang, Wenming; Liu, Xiang; Wang, Yantong; Yang, Cheng; Rao, Zihe; Guo, Yu

    2017-08-15

    Marburg virus (MARV) encodes a nucleoprotein (NP) to encapsidate its genome by oligomerization and form a ribonucleoprotein complex (RNP). According to previous investigation on nonsegmented negative-sense RNA viruses (nsNSV), the newly synthesized NPs must be prevented from indiscriminately binding to noncognate RNAs. During the viral RNA synthesis process, the RNPs undergo a transition from an RNA-bound form to a template-free form, to open access for the interaction between the viral polymerase and the RNA template. In filoviruses, this transition is regulated by VP35 peptide and other viral components. To further understand the dynamic process of filovirus RNP formation, we report here the structure of MARV NP core , both in the apo form and in the VP35 peptide-chaperoned form. These structures reveal a typical bilobed structure, with a positive-charged RNA binding groove between two lobes. In the apo form, the MARV NP exists in an interesting hexameric state formed by the hydrophobic interaction within the long helix of the NP core C-terminal region, which shows high structural flexibility among filoviruses and may imply critical function during RNP formation. Moreover, the VP35 peptide-chaperoned NP core remains in a monomeric state and completely loses its affinity for single-stranded RNA (ssRNA). The structural comparison reveals that the RNA binding groove undergoes a transition from closed state to open state, chaperoned by VP35 peptide, thus preventing the interaction for viral RNA. Our investigation provides considerable structural insight into the filovirus RNP working mechanism and may support the development of antiviral therapies targeting the RNP formation of filovirus. IMPORTANCE Marburg virus is one of the most dangerous viruses, with high morbidity and mortality. A recent outbreak in Angola in 2005 caused the deaths of 272 persons. NP is one of the most essential proteins, as it encapsidates and protects the whole virus genome simultaneously

  2. Dimerization Controls Marburg Virus VP24-dependent Modulation of Host Antioxidative Stress Responses.

    PubMed

    Johnson, Britney; Li, Jing; Adhikari, Jagat; Edwards, Megan R; Zhang, Hao; Schwarz, Toni; Leung, Daisy W; Basler, Christopher F; Gross, Michael L; Amarasinghe, Gaya K

    2016-08-28

    Marburg virus (MARV), a member of the Filoviridae family that also includes Ebola virus (EBOV), causes lethal hemorrhagic fever with case fatality rates that have exceeded 50% in some outbreaks. Within an infected cell, there are numerous host-viral interactions that contribute to the outcome of infection. Recent studies identified MARV protein 24 (mVP24) as a modulator of the host antioxidative responses, but the molecular mechanism remains unclear. Using a combination of biochemical and mass spectrometry studies, we show that mVP24 is a dimer in solution that directly binds to the Kelch domain of Kelch-like ECH-associated protein 1 (Keap1) to regulate nuclear factor (erythroid-derived 2)-like 2 (Nrf2). This interaction between Keap1 and mVP24 occurs through the Kelch interaction loop (K-Loop) of mVP24 leading to upregulation of antioxidant response element transcription, which is distinct from other Kelch binders that regulate Nrf2 activity. N-terminal truncations disrupt mVP24 dimerization, allowing monomeric mVP24 to bind Kelch with higher affinity and stimulate higher antioxidative stress response element (ARE) reporter activity. Mass spectrometry-based mapping of the interface revealed overlapping binding sites on Kelch for mVP24 and the Nrf2 proteins. Substitution of conserved cysteines, C209 and C210, to alanine in the mVP24 K-Loop abrogates Kelch binding and ARE activation. Our studies identify a shift in the monomer-dimer equilibrium of MARV VP24, driven by its interaction with Keap1 Kelch domain, as a critical determinant that modulates host responses to pathogenic Marburg viral infections. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Dimerization Controls Marburg Virus VP24-dependent Modulation of Host Antioxidative Stress Responses

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Johnson, Britney; Li, Jing; Adhikari, Jagat

    Marburg virus (MARV), a member of the Filoviridae family that also includes Ebola virus (EBOV), causes lethal hemorrhagic fever with case fatality rates that have exceeded 50% in some outbreaks. Within an infected cell, there are numerous host-viral interactions that contribute to the outcome of infection. Recent studies identified MARV protein 24 (mVP24) as a modulator of the host antioxidative responses, but the molecular mechanism remains unclear. Using a combination of biochemical and mass spectrometry studies, we show that mVP24 is a dimer in solution that directly binds to the Kelch domain of Kelch-like ECH-associated protein 1 (Keap1) to regulatemore » nuclear factor (erythroid-derived 2)-like 2 (Nrf2). This interaction between Keap1 and mVP24 occurs through the Kelch interaction loop (K-Loop) of mVP24 leading to upregulation of antioxidant response element transcription, which is distinct from other Kelch binders that regulate Nrf2 activity. N-terminal truncations disrupt mVP24 dimerization, allowing monomeric mVP24 to bind Kelch with higher affinity and stimulate higher antioxidative stress response element (ARE) reporter activity. Mass spectrometry-based mapping of the interface revealed overlapping binding sites on Kelch for mVP24 and the Nrf2 proteins. Substitution of conserved cysteines, C209 and C210, to alanine in the mVP24 K-Loop abrogates Kelch binding and ARE activation. Our studies identify a shift in the monomer-dimer equilibrium of MARV VP24, driven by its interaction with Keap1 Kelch domain, as a critical determinant that modulates host responses to pathogenic Marburg viral infections.« less

  4. Discovery and early development of AVI-7537 and AVI-7288 for the treatment of Ebola virus and Marburg virus infections.

    PubMed

    Iversen, Patrick L; Warren, Travis K; Wells, Jay B; Garza, Nicole L; Mourich, Dan V; Welch, Lisa S; Panchal, Rekha G; Bavari, Sina

    2012-11-06

    There are no currently approved treatments for filovirus infections. In this study we report the discovery process which led to the development of antisense Phosphorodiamidate Morpholino Oligomers (PMOs) AVI-6002 (composed of AVI-7357 and AVI-7539) and AVI-6003 (composed of AVI-7287 and AVI-7288) targeting Ebola virus and Marburg virus respectively. The discovery process involved identification of optimal transcript binding sites for PMO based RNA-therapeutics followed by screening for effective viral gene target in mouse and guinea pig models utilizing adapted viral isolates. An evolution of chemical modifications were tested, beginning with simple Phosphorodiamidate Morpholino Oligomers (PMO) transitioning to cell penetrating peptide conjugated PMOs (PPMO) and ending with PMOplus containing a limited number of positively charged linkages in the PMO structure. The initial lead compounds were combinations of two agents targeting separate genes. In the final analysis, a single agent for treatment of each virus was selected, AVI-7537 targeting the VP24 gene of Ebola virus and AVI-7288 targeting NP of Marburg virus, and are now progressing into late stage clinical development as the optimal therapeutic candidates.

  5. A Comparison of the Pathogenesis of Marburg Virus Disease in Humans and Nonhuman Primates and Evaluation of the Suitability of These Animal Models for Predicting Clinical Efficacy under the 'Animal Rule'.

    PubMed

    Glaze, Elizabeth R; Roy, Michael J; Dalrymple, Lonnie W; Lanning, Lynda L

    2015-06-01

    Marburg virus outbreaks are sporadic, infrequent, brief, and relatively small in terms of numbers of subjects affected. In addition, outbreaks most likely will occur in remote regions where clinical trials are not feasible; therefore, definitive, well-controlled human efficacy studies to test the effectiveness of a drug or biologic product are not feasible. Healthy human volunteers cannot ethically be deliberately exposed to a lethal agent such as Marburg virus in order to test the efficacy of a therapy or preventive prior to licensure. When human efficacy studies are neither ethical nor feasible, the US Food and Drug Administration may grant marketing approval of a drug or biologic product under the 'Animal Rule,' through which demonstration of the efficacy of a product can be 'based on adequate and well-controlled animal efficacy studies when the results of those studies establish that the drug is reasonably likely to produce clinical benefit in humans.' This process requires that the pathogenic determinants of the disease in the animal model are similar to those that have been identified in humans. After reviewing primarily English-language, peer-reviewed journal articles, we here summarize the clinical manifestations of Marburg virus disease and the results of studies in NHP showing the characteristics and progression of the disease. We also include a detailed comparison of the characteristics of the human disease relative to those for NHP. This review reveals that the disease characteristics of Marburg virus disease are generally similar for humans and 3 NHP species: cynomolgus macaques (Macaca fascicularis), rhesus macaques (Macaca mulatta), and African green monkeys (Chlorocebus aethiops).

  6. Considerations in the Use of Nonhuman Primate Models of Ebola Virus and Marburg Virus Infection.

    PubMed

    Geisbert, Thomas W; Strong, James E; Feldmann, Heinz

    2015-10-01

    The filoviruses, Ebola virus and Marburg virus, are zoonotic pathogens that cause severe hemorrhagic fever in humans and nonhuman primates (NHPs), with case-fatality rates ranging from 23% to 90%. The current outbreak of Ebola virus infection in West Africa, with >26 000 cases, demonstrates the long-underestimated public health danger that filoviruses pose as natural human pathogens. Currently, there are no vaccines or treatments licensed for human use. Licensure of any medical countermeasure may require demonstration of efficacy in the gold standard cynomolgus or rhesus macaque models of filovirus infection. Substantial progress has been made over the last decade in characterizing the filovirus NHP models. However, there is considerable debate over a variety of experimental conditions, including differences among filovirus isolates used, routes and doses of exposure, and euthanasia criteria, all of which may contribute to variability of results among different laboratories. As an example of the importance of understanding these differences, recent data with Ebola virus shows that an addition of a single uridine residue in the glycoprotein gene at the editing site attenuates the virus. Here, we draw on decades of experience working with filovirus-infected NHPs to provide a perspective on the importance of various experimental conditions. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  7. Discovery and Early Development of AVI-7537 and AVI-7288 for the Treatment of Ebola Virus and Marburg Virus Infections

    PubMed Central

    Iversen, Patrick L.; Warren, Travis K.; Wells, Jay B.; Garza, Nicole L.; Mourich, Dan V.; Welch, Lisa S.; Panchal, Rekha G.; Bavari, Sina

    2012-01-01

    There are no currently approved treatments for filovirus infections. In this study we report the discovery process which led to the development of antisense Phosphorodiamidate Morpholino Oligomers (PMOs) AVI-6002 (composed of AVI-7357 and AVI-7539) and AVI-6003 (composed of AVI-7287 and AVI-7288) targeting Ebola virus and Marburg virus respectively. The discovery process involved identification of optimal transcript binding sites for PMO based RNA-therapeutics followed by screening for effective viral gene target in mouse and guinea pig models utilizing adapted viral isolates. An evolution of chemical modifications were tested, beginning with simple Phosphorodiamidate Morpholino Oligomers (PMO) transitioning to cell penetrating peptide conjugated PMOs (PPMO) and ending with PMOplus containing a limited number of positively charged linkages in the PMO structure. The initial lead compounds were combinations of two agents targeting separate genes. In the final analysis, a single agent for treatment of each virus was selected, AVI-7537 targeting the VP24 gene of Ebola virus and AVI-7288 targeting NP of Marburg virus, and are now progressing into late stage clinical development as the optimal therapeutic candidates. PMID:23202506

  8. Digital sensing and sizing of vesicular stomatitis virus pseudotypes in complex media: a model for Ebola and Marburg detection.

    PubMed

    Daaboul, George G; Lopez, Carlos A; Chinnala, Jyothsna; Goldberg, Bennett B; Connor, John H; Ünlü, M Selim

    2014-06-24

    Rapid, sensitive, and direct label-free capture and characterization of nanoparticles from complex media such as blood or serum will broadly impact medicine and the life sciences. We demonstrate identification of virus particles in complex samples for replication-competent wild-type vesicular stomatitis virus (VSV), defective VSV, and Ebola- and Marburg-pseudotyped VSV with high sensitivity and specificity. Size discrimination of the imaged nanoparticles (virions) allows differentiation between modified viruses having different genome lengths and facilitates a reduction in the counting of nonspecifically bound particles to achieve a limit-of-detection (LOD) of 5 × 10(3) pfu/mL for the Ebola and Marburg VSV pseudotypes. We demonstrate the simultaneous detection of multiple viruses in a single sample (composed of serum or whole blood) for screening applications and uncompromised detection capabilities in samples contaminated with high levels of bacteria. By employing affinity-based capture, size discrimination, and a "digital" detection scheme to count single virus particles, we show that a robust and sensitive virus/nanoparticle sensing assay can be established for targets in complex samples. The nanoparticle microscopy system is termed the Single Particle Interferometric Reflectance Imaging Sensor (SP-IRIS) and is capable of high-throughput and rapid sizing of large numbers of biological nanoparticles on an antibody microarray for research and diagnostic applications.

  9. A Comparison of the Pathogenesis of Marburg Virus Disease in Humans and Nonhuman Primates and Evaluation of the Suitability of These Animal Models for Predicting Clinical Efficacy under the ‘Animal Rule’

    PubMed Central

    Glaze, Elizabeth R; Roy, Michael J; Dalrymple, Lonnie W; Lanning, Lynda L

    2015-01-01

    Marburg virus outbreaks are sporadic, infrequent, brief, and relatively small in terms of numbers of subjects affected. In addition, outbreaks most likely will occur in remote regions where clinical trials are not feasible; therefore, definitive, well-controlled human efficacy studies to test the effectiveness of a drug or biologic product are not feasible. Healthy human volunteers cannot ethically be deliberately exposed to a lethal agent such as Marburg virus in order to test the efficacy of a therapy or preventive prior to licensure. When human efficacy studies are neither ethical nor feasible, the US Food and Drug Administration may grant marketing approval of a drug or biologic product under the ‘Animal Rule,’ through which demonstration of the efficacy of a product can be ‘based on adequate and well-controlled animal efficacy studies when the results of those studies establish that the drug is reasonably likely to produce clinical benefit in humans.’ This process requires that the pathogenic determinants of the disease in the animal model are similar to those that have been identified in humans. After reviewing primarily English-language, peer-reviewed journal articles, we here summarize the clinical manifestations of Marburg virus disease and the results of studies in NHP showing the characteristics and progression of the disease. We also include a detailed comparison of the characteristics of the human disease relative to those for NHP. This review reveals that the disease characteristics of Marburg virus disease are generally similar for humans and 3 NHP species: cynomolgus macaques (Macaca fascicularis), rhesus macaques (Macaca mulatta), and African green monkeys (Chlorocebus aethiops). PMID:26141449

  10. Risk Factors Associated with Ebola and Marburg Viruses Seroprevalence in Blood Donors in the Republic of Congo.

    PubMed

    Moyen, Nanikaly; Thirion, Laurence; Emmerich, Petra; Dzia-Lepfoundzou, Amelia; Richet, Hervé; Boehmann, Yannik; Dimi, Yannick; Gallian, Pierre; Gould, Ernest A; Günther, Stephan; de Lamballerie, Xavier

    2015-01-01

    Ebola and Marburg viruses (family Filoviridae, genera Ebolavirus and Marburgvirus) cause haemorrhagic fevers in humans, often associated with high mortality rates. The presence of antibodies to Ebola virus (EBOV) and Marburg virus (MARV) has been reported in some African countries in individuals without a history of haemorrhagic fever. In this study, we present a MARV and EBOV seroprevalence study conducted amongst blood donors in the Republic of Congo and the analysis of risk factors for contact with EBOV. In 2011, we conducted a MARV and EBOV seroprevalence study amongst 809 blood donors recruited in rural (75; 9.3%) and urban (734; 90.7%) areas of the Republic of Congo. Serum titres of IgG antibodies to MARV and EBOV were assessed by indirect double-immunofluorescence microscopy. MARV seroprevalence was 0.5% (4 in 809) without any identified risk factors. Prevalence of IgG to EBOV was 2.5%, peaking at 4% in rural areas and in Pointe Noire. Independent risk factors identified by multivariate analysis were contact with bats and exposure to birds. This MARV and EBOV serological survey performed in the Republic of Congo identifies a probable role for environmental determinants of exposure to EBOV. It highlights the requirement for extending our understanding of the ecological and epidemiological risk of bats (previously identified as a potential ecological reservoir) and birds as vectors of EBOV to humans, and characterising the protection potentially afforded by EBOV-specific antibodies as detected in blood donors.

  11. Inhibition of Ebola and Marburg Virus Entry by G Protein-Coupled Receptor Antagonists

    PubMed Central

    Cheng, Han; Lear-Rooney, Calli M.; Johansen, Lisa; Varhegyi, Elizabeth; Chen, Zheng W.; Olinger, Gene G.

    2015-01-01

    ABSTRACT Filoviruses, consisting of Ebola virus (EBOV) and Marburg virus (MARV), are among the most lethal infectious threats to mankind. Infections by these viruses can cause severe hemorrhagic fevers in humans and nonhuman primates with high mortality rates. Since there is currently no vaccine or antiviral therapy approved for humans, there is an urgent need to develop prophylactic and therapeutic options for use during filoviral outbreaks and bioterrorist attacks. One of the ideal targets against filoviral infection and diseases is at the entry step, which is mediated by the filoviral glycoprotein (GP). In this report, we screened a chemical library of small molecules and identified numerous inhibitors, which are known G protein-coupled receptor (GPCR) antagonists targeting different GPCRs, including histamine receptors, 5-HT (serotonin) receptors, muscarinic acetylcholine receptor, and adrenergic receptor. These inhibitors can effectively block replication of both infectious EBOV and MARV, indicating a broad antiviral activity of the GPCR antagonists. The time-of-addition experiment and microscopic studies suggest that GPCR antagonists block filoviral entry at a step following the initial attachment but prior to viral/cell membrane fusion. These results strongly suggest that GPCRs play a critical role in filoviral entry and GPCR antagonists can be developed as an effective anti-EBOV/MARV therapy. IMPORTANCE Infection of Ebola virus and Marburg virus can cause severe illness in humans with a high mortality rate, and currently there is no FDA-approved vaccine or therapeutic treatment available. The 2013-2015 epidemic in West Africa underscores a lack of our understanding in the infection and pathogenesis of these viruses and the urgency of drug discovery and development. In this study, we have identified numerous inhibitors that are known G protein-coupled receptor (GPCR) antagonists targeting different GPCRs. These inhibitors can effectively block replication of

  12. Crystal Structure of the Marburg Virus Nucleoprotein Core Domain Chaperoned by a VP35 Peptide Reveals a Conserved Drug Target for Filovirus.

    PubMed

    Zhu, Tengfei; Song, Hao; Peng, Ruchao; Shi, Yi; Qi, Jianxun; Gao, George F

    2017-09-15

    Filovirus nucleoprotein (NP), viral protein 35 (VP35), and polymerase L are essential for viral replication and nucleocapsid formation. Here, we identify a 28-residue peptide (NP binding peptide [NPBP]) from Marburg virus (MARV) VP35 through sequence alignment with previously identified Ebola virus (EBOV) NPBP, which bound to the core region (residues 18 to 344) of the N-terminal portion of MARV NP with high affinity. The crystal structure of the MARV NP core/NPBP complex at a resolution of 2.6 Å revealed that NPBP binds to the C-terminal region of the NP core via electrostatic and nonpolar interactions. Further structural analysis revealed that the MARV and EBOV NP cores hold a conserved binding pocket for NPBP, and this pocket could serve as a promising target for the design of universal drugs against filovirus infection. In addition, cross-binding assays confirmed that the NP core of MARV or EBOV can bind the NPBP from the other virus, although with moderately reduced binding affinities that result from termini that are distinct between the MARV and EBOV NPBPs. IMPORTANCE Historically, Marburg virus (MARV) has caused severe disease with up to 90% lethality. Among the viral proteins produced by MARV, NP and VP35 are both multifunctional proteins that are essential for viral replication. In its relative, Ebola virus (EBOV), an N-terminal peptide from VP35 binds to the NP N-terminal region with high affinity. Whether this is a common mechanism among filoviruses is an unsolved question. Here, we present the crystal structure of a complex that consists of the core domain of MARV NP and the NPBP peptide from VP35. As we compared MARV NPBP with EBOV NPBP, several different features at the termini were identified. Although these differences reduce the affinity of the NP core for NPBPs across genera, a conserved pocket in the C-terminal region of the NP core makes cross-species binding possible. Our results expand our knowledge of filovirus NP-VP35 interactions and

  13. Risk Factors Associated with Ebola and Marburg Viruses Seroprevalence in Blood Donors in the Republic of Congo

    PubMed Central

    Moyen, Nanikaly; Thirion, Laurence; Emmerich, Petra; Dzia-Lepfoundzou, Amelia; Richet, Hervé; Boehmann, Yannik; Dimi, Yannick; Gallian, Pierre; Gould, Ernest A.; Günther, Stephan; de Lamballerie, Xavier

    2015-01-01

    Background Ebola and Marburg viruses (family Filoviridae, genera Ebolavirus and Marburgvirus) cause haemorrhagic fevers in humans, often associated with high mortality rates. The presence of antibodies to Ebola virus (EBOV) and Marburg virus (MARV) has been reported in some African countries in individuals without a history of haemorrhagic fever. In this study, we present a MARV and EBOV seroprevalence study conducted amongst blood donors in the Republic of Congo and the analysis of risk factors for contact with EBOV. Methodology and Findings In 2011, we conducted a MARV and EBOV seroprevalence study amongst 809 blood donors recruited in rural (75; 9.3%) and urban (734; 90.7%) areas of the Republic of Congo. Serum titres of IgG antibodies to MARV and EBOV were assessed by indirect double-immunofluorescence microscopy. MARV seroprevalence was 0.5% (4 in 809) without any identified risk factors. Prevalence of IgG to EBOV was 2.5%, peaking at 4% in rural areas and in Pointe Noire. Independent risk factors identified by multivariate analysis were contact with bats and exposure to birds. Conclusions/Significance This MARV and EBOV serological survey performed in the Republic of Congo identifies a probable role for environmental determinants of exposure to EBOV. It highlights the requirement for extending our understanding of the ecological and epidemiological risk of bats (previously identified as a potential ecological reservoir) and birds as vectors of EBOV to humans, and characterising the protection potentially afforded by EBOV-specific antibodies as detected in blood donors. PMID:26047124

  14. Amino Acid Residue at Position 79 of Marburg Virus VP40 Confers Interferon Antagonism in Mouse Cells.

    PubMed

    Feagins, Alicia R; Basler, Christopher F

    2015-10-01

    Marburg viruses (MARVs) cause highly lethal infections in humans and nonhuman primates. Mice are not generally susceptible to MARV infection; however, if the strain is first adapted to mice through serial passaging, it becomes able to cause disease in this animal. A previous study correlated changes accrued during mouse adaptation in the VP40 gene of a MARV strain known as Ravn virus (RAVV) with an increased capacity to inhibit interferon (IFN) signaling in mouse cell lines. The MARV strain Ci67, which belongs to a different phylogenetic clade than RAVV, has also been adapted to mice and in the process the Ci67 VP40 acquired a different collection of genetic changes than did RAVV VP40. Here, we demonstrate that the mouse-adapted Ci67 VP40 more potently antagonizes IFN-α/β-induced STAT1 and STAT2 tyrosine phosphorylation, gene expression, and antiviral activity in both mouse and human cell lines, compared with the parental Ci67 VP40. Ci67 VP40 is also demonstrated to target the activation of kinase Jak1. A single change at VP40 residue 79 was found to be sufficient for the increased VP40 IFN antagonism. These data argue that VP40 IFN-antagonist activity plays a key role in MARV pathogenesis in mice. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  15. Women otolaryngologist representation in specialty society membership and leadership positions.

    PubMed

    Choi, Sukgi S; Miller, Robert H

    2012-11-01

    otolaryngology leadership positions. As the number and seniority of women increase, the specialty should continue to monitor representation of women in leadership positions. Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.

  16. A bioluminescent imaging mouse model for Marburg virus based on a pseudovirus system.

    PubMed

    Zhang, Li; Li, Qianqian; Liu, Qiang; Huang, Weijin; Nie, Jianhui; Wang, Youchun

    2017-08-03

    Marburg virus (MARV) can cause lethal hemorrhagic fever in humans. Handling of MARV is restricted to high-containment biosafety level 4 (BSL-4) facilities, which greatly impedes research into this virus. In this study, a high titer of MARV pseudovirus was generated through optimization of the HIV backbone vectors, the ratio of backbone vector to MARV glycoprotein expression vector, and the transfection reagents. An in vitro neutralization assay and an in vivo bioluminescent imaging mouse model for MARV were developed based on the pseudovirus. Protective serum against MARV was successfully induced in guinea pigs, which showed high neutralization activity in vitro and could also protect Balb/c mice from MARV pseudovirus infection in vivo. This system could be a convenient tool to enable the evaluation of vaccines and therapeutic drugs against MARV in non-BSL-4 laboratories.

  17. Geographic potential of disease caused by Ebola and Marburg viruses in Africa.

    PubMed

    Peterson, A Townsend; Samy, Abdallah M

    2016-10-01

    Filoviruses represent a significant public health threat worldwide. West Africa recently experienced the largest-scale and most complex filovirus outbreak yet known, which underlines the need for a predictive understanding of the geographic distribution and potential for transmission to humans of these viruses. Here, we used ecological niche modeling techniques to understand the relationship between known filovirus occurrences and environmental characteristics. Our study derived a picture of the potential transmission geography of Ebola virus species and Marburg, paired with views of the spatial uncertainty associated with model-to-model variation in our predictions. We found that filovirus species have diverged ecologically, but only three species are sufficiently well known that models could be developed with significant predictive power. We quantified uncertainty in predictions, assessed potential for outbreaks outside of known transmission areas, and highlighted the Ethiopian Highlands and scattered areas across East Africa as additional potentially unrecognized transmission areas. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. A new construction of measurement system based on specialized microsystem design for laryngological application

    NASA Astrophysics Data System (ADS)

    Paczesny, Daniel; Mikłaszewicz, Franciszek

    2013-10-01

    This article describes the design, construction and parameters of diagnostic medical system for air humidity measurement which can be proceeded in various places of human nasal cavities and also human throat. The system can measure dynamic changes of dew point temperature (absolute value of humidity) of inspired and expired air in different places of human upper airways. During regular respiration process dew point temperature is measured in nasal cavity, middle part cavity and nasopharynx. The presented system is the next step in construction of measurement system based on specialized microsystem for laryngological application. The microsystem fabricated on silicon substrate includes microheater, microthermoresistor and interdigitated electrodes. In comparison with previously built measurement system with current version some system functionalities and measurement parameters were improved. Additionally 3D printing technology was applied for rapid prototyping a measurement system housing. Presented measurement system is set of microprocessor module with signal conditioning circuits; heated measurement head based on specialized microsystem with disposable heated pipe for air sucking from various places of upper airways; power supplier and computer application for monitoring all system parameters and presenting on-line and off-line measured results. Some example results of constructed measurement system and dew point temperature measurements during respiration cycle are presented.

  19. Dysphonia in performers: toward a clinical definition of laryngology of the performing voice.

    PubMed

    Guss, Joel; Sadoughi, Babak; Benson, Brian; Sulica, Lucian

    2014-05-01

    To identify causes of dysphonia in performers and compare causes and aspects of treatment of dysphonia in performers and nonperformers. Case-control study. A chart review of all new patients presenting with a chief complaint of dysphonia over a 1-year period was performed. The prevalence of laryngeal disorders was reviewed and differences between performers and nonperformers were analyzed. The odds ratio of the prevalence of each disorder was computed against performer status as a risk factor. Four hundred seventy-six new patients complaining of dysphonia presented over 12 months; 74 were vocal performers. The median duration of symptoms in performers was 90 days. Phonotraumatic lesions were significantly more prevalent in performers (63.5% vs. 28.6%, P < 0.001), particularly bilateral mid-fold swelling (4-fold increase in performers), pseudocysts (3-fold increase), and vocal fold hemorrhage/ectasia. Neurologic disorders (vocal fold paralysis and spasmodic dysphonia), neoplastic pathologies, and age-related phenomena (atrophy/presbyphonia) were significantly more common in nonperformers. Overall and diagnosis-specific rates of surgical intervention were equal between the two groups. Phonotraumatic injury is responsible for the majority of dysphonia in vocal performers, to a significantly greater extent than in nonperformers and requires the implementation of standard therapeutic strategies. Awareness of the specific risks and management needs of the performer is of paramount importance to the practice of laryngology of the performing voice. Copyright © 2014 The Voice Foundation. Published by Mosby, Inc. All rights reserved.

  20. Immune Response to Marburg Virus Angola Infection in Nonhuman Primates.

    PubMed

    Fernando, Lisa; Qiu, Xiangguo; Melito, P Leno; Williams, Kinola J N; Feldmann, Friederike; Feldmann, Heinz; Jones, Steven M; Alimonti, Judie B

    2015-10-01

    The 2005 outbreak of Marburg virus (MARV) infection in Angola was the most lethal MARV infection outbreak in history, with a case-fatality rate (90%) similar to that for Zaire ebolavirus (EBOV) infection. However, very little is known about the pathogenicity of MARV Angola, as few studies have been conducted to date. Therefore, the immune response was examined in MARV Angola-infected nonhuman primates. Cynomolgus macaques were infected with MARV Angola and monitored for survival. The effect of MARV Angola on the immune system was examined by immunophenotyping whole-blood and by analyzing cytokine and chemokine levels in plasma and spleen specimens, using flow cytometry. The prominent clinical findings were rapid onset of disease and death (mean time after infection, 6.7 days), fever, depression, anorexia, petechial rash, and lymphopenia. Specifically, T, B, and natural killer cells were severely depleted in the blood by day 6. The typical cytokine storm was present, with levels of interferon γ, tumor necrosis factor, interleukin 6, and CCL2 rising in the blood early during infection. MARV Angola displayed the same virulence and disease pathology as EBOV. MARV Angola appears to cause a more rapid onset and severe outcome of infection than other MARV strains. © Crown copyright 2015.

  1. Differential Regulation of Interferon Responses by Ebola and Marburg Virus VP35 Proteins

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Edwards, Megan R.; Liu, Gai; Mire, Chad E.

    2016-02-11

    Suppression of innate immune responses during filoviral infection contributes to disease severity. Ebola (EBOV) and Marburg (MARV) viruses each encode a VP35 protein that suppresses RIG-I-like receptor signaling and interferon-α/β (IFN-α/β) production by several mechanisms, including direct binding to double stranded RNA (dsRNA). Here, we demonstrate that in cell culture, MARV infection results in a greater upregulation of IFN responses as compared to EBOV infection. This correlates with differences in the efficiencies by which EBOV and MARV VP35s antagonize RIG-I signaling. Furthermore, structural and biochemical studies suggest that differential recognition of RNA elements by the respective VP35 C-terminal IFN inhibitorymore » domain (IID) rather than affinity for RNA by the respective VP35s is critical for this observation. Our studies reveal functional differences in EBOV versus MARV VP35 RNA binding that result in unexpected differences in the host response to deadly viral pathogens.« less

  2. Ebola Virus and Marburg Virus in Human Milk Are Inactivated by Holder Pasteurization.

    PubMed

    Hamilton Spence, Erin; Huff, Monica; Shattuck, Karen; Vickers, Amy; Yun, Nadezda; Paessler, Slobodan

    2017-05-01

    Potential donors of human milk are screened for Ebola virus (EBOV) using standard questions, but testing for EBOV and Marburg virus (MARV) is not part of routine serological testing performed by milk banks. Research aim: This study tested the hypothesis that EBOV would be inactivated in donor human milk (DHM) by standard pasteurization techniques (Holder) used in all North American nonprofit milk banks. Milk samples were obtained from a nonprofit milk bank. They were inoculated with EBOV (Zaire strain) and MARV (Angola strain) and processed by standard Holder pasteurization technique. Plaque assays for EBOV and MARV were performed to detect the presence of virus after pasteurization. Neither EBOV nor MARV was detectable by viral plaque assay in DHM or culture media samples, which were pasteurized by the Holder process. EBOV and MARV are safely inactivated in human milk by standard Holder pasteurization technique. Screening for EBOV or MARV beyond questionnaire and self-deferral is not needed to ensure safety of DHM for high-risk infants.

  3. Ecological Niche Modeling for Filoviruses: A Risk Map for Ebola and Marburg Virus Disease Outbreaks in Uganda.

    PubMed

    Nyakarahuka, Luke; Ayebare, Samuel; Mosomtai, Gladys; Kankya, Clovice; Lutwama, Julius; Mwiine, Frank Norbert; Skjerve, Eystein

    2017-09-05

    Uganda has reported eight outbreaks caused by filoviruses between 2000 to 2016, more than any other country in the world. We used species distribution modeling to predict where filovirus outbreaks are likely to occur in Uganda to help in epidemic preparedness and surveillance. The MaxEnt software, a machine learning modeling approach that uses presence-only data was used to establish filovirus - environmental relationships. Presence-only data for filovirus outbreaks were collected from the field and online sources. Environmental covariates from Africlim that have been downscaled to a nominal resolution of 1km x 1km were used. The final model gave the relative probability of the presence of filoviruses in the study area obtained from an average of 100 bootstrap runs. Model evaluation was carried out using Receiver Operating Characteristic (ROC) plots. Maps were created using ArcGIS 10.3 mapping software. We showed that bats as potential reservoirs of filoviruses are distributed all over Uganda. Potential outbreak areas for Ebola and Marburg virus disease were predicted in West, Southwest and Central parts of Uganda, which corresponds to bat distribution and previous filovirus outbreaks areas. Additionally, the models predicted the Eastern Uganda region and other areas that have not reported outbreaks before to be potential outbreak hotspots. Rainfall variables were the most important in influencing model prediction compared to temperature variables. Despite the limitations in the prediction model due to lack of adequate sample records for outbreaks, especially for the Marburg cases, the models provided risk maps to the Uganda surveillance system on filovirus outbreaks. The risk maps will aid in identifying areas to focus the filovirus surveillance for early detection and responses hence curtailing a pandemic. The results from this study also confirm previous findings that suggest that filoviruses are mainly limited by the amount of rainfall received in an area.

  4. Ecological Niche Modeling for Filoviruses: A Risk Map for Ebola and Marburg Virus Disease Outbreaks in Uganda

    PubMed Central

    Nyakarahuka, Luke; Ayebare, Samuel; Mosomtai, Gladys; Kankya, Clovice; Lutwama, Julius; Mwiine, Frank Norbert; Skjerve, Eystein

    2017-01-01

    Introduction: Uganda has reported eight outbreaks caused by filoviruses between 2000 to 2016, more than any other country in the world. We used species distribution modeling to predict where filovirus outbreaks are likely to occur in Uganda to help in epidemic preparedness and surveillance. Methods: The MaxEnt software, a machine learning modeling approach that uses presence-only data was used to establish filovirus – environmental relationships. Presence-only data for filovirus outbreaks were collected from the field and online sources. Environmental covariates from Africlim that have been downscaled to a nominal resolution of 1km x 1km were used. The final model gave the relative probability of the presence of filoviruses in the study area obtained from an average of 100 bootstrap runs. Model evaluation was carried out using Receiver Operating Characteristic (ROC) plots. Maps were created using ArcGIS 10.3 mapping software. Results: We showed that bats as potential reservoirs of filoviruses are distributed all over Uganda. Potential outbreak areas for Ebola and Marburg virus disease were predicted in West, Southwest and Central parts of Uganda, which corresponds to bat distribution and previous filovirus outbreaks areas. Additionally, the models predicted the Eastern Uganda region and other areas that have not reported outbreaks before to be potential outbreak hotspots. Rainfall variables were the most important in influencing model prediction compared to temperature variables. Conclusions: Despite the limitations in the prediction model due to lack of adequate sample records for outbreaks, especially for the Marburg cases, the models provided risk maps to the Uganda surveillance system on filovirus outbreaks. The risk maps will aid in identifying areas to focus the filovirus surveillance for early detection and responses hence curtailing a pandemic. The results from this study also confirm previous findings that suggest that filoviruses are mainly limited by

  5. Physicochemical inactivation of Lassa, Ebola, and Marburg viruses and effect on clinical laboratory analyses

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Mitchell, S.W.; McCormick, J.B.

    1984-09-01

    Clinical specimens from patients infected with Lassa, Ebola, or Marburg virus may present a serious biohazard to laboratory workers. The authors have examined the effects of heat, alteration of pH, and gamma radiation on these viruses in human blood and on the electrolytes, enzymes, and coagulation factors measured in laboratory tests that are important in the care of an infected patient. Heating serum at 60 degrees C for 1 h reduced high titers of these viruses to noninfectious levels without altering the serum levels of glucose, blood urea nitrogen, and electrolytes. Dilution of blood in 3% acetic acid, diluent formore » a leukocyte count, inactivated all of these viruses. All of the methods tested for viral inactivation markedly altered certain serum proteins, making these methods unsuitable for samples that are to be tested for certain enzyme levels and coagulation factors.« less

  6. Animal models for Ebola and Marburg virus infections

    PubMed Central

    Nakayama, Eri; Saijo, Masayuki

    2013-01-01

    Ebola and Marburg hemorrhagic fevers (EHF and MHF) are caused by the Filoviridae family, Ebolavirus and Marburgvirus (ebolavirus and marburgvirus), respectively. These severe diseases have high mortality rates in humans. Although EHF and MHF are endemic to sub-Saharan Africa. A novel filovirus, Lloviu virus, which is genetically distinct from ebolavirus and marburgvirus, was recently discovered in Spain where filoviral hemorrhagic fever had never been reported. The virulence of this virus has not been determined. Ebolavirus and marburgvirus are classified as biosafety level-4 (BSL-4) pathogens and Category A agents, for which the US government requires preparedness in case of bioterrorism. Therefore, preventive measures against these viral hemorrhagic fevers should be prepared, not only in disease-endemic regions, but also in disease-free countries. Diagnostics, vaccines, and therapeutics need to be developed, and therefore the establishment of animal models for EHF and MHF is invaluable. Several animal models have been developed for EHF and MHF using non-human primates (NHPs) and rodents, which are crucial to understand pathophysiology and to develop diagnostics, vaccines, and therapeutics. Rhesus and cynomolgus macaques are representative models of filovirus infection as they exhibit remarkably similar symptoms to those observed in humans. However, the NHP models have practical and ethical problems that limit their experimental use. Furthermore, there are no inbred and genetically manipulated strains of NHP. Rodent models such as mouse, guinea pig, and hamster, have also been developed. However, these rodent models require adaptation of the virus to produce lethal disease and do not mirror all symptoms of human filovirus infection. This review article provides an outline of the clinical features of EHF and MHF in animals, including humans, and discusses how the animal models have been developed to study pathophysiology, vaccines, and therapeutics. PMID:24046765

  7. Animal models for Ebola and Marburg virus infections.

    PubMed

    Nakayama, Eri; Saijo, Masayuki

    2013-09-05

    Ebola and Marburg hemorrhagic fevers (EHF and MHF) are caused by the Filoviridae family, Ebolavirus and Marburgvirus (ebolavirus and marburgvirus), respectively. These severe diseases have high mortality rates in humans. Although EHF and MHF are endemic to sub-Saharan Africa. A novel filovirus, Lloviu virus, which is genetically distinct from ebolavirus and marburgvirus, was recently discovered in Spain where filoviral hemorrhagic fever had never been reported. The virulence of this virus has not been determined. Ebolavirus and marburgvirus are classified as biosafety level-4 (BSL-4) pathogens and Category A agents, for which the US government requires preparedness in case of bioterrorism. Therefore, preventive measures against these viral hemorrhagic fevers should be prepared, not only in disease-endemic regions, but also in disease-free countries. Diagnostics, vaccines, and therapeutics need to be developed, and therefore the establishment of animal models for EHF and MHF is invaluable. Several animal models have been developed for EHF and MHF using non-human primates (NHPs) and rodents, which are crucial to understand pathophysiology and to develop diagnostics, vaccines, and therapeutics. Rhesus and cynomolgus macaques are representative models of filovirus infection as they exhibit remarkably similar symptoms to those observed in humans. However, the NHP models have practical and ethical problems that limit their experimental use. Furthermore, there are no inbred and genetically manipulated strains of NHP. Rodent models such as mouse, guinea pig, and hamster, have also been developed. However, these rodent models require adaptation of the virus to produce lethal disease and do not mirror all symptoms of human filovirus infection. This review article provides an outline of the clinical features of EHF and MHF in animals, including humans, and discusses how the animal models have been developed to study pathophysiology, vaccines, and therapeutics.

  8. A multiagent filovirus DNA vaccine delivered by intramuscular electroporation completely protects mice from ebola and Marburg virus challenge.

    PubMed

    Grant-Klein, Rebecca J; Van Deusen, Nicole M; Badger, Catherine V; Hannaman, Drew; Dupuy, Lesley C; Schmaljohn, Connie S

    2012-11-01

    We evaluated the immunogenicity and protective efficacy of DNA vaccines expressing the codon-optimized envelope glycoprotein genes of Zaire ebolavirus, Sudan ebolavirus, and Marburg marburgvirus (Musoke and Ravn). Intramuscular or intradermal delivery of the vaccines in BALB/c mice was performed using the TriGrid™ electroporation device. Mice that received DNA vaccines against the individual viruses developed robust glycoprotein-specific antibody titers as determined by ELISA and survived lethal viral challenge with no display of clinical signs of infection. Survival curve analysis revealed there was a statistically significant increase in survival compared to the control groups for both the Ebola and Ravn virus challenges. These data suggest that further analysis of the immune responses generated in the mice and additional protection studies in nonhuman primates are warranted.

  9. Interferon-β therapy prolongs survival in rhesus macaque models of Ebola and Marburg hemorrhagic fever.

    PubMed

    Smith, Lauren M; Hensley, Lisa E; Geisbert, Thomas W; Johnson, Joshua; Stossel, Andrea; Honko, Anna; Yen, Judy Y; Geisbert, Joan; Paragas, Jason; Fritz, Elizabeth; Olinger, Gene; Young, Howard A; Rubins, Kathleen H; Karp, Christopher L

    2013-07-15

    There is a clear need for novel, effective therapeutic approaches to hemorrhagic fever due to filoviruses. Ebola virus hemorrhagic fever is associated with robust interferon (IFN)-α production, with plasma concentrations of IFN-α that greatly (60- to 100-fold) exceed those seen in other viral infections, but little IFN-β production. While all of the type I IFNs signal through the same receptor complex, both quantitative and qualitative differences in biological activity are observed after stimulation of the receptor complex with different type I IFNs. Taken together, this suggested potential for IFN-β therapy in filovirus infection. Here we show that early postexposure treatment with IFN-β significantly increased survival time of rhesus macaques infected with a lethal dose of Ebola virus, although it failed to alter mortality. Early treatment with IFN-β also significantly increased survival time after Marburg virus infection. IFN-β may have promise as an adjunctive postexposure therapy in filovirus infection.

  10. A re-appraisal of publication rates of scientific papers presented at the Otorhinolaryngology Research Society meetings.

    PubMed

    Lau, A S; Krishnan, M; Williams, S P; Mamais, C; Sweed, A; Bhat, J; Somashekar, S; Leong, S C

    2016-12-01

    To review the rate of publication of papers in peer-reviewed journals after oral presentations at the Otorhinolaryngology Research Society meetings between 1996 and 2013 and to compare trends with the previous review (1979-1995). Literature review. Merseyside ENT Research Collaborative. The abstracts of presentations at Otorhinolaryngology Research Society meetings are published in Clinical Otolaryngology. A structured search of PubMed was undertaken to identify published Otorhinolaryngology Research Society presentations. Publication rates. A total of 460 abstracts were identified. The interobserver reliability among reviewers was 98%. Of the total, 259 (56.3%) abstracts were published in peer-reviewed journals. The average time from Otorhinolaryngology Research Society presentation to publication was 27.7 months (median 23), which was not significantly different from the previous review. Publication by subspeciality was as follows: head and neck (45.6%), otology (30.5%), rhinology (22%) and others (1.9%). Most published Otorhinolaryngology Research Society presentations were published in Clinical Otolaryngology (22.4%), followed by the Journal of Laryngology and Otology (8.1%) and the Laryngoscope (7.3%). Clinical research was the most common category of abstracts being presented at Otorhinolaryngology Research Society meetings, followed by laboratory-based research. Over half (56.5%) of laboratory research presented were head and neck themed, while otology and rhinology predominated clinical research presentations. Over half (52.1%) of Otorhinolaryngology Research Society abstracts originated from units in the North of England. Bristol presented the most abstracts (30.1%), followed by Newcastle (25.1%). The publication rate of Otorhinolaryngology Research Society presentations remains high and many are subsequently published in high-impact factor otolaryngology journals. More Otorhinolaryngology Research Society presentations are now published in American and

  11. The Use of a Mobile Laboratory Unit in Support of Patient Management and Epidemiological Surveillance during the 2005 Marburg Outbreak in Angola

    PubMed Central

    Grolla, Allen; Jones, Steven M.; Fernando, Lisa; Strong, James E.; Ströher, Ute; Möller, Peggy; Paweska, Janusz T.; Burt, Felicity; Pablo Palma, Pedro; Sprecher, Armand; Formenty, Pierre; Roth, Cathy; Feldmann, Heinz

    2011-01-01

    Background Marburg virus (MARV), a zoonotic pathogen causing severe hemorrhagic fever in man, has emerged in Angola resulting in the largest outbreak of Marburg hemorrhagic fever (MHF) with the highest case fatality rate to date. Methodology/Principal Findings A mobile laboratory unit (MLU) was deployed as part of the World Health Organization outbreak response. Utilizing quantitative real-time PCR assays, this laboratory provided specific MARV diagnostics in Uige, the epicentre of the outbreak. The MLU operated over a period of 88 days and tested 620 specimens from 388 individuals. Specimens included mainly oral swabs and EDTA blood. Following establishing on site, the MLU operation allowed a diagnostic response in <4 hours from sample receiving. Most cases were found among females in the child-bearing age and in children less than five years of age. The outbreak had a high number of paediatric cases and breastfeeding may have been a factor in MARV transmission as indicated by the epidemiology and MARV positive breast milk specimens. Oral swabs were a useful alternative specimen source to whole blood/serum allowing testing of patients in circumstances of resistance to invasive procedures but limited diagnostic testing to molecular approaches. There was a high concordance in test results between the MLU and the reference laboratory in Luanda operated by the US Centers for Disease Control and Prevention. Conclusions/Significance The MLU was an important outbreak response asset providing support in patient management and epidemiological surveillance. Field laboratory capacity should be expanded and made an essential part of any future outbreak investigation. PMID:21629730

  12. Development and characterization of a guinea pig model for Marburg virus.

    PubMed

    Wong, Gary; Cao, Wen-Guang; He, Shi-Hua; Zhang, Zi-Rui; Zhu, Wen-Jun; Moffat, Estella; Ebihara, Hideki; Embury-Hyatt, Carissa; Qiu, Xiang-Guo

    2018-01-18

    The Angolan strain of Marburg virus (MARV/Ang) can cause lethal disease in humans with a case fatality rate of up to 90%, but infection of immunocompetent rodents do not result in any observable symptoms. Our previous work includes the development and characterization of a MARV/Ang variant that can cause lethal disease in mice (MARV/Ang-MA), with the aim of using this tool to screen for promising prophylactic and therapeutic candidates. An intermediate animal model is needed to confirm any findings from mice studies before testing in the gold-standard non-human primate (NHP) model. In this study, we serially passaged the clinical isolate of MARV/Ang in the livers and spleens of guinea pigs until a variant emerged that causes 100% lethality in guinea pigs (MARV/Ang-GA). Animals infected with MARV/Ang-GA showed signs of filovirus infection including lymphocytopenia, thrombocytopenia, and high viremia leading to spread to major organs, including the liver, spleen, lungs, and kidneys. The MARV/Ang-GA guinea pigs died between 7-9 days after infection, and the LD 50 was calculated to be 1.1×10 -1 TCID 50 (median tissue culture infective dose). Mutations in MARV/Ang-GA were identified and compared to sequences of known rodent-adapted MARV/Ang variants, which may benefit future studies characterizing important host adaptation sites in the MARV/Ang viral genome.

  13. Complex adenovirus-vectored vaccine protects guinea pigs from three strains of Marburg virus challenges.

    PubMed

    Wang, Danher; Hevey, Michael; Juompan, Laure Y; Trubey, Charles M; Raja, Nicholas U; Deitz, Stephen B; Woraratanadharm, Jan; Luo, Min; Yu, Hong; Swain, Benjamin M; Moore, Kevin M; Dong, John Y

    2006-09-30

    The Marburg virus (MARV), an African filovirus closely related to the Ebola virus, causes a deadly hemorrhagic fever in humans, with up to 90% mortality. Currently, treatment of disease is only supportive, and no vaccines are available to prevent spread of MARV infections. In order to address this need, we have developed and characterized a novel recombinant vaccine that utilizes a single complex adenovirus-vectored vaccine (cAdVax) to overexpress a MARV glycoprotein (GP) fusion protein derived from the Musoke and Ci67 strains of MARV. Vaccination with the cAdVaxM(fus) vaccine led to efficient production of MARV-specific antibodies in both mice and guinea pigs. Significantly, guinea pigs vaccinated with at least 5 x 10(7) pfu of cAdVaxM(fus) vaccine were 100% protected against lethal challenges by the Musoke, Ci67 and Ravn strains of MARV, making it a vaccine with trivalent protective efficacy. Therefore, the cAdVaxM(fus) vaccine serves as a promising vaccine candidate to prevent and contain multi-strain infections by MARV.

  14. Marburg virus survivor immune responses are Th1 skewed with limited neutralizing antibody responses.

    PubMed

    Stonier, Spencer W; Herbert, Andrew S; Kuehne, Ana I; Sobarzo, Ariel; Habibulin, Polina; Dahan, Chen V Abramovitch; James, Rebekah M; Egesa, Moses; Cose, Stephen; Lutwama, Julius Julian; Lobel, Leslie; Dye, John M

    2017-09-04

    Until recently, immune responses in filovirus survivors remained poorly understood. Early studies revealed IgM and IgG responses to infection with various filoviruses, but recent outbreaks have greatly expanded our understanding of filovirus immune responses. Immune responses in survivors of Ebola virus (EBOV) and Sudan virus (SUDV) infections have provided the most insight, with T cell responses as well as detailed antibody responses having been characterized. Immune responses to Marburg virus (MARV), however, remain almost entirely uncharacterized. We report that immune responses in MARV survivors share characteristics with EBOV and SUDV infections but have some distinct differences. MARV survivors developed multivariate CD4 + T cell responses but limited CD8 + T cell responses, more in keeping with SUDV survivors than EBOV survivors. In stark contrast to SUDV survivors, rare neutralizing antibody responses in MARV survivors diminished rapidly after the outbreak. These results warrant serious consideration for any vaccine or therapeutic that seeks to be broadly protective, as different filoviruses may require different immune responses to achieve immunity. © 2017 Stonier et al.

  15. Complex adenovirus-vectored vaccine protects guinea pigs from three strains of Marburg virus challenges

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wang Danher; Hevey, Michael; Juompan, Laure Y.

    2006-09-30

    The Marburg virus (MARV), an African filovirus closely related to the Ebola virus, causes a deadly hemorrhagic fever in humans, with up to 90% mortality. Currently, treatment of disease is only supportive, and no vaccines are available to prevent spread of MARV infections. In order to address this need, we have developed and characterized a novel recombinant vaccine that utilizes a single complex adenovirus-vectored vaccine (cAdVax) to overexpress a MARV glycoprotein (GP) fusion protein derived from the Musoke and Ci67 strains of MARV. Vaccination with the cAdVaxM(fus) vaccine led to efficient production of MARV-specific antibodies in both mice and guineamore » pigs. Significantly, guinea pigs vaccinated with at least 5 x 10{sup 7} pfu of cAdVaxM(fus) vaccine were 100% protected against lethal challenges by the Musoke, Ci67 and Ravn strains of MARV, making it a vaccine with trivalent protective efficacy. Therefore, the cAdVaxM(fus) vaccine serves as a promising vaccine candidate to prevent and contain multi-strain infections by MARV.« less

  16. Biophysical characterization and conformational stability of Ebola and Marburg virus-like particles.

    PubMed

    Hu, Lei; Trefethen, Jared M; Zeng, Yuhong; Yee, Luisa; Ohtake, Satoshi; Lechuga-Ballesteros, David; Warfield, Kelly L; Aman, M Javad; Shulenin, Sergey; Unfer, Robert; Enterlein, Sven G; Truong-Le, Vu; Volkin, David B; Joshi, Sangeeta B; Middaugh, C Russell

    2011-12-01

    The filoviruses, Ebola virus and Marburg virus, cause severe hemorrhagic fever with up to 90% human mortality. Virus-like particles of EBOV (eVLPs) and MARV (mVLPs) are attractive vaccine candidates. For the development of stable vaccines, the conformational stability of these two enveloped VLPs produced in insect cells was characterized by various spectroscopic techniques over a wide pH and temperature range. Temperature-induced aggregation of the VLPs at various pH values was monitored by light scattering. Temperature/pH empirical phase diagrams (EPDs) of the two VLPs were constructed to summarize the large volume of data generated. The EPDs show that both VLPs lose their conformational integrity above about 50°C-60°C, depending on solution pH. The VLPs were maximally thermal stable in solution at pH 7-8, with a significant reduction in stability at pH 5 and 6. They were much less stable in solution at pH 3-4 due to increased susceptibility of the VLPs to aggregation. The characterization data and conformational stability profiles from these studies provide a basis for selection of optimized solution conditions for further vaccine formulation and long-term stability studies of eVLPs and mVLPs. Copyright © 2011 Wiley-Liss, Inc.

  17. The glycoproteins of Marburg and Ebola virus and their potential roles in pathogenesis.

    PubMed

    Feldmann, H; Volchkov, V E; Volchkova, V A; Klenk, H D

    1999-01-01

    Filoviruses cause systemic infections that can lead to severe hemorrhagic fever in human and non-human primates. The primary target of the virus appears to be the mononuclear phagocytic system. As the virus spreads through the organism, the spectrum of target cells increases to include endothelial cells, fibroblasts, hepatocytes, and many other cells. There is evidence that the filovirus glycoprotein plays an important role in cell tropism, spread of infection, and pathogenicity. Biosynthesis of the glycoprotein forming the spikes on the virion surface involves cleavage by the host cell protease furin into two disulfide linked subunits GP1 and GP2. GP1 is also shed in soluble form from infected cells. Different strains of Ebola virus show variations in the cleavability of the glycoprotein, that may account for differences in pathogenicity, as has been observed with influenza viruses and paramyxoviruses. Expression of the spike glycoprotein of Ebola virus, but not of Marburg virus, requires transcriptional editing. Unedited GP mRNA yields the nonstructural glycoprotein sGP, which is secreted extensively from infected cells. Whether the soluble glycoproteins GP1 and sGP interfere with the humoral immune response and other defense mechanisms remains to be determined.

  18. Egyptian rousette bats maintain long-term protective immunity against Marburg virus infection despite diminished antibody levels.

    PubMed

    Schuh, Amy J; Amman, Brian R; Sealy, Tara K; Spengler, Jessica R; Nichol, Stuart T; Towner, Jonathan S

    2017-08-18

    Although bats are natural reservoir hosts for numerous zoonotic viruses, little is known about the long-term dynamics of the host immune response following infection and how these viruses are maintained in nature. The Egyptian rousette bat (ERB) is a known reservoir host for Marburg virus (MARV). Following infection of ERBs with MARV, virus-specific IgG antibodies are induced but rapidly wane and by 3 months post-infection the bats are seronegative. To determine whether reinfection of ERBs plays a role in MARV maintenance, we challenge groups of ERBs that were "naturally" or experimentally infected with MARV 17-24 months prior. No bats in either group exhibit evidence of MARV replication or shedding and all bats develop virus-specific secondary immune responses. This study demonstrates that infection of ERBs with MARV induces long-term protective immunity against reinfection and indicates that other factors, such as host population dynamics, drive MARV maintenance in nature.

  19. An active site mutation increases the polymerase activity of the guinea pig-lethal Marburg virus.

    PubMed

    Koehler, Alexander; Kolesnikova, Larissa; Becker, Stephan

    2016-10-01

    Marburg virus (MARV) causes severe, often fatal, disease in humans and transient illness in rodents. Sequential passaging of MARV in guinea pigs resulted in selection of a lethal virus containing 4 aa changes. A D184N mutation in VP40 (VP40D184N), which leads to a species-specific gain of viral fitness, and three mutations in the active site of viral RNA-dependent RNA polymerase L, which were investigated in the present study for functional significance in human and guinea pig cells. The transcription/replication activity of L mutants was strongly enhanced by a substitution at position 741 (S741C), and inhibited by other substitutions (D758A and A759D) in both species. The polymerase activity of L carrying the S741C substitution was eightfold higher in guinea pig cells than in human cells upon co-expression with VP40D184N, suggesting that the additive effect of the two mutations provides MARV a replicative advantage in the new host.

  20. Genetic and physiological characterization of the purine salvage pathway in the archaebacterium Methanobacterium thermoautotrophicum Marburg.

    PubMed Central

    Worrell, V E; Nagle, D P

    1990-01-01

    The enzymes involved in the purine interconversion pathway of wild-type and purine analog-resistant strains of Methanobacterium thermoautotrophicum Marburg were assayed by radiometric and spectrophotometric methods. Wild-type cells incorporated labeled adenine, guanine, and hypoxanthine, whereas mutant strains varied in their ability to incorporate these bases. Adenine, guanine, hypoxanthine, and xanthine were activated by phosphoribosyltransferase activities present in wild-type cell extracts. Some mutant strains simultaneously lost the ability to convert both guanine and hypoxanthine to the respective nucleotide, suggesting that the same enzyme activates both bases. Adenosine, guanosine, and inosine phosphorylase activities were detected for the conversion of base to nucleoside. Adenine deaminase activity was detected at low levels. Guanine deaminase activity was not detected. Nucleoside kinase activities for the conversion of adenosine, guanosine, and inosine to the respective nucleotides were detected by a new assay. The nucleotide-interconverting enzymes AMP deaminase, succinyl-AMP synthetase, succinyl-AMP lyase, IMP dehydrogenase, and GMP synthetase were present in extracts; GMP reductase was not detected. The results indicate that this autotrophic methanogen has a complex system for the utilization of exogenous purines. PMID:2345148

  1. Three of the Four Nucleocapsid Proteins of Marburg Virus, NP, VP35, and L, Are Sufficient To Mediate Replication and Transcription of Marburg Virus-Specific Monocistronic Minigenomes

    PubMed Central

    Mühlberger, Elke; Lötfering, Beate; Klenk, Hans-Dieter; Becker, Stephan

    1998-01-01

    This paper describes the first reconstituted replication system established for a member of the Filoviridae, Marburg virus (MBGV). MBGV minigenomes containing the leader and trailer regions of the MBGV genome and the chloramphenicol acetyltransferase (CAT) gene were constructed. In MBGV-infected cells, these minigenomes were replicated and encapsidated and could be passaged. Unlike most other members of the order Mononegavirales, filoviruses possess four proteins presumed to be components of the nucleocapsid (NP, VP35, VP30, and L). To determine the protein requirements for replication and transcription, a reverse genetic system was established for MBGV based on the vaccinia virus T7 expression system. Northern blot analysis of viral RNA revealed that three nucleocapsid proteins (NP, VP35, and L) were essential and sufficient for transcription as well as replication and encapsidation. These data indicate that VP35, rather than VP30, is the functional homologue of rhabdo- and paramyxovirus P proteins. The reconstituted replication system was profoundly affected by the NP-to-VP35 expression ratio. To investigate whether CAT gene expression was achieved entirely by mRNA or in part by full-length plus-strand minigenomes, a copy-back minireplicon containing the CAT gene but lacking MBGV-specific transcriptional start sites was employed in the artificial replication system. This construct was replicated without accompanying CAT activity. It was concluded that the CAT activity reflected MBGV-specific transcription and not replication. PMID:9765419

  2. Durability of a vesicular stomatitis virus-based marburg virus vaccine in nonhuman primates.

    PubMed

    Mire, Chad E; Geisbert, Joan B; Agans, Krystle N; Satterfield, Benjamin A; Versteeg, Krista M; Fritz, Elizabeth A; Feldmann, Heinz; Hensley, Lisa E; Geisbert, Thomas W

    2014-01-01

    The filoviruses, Marburg virus (MARV) and Ebola virus, causes severe hemorrhagic fever with high mortality in humans and nonhuman primates. A promising filovirus vaccine under development is based on a recombinant vesicular stomatitis virus (rVSV) that expresses individual filovirus glycoproteins (GPs) in place of the VSV glycoprotein (G). These vaccines have shown 100% efficacy against filovirus infection in nonhuman primates when challenge occurs 28-35 days after a single injection immunization. Here, we examined the ability of a rVSV MARV-GP vaccine to provide protection when challenge occurs more than a year after vaccination. Cynomolgus macaques were immunized with rVSV-MARV-GP and challenged with MARV approximately 14 months after vaccination. Immunization resulted in the vaccine cohort of six animals having anti-MARV GP IgG throughout the pre-challenge period. Following MARV challenge none of the vaccinated animals showed any signs of clinical disease or viremia and all were completely protected from MARV infection. Two unvaccinated control animals exhibited signs consistent with MARV infection and both succumbed. Importantly, these data are the first to show 100% protective efficacy against any high dose filovirus challenge beyond 8 weeks after final vaccination. These findings demonstrate the durability of VSV-based filovirus vaccines.

  3. Protection against lethal Marburg virus infection mediated by lipid encapsulated small interfering RNA.

    PubMed

    Ursic-Bedoya, Raul; Mire, Chad E; Robbins, Marjorie; Geisbert, Joan B; Judge, Adam; MacLachlan, Ian; Geisbert, Thomas W

    2014-02-15

    Marburg virus (MARV) infection causes severe morbidity and mortality in humans and nonhuman primates. Currently, there are no licensed therapeutics available for treating MARV infection. Here, we present the in vitro development and in vivo evaluation of lipid-encapsulated small interfering RNA (siRNA) as a potential therapeutic for the treatment of MARV infection. The activity of anti-MARV siRNAs was assessed using dual luciferase reporter assays followed by in vitro testing against live virus. Lead candidates were tested in lethal guinea pig models of 3 different MARV strains (Angola, Ci67, Ravn). Treatment resulted in 60%-100% survival of guinea pigs infected with MARV. Although treatment with siRNA targeting other MARV messenger RNA (mRNA) had a beneficial effect, targeting the MARV NP mRNA resulted in the highest survival rates. NP-718m siRNA in lipid nanoparticles provided 100% protection against MARV strains Angola and Ci67, and 60% against Ravn. A cocktail containing NP-718m and NP-143m provided 100% protection against MARV Ravn. These data show protective efficacy against the most pathogenic Angola strain of MARV. Further development of the lipid nanoparticle technology has the potential to yield effective treatments for MARV infection.

  4. Protection Against Lethal Marburg Virus Infection Mediated by Lipid Encapsulated Small Interfering RNA

    PubMed Central

    Ursic-Bedoya, Raul; Mire, Chad E.; Robbins, Marjorie; Geisbert, Joan B.; Judge, Adam; MacLachlan, Ian; Geisbert, Thomas W.

    2014-01-01

    Background. Marburg virus (MARV) infection causes severe morbidity and mortality in humans and nonhuman primates. Currently, there are no licensed therapeutics available for treating MARV infection. Here, we present the in vitro development and in vivo evaluation of lipid-encapsulated small interfering RNA (siRNA) as a potential therapeutic for the treatment of MARV infection. Methods. The activity of anti-MARV siRNAs was assessed using dual luciferase reporter assays followed by in vitro testing against live virus. Lead candidates were tested in lethal guinea pig models of 3 different MARV strains (Angola, Ci67, Ravn). Results. Treatment resulted in 60%–100% survival of guinea pigs infected with MARV. Although treatment with siRNA targeting other MARV messenger RNA (mRNA) had a beneficial effect, targeting the MARV NP mRNA resulted in the highest survival rates. NP-718m siRNA in lipid nanoparticles provided 100% protection against MARV strains Angola and Ci67, and 60% against Ravn. A cocktail containing NP-718m and NP-143m provided 100% protection against MARV Ravn. Conclusions. These data show protective efficacy against the most pathogenic Angola strain of MARV. Further development of the lipid nanoparticle technology has the potential to yield effective treatments for MARV infection. PMID:23990568

  5. Interaction of Tsg101 with Marburg Virus VP40 Depends on the PPPY Motif, but Not the PT/SAP Motif as in the Case of Ebola Virus, and Tsg101 Plays a Critical Role in the Budding of Marburg Virus-Like Particles Induced by VP40, NP, and GP▿

    PubMed Central

    Urata, Shuzo; Noda, Takeshi; Kawaoka, Yoshihiro; Morikawa, Shigeru; Yokosawa, Hideyoshi; Yasuda, Jiro

    2007-01-01

    Marburg virus (MARV) VP40 is a matrix protein that can be released from mammalian cells in the form of virus-like particles (VLPs) and contains the PPPY sequence, which is an L-domain motif. Here, we demonstrate that the PPPY motif is important for VP40-induced VLP budding and that VLP production is significantly enhanced by coexpression of NP and GP. We show that Tsg101 interacts with VP40 depending on the presence of the PPPY motif, but not the PT/SAP motif as in the case of Ebola virus, and plays an important role in VLP budding. These findings provide new insights into the mechanism of MARV budding. PMID:17301151

  6. [A paradigm change in German academic medicine. Merger and privatization as exemplified with the university hospitals in Marburg and Giessen].

    PubMed

    Maisch, Bernhard

    2005-03-01

    1. The intended fusion of the university hospitals Marburg and Giessen in the state of Hessia is "a marriage under pressure with uncalculated risk" (Spiegel 2005). In the present political and financial situation it hardly appears to be avoidable. From the point of the view of the faculty of medicine in Marburg it is difficult to understand, that the profits of this well guided university hospital with a positive yearly budget should go to the neighboring university hospital which still had a fair amount of deficit spending in the last years.2. Both medical faculties suffer from a very low budget from the state of Hessia for research and teaching. Giessen much more than Marburg, have a substantial need for investments in buildings and infrastructure. Both institutions have a similar need for investments in costly medical apparatuses. This is a problem, which many university hospitals face nowadays.3. The intended privatisation of one or both university hospitals will need sound answers to several fundamental questions and problems:a) A privatisation potentially endangers the freedom of research and teaching garanteed by the German constitution. A private company will undoubtedly influence by active or missing additional support the direction of research in the respective academic institution. An example is the priorisation of clinical in contrast to basic research.b) With the privatisation practical absurdities in the separation of research and teaching on one side and hospital care on the other will become obvious with respect to the status of the academic employees, the obligatory taxation (16%) when a transfer of labor from one institution to the other is taken into account. The use of rooms for seminars, lectures and bedside with a double function for both teaching, research and hospital care has to be clarified with a convincing solution in everyday practice.c) The potential additional acquisition of patients, which has been advocated by the Hessian state

  7. Detection of lipid-induced structural changes of the Marburg virus matrix protein VP40 using hydrogen/deuterium exchange-mass spectrometry.

    PubMed

    Wijesinghe, Kaveesha J; Urata, Sarah; Bhattarai, Nisha; Kooijman, Edgar E; Gerstman, Bernard S; Chapagain, Prem P; Li, Sheng; Stahelin, Robert V

    2017-04-14

    Marburg virus (MARV) is a lipid-enveloped virus from the Filoviridae family containing a negative sense RNA genome. One of the seven MARV genes encodes the matrix protein VP40, which forms a matrix layer beneath the plasma membrane inner leaflet to facilitate budding from the host cell. MARV VP40 (mVP40) has been shown to be a dimeric peripheral protein with a broad and flat basic surface that can associate with anionic phospholipids such as phosphatidylserine. Although a number of mVP40 cationic residues have been shown to facilitate binding to membranes containing anionic lipids, much less is known on how mVP40 assembles to form the matrix layer following membrane binding. Here we have used hydrogen/deuterium exchange (HDX) mass spectrometry to determine the solvent accessibility of mVP40 residues in the absence and presence of phosphatidylserine and phosphatidylinositol 4,5-bisphosphate. HDX analysis demonstrates that two basic loops in the mVP40 C-terminal domain make important contributions to anionic membrane binding and also reveals a potential oligomerization interface in the C-terminal domain as well as a conserved oligomerization interface in the mVP40 N-terminal domain. Lipid binding assays confirm the role of the two basic patches elucidated with HD/X measurements, whereas molecular dynamics simulations and membrane insertion measurements complement these studies to demonstrate that mVP40 does not appreciably insert into the hydrocarbon region of anionic membranes in contrast to the matrix protein from Ebola virus. Taken together, we propose a model by which association of the mVP40 dimer with the anionic plasma membrane facilitates assembly of mVP40 oligomers. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  8. Multiagent vaccines vectored by Venezuelan equine encephalitis virus replicon elicits immune responses to Marburg virus and protection against anthrax and botulinum neurotoxin in mice.

    PubMed

    Lee, John S; Groebner, Jennifer L; Hadjipanayis, Angela G; Negley, Diane L; Schmaljohn, Alan L; Welkos, Susan L; Smith, Leonard A; Smith, Jonathan F

    2006-11-17

    The development of multiagent vaccines offers the advantage of eliciting protection against multiple diseases with minimal inoculations over a shorter time span. We report here the results of using formulations of individual Venezuelan equine encephalitis (VEE) virus replicon-vectored vaccines against a bacterial disease, anthrax; a viral disease, Marburg fever; and against a toxin-mediated disease, botulism. The individual VEE replicon particles (VRP) expressed mature 83-kDa protective antigen (MAT-PA) from Bacillus anthracis, the glycoprotein (GP) from Marburg virus (MBGV), or the H(C) fragment from botulinum neurotoxin (BoNT H(C)). CBA/J mice inoculated with a mixture of VRP expressing BoNT H(C) serotype C (BoNT/C H(C)) and MAT-PA were 80% protected from a B. anthracis (Sterne strain) challenge and then 100% protected from a sequential BoNT/C challenge. Swiss mice inoculated with individual VRP or with mixtures of VRP vaccines expressing BoNT H(C) serotype A (BoNT/A H(C)), MAT-PA, and MBGV-GP produced antibody responses specific to the corresponding replicon-expressed protein. Combination of the different VRP vaccines did not diminish the antibody responses measured for Swiss mice inoculated with formulations of two or three VRP vaccines as compared to mice that received only one VRP vaccine. Swiss mice inoculated with VRP expressing BoNT/A H(C) alone or in combination with VRP expressing MAT-PA and MBGV GP, were completely protected from a BoNT/A challenge. These studies demonstrate the utility of combining individual VRP vaccines into multiagent formulations for eliciting protective immune responses to various types of diseases.

  9. Lectin Affinity Plasmapheresis for Middle East Respiratory Syndrome-Coronavirus and Marburg Virus Glycoprotein Elimination.

    PubMed

    Koch, Benjamin; Schult-Dietrich, Patricia; Büttner, Stefan; Dilmaghani, Bijan; Lohmann, Dario; Baer, Patrick C; Dietrich, Ursula; Geiger, Helmut

    2018-04-26

    Middle East respiratory syndrome coronavirus (MERS-CoV) and Marburg virus (MARV) are among the World Health Organization's top 8 emerging pathogens. Both zoonoses share nonspecific early symptoms, a high lethality rate, and a reduced number of specific treatment options. Therefore, we evaluated extracorporeal virus and glycoprotein (GP) elimination by lectin affinity plasmapheresis (LAP). For both MERS-CoV (pseudovirus) as well as MARV (GPs), 4 LAP devices (Mini Hemopurifiers, Aethlon Medical, San Diego, CA, USA) and 4 negative controls were tested. Samples were collected every 30 min and analyzed for reduction in virus infectivity by a flow cytometry-based infectivity assay (MERS-CoV) and in soluble GP content (MARV) by an immunoassay. The experiments show a time-dependent clearance of MERS-CoV of up to 80% within 3 h (pseudovirus). Up to 70% of MARV-soluble GPs were eliminated at the same time. Substantial saturation of the binding resins was detected within the first treatment hour. MERS-CoV (pseudovirus) and MARV soluble GPs are eliminated by LAP in vitro. Considering the high lethality and missing established treatment options, LAP should be evaluated in vivo. Especially early initiation, continuous therapy, and timed cartridge exchanges could be of importance. The Author(s). Published by S. Karger AG, Basel.

  10. Safety and immunogenicity of Ebola virus and Marburg virus glycoprotein DNA vaccines assessed separately and concomitantly in healthy Ugandan adults: a phase 1b, randomised, double-blind, placebo-controlled clinical trial.

    PubMed

    Kibuuka, Hannah; Berkowitz, Nina M; Millard, Monica; Enama, Mary E; Tindikahwa, Allan; Sekiziyivu, Arthur B; Costner, Pamela; Sitar, Sandra; Glover, Deline; Hu, Zonghui; Joshi, Gyan; Stanley, Daphne; Kunchai, Meghan; Eller, Leigh Anne; Bailer, Robert T; Koup, Richard A; Nabel, Gary J; Mascola, John R; Sullivan, Nancy J; Graham, Barney S; Roederer, Mario; Michael, Nelson L; Robb, Merlin L; Ledgerwood, Julie E

    2015-04-18

    Ebola virus and Marburg virus cause serious disease outbreaks with high case fatality rates. We aimed to assess the safety and immunogenicity of two investigational DNA vaccines, one (EBO vaccine) encoding Ebola virus Zaire and Sudan glycoproteins and one (MAR) encoding Marburg virus glycoprotein. RV 247 was a phase 1b, double-blinded, randomised, placebo-controlled clinical trial in Kampala, Uganda to examine the safety and immunogenicity of the EBO and MAR vaccines given individually and concomitantly. Healthy adult volunteers aged 18-50 years were randomly assigned (5:1) to receive three injections of vaccine or placebo at weeks 0, 4, and 8, with vaccine allocations divided equally between three active vaccine groups: EBO vaccine only, MAR vaccine only, and both vaccines. The primary study objective was to investigate the safety and tolerability of the vaccines, as assessed by local and systemic reactogenicity and adverse events. We also assessed immunogenicity on the basis of antibody responses (ELISA) and T-cell responses (ELISpot and intracellular cytokine staining assays) 4 weeks after the third injection. Participants and investigators were masked to group assignment. Analysis was based on the intention-to-treat principle. This trial is registered at ClinicalTrials.gov, number NCT00997607. 108 participants were enrolled into the study between Nov 2, 2009, and April 15, 2010. All 108 participants received at least one study injection (including 100 who completed the injection schedule) and were included in safety and tolerability analyses; 107 for whom data were available were included in the immunogenicity analyses. Study injections were well tolerated, with no significant differences in local or systemic reactions between groups. The vaccines elicited antibody and T-cell responses specific to the glycoproteins received and we detected no differences between the separate and concomitant use of the two vaccines. 17 of 30 (57%, 95% CI 37-75) participants in

  11. Recombinant Marburg viruses containing mutations in the IID region of VP35 prevent inhibition of Host immune responses.

    PubMed

    Albariño, César G; Wiggleton Guerrero, Lisa; Spengler, Jessica R; Uebelhoer, Luke S; Chakrabarti, Ayan K; Nichol, Stuart T; Towner, Jonathan S

    2015-02-01

    Previous in vitro studies have demonstrated that Ebola and Marburg virus (EBOV and MARV) VP35 antagonize the host cell immune response. Moreover, specific mutations in the IFN inhibitory domain (IID) of EBOV and MARV VP35 that abrogate their interaction with virus-derived dsRNA, lack the ability to inhibit the host immune response. To investigate the role of MARV VP35 in the context of infectious virus, we used our reverse genetics system to generate two recombinant MARVs carrying specific mutations in the IID region of VP35. Our data show that wild-type and mutant viruses grow to similar titers in interferon deficient cells, but exhibit attenuated growth in interferon-competent cells. Furthermore, in contrast to wild-type virus, both MARV mutants were unable to inhibit expression of various antiviral genes. The MARV VP35 mutants exhibit similar phenotypes to those previously described for EBOV, suggesting the existence of a shared immune-modulatory strategy between filoviruses. Published by Elsevier Inc.

  12. The academic impact of the Triological Society theses--Mosher and Fowler awards: citations, impact factor, and h-index.

    PubMed

    Badran, Karam W; Lahham, Sari; Mahboubi, Hossein; Crumley, Roger L; Wong, Brian J F

    2013-11-01

    The Triological Society requires thesis submission for full membership. Accepted theses (AT) may be recognized with designations of: Mosher Awards (MA), Fowler Awards (FA), Honorable Mention for Basic Science (HMBS), and Honorable Mention for Clinical Science (HMCS). We sought to determine and compare the scholarly impact of Triological Society theses, their authors, and whether differences exist between AT and those that receive special recognition. Retrospective analysis of awards and theses compiled by The Triological Society home office from 1998 to 2011. Thomson Reuters' Integrated Search Interface (ISI) Web of Knowledge and Google Scholar and were used to determine citations and the author's h-index. Trend and statistical analysis was performed. Of the 307 Triological Society theses examined, 275 were published and had record of citation. H-indices and number of citations were found to be nonparametric; thus, median and quartile (1(st) -3(rd) quartiles) values were found to be the following: AT 11 (4-26), MA 18 (9-25), FA 6 (1-28), HMBS 11 (4-26), and HMCS 16 (1-28) for number of citations per published thesis. H-indices of authors with accepted theses were AT 15 (10-19), MA 16 (15-23), FA 18 (10-23), HMBS 16 (11-19), and HMCS 15 (11-21). When comparing all groupings of theses and award winners with bibliometric indices, no statistical significance was found (P >0.5). The Triological Society cultivates a competitive pool of applicants as membership is highly regarded. Negligible difference in citations and author h-index were observed between AT, MA, and FA theses indicated that the level of excellence is uniform, and thesis submission remains influential and prestigious. Copyright © 2013 The American Laryngological, Rhinological and Otological Society, Inc.

  13. [A Japanese in Marburg : Excerpts from the Memories - Jiden - of the Japanese Bacteriologist Taichi Kitashima (1870-1956)].

    PubMed

    Enke, Ulrike; Ishihara, Aeka

    2017-06-01

    The heart of this article is the transmission of selected chapters from the Japanese bacteriologist Taichi Kitashima's (1870-1956) autobiographical memoirs (in Japanese, Jiden) published in 1955, in which Kitashima reports on his stay in Marburg in a very personal and subjective way. Like other Japanese physicians of his generation, Kitashima spent several years in Germany in order to work with the serum researcher Emil von Behring and continued his education there. The contact came through Kitashima's teacher Shibasaburô Kitasato, who had worked with Behring in Berlin on questions of immunology. The memoir gives insight into Behring's laboratory work and his relation to his "subordinates". The editors investigate to what extent Kitashima's assessment, made from a distance of fifty years, of his stay in Germany as "wasted time" was accurate, given the advantages that arose from having been part of a vibrant European scientific community, including encounters in the Pasteur Institute in Paris, and why he cultivated his contacts with Germany and the Behring family during National Socialism.

  14. A parallel genome-wide RNAi screening strategy to identify host proteins important for entry of Marburg virus and H5N1 influenza virus.

    PubMed

    Cheng, Han; Koning, Katie; O'Hearn, Aileen; Wang, Minxiu; Rumschlag-Booms, Emily; Varhegyi, Elizabeth; Rong, Lijun

    2015-11-24

    Genome-wide RNAi screening has been widely used to identify host proteins involved in replication and infection of different viruses, and numerous host factors are implicated in the replication cycles of these viruses, demonstrating the power of this approach. However, discrepancies on target identification of the same viruses by different groups suggest that high throughput RNAi screening strategies need to be carefully designed, developed and optimized prior to the large scale screening. Two genome-wide RNAi screens were performed in parallel against the entry of pseudotyped Marburg viruses and avian influenza virus H5N1 utilizing an HIV-1 based surrogate system, to identify host factors which are important for virus entry. A comparative analysis approach was employed in data analysis, which alleviated systematic positional effects and reduced the false positive number of virus-specific hits. The parallel nature of the strategy allows us to easily identify the host factors for a specific virus with a greatly reduced number of false positives in the initial screen, which is one of the major problems with high throughput screening. The power of this strategy is illustrated by a genome-wide RNAi screen for identifying the host factors important for Marburg virus and/or avian influenza virus H5N1 as described in this study. This strategy is particularly useful for highly pathogenic viruses since pseudotyping allows us to perform high throughput screens in the biosafety level 2 (BSL-2) containment instead of the BSL-3 or BSL-4 for the infectious viruses, with alleviated safety concerns. The screening strategy together with the unique comparative analysis approach makes the data more suitable for hit selection and enables us to identify virus-specific hits with a much lower false positive rate.

  15. Safety and pharmacokinetic profiles of phosphorodiamidate morpholino oligomers with activity against ebola virus and marburg virus: results of two single-ascending-dose studies.

    PubMed

    Heald, Alison E; Iversen, Patrick L; Saoud, Jay B; Sazani, Peter; Charleston, Jay S; Axtelle, Tim; Wong, Michael; Smith, William B; Vutikullird, Apinya; Kaye, Edward

    2014-11-01

    Two identical single-ascending-dose studies evaluated the safety and pharmacokinetics (PK) of AVI-6002 and AVI-6003, two experimental combinations of phosphorodiamidate morpholino oligomers with positive charges (PMOplus) that target viral mRNA encoding Ebola virus and Marburg virus proteins, respectively. Both AVI-6002 and AVI-6003 were found to suppress disease in virus-infected nonhuman primates in previous studies. AVI-6002 (a combination of AVI-7537 and AVI-7539) or AVI-6003 (a combination of AVI-7287 and AVI-7288) were administered as sequential intravenous (i.v.) infusions of a 1:1 fixed dose ratio of the two subcomponents. In each study, 30 healthy male and female subjects between 18 and 50 years of age were enrolled in six-dose escalation cohorts of five subjects each and received a single i.v. infusion of active study drug (0.005, 0.05, 0.5, 1.5, 3, and 4.5 mg/kg per component) or placebo in a 4:1 ratio. Both AVI-6002 and AVI-6003 were safe and well tolerated at the doses studied. A maximum tolerated dose was not observed in either study. The four chemically similar PMOplus components exhibited generally similar PK profiles. The mean peak plasma concentration and area under the concentration-time curve values of the four components exhibited dose-proportional PK. The estimated plasma half-life of all four components was 2 to 5 h. The safety of the two combinations and the PK of the four components were similar, regardless of the target RNA sequence. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  16. Codon-optimized filovirus DNA vaccines delivered by intramuscular electroporation protect cynomolgus macaques from lethal Ebola and Marburg virus challenges.

    PubMed

    Grant-Klein, Rebecca J; Altamura, Louis A; Badger, Catherine V; Bounds, Callie E; Van Deusen, Nicole M; Kwilas, Steven A; Vu, Hong A; Warfield, Kelly L; Hooper, Jay W; Hannaman, Drew; Dupuy, Lesley C; Schmaljohn, Connie S

    2015-01-01

    Cynomolgus macaques were vaccinated by intramuscular electroporation with DNA plasmids expressing codon-optimized glycoprotein (GP) genes of Ebola virus (EBOV) or Marburg virus (MARV) or a combination of codon-optimized GP DNA vaccines for EBOV, MARV, Sudan virus and Ravn virus. When measured by ELISA, the individual vaccines elicited slightly higher IgG responses to EBOV or MARV than did the combination vaccines. No significant differences in immune responses of macaques given the individual or combination vaccines were measured by pseudovirion neutralization or IFN-γ ELISpot assays. Both the MARV and mixed vaccines were able to protect macaques from lethal MARV challenge (5/6 vs. 6/6). In contrast, a greater proportion of macaques vaccinated with the EBOV vaccine survived lethal EBOV challenge in comparison to those that received the mixed vaccine (5/6 vs. 1/6). EBOV challenge survivors had significantly higher pre-challenge neutralizing antibody titers than those that succumbed.

  17. High-throughput, luciferase-based reverse genetics systems for identifying inhibitors of Marburg and Ebola viruses.

    PubMed

    Uebelhoer, Luke S; Albariño, César G; McMullan, Laura K; Chakrabarti, Ayan K; Vincent, Joel P; Nichol, Stuart T; Towner, Jonathan S

    2014-06-01

    Marburg virus (MARV) and Ebola virus (EBOV), members of the family Filoviridae, represent a significant challenge to global public health. Currently, no licensed therapies exist to treat filovirus infections, which cause up to 90% mortality in human cases. To facilitate development of antivirals against these viruses, we established two distinct screening platforms based on MARV and EBOV reverse genetics systems that express secreted Gaussia luciferase (gLuc). The first platform is a mini-genome replicon to screen viral replication inhibitors using gLuc quantification in a BSL-2 setting. The second platform is complementary to the first and expresses gLuc as a reporter gene product encoded in recombinant infectious MARV and EBOV, thereby allowing for rapid quantification of viral growth during treatment with antiviral compounds. We characterized these viruses by comparing luciferase activity to virus production, and validated luciferase activity as an authentic real-time measure of viral growth. As proof of concept, we adapt both mini-genome and infectious virus platforms to high-throughput formats, and demonstrate efficacy of several antiviral compounds. We anticipate that both approaches will prove highly useful in the development of anti-filovirus therapies, as well as in basic research on the filovirus life cycle. Published by Elsevier B.V.

  18. Efficacy of favipiravir (T-705) in nonhuman primates infected with Ebola virus or Marburg virus.

    PubMed

    Bixler, Sandra L; Bocan, Thomas M; Wells, Jay; Wetzel, Kelly S; Van Tongeren, Sean A; Dong, Lian; Garza, Nicole L; Donnelly, Ginger; Cazares, Lisa H; Nuss, Jonathan; Soloveva, Veronica; Koistinen, Keith A; Welch, Lisa; Epstein, Carol; Liang, Li-Fang; Giesing, Dennis; Lenk, Robert; Bavari, Sina; Warren, Travis K

    2018-03-01

    Favipiravir is a broad-spectrum antiviral agent that has demonstrated efficacy against Ebola virus (EBOV) in rodents. However, there are no published reports of favipiravir efficacy for filovirus infection of nonhuman primates (NHPs). Here we evaluated the pharmacokinetic profile of favipiravir in NHPs, as well as in vivo efficacy against two filoviruses, EBOV and Marburg virus (MARV). While no survival benefit was observed in two studies employing once- or twice-daily oral dosing of favipiravir during EBOV infection of NHPs, an antiviral effect was observed in terms of extended time-to-death and reduced levels of viral RNA. However, oral dosing in biosafety level-4 (BSL-4) presents logistical and technical challenges, and repeated anesthesia events may potentially worsen survival outcome in animals. For the third study of treatment of MARV infection, we therefore made use of catheters, jackets, and tethers for intravenous (IV) dosing and blood collection, which minimized the requirement for repeated anesthesia events. When MARV infection was treated with IV favipiravir, five of six animals (83%) survived infection, while all untreated NHPs succumbed. An accompanying report presents the results of favipiravir treatment of EBOV infection in mice. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  19. Marburg virus-like particles produced in insect cells induce neutralizing antibodies in rhesus macaques.

    PubMed

    Weiwei, Gai; Xuexing, Zheng; Chong, Wang; Yongkun, Zhao; Qi, Wang; Hualei, Wang; Gary, Wong; Ying, Xie; Haijun, Wang; Zengguo, Cao; Na, Feng; Hang, Chi; Tiecheng, Wang; Yuwei, Gao; Junjie, Shan; Songtao, Yang; Xianzhu, Xia

    2017-12-01

    Marburg virus (MARV), which is one of the most virulent agents in the world, causes lethal haemorrhagic fever in humans and nonhuman primates (NHPs) with a mortality rate of up to 90%. Currently, there is no effective treatment or approved vaccine for MARV for human use to control disease outbreak and spread. Virus-like particles (VLPs), which are morphologically identical to the native infectious virus particle, are efficacious as vaccines against many viruses, including human papilloma virus (HPV), porcine circovirus (PCV) type 2 and hepatitis B virus (HBV). In this study, we generated MARV virus-like particles (VLPs) by co-expressing a glycoprotein (GP) and matrix protein (VP40) using the baculovirus expression system. Rhesus macaques vaccinated with MARV VLPs mixed with adjuvant Poria cocos polysaccharides (PCP-II) produced a GP-specific IgG titer of up to 1:1280 and virus-neutralizing antibody titers that reached 1:320. MARV VLPs also elicited interferon-γ (IFN-γ) and interleukin-4 (IL-4) secretion associated with T-helper 1 cell (Th1)- and T-helper 2 cell (Th2)-mediated immunity, as detected using enzyme-linked immunospot (ELISpot) assays. These data indicate that MARV VLPs mixed with adjuvant PCP-II have excellent immunogenicity in rhesus macaques and may be a promising candidate vaccine against MARV. © 2017 Wiley Periodicals, Inc.

  20. Marburg Virus VP24 Protein Relieves Suppression of the NF-κB Pathway Through Interaction With Kelch-like ECH-Associated Protein 1.

    PubMed

    Edwards, Megan R; Basler, Christopher F

    2015-10-01

    Marburg virus (MARV) is an emerging zoonotic pathogen that causes hemorrhagic fever. MARV VP24 (mVP24) protein interacts with the host cell protein Kelch-like-ECH-associated protein 1 (Keap1). Keap1 interacts with and promotes the degradation of IκB kinase β (IKKβ), a component of the IκB kinase (IKK) complex that regulates nuclear factor-κB (NF-κB) activity. We studied whether mVP24 could relieve Keap1 repression of the NF-κB pathway. Coimmunoprecipitation assays were used to examine the interaction between Keap1 and IKKβ in the presence of wild-type mVP24 and mutants of mVP24 defective for binding to Keap1. Western blotting was used to determine levels of IKKβ expression in the presence of Keap1 and mVP24. NF-κB promoter-luciferase assays were used to determine the effect of mVP24 on Keap1-induced repression of activity. Expression of wild-type mVP24 disrupted the interaction of IKKβ and Keap1, whereas weakly interacting and noninteracting mVP24 mutants did not disrupt the interaction between Keap1 and IKKβ. The interaction of mVP24 with Keap1 enhanced IKKβ levels in the presence of Keap1. The interaction of mVP24 with Keap1 also relieved Keap1 repression of NF-κB reporter activity. mVP24 can relieve Keap1 repression of the NF-κB pathway through its interaction with Keap1. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  1. Activation of triggering receptor expressed on myeloid cells-1 on human neutrophils by marburg and ebola viruses.

    PubMed

    Mohamadzadeh, Mansour; Coberley, Sadie S; Olinger, Gene G; Kalina, Warren V; Ruthel, Gordon; Fuller, Claudette L; Swenson, Dana L; Pratt, William D; Kuhns, Douglas B; Schmaljohn, Alan L

    2006-07-01

    Marburg virus (MARV) and Ebola virus (EBOV), members of the viral family Filoviridae, cause fatal hemorrhagic fevers in humans and nonhuman primates. High viral burden is coincident with inadequate adaptive immune responses and robust inflammatory responses, and virus-mediated dysregulation of early host defenses has been proposed. Recently, a novel class of innate receptors called the triggering receptors expressed in myeloid cells (TREM) has been discovered and shown to play an important role in innate inflammatory responses and sepsis. Here, we report that MARV and EBOV activate TREM-1 on human neutrophils, resulting in DAP12 phosphorylation, TREM-1 shedding, mobilization of intracellular calcium, secretion of proinflammatory cytokines, and phenotypic changes. A peptide specific to TREM-1 diminished the release of tumor necrosis factor alpha by filovirus-activated human neutrophils in vitro, and a soluble recombinant TREM-1 competitively inhibited the loss of cell surface TREM-1 that otherwise occurred on neutrophils exposed to filoviruses. These data imply direct activation of TREM-1 by filoviruses and also indicate that neutrophils may play a prominent role in the immune and inflammatory responses to filovirus infections.

  2. Membrane insertion of fusion peptides from Ebola and Marburg viruses studied by replica-exchange molecular dynamics simulations.

    PubMed

    Olson, Mark A; Lee, Michael S; Yeh, In-Chul

    2017-06-15

    This work presents replica-exchange molecular dynamics simulations of inserting a 16-residue Ebola virus fusion peptide into a membrane bilayer. A computational approach is applied for modeling the peptide at the explicit all-atom level and the membrane-aqueous bilayer by a generalized Born continuum model with a smoothed switching function (GBSW). We provide an assessment of the model calculations in terms of three metrics: (1) the ability to reproduce the NMR structure of the peptide determined in the presence of SDS micelles and comparable structural data on other fusion peptides; (2) determination of the effects of the mutation Trp-8 to Ala and sequence discrimination of the homologous Marburg virus; and (3) calculation of potentials of mean force for estimating the partitioning free energy and their comparison to predictions from the Wimley-White interfacial hydrophobicity scale. We found the GBSW implicit membrane model to produce results of limited accuracy in conformational properties of the peptide when compared to the NMR structure, yet the model resolution is sufficient to determine the effect of sequence differentiation on peptide-membrane integration. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  3. Marburg virus infection in nonhuman primates: Therapeutic treatment by lipid-encapsulated siRNA.

    PubMed

    Thi, Emily P; Mire, Chad E; Ursic-Bedoya, Raul; Geisbert, Joan B; Lee, Amy C H; Agans, Krystle N; Robbins, Marjorie; Deer, Daniel J; Fenton, Karla A; MacLachlan, Ian; Geisbert, Thomas W

    2014-08-20

    Marburg virus (MARV) and the closely related filovirus Ebola virus cause severe and often fatal hemorrhagic fever (HF) in humans and nonhuman primates with mortality rates up to 90%. There are no vaccines or drugs approved for human use, and no postexposure treatment has completely protected nonhuman primates against MARV-Angola, the strain associated with the highest rate of mortality in naturally occurring human outbreaks. Studies performed with other MARV strains assessed candidate treatments at times shortly after virus exposure, before signs of disease are detectable. We assessed the efficacy of lipid nanoparticle (LNP) delivery of anti-MARV nucleoprotein (NP)-targeting small interfering RNA (siRNA) at several time points after virus exposure, including after the onset of detectable disease in a uniformly lethal nonhuman primate model of MARV-Angola HF. Twenty-one rhesus monkeys were challenged with a lethal dose of MARV-Angola. Sixteen of these animals were treated with LNP containing anti-MARV NP siRNA beginning at 30 to 45 min, 1 day, 2 days, or 3 days after virus challenge. All 16 macaques that received LNP-encapsulated anti-MARV NP siRNA survived infection, whereas the untreated or mock-treated control subjects succumbed to disease between days 7 and 9 after infection. These results represent the successful demonstration of therapeutic anti-MARV-Angola efficacy in nonhuman primates and highlight the substantial impact of an LNP-delivered siRNA therapeutic as a countermeasure against this highly lethal human disease. Copyright © 2014, American Association for the Advancement of Science.

  4. [The Marburg surgical curriculum - improving the attraction of medical education by teaching central surgical competence].

    PubMed

    Schwarting, T; Ruchholtz, S; Josephs, D; Oberkircher, L; Bartsch, D K; Fendrich, V

    2012-04-01

    The quality of medical education is an ongoing challenge due to the continuing changes of the health-care politics and general social conditions. At many German university hospitals the dominating picture is overfilled courses, lack of hands-on practice, reduced patient contact and the dull provision of theoretical, abstract knowledge. The reformed surgical curriculum at the University of Marburg university hospital is used to demonstrate that, in spite of large student numbers, a practice-oriented, small-group training at a high didactic level is possible. The surgical training courses are organized in detail and coordinated. Course contents and structure are media available in print and online versions for both students and teachers and thus fulfill not only transparency needs but also contemporary requirements. The strategy of a practice- and patient-oriented, small-group training is followed strictly in the surgical curriculum. In addition, accompanying tutorial possibilities for individual study in an up-to-date learning center are offered. Here the students have the opportunity to intensify knowledge acquired in previous or future courses with numerous attractive education means. Continuous evaluation of the individual training courses at the end of each semester not only document motivation of the students but also serve to continuously improve the training concepts. © Georg Thieme Verlag KG Stuttgart · New York.

  5. Comparison of the Transcription and Replication Strategies of Marburg Virus and Ebola Virus by Using Artificial Replication Systems

    PubMed Central

    Mühlberger, Elke; Weik, Michael; Volchkov, Viktor E.; Klenk, Hans-Dieter; Becker, Stephan

    1999-01-01

    The members of the family Filoviridae, Marburg virus (MBGV) and Ebola virus (EBOV), are very similar in terms of morphology, genome organization, and protein composition. To compare the replication and transcription strategies of both viruses, an artificial replication system based on the vaccinia virus T7 expression system was established for EBOV. Specific transcription and replication of an artificial monocistronic minireplicon was demonstrated by reporter gene expression and detection of the transcribed and replicated RNA species. As it was shown previously for MBGV, three of the four EBOV nucleocapsid proteins, NP, VP35, and L, were essential and sufficient for replication. In contrast to MBGV, EBOV-specific transcription was dependent on the presence of the fourth nucleocapsid protein, VP30. When EBOV VP30 was replaced by MBGV VP30, EBOV-specific transcription was observed but with lower efficiency. Exchange of NP, VP35, and L between the two replication systems did not lead to detectable reporter gene expression. It was further observed that neither MBGV nor EBOV were able to replicate the heterologous minigenomes. A chimeric minigenome, however, containing the EBOV leader and the MBGV trailer was encapsidated, replicated, transcribed, and packaged by both viruses. PMID:9971816

  6. Cryo-Electron Tomography of Marburg Virus Particles and Their Morphogenesis within Infected Cells

    PubMed Central

    Kolesnikova, Larissa; Welsch, Sonja; Krähling, Verena; Davey, Norman; Parsy, Marie-Laure; Becker, Stephan; Briggs, John A. G.

    2011-01-01

    Several major human pathogens, including the filoviruses, paramyxoviruses, and rhabdoviruses, package their single-stranded RNA genomes within helical nucleocapsids, which bud through the plasma membrane of the infected cell to release enveloped virions. The virions are often heterogeneous in shape, which makes it difficult to study their structure and assembly mechanisms. We have applied cryo-electron tomography and sub-tomogram averaging methods to derive structures of Marburg virus, a highly pathogenic filovirus, both after release and during assembly within infected cells. The data demonstrate the potential of cryo-electron tomography methods to derive detailed structural information for intermediate steps in biological pathways within intact cells. We describe the location and arrangement of the viral proteins within the virion. We show that the N-terminal domain of the nucleoprotein contains the minimal assembly determinants for a helical nucleocapsid with variable number of proteins per turn. Lobes protruding from alternate interfaces between each nucleoprotein are formed by the C-terminal domain of the nucleoprotein, together with viral proteins VP24 and VP35. Each nucleoprotein packages six RNA bases. The nucleocapsid interacts in an unusual, flexible “Velcro-like” manner with the viral matrix protein VP40. Determination of the structures of assembly intermediates showed that the nucleocapsid has a defined orientation during transport and budding. Together the data show striking architectural homology between the nucleocapsid helix of rhabdoviruses and filoviruses, but unexpected, fundamental differences in the mechanisms by which the nucleocapsids are then assembled together with matrix proteins and initiate membrane envelopment to release infectious virions, suggesting that the viruses have evolved different solutions to these conserved assembly steps. PMID:22110401

  7. Novel Chemical Ligands to Ebola Virus and Marburg Virus Nucleoproteins Identified by Combining Affinity Mass Spectrometry and Metabolomics Approaches

    PubMed Central

    Fu, Xu; Wang, Zhihua; Li, Lixin; Dong, Shishang; Li, Zhucui; Jiang, Zhenzuo; Wang, Yuefei; Shui, Wenqing

    2016-01-01

    The nucleoprotein (NP) of Ebola virus (EBOV) and Marburg virus (MARV) is an essential component of the viral ribonucleoprotein complex and significantly impacts replication and transcription of the viral RNA genome. Although NP is regarded as a promising antiviral druggable target, no chemical ligands have been reported to interact with EBOV NP or MARV NP. We identified two compounds from a traditional Chinese medicine Gancao (licorice root) that can bind both NPs by combining affinity mass spectrometry and metabolomics approaches. These two ligands, 18β-glycyrrhetinic acid and licochalcone A, were verified by defined compound mixture screens and further characterized with individual ligand binding assays. Accompanying biophysical analyses demonstrate that binding of 18β-glycyrrhetinic acid to EBOV NP significantly reduces protein thermal stability, induces formation of large NP oligomers, and disrupts the critical association of viral ssRNA with NP complexes whereas the compound showed no such activity on MARV NP. Our study has revealed the substantial potential of new analytical techniques in ligand discovery from natural herb resources. In addition, identification of a chemical ligand that influences the oligomeric state and RNA-binding function of EBOV NP sheds new light on antiviral drug development. PMID:27403722

  8. Recombinant Marburg Virus Expressing EGFP Allows Rapid Screening of Virus Growth and Real-time Visualization of Virus Spread

    PubMed Central

    Schmidt, Kristina Maria; Schümann, Michael; Olejnik, Judith; Krähling, Verena

    2011-01-01

    The generation of recombinant enhanced green fluorescent protein (EGFP)--expressing viruses has significantly improved the study of their life cycle and opened up the possibility for the rapid screening of antiviral drugs. Here we report rescue of a recombinant Marburg virus (MARV) expressing EGFP from an additional transcription unit (ATU). The ATU was inserted between the second and third genes, encoding VP35 and VP40, respectively. Live-cell imaging was used to follow virus spread in real time. EGFP expression was detected at 32 hours postinfection (hpi), and infection of neighboring cells was monitored at 55 hpi. Compared to the parental virus, production of progeny rMARV-EGFP was reduced 4-fold and lower protein levels of VP40, but not nucleoprotein, were observed, indicating a decrease in downstream protein expression due to the insertion of an ATU. Interestingly, EGFP concentrated in viral inclusions in infected cells. This was reproduced by transient expression of both EGFP and other fluorescent proteins along with filovirus nucleocapsid proteins, and may suggest that a general increase in protein synthesis occurs at viral inclusion sites. In conclusion, the EGFP-expressing MARV will be a useful tool not only to monitor virus spread and screen for antiviral compounds, but also to investigate the biology of inclusion body formation. PMID:21987762

  9. [Evaluation of the Marburg Spelling Training (MRT) in 2nd- and 3rd-grade students with spelling difficulties].

    PubMed

    Barkmann, Claus; Kuhlmann, Ester; Rosenboom, Lea; Wessolowski, Nino; Schulte-Markwort, Michael

    2012-05-01

    Children with severe dyslexia are substantially impaired because reading and writing are key competencies necessary for a successful academic and occupational career. In this evaluation study, a cohort of 2nd- and 3rd-grade students from a variety of Hamburg primary schools was trained with the Marburger Rechtschreibtraining (MRT) by supervised university graduates. The research questions focused on the feasibility of the MRT as a within-school training, the improvement of spelling and reading skills of the participants, subjective assessments of success, as well as potential predictors. Besides established performance tests, we also considered the subjective appraisals of parents, teachers, and coaches. The results demonstrate that standardized spelling training methods like the MRT can be consistently used during morning hours at schools. Within a year of starting MRT exercises, mean effect sizes in writing and reading were observed in performance tests using test norms. However, parent, teacher, and coach reports failed to replicate these improvements. Changes in writing performance were mainly associated with school class level; improvements in reading ability were dependent on initial writing performance. The results provide starting points for optimizing current training practices in elementary schools and for posing questions regarding the effectiveness of the MRT, as well as for training programs in general.

  10. Intracellular transport and processing of the Marburg virus surface protein in vertebrate and insect cells.

    PubMed

    Becker, S; Klenk, H D; Mühlberger, E

    1996-11-01

    The surface protein (GP) of Marburg virus (MBG) is synthesized as a 90-kDa precursor protein which is cotranslationally modified by the addition of high-mannose sugars (140 kDa). This step is followed by the conversion of the N-linked sugars to endoglycosidase H (endo H)-resistant species and the addition of O-linked oliosaccharides leading to a mature protein of 170-200 kDa approximately 30 min after pulse labelling. The mature form of GP is efficiently transported to the plasma membrane. GP synthesized using the T7 polymerase-driven vaccinia virus expression system was transported with essentially the same kinetics as the authentic GP. However, the protein that is shown to appear 30 min after pulse labeling at the plasma membrane was slighly smaller (160 kDa) than GP incorporated into the virions (170 kDa). Using a recombinant baculovirus, GP was expressed at high levels in insect cells. Three different species could be identified: a 90-kDa unglycosylated GP localized in the cytoplasm and two 140-kDa glycosylated proteins. Characterization of the glycosylated GPs revealed that processing of the oligosaccharides of GP was less efficient in insect cells than in mammalian cells. The majority of GP remained endo H sensitive containing high-mannose type N-linked glycans, whereas only a small fraction became endo H resistant carrying processed N-glycans and O-glycans. Tunicamycin treatment of the GP-expressing cells demonstrated that N-glycosylation is essential for the transport of the MBG surface protein.

  11. Antibody Responses to Marburg Virus in Egyptian Rousette Bats and Their Role in Protection against Infection.

    PubMed

    Storm, Nadia; Jansen Van Vuren, Petrus; Markotter, Wanda; Paweska, Janusz T

    2018-02-10

    Egyptian rousette bats (ERBs) are reservoir hosts for the Marburg virus (MARV). The immune dynamics and responses to MARV infection in ERBs are poorly understood, and limited information exists on the role of antibodies in protection of ERBs against MARV infection. Here, we determine the duration of maternal immunity to MARV in juvenile ERBs, and evaluate the duration of the antibody response to MARV in bats naturally or experimentally infected with the virus. We further explore whether antibodies in previously naturally exposed bats is fully protective against experimental reinfection with MARV. Maternal immunity was lost in juvenile ERBs by 5 months of age. Antibodies to MARV remained detectable in 67% of experimentally infected bats approximately 4 months post inoculation (p.i.), while antibodies to MARV remained present in 84% of naturally exposed bats at least 11 months after capture. Reinfection of seropositive ERBs with MARV produced an anamnestic response from day 5 p.i. Although PCR-defined viremia was present in 73.3% of reinfected ERBs, replicating virus was recovered from the serum of only one bat on day 3 p.i. The negative PCR results in the salivary glands, intestines, bladders and reproductive tracts of reinfected bats, and the apparent absence of MARV in the majority of swabs collected from these bats suggest that reinfection may only play a minor role in the transmission and maintenance of MARV amongst ERBs in nature.

  12. Survey of methods of facial palsy documentation in use by members of the Sir Charles Bell Society.

    PubMed

    Fattah, Adel Y; Gavilan, Javier; Hadlock, Tessa A; Marcus, Jeffrey R; Marres, Henri; Nduka, Charles; Slattery, William H; Snyder-Warwick, Alison K

    2014-10-01

    Facial palsy manifests a broad array of deficits affecting function, form, and psychological well-being. Assessment scales were introduced to standardize and document the features of facial palsy and to facilitate the exchange of information and comparison of outcomes. The aim of this study was to determine which assessment methodologies are currently employed by those involved in the care of patients with facial palsy as a first step toward the development of consensus on the appropriate assessments for this patient population. Online questionnaire. The Sir Charles Bell Society, a group of professionals dedicated to the care of patients with facial palsy, were surveyed to determine the scales used to document facial nerve function, patient reported outcome measures (PROM), and photographic documentation. Fifty-five percent of the membership responded (n = 83). Grading scales were used by 95%, most commonly the House-Brackmann and Sunnybrook scales. PROMs were used by 58%, typically the Facial Clinimetric Evaluation scale or Facial Disability Index. All used photographic recordings, but variability existed among the facial expressions used. Videography was performed by 82%, and mostly involved the same views as still photography; it was also used to document spontaneous movement and speech. Three-dimensional imaging was employed by 18% of respondents. There exists significant heterogeneity in assessments among clinicians, which impedes straightforward comparisons of outcomes following recovery and intervention. Widespread adoption of structured assessments, including scales, PROMs, photography, and videography, will facilitate communication and comparison among those who study the effects of interventions on this population. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

  13. Delayed Time-to-Treatment of an Antisense Morpholino Oligomer Is Effective against Lethal Marburg Virus Infection in Cynomolgus Macaques.

    PubMed

    Warren, Travis K; Whitehouse, Chris A; Wells, Jay; Welch, Lisa; Charleston, Jay S; Heald, Alison; Nichols, Donald K; Mattix, Marc E; Palacios, Gustavo; Kugleman, Jeffrey R; Iversen, Patrick L; Bavari, Sina

    2016-02-01

    Marburg virus (MARV) is an Ebola-like virus in the family Filovirdae that causes sporadic outbreaks of severe hemorrhagic fever with a case fatality rate as high as 90%. AVI-7288, a positively charged antisense phosphorodiamidate morpholino oligomer (PMOplus) targeting the viral nucleoprotein gene, was evaluated as a potential therapeutic intervention for MARV infection following delayed treatment of 1, 24, 48, and 96 h post-infection (PI) in a nonhuman primate lethal challenge model. A total of 30 cynomolgus macaques were divided into 5 groups of 6 and infected with 1,830 plaque forming units of MARV subcutaneously. AVI-7288 was administered by bolus infusion daily for 14 days at 15 mg/kg body weight. Survival was the primary endpoint of the study. While none (0 of 6) of the saline group survived, 83-100% of infected monkeys survived when treatment was initiated 1, 24, 48, or 96 h post-infection (PI). The antisense treatment also reduced serum viremia and inflammatory cytokines in all treatment groups compared to vehicle controls. The antibody immune response to virus was preserved and tissue viral antigen was cleared in AVI-7288 treated animals. These data show that AVI-7288 protects NHPs against an otherwise lethal MARV infection when treatment is initiated up to 96 h PI.

  14. Chaperone-Mediated Autophagy Protein BAG3 Negatively Regulates Ebola and Marburg VP40-Mediated Egress

    PubMed Central

    Liang, Jingjing; Sagum, Cari A.; Bedford, Mark T.; Sudol, Marius; Han, Ziying

    2017-01-01

    Ebola (EBOV) and Marburg (MARV) viruses are members of the Filoviridae family which cause outbreaks of hemorrhagic fever. The filovirus VP40 matrix protein is essential for virus assembly and budding, and its PPxY L-domain motif interacts with WW-domains of specific host proteins, such as Nedd4 and ITCH, to facilitate the late stage of virus-cell separation. To identify additional WW-domain-bearing host proteins that interact with VP40, we used an EBOV PPxY-containing peptide to screen an array of 115 mammalian WW-domain-bearing proteins. Using this unbiased approach, we identified BCL2 Associated Athanogene 3 (BAG3), a member of the BAG family of molecular chaperone proteins, as a specific VP40 PPxY interactor. Here, we demonstrate that the WW-domain of BAG3 interacts with the PPxY motif of both EBOV and MARV VP40 and, unexpectedly, inhibits budding of both eVP40 and mVP40 virus-like particles (VLPs), as well as infectious VSV-EBOV recombinants. BAG3 is a stress induced protein that regulates cellular protein homeostasis and cell survival through chaperone-mediated autophagy (CMA). Interestingly, our results show that BAG3 alters the intracellular localization of VP40 by sequestering VP40 away from the plasma membrane. As BAG3 is the first WW-domain interactor identified that negatively regulates budding of VP40 VLPs and infectious virus, we propose that the chaperone-mediated autophagy function of BAG3 represents a specific host defense strategy to counteract the function of VP40 in promoting efficient egress and spread of virus particles. PMID:28076420

  15. Chaperone-Mediated Autophagy Protein BAG3 Negatively Regulates Ebola and Marburg VP40-Mediated Egress.

    PubMed

    Liang, Jingjing; Sagum, Cari A; Bedford, Mark T; Sidhu, Sachdev S; Sudol, Marius; Han, Ziying; Harty, Ronald N

    2017-01-01

    Ebola (EBOV) and Marburg (MARV) viruses are members of the Filoviridae family which cause outbreaks of hemorrhagic fever. The filovirus VP40 matrix protein is essential for virus assembly and budding, and its PPxY L-domain motif interacts with WW-domains of specific host proteins, such as Nedd4 and ITCH, to facilitate the late stage of virus-cell separation. To identify additional WW-domain-bearing host proteins that interact with VP40, we used an EBOV PPxY-containing peptide to screen an array of 115 mammalian WW-domain-bearing proteins. Using this unbiased approach, we identified BCL2 Associated Athanogene 3 (BAG3), a member of the BAG family of molecular chaperone proteins, as a specific VP40 PPxY interactor. Here, we demonstrate that the WW-domain of BAG3 interacts with the PPxY motif of both EBOV and MARV VP40 and, unexpectedly, inhibits budding of both eVP40 and mVP40 virus-like particles (VLPs), as well as infectious VSV-EBOV recombinants. BAG3 is a stress induced protein that regulates cellular protein homeostasis and cell survival through chaperone-mediated autophagy (CMA). Interestingly, our results show that BAG3 alters the intracellular localization of VP40 by sequestering VP40 away from the plasma membrane. As BAG3 is the first WW-domain interactor identified that negatively regulates budding of VP40 VLPs and infectious virus, we propose that the chaperone-mediated autophagy function of BAG3 represents a specific host defense strategy to counteract the function of VP40 in promoting efficient egress and spread of virus particles.

  16. Cathepsins B and L activate Ebola but not Marburg virus glycoproteins for efficient entry into cell lines and macrophages independent of TMPRSS2 expression.

    PubMed

    Gnirss, Kerstin; Kühl, Annika; Karsten, Christina; Glowacka, Ilona; Bertram, Stephanie; Kaup, Franziska; Hofmann, Heike; Pöhlmann, Stefan

    2012-03-01

    Ebola (EBOV) and Marburg virus (MARV) cause severe hemorrhagic fever. The host cell proteases cathepsin B and L activate the Zaire ebolavirus glycoprotein (GP) for cellular entry and constitute potential targets for antiviral intervention. However, it is unclear if different EBOV species and MARV equally depend on cathepsin B/L activity for infection of cell lines and macrophages, important viral target cells. Here, we show that cathepsin B/L inhibitors markedly reduce 293T cell infection driven by the GPs of all EBOV species, independent of the type II transmembrane serine protease TMPRSS2, which cleaved but failed to activate EBOV-GPs. Similarly, a cathepsin B/L inhibitor blocked macrophage infection mediated by different EBOV-GPs. In contrast, MARV-GP-driven entry exhibited little dependence on cathepsin B/L activity. Still, MARV-GP-mediated entry was efficiently blocked by leupeptin. These results suggest that cathepsins B/L promote entry of EBOV while MARV might employ so far unidentified proteases for GP activation. Copyright © 2011 Elsevier Inc. All rights reserved.

  17. 75 FR 20828 - Availability for Non-Exclusive, Exclusive, or Partially Exclusive Licensing of U.S. Patent...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-21

    ... Partially Exclusive Licensing of U.S. Patent Application Concerning a Chimeric Ebola and Marburg Virus Glycoproteins Virus Like Particle Vaccine To Protect Against Diverse Ebola and Marburg Viruses AGENCY... Ebola and Marburg Virus Glycoproteins Virus Like Particle Vaccine To Protect Against Diverse Ebola and...

  18. Marburg Hemorrhagic Fever (Marburg HF)

    MedlinePlus

    ... infected had been exposed to imported African green monkeys or their tissues while conducting research. One additional ... OIG 1600 Clifton Road Atlanta , GA 30329-4027 USA 800-CDC-INFO (800-232-4636) , TTY: 888- ...

  19. Guideline on allergen-specific immunotherapy in IgE-mediated allergic diseases: S2k Guideline of the German Society for Allergology and Clinical Immunology (DGAKI), the Society for Pediatric Allergy and Environmental Medicine (GPA), the Medical Association of German Allergologists (AeDA), the Austrian Society for Allergy and Immunology (ÖGAI), the Swiss Society for Allergy and Immunology (SGAI), the German Society of Dermatology (DDG), the German Society of Oto- Rhino-Laryngology, Head and Neck Surgery (DGHNO-KHC), the German Society of Pediatrics and Adolescent Medicine (DGKJ), the Society for Pediatric Pneumology (GPP), the German Respiratory Society (DGP), the German Association of ENT Surgeons (BV-HNO), the Professional Federation of Paediatricians and Youth Doctors (BVKJ), the Federal Association of Pulmonologists (BDP) and the German Dermatologists Association (BVDD).

    PubMed

    Pfaar, Oliver; Bachert, Claus; Bufe, Albrecht; Buhl, Roland; Ebner, Christof; Eng, Peter; Friedrichs, Frank; Fuchs, Thomas; Hamelmann, Eckard; Hartwig-Bade, Doris; Hering, Thomas; Huttegger, Isidor; Jung, Kirsten; Klimek, Ludger; Kopp, Matthias Volkmar; Merk, Hans; Rabe, Uta; Saloga, Joachim; Schmid-Grendelmeier, Peter; Schuster, Antje; Schwerk, Nicolaus; Sitter, Helmut; Umpfenbach, Ulrich; Wedi, Bettina; Wöhrl, Stefan; Worm, Margitta; Kleine-Tebbe, Jörg; Kaul, Susanne; Schwalfenberg, Anja

    , Ebner C, Eng P, Friedrichs F, Fuchs T, Hamelmann E, Hartwig-Bade D, Hering T, Huttegger I, Jung K, Klimek L, Kopp MV, Merk H, Rabe U, Saloga J, Schmid-Grendelmeier P, Schuster A, Schwerk N, Sitter H, Umpfenbach U, Wedi B, Wöhrl S, Worm M, Kleine-Tebbe J. Guideline on allergen-specific immunotherapy in IgE-mediated allergic diseases - S2k Guideline of the German Society for Allergology and Clinical Immunology (DGAKI), the Society for Pediatric Allergy and Environmental Medicine (GPA), the Medical Association of German Allergologists (AeDA), the Austrian Society for Allergy and Immunology (ÖGAI), the Swiss Society for Allergy and Immunology (SGAI), the German Society of Dermatology (DDG), the German Society of Oto-Rhino-Laryngology, Head and Neck Surgery (DGHNO-KHC), the German Society of Pediatrics and Adolescent Medicine (DGKJ), the Society for Pediatric Pneumology (GPP), the German Respiratory Society (DGP), the German Association of ENT Surgeons (BV-HNO), the Professional Federation of Paediatricians and Youth Doctors (BVKJ), the Federal Association of Pulmonologists (BDP) and the German Dermatologists Association (BVDD). Allergo J Int 2014;23:282-319.

  20. Monovalent virus-like particle vaccine protects guinea pigs and nonhuman primates against infection with multiple Marburg viruses.

    PubMed

    Swenson, Dana L; Warfield, Kelly L; Larsen, Tom; Alves, D Anthony; Coberley, Sadie S; Bavari, Sina

    2008-05-01

    Virus-like particle (VLP)-based vaccines have the advantage of being morphologically and antigenically similar to the live virus from which they are derived. Expression of the glycoprotein and VP40 matrix protein from Lake Victoria marburgvirus (MARV) results in spontaneous production of VLPs in mammalian cells. Guinea pigs vaccinated with Marburg virus VLPs (mVLPs) or inactivated MARV (iMARV) develop homologous humoral and T-cell responses and are completely protected from a lethal homologous MARV challenge. To determine whether mVLPs based on the Musoke (aka Lake Victoria) isolate of MARV could broadly protect against diverse isolates of MARV, guinea pigs were vaccinated with mVLPs or iMARV-Musoke and challenged with MARV-Musoke, -Ravn or -Ci67. Prior to challenge, the mVLP- and iMARV-vaccinated guinea pigs had high levels of homologous MARV-Musoke and heterologous MARV-Ravn and -Ci67 antibodies. The Musoke-based mVLPs and iMARV vaccines provided complete protection in guinea pigs against viremia, viral replication and pathological changes in tissues, and lethal disease following challenge with MARV-Musoke, -Ravn or -Ci67. Guinea pigs vaccinated with RIBI adjuvant alone and infected with guinea pig-adapted MARV-Musoke, -Ravn or -Ci67 had histopathologic findings similar to those seen in the nonhuman primate model for MARV infection. Based on the strong protection observed in guinea pigs, we next vaccinated cynomolgus macaques with Musoke-based mVLPs and showed the VLP-vaccinated monkeys were broadly protected against three isolates of MARV (Musoke, Ravn and Ci67). Musoke mVLPs are effective at inducing broad heterologous immunity and protection against multiple MARV isolates.

  1. Marburg virus inclusions: A virus-induced microcompartment and interface to multivesicular bodies and the late endosomal compartment.

    PubMed

    Dolnik, Olga; Stevermann, Lea; Kolesnikova, Larissa; Becker, Stephan

    2015-01-01

    Filovirus infection of target cells leads to the formation of virally induced cytoplasmic inclusions that contain viral nucleocapsids at different stages of maturation. While the role of the inclusions has been unclear since the identification of Marburg and Ebola viruses, it recently became clear that the inclusions are the sites of viral replication, nucleocapsid formation and maturation. Live cell imaging analyses revealed that mature nucleocapsids are transported from inclusions to the filopodia, which represent the major budding sites. Moreover, inclusions recruit cellular proteins that have been shown to support the transport of nucleocapsids. For example, the tumor susceptibility gene 101 protein (Tsg101) interacts with a late domain motif in the nucleocapsid protein NP and recruits the actin-nucleation factor IQGAP1. Complexes of nucleocapsids together with Tsg101 and IQGAP1 are then co-transported along actin filaments. We detected additional proteins (Alix, Nedd4 and the AAA-type ATPase VPS4) of the endosomal sorting complex required for transport (ESCRT) that are recruited into inclusions. Together, the results suggest that nucleocapsids recruit the machinery that enhances viral budding at the plasma membrane. Furthermore, we identified Lamp1 as a marker of the late endosomal compartment in inclusions, while ER, Golgi, TGN and early endosomal markers were absent. In addition, we observed that LC3, a marker of autophagosomal membranes, was present in inclusions. The 3D structures of inclusions show an intricate structure that seems to accommodate an intimate cooperation between cellular and viral components with the intention to support viral transport and budding. Copyright © 2015 Elsevier GmbH. All rights reserved.

  2. Marburg Virus Glycoprotein GP2: pH-Dependent Stability of the Ectodomain α-Helical Bundle†

    PubMed Central

    Harrison, Joseph S.; Koellhoffer, Jayne F.; Chandran, Kartik; Lai, Jonathan R.

    2012-01-01

    Marburg virus (MARV) and Ebola virus (EBOV) constitute the family Filoviridae of enveloped viruses (filoviruses) that cause severe hemorrhagic fever. Infection by MARV is required for fusion between the host cell and viral membranes, a process that is mediated by the two subunits of the envelope glycoprotein GP1 (surface subunit) and GP2 (transmembrane subunit). Upon viral attachment and uptake, it is believed that the MARV viral fusion machinery is triggered by host factors and environmental conditions found in the endosome. Next, conformational rearrangements in the GP2 ectodomain result in the formation of a highly stable six-helix bundle; this refolding event provides the energetic driving force for membrane fusion. Both GP1 and GP2 from EBOV have been extensively studied, but there is little information available for the MARV glycoproteins. Here we have expressed two variants of the MARV GP2 ectodomain in Escherichia coli and analyzed their biophysical properties. Circular dichroism indicates that the MARV GP2 ectodomain adopts an α-helical conformation, and one variant sediments as a trimer by equilibrium analytical ultracentrifugation. Denaturation studies indicate the α-helical structure is highly stable at pH 5.3 (unfolding energy, ΔGunf H2O, of 33.4 ± 2.5 kcal/mol and melting temperature, Tm, of 75.3 ± 2.1 °C for one variant). Furthermore, we found the α-helical stability to be strongly dependent on pH with higher stability under lower pH conditions (Tm values ranging from ~92 °C at pH 4.0 to ~38 °C at pH 8.0). Mutational analysis suggests two glutamic acid residues (E579 and E580) are partially responsible for this pH-dependent behavior. Based on these results, we hypothesize that pH-dependent folding stability of the MARV GP2 ectodomain provides a mechanism to control conformational preferences such that the six-helix bundle ‘post-fusion’ state is preferred under conditions of appropriately matured endosomes. PMID:22369502

  3. Lyophilisation of influenza, rabies and Marburg lentiviral pseudotype viruses for the development and distribution of a neutralisation -assay-based diagnostic kit.

    PubMed

    Mather, Stuart T; Wright, Edward; Scott, Simon D; Temperton, Nigel J

    2014-12-15

    Pseudotype viruses (PVs) are chimeric, replication-deficient virions that mimic wild-type virus entry mechanisms and can be safely employed in neutralisation assays, bypassing the need for high biosafety requirements and performing comparably to established serological assays. However, PV supernatant necessitates -80°C long-term storage and cold-chain maintenance during transport, which limits the scope of dissemination and application throughout resource-limited laboratories. We therefore investigated the effects of lyophilisation on influenza, rabies and Marburg PV stability, with a view to developing a pseudotype virus neutralisation assay (PVNA) based kit suitable for affordable global distribution. Infectivity of each PV was calculated after lyophilisation and immediate reconstitution, as well as subsequent to incubation of freeze-dried pellets at varying temperatures, humidities and timepoints. Integrity of glycoprotein structure following treatment was also assessed by employing lyophilised PVs in downstream PVNAs. In the presence of 0.5M sucrose-PBS cryoprotectant, each freeze-dried pseudotype was stably stored for 4 weeks at up to 37°C and could be neutralised to the same potency as unlyophilised PVs when employed in PVNAs. These results confirm the viability of a freeze-dried PVNA-based kit, which could significantly facilitate low-cost serology for a wide portfolio of emerging infectious viruses. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Broad and Temperature Independent Replication Potential of Filoviruses on Cells Derived From Old and New World Bat Species.

    PubMed

    Miller, Megan R; McMinn, Rebekah J; Misra, Vikram; Schountz, Tony; Müller, Marcel A; Kurth, Andreas; Munster, Vincent J

    2016-10-15

    Filoviruses are strongly associated with several species of bats as their natural reservoirs. In this study, we determined the replication potential of all filovirus species: Marburg marburgvirus, Taï Forest ebolavirus, Reston ebolavirus, Sudan ebolavirus, Zaire ebolavirus, and Bundibugyo ebolavirus. Filovirus replication was supported by all cell lines derived from 6 Old and New World bat species: the hammer-headed fruit bat, Buettikofer's epauletted fruit bat, the Egyptian fruit bat, the Jamaican fruit bat, the Mexican free-tailed bat and the big brown bat. In addition, we showed that Marburg virus Angola and Ebola virus Makona-WPGC07 efficiently replicated at 37°C, 37°-41°C, or 41°C, contrary to the hypothesis that temporal elevation in temperature due to flight affects filovirus replication in bats. Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  5. Single-Injection Vaccine Protects Nonhuman Primates against Infection with Marburg Virus and Three Species of Ebola Virus▿

    PubMed Central

    Geisbert, Thomas W.; Geisbert, Joan B.; Leung, Anders; Daddario-DiCaprio, Kathleen M.; Hensley, Lisa E.; Grolla, Allen; Feldmann, Heinz

    2009-01-01

    The filoviruses Marburg virus and Ebola virus cause severe hemorrhagic fever with high mortality in humans and nonhuman primates. Among the most promising filovirus vaccines under development is a system based on recombinant vesicular stomatitis virus (VSV) that expresses a single filovirus glycoprotein (GP) in place of the VSV glycoprotein (G). Here, we performed a proof-of-concept study in order to determine the potential of having one single-injection vaccine capable of protecting nonhuman primates against Sudan ebolavirus (SEBOV), Zaire ebolavirus (ZEBOV), Cote d'Ivoire ebolavirus (CIEBOV), and Marburgvirus (MARV). In this study, 11 cynomolgus monkeys were vaccinated with a blended vaccine consisting of equal parts of the vaccine vectors VSVΔG/SEBOVGP, VSVΔG/ZEBOVGP, and VSVΔG/MARVGP. Four weeks later, three of these animals were challenged with MARV, three with CIEBOV, three with ZEBOV, and two with SEBOV. Three control animals were vaccinated with VSV vectors encoding a nonfilovirus GP and challenged with SEBOV, ZEBOV, and MARV, respectively, and five unvaccinated control animals were challenged with CIEBOV. Importantly, none of the macaques vaccinated with the blended vaccine succumbed to a filovirus challenge. As expected, an experimental control animal vaccinated with VSVΔG/ZEBOVGP and challenged with SEBOV succumbed, as did the positive controls challenged with SEBOV, ZEBOV, and MARV, respectively. All five control animals challenged with CIEBOV became severely ill, and three of the animals succumbed on days 12, 12, and 14, respectively. The two animals that survived CIEBOV infection were protected from subsequent challenge with either SEBOV or ZEBOV, suggesting that immunity to CIEBOV may be protective against other species of Ebola virus. In conclusion, we developed an immunization scheme based on a single-injection vaccine that protects nonhuman primates against lethal challenge with representative strains of all human pathogenic filovirus species

  6. Anatomy during the Third Reich--the Institute of Anatomy at the University of Marburg, as an example.

    PubMed

    Aumüller, G; Grundmann, K

    2002-05-01

    A complete documentation of German anatomical science and its representatives during the period of national socialism has not been published as yet--contrary to the situation in other medical disciplines. Instead of German anatomists, American anatomists have occasionally addressed this issue during their meetings and have reported on special aspects, such as the use of Nazi symbols in anatomical textbooks and atlases (Pernkopf 1952) and the use of corpses of justice victims for anatomical research and student education. Also, the genesis of the atrocious collection of "racial" skulls, initiated along with the SS-institution of the "Ahnenerbe" by the anatomist August Hirt of Strasbourg (who ordered more than 90 inmates from concentration camps to be murdered in the gas chamber built in the concentration camp of Natzweiler-Struthof close to Strasbourg, Alsace) has been described by Frederic Kasten and others. A broader view of the patterns of behaviour and political actions and fates of contemporary scientists, ranging from dismissal to clandestine opportunism, affirmative cooperation and fanatic activism can be obtained by the analysis of the activities in research, medical education and academic positions of the following members of the Institute of Anatomy at the Philipp-University in Marburg: Ernst Göppert, Eduard Jacobshagen, Ernst-Theodor Nauck, Adolf Dabelow, Helmut Becher and Alfred Benninghoff, whose activities and fates differ in several respects and allow more general deductions. Also, the individual fates of a number of prosecuted Jewish anatomists (Wassermann, München; Poll, Hamburg), of devoted and active members of the Nazi party (Clara, Leipzig; Blotevogel, Breslau) and of criminal fanatics (Hirt, Strasbourg; Kremer, Münster) are briefly discussed. The present contribution is an attempt to initiate a more detailed study of all German departments of anatomy during the Hitler regime and to generate a public discussion among the younger generation of

  7. Single-injection vaccine protects nonhuman primates against infection with marburg virus and three species of ebola virus.

    PubMed

    Geisbert, Thomas W; Geisbert, Joan B; Leung, Anders; Daddario-DiCaprio, Kathleen M; Hensley, Lisa E; Grolla, Allen; Feldmann, Heinz

    2009-07-01

    The filoviruses Marburg virus and Ebola virus cause severe hemorrhagic fever with high mortality in humans and nonhuman primates. Among the most promising filovirus vaccines under development is a system based on recombinant vesicular stomatitis virus (VSV) that expresses a single filovirus glycoprotein (GP) in place of the VSV glycoprotein (G). Here, we performed a proof-of-concept study in order to determine the potential of having one single-injection vaccine capable of protecting nonhuman primates against Sudan ebolavirus (SEBOV), Zaire ebolavirus (ZEBOV), Cote d'Ivoire ebolavirus (CIEBOV), and Marburgvirus (MARV). In this study, 11 cynomolgus monkeys were vaccinated with a blended vaccine consisting of equal parts of the vaccine vectors VSVDeltaG/SEBOVGP, VSVDeltaG/ZEBOVGP, and VSVDeltaG/MARVGP. Four weeks later, three of these animals were challenged with MARV, three with CIEBOV, three with ZEBOV, and two with SEBOV. Three control animals were vaccinated with VSV vectors encoding a nonfilovirus GP and challenged with SEBOV, ZEBOV, and MARV, respectively, and five unvaccinated control animals were challenged with CIEBOV. Importantly, none of the macaques vaccinated with the blended vaccine succumbed to a filovirus challenge. As expected, an experimental control animal vaccinated with VSVDeltaG/ZEBOVGP and challenged with SEBOV succumbed, as did the positive controls challenged with SEBOV, ZEBOV, and MARV, respectively. All five control animals challenged with CIEBOV became severely ill, and three of the animals succumbed on days 12, 12, and 14, respectively. The two animals that survived CIEBOV infection were protected from subsequent challenge with either SEBOV or ZEBOV, suggesting that immunity to CIEBOV may be protective against other species of Ebola virus. In conclusion, we developed an immunization scheme based on a single-injection vaccine that protects nonhuman primates against lethal challenge with representative strains of all human pathogenic

  8. A Single Amino Acid Change in the Marburg Virus Glycoprotein Arises during Serial Cell Culture Passages and Attenuates the Virus in a Macaque Model of Disease.

    PubMed

    Alfson, Kendra J; Avena, Laura E; Delgado, Jenny; Beadles, Michael W; Patterson, Jean L; Carrion, Ricardo; Griffiths, Anthony

    2018-01-01

    Marburg virus (MARV) causes disease with high case fatality rates, and there are no approved vaccines or therapies. Licensing of MARV countermeasures will likely require approval via the FDA's Animal Efficacy Rule, which requires well-characterized animal models that recapitulate human disease. This includes selection of the virus used for exposure and ensuring that it retains the properties of the original isolate. The consequences of amplification of MARV for challenge studies are unknown. Here, we serially passaged and characterized MARV through 13 passes from the original isolate. Surprisingly, the viral genome was very stable, except for a single nucleotide change that resulted in an amino acid substitution in the hydrophobic region of the signal peptide of the glycoprotein (GP). The particle/PFU ratio also decreased following passages, suggesting a role for the amino acid in viral infectivity. To determine if amplification introduces a phenotype in an animal model, cynomolgus macaques were exposed to either 100 or 0.01 PFU of low- and high-passage-number MARV. All animals succumbed when exposed to 100 PFU of either passage 3 or 13 viruses, although animals exposed to the high-passage-number virus survived longer. However, none of the passage 13 MARV-exposed animals succumbed to 0.01-PFU exposure compared to 75% of passage 3-exposed animals. This is consistent with other filovirus studies that show some particles that are unable to yield a plaque in cell culture can cause lethal disease in vivo . These results have important consequences for the design of experiments that investigate MARV pathogenesis and that test the efficacy of MARV countermeasures. IMPORTANCE Marburg virus (MARV) causes disease with a high case fatality rate, and there are no approved vaccines or therapies. Serial amplification of viruses in cell culture often results in accumulation of mutations, but the effect of such cell culture passage on MARV is unclear. Serial passages of MARV

  9. Presence and Persistence of Ebola or Marburg Virus in Patients and Survivors: A Rapid Systematic Review.

    PubMed

    Brainard, Julii; Pond, Katherine; Hooper, Lee; Edmunds, Kelly; Hunter, Paul

    2016-02-01

    The 2013-15 Ebola outbreak was unprecedented due to sustained transmission within urban environments and thousands of survivors. In 2014 the World Health Organization stated that there was insufficient evidence to give definitive guidance about which body fluids are infectious and when they pose a risk to humans. We report a rapid systematic review of published evidence on the presence of filoviruses in body fluids of infected people and survivors. Scientific articles were screened for information about filovirus in human body fluids. The aim was to find primary data that suggested high likelihood of actively infectious filovirus in human body fluids (viral RNA). Eligible infections were from Marburg virus (MARV or RAVV) and Zaire, Sudan, Taï Forest and Bundibugyo species of Ebola. Cause of infection had to be laboratory confirmed (in practice either tissue culture or RT-PCR tests), or evidenced by compatible clinical history with subsequent positivity for filovirus antibodies or inflammatory factors. Data were extracted and summarized narratively. 6831 unique articles were found, and after screening, 33 studies were eligible. For most body fluid types there were insufficient patients to draw strong conclusions, and prevalence of positivity was highly variable. Body fluids taken >16 days after onset were usually negative. In the six studies that used both assay methods RT-PCR tests for filovirus RNA gave positive results about 4 times more often than tissue culture. Filovirus was reported in most types of body fluid, but not in every sample from every otherwise confirmed patient. Apart from semen, most non-blood, RT-PCR positive samples are likely to be culture negative and so possibly of low infectious risk. Nevertheless, it is not apparent how relatively infectious many body fluids are during or after illness, even when culture-positive, not least because most test results come from more severe cases. Contact with blood and blood-stained body fluids remains the

  10. A Single Amino Acid Change in the Marburg Virus Glycoprotein Arises during Serial Cell Culture Passages and Attenuates the Virus in a Macaque Model of Disease

    PubMed Central

    Alfson, Kendra J.; Avena, Laura E.; Delgado, Jenny; Beadles, Michael W.; Patterson, Jean L.; Carrion, Ricardo

    2018-01-01

    ABSTRACT Marburg virus (MARV) causes disease with high case fatality rates, and there are no approved vaccines or therapies. Licensing of MARV countermeasures will likely require approval via the FDA’s Animal Efficacy Rule, which requires well-characterized animal models that recapitulate human disease. This includes selection of the virus used for exposure and ensuring that it retains the properties of the original isolate. The consequences of amplification of MARV for challenge studies are unknown. Here, we serially passaged and characterized MARV through 13 passes from the original isolate. Surprisingly, the viral genome was very stable, except for a single nucleotide change that resulted in an amino acid substitution in the hydrophobic region of the signal peptide of the glycoprotein (GP). The particle/PFU ratio also decreased following passages, suggesting a role for the amino acid in viral infectivity. To determine if amplification introduces a phenotype in an animal model, cynomolgus macaques were exposed to either 100 or 0.01 PFU of low- and high-passage-number MARV. All animals succumbed when exposed to 100 PFU of either passage 3 or 13 viruses, although animals exposed to the high-passage-number virus survived longer. However, none of the passage 13 MARV-exposed animals succumbed to 0.01-PFU exposure compared to 75% of passage 3-exposed animals. This is consistent with other filovirus studies that show some particles that are unable to yield a plaque in cell culture can cause lethal disease in vivo. These results have important consequences for the design of experiments that investigate MARV pathogenesis and that test the efficacy of MARV countermeasures. IMPORTANCE Marburg virus (MARV) causes disease with a high case fatality rate, and there are no approved vaccines or therapies. Serial amplification of viruses in cell culture often results in accumulation of mutations, but the effect of such cell culture passage on MARV is unclear. Serial passages

  11. Ebola Virus Disease Candidate Vaccines Under Evaluation in Clinical Trials

    DTIC Science & Technology

    2016-06-02

    studies in HPIV-3-immune guinea pigs with EBOV GP1,2-expressing HPIV-3 have suggested that while pre-existing immunity to the vector suppressed... guinea pigs and nonhuman primates against infection with multiple Marburg viruses. Expert Rev Vaccines, 7(4), 417-429 (2008). 98. Warfield KL...Swenson DL, Negley DL et al. Marburg virus-like particles protect guinea pigs from lethal Marburg virus infection. Vaccine, 22(25-26), 3495-3502 (2004

  12. Nucleoprotein-based indirect enzyme-linked immunosorbent assay (indirect ELISA) for detecting antibodies specific to Ebola virus and Marbug virus.

    PubMed

    Huang, Yi; Zhu, Youjie; Yang, Mengshi; Zhang, Zhenqing; Song, Donglin; Yuan, Zhiming

    2014-12-01

    Full-length nucleoproteins from Ebola and Marburg viruses were expressed as His-tagged recombinant proteins in Escherichia coli and nucleoprotein-based enzyme-linked immunosorbent assays (ELISAs) were established for the detection of antibodies specific to Ebola and Marburg viruses. The ELISAs were evaluated by testing antisera collected from rabbit immunized with Ebola and Marburg virus nucleoproteins. Although little cross-reactivity of antibodies was observed in anti-Ebola virus nucleoprotein rabbit antisera, the highest reactions to immunoglobulin G (IgG) were uniformly detected against the nucleoprotein antigens of homologous viruses. We further evaluated the ELISA's ability to detect antibodies to Ebola and Marburg viruses using human sera samples collected from individuals passing through the Guangdong port of entry. With a threshold set at the mean plus three standard deviations of average optical densities of sera tested, the ELISA systems using these two recombinant nucleoproteins have good sensitivity and specificity. These results demonstrate the usefulness of ELISA for diagnostics as well as ecological and serosurvey studies of Ebola and Marburg virus infection.

  13. Genomic analysis of codon usage shows influence of mutation pressure, natural selection, and host features on Marburg virus evolution.

    PubMed

    Nasrullah, Izza; Butt, Azeem M; Tahir, Shifa; Idrees, Muhammad; Tong, Yigang

    2015-08-26

    The Marburg virus (MARV) has a negative-sense single-stranded RNA genome, belongs to the family Filoviridae, and is responsible for several outbreaks of highly fatal hemorrhagic fever. Codon usage patterns of viruses reflect a series of evolutionary changes that enable viruses to shape their survival rates and fitness toward the external environment and, most importantly, their hosts. To understand the evolution of MARV at the codon level, we report a comprehensive analysis of synonymous codon usage patterns in MARV genomes. Multiple codon analysis approaches and statistical methods were performed to determine overall codon usage patterns, biases in codon usage, and influence of various factors, including mutation pressure, natural selection, and its two hosts, Homo sapiens and Rousettus aegyptiacus. Nucleotide composition and relative synonymous codon usage (RSCU) analysis revealed that MARV shows mutation bias and prefers U- and A-ended codons to code amino acids. Effective number of codons analysis indicated that overall codon usage among MARV genomes is slightly biased. The Parity Rule 2 plot analysis showed that GC and AU nucleotides were not used proportionally which accounts for the presence of natural selection. Codon usage patterns of MARV were also found to be influenced by its hosts. This indicates that MARV have evolved codon usage patterns that are specific to both of its hosts. Moreover, selection pressure from R. aegyptiacus on the MARV RSCU patterns was found to be dominant compared with that from H. sapiens. Overall, mutation pressure was found to be the most important and dominant force that shapes codon usage patterns in MARV. To our knowledge, this is the first detailed codon usage analysis of MARV and extends our understanding of the mechanisms that contribute to codon usage and evolution of MARV.

  14. Inverted schneiderian papilloma of the supraglottis: Case report.

    PubMed

    Saddawi-Konefka, Robert; Hariri, Nosaibah; Shabaik, Ahmed; Weissbrod, Philip A

    2017-12-01

    Inverted schneiderian papillomas are rare benign tumors, most often arising from the sinonasal mucosa. We describe a case of a 59-year-old female with an inverted papilloma of the supraglottis. This is the first reported case of a supraglottic-presenting inverted papilloma. Although rare, this case demonstrates that these tumors should be considered during workup of supraglottic laryngeal masses. Laryngoscope, 127:2830-2832, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

  15. Hemorrhagic Fevers

    MedlinePlus

    ... by four families of viruses. These include the Ebola and Marburg, Lassa fever, and yellow fever viruses. ... Some VHFs cause mild disease, but some, like Ebola or Marburg, cause severe disease and death. VHFs ...

  16. From hybridomas to a robust microalgal-based production platform: molecular design of a diatom secreting monoclonal antibodies directed against the Marburg virus nucleoprotein.

    PubMed

    Hempel, Franziska; Maurer, Michael; Brockmann, Björn; Mayer, Christian; Biedenkopf, Nadine; Kelterbaum, Anne; Becker, Stephan; Maier, Uwe G

    2017-07-27

    The ideal protein expression system should provide recombinant proteins in high quality and quantity involving low production costs only. However, especially for complex therapeutic proteins like monoclonal antibodies many challenges remain to meet this goal and up to now production of monoclonal antibodies is very costly and delicate. Particularly, emerging disease outbreaks like Ebola virus in Western Africa in 2014-2016 make it necessary to reevaluate existing production platforms and develop robust and cheap alternatives that are easy to handle. In this study, we engineered the microalga Phaeodactylum tricornutum to produce monoclonal IgG antibodies against the nucleoprotein of Marburg virus, a close relative of Ebola virus causing severe hemorrhagic fever with high fatality rates in humans. Sequences for both chains of a mouse IgG antibody were retrieved from a murine hybridoma cell line and implemented in the microalgal system. Fully assembled antibodies were shown to be secreted by the alga and antibodies were proven to be functional in western blot, ELISA as well as IFA studies just like the original hybridoma produced IgG. Furthermore, synthetic variants with constant regions of a rabbit IgG and human IgG with optimized codon usage were produced and characterized. This study highlights the potential of microalgae as robust and low cost expression platform for monoclonal antibodies secreting IgG antibodies directly into the culture medium. Microalgae possess rapid growth rates, need basically only water, air and sunlight for cultivation and are very easy to handle.

  17. Planetary Society

    NASA Astrophysics Data System (ADS)

    Murdin, P.

    2000-11-01

    Carl Sagan, Bruce Murray and Louis Friedman founded the non-profit Planetary Society in 1979 to advance the exploration of the solar system and to continue the search for extraterrestrial life. The Society has its headquarters in Pasadena, California, but is international in scope, with 100 000 members worldwide, making it the largest space interest group in the world. The Society funds a var...

  18. Detection of lipid-induced structural changes of the Marburg virus matrix protein VP40 using hydrogen/deuterium exchange-mass spectrometry

    PubMed Central

    Wijesinghe, Kaveesha J.; Urata, Sarah; Bhattarai, Nisha; Kooijman, Edgar E.; Gerstman, Bernard S.; Chapagain, Prem P.; Li, Sheng; Stahelin, Robert V.

    2017-01-01

    Marburg virus (MARV) is a lipid-enveloped virus from the Filoviridae family containing a negative sense RNA genome. One of the seven MARV genes encodes the matrix protein VP40, which forms a matrix layer beneath the plasma membrane inner leaflet to facilitate budding from the host cell. MARV VP40 (mVP40) has been shown to be a dimeric peripheral protein with a broad and flat basic surface that can associate with anionic phospholipids such as phosphatidylserine. Although a number of mVP40 cationic residues have been shown to facilitate binding to membranes containing anionic lipids, much less is known on how mVP40 assembles to form the matrix layer following membrane binding. Here we have used hydrogen/deuterium exchange (HDX) mass spectrometry to determine the solvent accessibility of mVP40 residues in the absence and presence of phosphatidylserine and phosphatidylinositol 4,5-bisphosphate. HDX analysis demonstrates that two basic loops in the mVP40 C-terminal domain make important contributions to anionic membrane binding and also reveals a potential oligomerization interface in the C-terminal domain as well as a conserved oligomerization interface in the mVP40 N-terminal domain. Lipid binding assays confirm the role of the two basic patches elucidated with HD/X measurements, whereas molecular dynamics simulations and membrane insertion measurements complement these studies to demonstrate that mVP40 does not appreciably insert into the hydrocarbon region of anionic membranes in contrast to the matrix protein from Ebola virus. Taken together, we propose a model by which association of the mVP40 dimer with the anionic plasma membrane facilitates assembly of mVP40 oligomers. PMID:28167534

  19. International Disease Surveillance: United States Government Goals and Paths Forward

    DTIC Science & Technology

    2010-06-01

    convincing case to funders (ie, the U.S. Congress) showing how investment in surveillance for routine disease (eg, rotavirus ) prepares countries to detect...Hemorrhagic Fevers (Lassa, Marburg, Ebola) Viral Hemorrhagic Fevers (Lassa, Marburg, Ebola) Rotavirus Center for Biosecurity of UPMC | June 2010 Page 18

  20. Advanced titration to treat a floppy epiglottis in selective upper airway stimulation.

    PubMed

    Heiser, Clemens

    2016-09-01

    The following report presents a case of a patient with high residual apnea-hypopnea index at 6 months following implantation of an upper airway stimulation device who improved significantly after advanced titration via drug-induced sedated endoscopy by changing the electrode configuration for stimulation from bipolar to monopolar. This case demonstrates the utility of postsurgical advanced titration to optimize programming settings for improved clinical outcomes. Laryngoscope, 126:S22-S24, 2016. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

  1. Interaction with Tsg101 is necessary for the efficient transport and release of nucleocapsids in marburg virus-infected cells.

    PubMed

    Dolnik, Olga; Kolesnikova, Larissa; Welsch, Sonja; Strecker, Thomas; Schudt, Gordian; Becker, Stephan

    2014-10-01

    Endosomal sorting complex required for transport (ESCRT) machinery supports the efficient budding of Marburg virus (MARV) and many other enveloped viruses. Interaction between components of the ESCRT machinery and viral proteins is predominantly mediated by short tetrapeptide motifs, known as late domains. MARV contains late domain motifs in the matrix protein VP40 and in the genome-encapsidating nucleoprotein (NP). The PSAP late domain motif of NP recruits the ESCRT-I protein tumor susceptibility gene 101 (Tsg101). Here, we generated a recombinant MARV encoding NP with a mutated PSAP late domain (rMARV(PSAPmut)). rMARV(PSAPmut) was attenuated by up to one log compared with recombinant wild-type MARV (rMARV(wt)), formed smaller plaques and exhibited delayed virus release. Nucleocapsids in rMARV(PSAPmut)-infected cells were more densely packed inside viral inclusions and more abundant in the cytoplasm than in rMARV(wt)-infected cells. A similar phenotype was detected when MARV-infected cells were depleted of Tsg101. Live-cell imaging analyses revealed that Tsg101 accumulated in inclusions of rMARV(wt)-infected cells and was co-transported together with nucleocapsids. In contrast, rMARV(PSAPmut) nucleocapsids did not display co-localization with Tsg101, had significantly shorter transport trajectories, and migration close to the plasma membrane was severely impaired, resulting in reduced recruitment into filopodia, the major budding sites of MARV. We further show that the Tsg101 interacting protein IQGAP1, an actin cytoskeleton regulator, was recruited into inclusions and to individual nucleocapsids together with Tsg101. Moreover, IQGAP1 was detected in a contrail-like structure at the rear end of migrating nucleocapsids. Down regulation of IQGAP1 impaired release of MARV. These results indicate that the PSAP motif in NP, which enables binding to Tsg101, is important for the efficient actin-dependent transport of nucleocapsids to the sites of budding. Thus, the

  2. Indian Vacuum Society: The Indian Vacuum Society

    NASA Astrophysics Data System (ADS)

    Saha, T. K.

    2008-03-01

    The Indian Vacuum Society (IVS) was established in 1970. It has over 800 members including many from Industry and R & D Institutions spread throughout India. The society has an active chapter at Kolkata. The society was formed with the main aim to promote, encourage and develop the growth of Vacuum Science, Techniques and Applications in India. In order to achieve this aim it has conducted a number of short term courses at graduate and technician levels on vacuum science and technology on topics ranging from low vacuum to ultrahigh vacuum So far it has conducted 39 such courses at different parts of the country and imparted training to more than 1200 persons in the field. Some of these courses were in-plant training courses conducted on the premises of the establishment and designed to take care of the special needs of the establishment. IVS also regularly conducts national and international seminars and symposia on vacuum science and technology with special emphasis on some theme related to applications of vacuum. A large number of delegates from all over India take part in the deliberations of such seminars and symposia and present their work. IVS also arranges technical visits to different industries and research institutes. The society also helped in the UNESCO sponsored post-graduate level courses in vacuum science, technology and applications conducted by Mumbai University. The society has also designed a certificate and diploma course for graduate level students studying vacuum science and technology and has submitted a syllabus to the academic council of the University of Mumbai for their approval, we hope that some colleges affiliated to the university will start this course from the coming academic year. IVS extended its support in standardizing many of the vacuum instruments and played a vital role in helping to set up a Regional Testing Centre along with BARC. As part of the development of vacuum education, the society arranges the participation of

  3. Evolving role of mitomycin-C laryngology

    NASA Astrophysics Data System (ADS)

    Richards, Steven V.; Garrett, C. Gaelyn

    2001-05-01

    Topical mitomycin-C, a chemotherapeutic agent and a fibroblast inhibitor, has been successfully used in larynx, primarily to treat stenosis. Subglottic, tracheal, and anterior glottic stenosis have all shown promising results in a canine model. Less favorable results have been obtained when topical mitomycin-C is used on the vocal folds following surgical excision of mucosa. In the vocal fold studies, laryngeal videostroboscopy revealed diminished mucosal wave vibration in the vocal folds treated with mitomycin-C as well as a more atrophic appearance to the vibratory surface. The tissue treated with mitomycin-C showed fewer fibroblasts and less collagen. However, inflammatory infiltrate was not significantly different between the treated and untreated tissue. These results are consistent with the known suppression of fibroblast proliferation by mitomycin-C. In contrast to the positive effects of mitomycin-C on stenosis, the observed decrease in the healing response in the vocal fold had negative consequences on vocal fold vibratory pattern.

  4. Information exchange of the Atomic Energy Society of Japan with nuclear societies worldwide

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hori, Masao; Tomita, Yasushi

    2000-07-01

    The Atomic Energy Society of Japan (AESJ) exchanges information with nuclear societies worldwide by intersocietal communication through international councils of nuclear societies and through bilateral agreements between foreign societies and by such media as international meetings, publications, and Internet applications.

  5. Duplicated facial nerve trunk with a first branchial cleft cyst.

    PubMed

    Hinson, Drew; Poteet, Perry; Bower, Charles

    2014-03-01

    First branchial cleft anomalies are rare and their various anatomical relationships to the facial nerve have been described. We encountered a 15-year-old female with a type II first branchial cleft cyst presenting as a right neck mass that we found during surgical excision to transverse two main facial nerve trunks. To our knowledge, this is the first reported case of a first branchial cleft anomaly in conjunction with a duplicated facial nerve trunk. © 2013 The American Laryngological, Rhinological and Otological Society, Inc.

  6. Ebola/Marburg

    MedlinePlus

    ... Award Negotiation & Initial Award After Award Foreign Grants Management Getting Your Initial International Award Actions You Can Take as the Project Leader on a Foreign Grant Subawards for Foreign ...

  7. The National Cardiac Societies of the European Society of Cardiology.

    PubMed

    Atar, Dan

    2015-06-01

    The National Cardiac Societies are one of the Constituent Bodies of the European Society of Cardiology (ESC). They are the backbone of the ESC and together form the "Cardiology of Europe" in 56 European and Mediterranean countries.

  8. Strain characteristics of Marburg double crown-retained implant overdentures compared with bar and ball-retained implant overdentures, with and without a rigid major connector.

    PubMed

    Kazokoğlu, F Şehnaz; Akaltan, Funda

    2014-12-01

    It is hard to identify the most favorable retainer type and the denture design when considering strain levels around implants and in edentulous ridges for implant overdentures (IOVD). The purpose of this study was to evaluate the strain transmitted to the implants and edentulous ridges by Marburg double crown (MDC)-retained IOVD as opposed to bar and ball-retained IOVD and the efficiency of a rigid major connector in the maxilla. An in vitro maxillary model was prepared with 4 implants, with strain gauges placed distally to each implant and also in the anterior and posterior edentulous ridges. Five overdentures were fabricated for each MDC and each ball and bar attachment retainers. Vertical loads of 280 N were applied bilaterally on the first molar region. Then the palatal bars of each IOVD were disconnected, and loading procedures were repeated for the prostheses. No significant difference was observed among the MDC and the bar and ball-retained IOVD, with and without a rigid bar according to the data taken from both the implants and edentulous ridges. However, when the strain values attained from each strain gauge separately were considered, a slight difference was observed around the implants of ball-retained overdentures and in the edentulous ridges of MDC-retained overdentures. Within the limitations of this in vitro study, MDC-retained maxillary overdentures with 4 parallel and symmetrically placed implants can be used safely without a rigid major connector as with bar and ball-retained IOVD with regard to the strains generated in the edentulous ridge and around implants. Copyright © 2014 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

  9. Consumption in the Information Society

    ERIC Educational Resources Information Center

    Zherebin, V. M.; Ermakova, N. A.; Makhrova, O. N.

    2010-01-01

    The current state of the economy in the developed countries make it possible to characterize them using concepts and terms such as the postindustrial society, the new economy, the service economy, the creative economy, the posteconomic society, the information society, the knowledge society, and the consumer society. Among these terms and…

  10. Laryngoscopy during swimming: A novel diagnostic technique to characterize swimming-induced laryngeal obstruction.

    PubMed

    Walsted, Emil S; Swanton, Laura L; van van Someren, Ken; Morris, Tessa E; Furber, Matthew; Backer, Vibeke; Hull, James H

    2017-10-01

    Exercise-induced laryngeal obstruction (EILO) is a key differential diagnosis for respiratory symptoms in athletes and is particularly prevalent in aquatic athletes. A definitive diagnosis of EILO is dependent on laryngoscopy, performed continuously, while an athlete engages in the sport that precipitates their symptoms. This report provides the first description of the feasibility of performing continuous laryngoscopy during exercise in a swimming environment. The report describes the methodology and safety of the use of continuous laryngoscopy while swimming. Laryngoscope, 127:2298-2301, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

  11. American Rocket Society

    NASA Technical Reports Server (NTRS)

    2004-01-01

    In addition to Dr. Robert Goddard's pioneering work, American experimentation in rocketry prior to World War II grew, primarily in technical societies. This is an early rocket motor designed and developed by the American Rocket Society in 1932.

  12. Vocal fold hemorrhage: factors predicting recurrence.

    PubMed

    Lennon, Christen J; Murry, Thomas; Sulica, Lucian

    2014-01-01

    Vocal fold hemorrhage is an acute phonotraumatic injury treated with voice rest; recurrence is a generally accepted indication for surgical intervention. This study aims to identify factors predictive of recurrence based on outcomes of a large clinical series. Retrospective cohort. Retrospective review of cases of vocal fold hemorrhage presenting to a university laryngology service. Demographic information was compiled. Videostroboscopic exams were evaluated for hemorrhage extent, presence of varix, mucosal lesion, and/or vocal fold paresis. Vocal fold hemorrhage recurrence was the main outcome measure. Follow-up telephone survey was used to complement clinical data. Forty-seven instances of vocal fold hemorrhage were evaluated (25M:22F; 32 professional voice users). Twelve of the 47 (26%) patients experienced recurrence. Only the presence of varix demonstrated significant association with recurrence (P = 0.0089) on multivariate logistic regression. Vocal fold hemorrhage recurred in approximately 26% of patients. Varix was a predictor of recurrence, with 48% of those with varix experiencing recurrence. Monitoring, behavioral management and/or surgical intervention may be indicated to treat patients with such characteristics. © 2013 The American Laryngological, Rhinological and Otological Society, Inc.

  13. Multisociety consensus quality improvement guidelines for intraarterial catheter-directed treatment of acute ischemic stroke, from the American Society of Neuroradiology, Canadian Interventional Radiology Association, Cardiovascular and Interventional Radiological Society of Europe, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society of NeuroInterventional Surgery, European Society of Minimally Invasive Neurological Therapy, and Society of Vascular and Interventional Neurology.

    PubMed

    Sacks, David; Black, Carl M; Cognard, Christophe; Connors, John J; Frei, Donald; Gupta, Rishi; Jovin, Tudor G; Kluck, Bryan; Meyers, Philip M; Murphy, Kieran J; Ramee, Stephen; Rüfenacht, Daniel A; Bernadette Stallmeyer, M J; Vorwerk, Dierk

    2013-02-01

    In this international multispecialty document, quality benchmarks for processes of care and clinical outcomes are defined. It is intended that these benchmarks be used in a quality assurance program to assess and improve processes and outcomes in acute stroke revascularization. Members of the writing group were appointed by the American Society of Neuroradiology, Canadian Interventional Radiology Association, Cardiovascular and Interventional Radiological Society of Europe, Society of Cardiac Angiography and Interventions, Society of Interventional Radiology, Society of NeuroInterventional Surgery, European Society of Minimally Invasive Neurological Therapy, and Society of Vascular and Interventional Neurology. The writing group reviewed the relevant literature from 1986 through February 2012 to create an evidence table summarizing processes and outcomes of care. Performance metrics and thresholds were then created by consensus. The guideline was approved by the sponsoring societies. It is intended that this guideline be fully updated in 3 years. In this international multispecialty document, quality benchmarks for processes of care and clinical outcomes are defined. These include process measures of time to imaging, arterial puncture, and revascularization and measures of clinical outcome up to 90 days. Quality improvement guidelines are provided for endovascular acute ischemic stroke revascularization procedures. Copyright © 2013 SIR. Published by Elsevier Inc. All rights reserved.

  14. Participation of women in neurochemistry societies.

    PubMed

    Lees, Marjorie B

    2002-11-01

    Women have made important scientific contributions to the field of neurochemistry, and they have also been leaders in neurochemical societies throughout the world. Here I discuss women's involvement and leadership in six neurochemistry societies: American Society for Neurochemistry, Argentine Society for Neurochemistry, International Society for Neurochemistry, European Society for Neurochemistry, Japanese Society for Neurochemistry, and Asian-Pacific Society for Neurochemistry. The number of women who have been active in these societies and the level of their activity vary considerably. Neurochemical societies in the Western hemisphere, i.e., the American and the Argentine Society for Neurochemistry, have much greater numbers of women who have held office, been on council, or engaged in other leadership activities than in the rest of the world. The limited participation of women in the Japanese Neurochemistry Society relates to Japanese cultural views and was not unexpected. However, the relatively few women leaders in the International Society for Neurochemistry was a surprise. The European Society had a somewhat better record of female participation than did the International Society. The reasons for these differences are partly cultural, but factors related to when each society was formed, how it is organized, and how elections are structured undoubtedly play a role. Further analysis of these observations would be of interest from a sociological and a women's studies point of view.

  15. The Marburg-Münster Affective Disorders Cohort Study (MACS): A quality assurance protocol for MR neuroimaging data.

    PubMed

    Vogelbacher, Christoph; Möbius, Thomas W D; Sommer, Jens; Schuster, Verena; Dannlowski, Udo; Kircher, Tilo; Dempfle, Astrid; Jansen, Andreas; Bopp, Miriam H A

    2018-05-15

    Large, longitudinal, multi-center MR neuroimaging studies require comprehensive quality assurance (QA) protocols for assessing the general quality of the compiled data, indicating potential malfunctions in the scanning equipment, and evaluating inter-site differences that need to be accounted for in subsequent analyses. We describe the implementation of a QA protocol for functional magnet resonance imaging (fMRI) data based on the regular measurement of an MRI phantom and an extensive variety of currently published QA statistics. The protocol is implemented in the MACS (Marburg-Münster Affective Disorders Cohort Study, http://for2107.de/), a two-center research consortium studying the neurobiological foundations of affective disorders. Between February 2015 and October 2016, 1214 phantom measurements have been acquired using a standard fMRI protocol. Using 444 healthy control subjects which have been measured between 2014 and 2016 in the cohort, we investigate the extent of between-site differences in contrast to the dependence on subject-specific covariates (age and sex) for structural MRI, fMRI, and diffusion tensor imaging (DTI) data. We show that most of the presented QA statistics differ severely not only between the two scanners used for the cohort but also between experimental settings (e.g. hardware and software changes), demonstrate that some of these statistics depend on external variables (e.g. time of day, temperature), highlight their strong dependence on proper handling of the MRI phantom, and show how the use of a phantom holder may balance this dependence. Site effects, however, do not only exist for the phantom data, but also for human MRI data. Using T1-weighted structural images, we show that total intracranial (TIV), grey matter (GMV), and white matter (WMV) volumes significantly differ between the MR scanners, showing large effect sizes. Voxel-based morphometry (VBM) analyses show that these structural differences observed between scanners are

  16. Advanced Development of Antiviral Prophylactics and Therapeutics (ADAPT) - Research Area 10

    DTIC Science & Technology

    2014-11-17

    various Prosetta compounds against Rift Valley Fever Virus (RVFV), Lassa virus (LASV) and Marburg virus (MARV), respectively. Activity is demonstrated as...USAMRIID for in vitro efficacy testing against various hemorrhagic fever viruses, including Ebola (EBOV), Marburg (MARV), Lassa (LASV), Rift Valley...unless so designated by other documentation. 14. ABSTRACT The pmpose of the proposed work is to continue the promising anti-hemonhagic fever vims (HFV

  17. Exploratory of society

    NASA Astrophysics Data System (ADS)

    Cederman, L.-E.; Conte, R.; Helbing, D.; Nowak, A.; Schweitzer, F.; Vespignani, A.

    2012-11-01

    A huge flow of quantitative social, demographic and behavioral data is becoming available that traces the activities and interactions of individuals, social patterns, transportation infrastructures and travel fluxes. This has caused, together with innovative computational techniques and methods for modeling social actions in hybrid (natural and artificial) societies, a qualitative change in the ways we model socio-technical systems. For the first time, society can be studied in a comprehensive fashion that addresses social and behavioral complexity. In other words we are in the position to envision the development of large data and computational cyber infrastructure defining an exploratory of society that provides quantitative anticipatory, explanatory and scenario analysis capabilities ranging from emerging infectious disease to conflict and crime surges. The goal of the exploratory of society is to provide the basic infrastructure embedding the framework of tools and knowledge needed for the design of forecast/anticipatory/crisis management approaches to socio technical systems, supporting future decision making procedures by accelerating the scientific cycle that goes from data generation to predictions.

  18. Next Generation Diagnostic System (NGDS) Increment 1 Early Fielding Report

    DTIC Science & Technology

    2017-06-07

    for a NGDS Warrior Panel test FOB 5- Marburg Virus 2 – Marburg 1 – Staph infection 1 – Flu Yes 5 days post -exposure 70 minutes after...Director, Operational Test and Evaluation Next Generation Diagnostic System (NGDS) Increment 1 Early Fielding Report   June 2017...Increment 1 Early Fielding Report Summary This report provides the Director, Operational Test and Evaluation’s (DOT&E) operational assessment of the

  19. [Laryngological experiences in treatment of Bell's palsy].

    PubMed

    Obrebowski, A; Pruszewicz, A

    2001-01-01

    Between 1990-2000 15 cases of unilateral Bell paresis of the VIIth nerve were treated using local injection of hydrocortisone in the region of the foramen stylomastoideum. Paralelly were administered iontophoresis, galvanisation of the facial mimic muscles together with vasodilating drugs. Early introduced treatment gave complete return of facialis function. The usefulness of treatment monitoring with topodiagnostic tests is stressed.

  20. Rapidly fluctuating anosmia: A clinical sign for unilateral smell impairment.

    PubMed

    Negoias, Simona; Friedrich, Hergen; Caversaccio, Marco D; Landis, Basile N

    2016-02-01

    Reports about fluctuating olfactory deficits are rare, as are reports of unilateral olfactory loss. We present a case of unilateral anosmia with contralateral normosmia, presenting as rapidly fluctuating anosmia. The olfactory fluctuation occurred in sync with the average nasal cycle duration. Examination after nasal decongestion, formal smell testing, and imaging revealed unilateral, left-sided anosmia of sinonasal cause, with right-sided normosmia. We hypothesize that the nasal cycle induced transient anosmia when blocking the normosmic side. Fluctuating olfactory deficits might hide a unilateral olfactory loss and require additional unilateral testing and thorough workup. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

  1. Insights into horizontal canal benign paroxysmal positional vertigo from a human case report.

    PubMed

    Aron, Margaret; Bance, Manohar

    2013-12-01

    For horizontal canal benign paroxysmal positional vertigo, determination of the pathologic side is difficult and based on many physiological assumptions. This article reports findings on a patient who had one dysfunctional inner ear and who presented with horizontal canal benign paroxysmal positional vertigo, giving us a relatively pure model for observing nystagmus arising in a subject in whom the affected side is known a priori. It is an interesting human model corroborating theories of nystagmus generation in this pathology and also serves to validate Ewald's second law in a living human subject. Copyright © 2013 The American Laryngological, Rhinological and Otological Society, Inc.

  2. Information Exchange of the Atomic Energy Society of Japan with Nuclear Societies Worldwide

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Masao Hori; Yasushi Tomita

    2000-06-04

    This paper describes committees of the Atomic Energy Society of Japan (AESJ) related to information exchange, AESJ publications, AESJ Internet applications, and means for future information exchange between nuclear societies.

  3. Risk society and the distribution of bads: theorizing class in the risk society.

    PubMed

    Curran, Dean

    2013-03-01

    Ulrich Beck states in the Risk Society (1992) that the rise of the social production of risks in the risk society signals that class ceases to be of relevance; instead the hierarchical logic of class will be supplanted by the egalitarian logic of the distribution of risks. Several trenchant critiques of Beck's claim have justified the continued relevance of class to contemporary society. While these accounts have emphasized continuity, they have not attempted to chart, as this paper will, how the growing social production of risk increases the importance of class. This paper argues that it is Beck's undifferentiated, catastrophic account of risk that undergirds his rejection of class, and that by inserting an account of risk involving gradations in both damages and calculability into Beck's framework, his theory of risk society may be used to develop a critical theory of class. Such a theory can be used to reveal how wealth differentials associated with class relations actually increase in importance to individuals' life-chances in the risk society. With the growing production and distribution of bads, class inequalities gain added significance, since it will be relative wealth differentials that both enables the advantaged to minimize their risk exposure and imposes on others the necessity of facing the intensified risks of the risk society. © London School of Economics and Political Science 2013.

  4. Ecologic and Geographic Distribution of Filovirus Disease

    PubMed Central

    Bauer, John T.; Mills, James N.

    2004-01-01

    We used ecologic niche modeling of outbreaks and sporadic cases of filovirus-associated hemorrhagic fever (HF) to provide a large-scale perspective on the geographic and ecologic distributions of Ebola and Marburg viruses. We predicted that filovirus would occur across the Afrotropics: Ebola HF in the humid rain forests of central and western Africa, and Marburg HF in the drier and more open areas of central and eastern Africa. Most of the predicted geographic extent of Ebola HF has been observed; Marburg HF has the potential to occur farther south and east. Ecologic conditions appropriate for Ebola HF are also present in Southeast Asia and the Philippines, where Ebola Reston is hypothesized to be distributed. This first large-scale ecologic analysis provides a framework for a more informed search for taxa that could constitute the natural reservoir for this virus family. PMID:15078595

  5. Implementation of study results in guidelines and adherence to guidelines in clinical practice.

    PubMed

    Waldfahrer, Frank

    2016-01-01

    Guidelines were introduced in hospital- and practice-based otorhinolaryngology in the 1990ies, and have been undergoing further development ever since. There are currently 20 guidelines on file at the German Society of Oto-Rhino-Laryngology, Head & Neck Surgery. The society has cooperated in further 34 guidelines. The quality of the guidelines has been continuously improved by concrete specifications put forward by the Association of the Scientific Medical Societies in Germany (Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e.V., AWMF). Since increasing digitalization has made access to scientific publications quicker and simpler, relevant study results can be incorporated in guidelines more easily today than in the analog world. S2e and S3 guidelines must be based on a formal literature search with subsequent evaluation of the evidence. The consensus procedure for S2k guidelines is also regulated. However, the implementation of guidelines in routine medical practice must still be considered inadequate, and there is still a considerable need for improvement in adherence to these guidelines.

  6. Did Educational Expansion Trigger the Development of an Education Society? Chances and Risks of a New Model of Society

    ERIC Educational Resources Information Center

    Haunberger, Sigrid

    2010-01-01

    This article focuses on the question of whether educational expansion leads to a new type of society, the education society. Taking into consideration the combined elements of three models of society (the post-industrial society, the knowledge society and the information society)--the chances and risks of an educational society will be elicited…

  7. Guidance for contact tracing of cases of Lassa fever, Ebola or Marburg haemorrhagic fever on an airplane: results of a European expert consultation.

    PubMed

    Gilsdorf, Andreas; Morgan, Dilys; Leitmeyer, Katrin

    2012-11-21

    Travel from countries where viral haemorrhagic fevers (VHF) are endemic has increased significantly over the past decades. In several reported VHF events on airplanes, passenger trace back was initiated but the scale of the trace back differed considerably. The absence of guidance documents to help the decision on necessity and scale of the trace back contributed to this variation.This article outlines the recommendations of an expert panel on Lassa fever, Ebola and Marburg haemorrhagic fever to the wider scientific community in order to advise the relevant stakeholders in the decision and scale of a possible passenger trace back. The evidence was collected through review of published literature and through the views of an expert panel. The guidance was agreed by consensus. Only a few events of VHF cases during air travel are reported in literature, with no documented infection in followed up contacts, so that no evidence of transmission of VHF during air travel exists to date. Based on this and the expert opinion, it was recommended that passenger trace back was undertaken only if: the index case had symptoms during the flight; the flight was within 21 days after detection of the event; and for Lassa fever if exposure of body fluid has been reported. The trace back should only be done after confirmation of the index case. Passengers and crew with direct contact, seat neighbours (+/- 1 seat), crew and cleaning personal of the section of the index case should be included in the trace back. No evidence has been found for the transmission of VHF in airplanes. This information should be taken into account, when a trace back decision has to be taken, because such a measure produces an enormous work load. The procedure suggested by the expert group can guide decisions made in future events, where a patient with suspected VHF infection travelled on a plane. However, the actual decision on start and scale of a trace back always lies in the hands of the responsible people

  8. Power Scaling of CW and Pulsed IR and Mid-IR OPSLs (Postprint)

    DTIC Science & Technology

    2013-01-01

    T. J. Rotter, G. Balakrishnan, and C. Hains University of New Mexico S. W . Koch, W . Stolz, and B . Kunert University of Marburg...Balakrishnan, and C. Hains (University of New Mexico ) S. W . Koch, W . Stolz, and B . Kunert (University of Marburg) 5d. PROJECT NUMBER 2002 5e. TASK...Yarboroughb, T. J Rotterc, G. Balakrishnanc, C. Hainsc, S.W. Kochd, W . Stolzd, B . Kunertd,R. Bedforde aNonlinear Control Strategies Inc, 3542 N

  9. Breast feeding and society.

    PubMed

    Hunt, Felicity

    2006-10-01

    Britain has the lowest breastfeeding rate of all countries in Europe; it is no longer the cultural norm in our society. Breastfeeding rates are affected by public attitude. This state of affairs is partly because of society's views on breastfeeding mothers, even though breastfeeding is known to be the optimum method of infant feeding for the baby, family and society. Common themes in the literature and websites are the economic advantages of breastfeeding, the public health benefits and the social construct of breastfeeding. Paediatric nurses have an important role in supporting breastfeeding mothers so that they are able to continue breastfeeding.

  10. Quality and readability assessment of websites related to recurrent respiratory papillomatosis.

    PubMed

    San Giorgi, Michel R M; de Groot, Olivier S D; Dikkers, Frederik G

    2017-10-01

    Recurrent respiratory papillomatosis (RRP) is a rare disease for which a limited number of information sources for patients exist. The role of the Internet in the patient-physician relationship is increasing. More and more patients search for online health information, which should be of good quality and easy readable. The study aim was to investigate the quality and readability of English online health information about RRP. Quality and readability assessment of online information. Relevant information was collected using three different search engines and seven different search terms. Quality was assessed with the DISCERN instrument. The Flesch Reading Ease Score (FRES) and average grade level (AGL) were determined to measure readability of the English websites. Fifty-one English websites were included. The mean DISCERN score of the websites is 28.1 ± 9.7 (poor quality); the mean FRES is 41.3 ± 14.9 (difficult to read); and the mean AGL is 12.6 ± 2.3. The quality and readability of English websites about RRP is alarmingly poor. NA. Laryngoscope, 127:2293-2297, 2017. © 2017 The Authors The Laryngoscope published by Wiley Periodicals, Inc. on behalf of American Laryngological, Rhinological and Otological Society Inc, “The Triological Society” and American Laryngological Association (ALA).

  11. Learning Society

    ERIC Educational Resources Information Center

    Cross, K. Patricia

    1974-01-01

    Campus-expansiveness, decentralization, cooperative movements in education and nontraditional study all have changed the national picture of education as one to embrace everyone in the new learning society. (Author/PG)

  12. Mobilising Data in a Knowledge Society

    NASA Astrophysics Data System (ADS)

    Wessels, Bridgette; Finn, Rachel; Wadhwa, Kush; Bigagli, Lorenzo; Nativi, Stefano; Noorman, Merel

    2016-04-01

    We address how the open data movement is fostering change in institutions, in data, and in social participation in the mobilisation of knowledge society. The idea of a knowledge society has been raised over the last two decades but the transition to such as society has not been realised. Up to the present time, discussion about a knowledge society have largely focused on a knowledge economy and information society rather than a mobilisation to a knowledge society. These debates have, however, taken place before the rise of open data and big data and the development of an open data movement. We consider the role of the open data movement in fostering transformation to a knowledge society. The characteristics of the open data movement that include the strong conviction of the value of open data for society, the attention to the institutional aspects of making data open in an inclusive way, the practical focus on the technological infrastructure are key in mobilising a knowledge society. At the heart of any mobilisation is an emerging open data ecosystem and new ways of producing and using data - whether 'born digital' data, digitised data or big data - and how that data, when made openly available, can be used in a knowledgeable way by societal actors.

  13. Marburg Virus Disease

    MedlinePlus

    ... MVD from other infectious diseases such as malaria, typhoid fever, shigellosis, meningitis and other viral haemorrhagic fevers. Confirmation ... MVD from other infectious diseases such as malaria, typhoid fever, shigellosis, meningitis and other viral haemorrhagic fevers. Confirmation ...

  14. World Society and Globalisation

    ERIC Educational Resources Information Center

    Wittmann, Veronika

    2014-01-01

    Purpose: The purpose of this paper is to illustrate discourses on globalisation and world society and to disclose the commonalities and differences of both scientific debates. In particular, it draws attention to theoretical concepts of globalisation and world society. This is considered fruitful for comprehending the complex mechanisms of…

  15. Finnish Society of Soil Sciences

    NASA Astrophysics Data System (ADS)

    Rankinen, Katri; Hänninen, Pekka; Soinne, Helena; Leppälammi-Kujansuu, Jaana; Salo, Tapio; Pennanen, Taina

    2017-04-01

    In 1998 the organization of the International Union of Soil Sciences (IUSS) was renewed to better support national activities. That was also the new start in the operation of the Finnish Society of Soil Sciences, which became affiliated to the IUSS. The society was originally established in 1971 but it remained relatively inactive. Currently, there are around 200 members in the Finnish Society of Soil Sciences. The members of the executive board cover different fields of soil science from geology to microbiology. Mission statement of the society is to promote the soil sciences and their application in Finland, to act as a forum for creation of better links between soil scientists, interested end users and the public, and to promote distribution and appreciation of general and Finnish research findings in soil science. Every second year the society organizes a national two-day long conference. In 2017 the theme 'circular economy' collected all together 57 presentations. The members of the incoming student division carried responsibility in practical co-ordination committee, acting also as session chairs. In the intervening years the society organizes a weekend excursion to neighboring areas. Lately we have explored the use of biochar in landscaping of Stockholm.

  16. Environment, energy, and society

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Humphrey, C.R.; Buttel, F.R.

    1986-01-01

    This book delineates the major ways in which human society and the environment affect each other. To study the structure of societies, it employs three conceptual models, or sociological paradigms, conservative, liberal, and radical. The book explains the courses in environmental sociology, international development, natural resources, agriculture, and urban or regional planning.

  17. Nursing in a postemotional society.

    PubMed

    Herdman, Elizabeth A

    2004-07-01

    Globalization is often seen as the final stage in the transition towards a market economy. It is argued that a side-effect of globalization is cultural homogeneity and loss of life world, or 'McDonaldization'. McDonaldization represents the rationalization of society in the quest for extreme efficiency. More recently, Mestrović has argued that the rationalization of emotions has also occurred and that Western societies are entering a postemotional phase. In postemotional societies there has been a separation of emotion from action. The result is synthetic, manufactured emotions manipulated and standardized for mass consumption. In this paper I explore what it means to nurse in a 'postemotional society' and what impact this dulling of the emotions has had on a profession that locates 'care' as its central defining concept. My aim is to generate critical discussion of the shape and direction of contemporary society and the role of nursing within it.

  18. Atraumatic intubation: experience using a 5.0 endotracheal tube without a stylet for laryngeal surgery.

    PubMed

    Moore, Jaime E; Hu, Amanda; Rutt, Amy; Green, Parmis; Hawkshaw, Mary; Sataloff, Robert T

    2015-02-01

    Vocal fold injury is a well-know complication of intubation, with rates reported as high as 69%. Laryngology textbooks recommend the use of a small endotracheal tube (ETT) to help avoid these complications and optimize visualization. Case reports have suggested that the rigid stylet can lead to laryngeal injury. Given the additional risks, intubation without the stylet is our preferred practice. There is limited documentation in the literature regarding this viewpoint. Our study investigated the feasibility of and potential barriers to intubation using 5.0 ETT without a stylet. Prospective study. Consecutive adult patients undergoing laryngeal surgery were recruited for intubation with a 5.0 ETT without a stylet. Demographic data, specialty and training level of the intubator, and factors that would predict a difficult intubation were recorded. Descriptive statistical analysis was performed. Findings of the participants (n = 67) included average American Society of Anesthesiologists (ASA) physical status classification (2.2), average Mallampati score (1.7), average Cormack-Lehane grade (1.5), and average body mass index (28.0). Five patients (7.4%) required intubation using a stylet, and one of these five participants was intubated initially with a stylet. Of these five participants, 80% required use of a GlideScope (P < .001), and they had significantly higher ASA classification (P = .047) and number of intubation attempts (P = .042). One patient sustained an oropharyngeal injury during intubation with a stylet. No participants had laryngeal injury. Most patients can be intubated successfully using a 5.0 ETT without a stylet. There were no cases of laryngeal trauma with this technique. 2b. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

  19. Science communication at scientific societies.

    PubMed

    Braha, Jeanne

    2017-10-01

    Scientific societies can play a key role in bridging the research and practice of scientists' engagement of public audiences. Societies are beginning to support translation of science communication research, connections between scientists and audiences, and the creation of opportunities for scientists to engage publics without extensive customization. This article suggests roles, strategies, and mechanisms for scientific societies to promote and enhance their member's engagement of public audiences. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. American Head and Neck Society

    MedlinePlus

    American Head & Neck Society Mission Statement: Advance Education, Research, and Quality of Care for the head and neck oncology patient. American Head & Neck Society | AHNS The mission of the AHNS is ...

  1. Advanced information society(2)

    NASA Astrophysics Data System (ADS)

    Masuyama, Keiichi

    Our modern life is full of information and information infiltrates into our daily life. Networking of the telecommunication is extended to society, company, and individual level. Although we have just entered the advanced information society, business world and our daily life have been steadily transformed by the advancement of information network. This advancement of information brings a big influence on economy, and will play they the main role in the expansion of domestic demands. This paper tries to view the image of coming advanced information society, focusing on the transforming businessman's life and the situation of our daily life, which became wealthy by the spread of daily life information and the visual information by satellite system, in the development of the intelligent city.

  2. Palatal botulinum toxin as a novel therapy for objective tinnitus in forced eyelid closure syndrome.

    PubMed

    Kaffenberger, Thomas M; Mandal, Rajarsi; Schaitkin, Barry M; Hirsch, Barry E

    2017-05-01

    Objective tinnitus associated with eyelid closure is a rare clinical entity with only a few reported cases. This association previously was identified as forced eyelid closure syndrome (FECS) and involves an aberrant neural reflex between cranial nerve VII (activating the orbicularis oculi muscle) and cranial nerve V (activating the tensor tympani muscle). We present a 52-year-old Caucasian female with a 2-month history of FECS who was successfully treated with intrapalatal botulinum toxin, with full resolution of her objective tinnitus symptoms. This is the first reported use of botulinum toxin in FECS. Laryngoscope, 127:1199-1201, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

  3. The catheter hub disinfection cap as esophageal foreign body.

    PubMed

    Tawfik, Kareem O; Myer, Charles M; Shikary, Tasneem; Goldschneider, Kenneth R

    2015-12-01

    Disinfection caps are increasingly being used to prevent catheter-associated bloodstream infections. These devices, designed for continuous passive disinfection of catheter hubs, are typically small and often brightly colored. As such, they have the potential to become pediatric airway and esophageal foreign bodies. We report two patients who developed esophageal foreign body following ingestion of disinfection caps. Given the increasing use of these devices, it is imperative that health care providers be aware of this potential iatrogenic problem. We propose that the use of disinfection caps may not be appropriate in pediatric patients with risk factors for foreign body ingestion. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

  4. Congenital stapes malformation: Rare conductive hearing loss in a patient with Waardenburg syndrome.

    PubMed

    Melzer, Jonathan M; Eliason, Michael; Conley, George S

    2016-04-01

    Waardenburg syndrome is a known autosomal dominant cause of congenital hearing loss. It is characterized by a distinctive phenotypic appearance and often involves sensorineural hearing loss. Temporal bone abnormalities and inner ear dysmorphisms have been described in association with the disease. However, middle ear abnormalities as causes of conductive hearing loss are not typically seen in Waardenburg syndrome. We discuss a case of an 8-year-old female who meets diagnostic criteria for Waardenburg syndrome type 3 and who presented with a bilateral conductive hearing loss associated with congenital stapes fixation. We discuss management strategy in this previously unreported phenotype. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

  5. Abortion in a just society.

    PubMed

    Hunt, M E

    1993-01-01

    A female Catholic theologian imagines a just society that does not judge women who decide to undergo an abortion. The Church, practitioners, and the courts must trust that women do make person-enhancing choices about the quality of life. In the last 15 years most progress in securing a woman's right to abortion has been limited to white, well-educated, and middle or upper middle class women. A just society would consider reproductive options a human right. Abortion providers are examples of a move to a just society; they are committed to women's well-being. There are some facts that make one pessimistic about achieving abortion in a just society. The US Supreme Court plans to review important decisions establishing abortion as a civil right. Further, some men insist on suing women who want to make their own reproductive decisions--an anti-choice tactic to wear away women's right to reproductive choice. Bombings of abortion clinics and harassment campaigns by anti-choice groups are common. These behaviors strain pro-choice proponents emotionally, psychically, and spiritually. Their tactics often lead to theologians practicing self-censorship because they fear backlash. Abortion providers also do this. Further, the reaction to AIDS is that sex is bad. Anti-abortion groups use AIDS to further their campaigns, claiming that AIDS is a punishment for sex. Strategies working towards abortion in a just society should be education and persuasion of policymakers and citizens about women's right to choose, since they are the ones most affected by abortion. Moreover, only women can secure their rights to abortion. In a just society, every health maintenance organization, insurance company, and group practice would consider abortion a normal service. A just society provides for the survival needs of the most marginalized.

  6. Languages in Contemporary Anglophone Caribbean Societies

    ERIC Educational Resources Information Center

    Davids, Melva P.

    2013-01-01

    The paper Languages in Contemporary Anglophone Caribbean Societies examines how language is treated in Jamaica and other Anglophone Caribbean societies and the effects of a haphazard approach to language planning on the social dynamics of the society as well as the individual. It briefly explores how Language is handled in Francophone or…

  7. The Contemporary Medical Society Library

    PubMed Central

    Crawford, Susan; Michel, Carol; Waligorski, Conrad

    1965-01-01

    Four hundred sixty-eight medical societies in the United States were surveyed to determine those which sponsor libraries. Seventy-eight libraries were identified, of which eighteen are “marginal” and nine are jointly supported by a medical school and a society, leaving fifty-one relatively “substantial” libraries whose major support is through society membership. Characteristics measured include size of collection, types of media, staff, budget, services, and sources of support. Questions are raised concerning the role of the medical library as one institution which participates in the continuing education of the physician. PMID:14271112

  8. A Case Series of the Probability Density and Cumulative Distribution of Laryngeal Disease in a Tertiary Care Voice Center.

    PubMed

    de la Fuente, Jaime; Garrett, C Gaelyn; Ossoff, Robert; Vinson, Kim; Francis, David O; Gelbard, Alexander

    2017-11-01

    To examine the distribution of clinic and operative pathology in a tertiary care laryngology practice. Probability density and cumulative distribution analyses (Pareto analysis) was used to rank order laryngeal conditions seen in an outpatient tertiary care laryngology practice and those requiring surgical intervention during a 3-year period. Among 3783 new clinic consultations and 1380 operative procedures, voice disorders were the most common primary diagnostic category seen in clinic (n = 3223), followed by airway (n = 374) and swallowing (n = 186) disorders. Within the voice strata, the most common primary ICD-9 code used was dysphonia (41%), followed by unilateral vocal fold paralysis (UVFP) (9%) and cough (7%). Among new voice patients, 45% were found to have a structural abnormality. The most common surgical indications were laryngotracheal stenosis (37%), followed by recurrent respiratory papillomatosis (18%) and UVFP (17%). Nearly 55% of patients presenting to a tertiary referral laryngology practice did not have an identifiable structural abnormality in the larynx on direct or indirect examination. The distribution of ICD-9 codes requiring surgical intervention was disparate from that seen in clinic. Application of the Pareto principle may improve resource allocation in laryngology, but these initial results require confirmation across multiple institutions.

  9. Children in Contemporary Society. IYC Series: Part I. A Changing Society and the Family.

    ERIC Educational Resources Information Center

    Frank, Mary, Ed.

    1979-01-01

    This collection of seven abridged symposium papers discusses contemporary social conditions which affect the nuclear family and suggests directions for intervention. The introduction declares that the family remains the single most important unit in civilized society. Its destruction is seen to be the destruction of society as we know it. The…

  10. Civil Society Participation at CONFINTEA VI

    ERIC Educational Resources Information Center

    Haddad, Sergio

    2012-01-01

    This article analyzes the participation of civil society in the Sixth International Conference on Adult Education held in Belem do Para, Brazil, 1-4 December 2009. As a foundation, the discussion first illuminates the important role that civil society in general plays in democratic issues and the relation between the state and society followed by…

  11. The socio-genetics of a complex society: female gelada relatedness patterns mirror association patterns in a multilevel society.

    PubMed

    Snyder-Mackler, Noah; Alberts, Susan C; Bergman, Thore J

    2014-12-01

    Multilevel societies with fission-fusion dynamics--arguably the most complex animal societies--are defined by two or more nested levels of organization. The core of these societies are modular social units that regularly fission and fuse with one another. Despite convergent evolution in disparate taxa, we know strikingly little about how such societies form and how fitness benefits operate. Understanding the kinship structure of complex societies could inform us about the origins of the social structure as well as about the potential for individuals in these societies to accrue indirect fitness benefits. Here, we combined genetic and behavioural data on geladas (Theropithecus gelada), an Old World Monkey, to complete the most comprehensive socio-genetic analysis of a multilevel society to date. In geladas, individuals in the core social 'units', associate at different frequencies to form 'teams', 'bands' and, the largest aggregations, 'communities'. Units were composed of closely related females, and females remained with their close kin during permanent fissions of units. Interestingly, female-female relatedness also significantly predicted between-unit, between-team and between-band association patterns, while male-male relatedness did not. Thus, it is likely that the socio-genetic structure of gelada society results from females maintaining associations with their female relatives during successive unit fissions--possibly in an attempt to balance the direct and indirect fitness benefits of group living. Overall, the persistence of associations among related females across generations appears to drive the formation of higher levels of gelada society, suggesting that females seek kin for inclusive fitness benefits at multiple levels of gelada society. © 2014 John Wiley & Sons Ltd.

  12. Guidance for contact tracing of cases of Lassa fever, Ebola or Marburg haemorrhagic fever on an airplane: results of a European expert consultation

    PubMed Central

    2012-01-01

    Background Travel from countries where viral haemorrhagic fevers (VHF) are endemic has increased significantly over the past decades. In several reported VHF events on airplanes, passenger trace back was initiated but the scale of the trace back differed considerably. The absence of guidance documents to help the decision on necessity and scale of the trace back contributed to this variation. This article outlines the recommendations of an expert panel on Lassa fever, Ebola and Marburg haemorrhagic fever to the wider scientific community in order to advise the relevant stakeholders in the decision and scale of a possible passenger trace back. Method The evidence was collected through review of published literature and through the views of an expert panel. The guidance was agreed by consensus. Results Only a few events of VHF cases during air travel are reported in literature, with no documented infection in followed up contacts, so that no evidence of transmission of VHF during air travel exists to date. Based on this and the expert opinion, it was recommended that passenger trace back was undertaken only if: the index case had symptoms during the flight; the flight was within 21 days after detection of the event; and for Lassa fever if exposure of body fluid has been reported. The trace back should only be done after confirmation of the index case. Passengers and crew with direct contact, seat neighbours (+/− 1 seat), crew and cleaning personal of the section of the index case should be included in the trace back. Conclusion No evidence has been found for the transmission of VHF in airplanes. This information should be taken into account, when a trace back decision has to be taken, because such a measure produces an enormous work load. The procedure suggested by the expert group can guide decisions made in future events, where a patient with suspected VHF infection travelled on a plane. However, the actual decision on start and scale of a trace back always lies

  13. European Federation of Neurological Societies/Peripheral Nerve Society guideline on management of multifocal motor neuropathy. Report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society--first revision.

    PubMed

    2010-12-01

    A European Federation of Neurological Societies/Peripheral Nerve Society consensus guideline on the definition, investigation, and treatment of multifocal motor neuropathy (MMN) was published in 2006. The aim is to revise this guideline. Disease experts considered references retrieved from MEDLINE and Cochrane Systematic Reviews published between August 2004 and July 2009 and prepared statements that were agreed to in an iterative fashion. The Task Force agreed on Good Practice Points to define clinical and electrophysiological diagnostic criteria for MMN, investigations to be considered, and principal recommendations for treatment. © 2010 Peripheral Nerve Society.

  14. OCT in the field of laryngology: further perspectives

    NASA Astrophysics Data System (ADS)

    Just, T.; Pau, H. W.; Lankenau, E.; Hüttmann, G.

    2011-03-01

    Early detection of cancerous lesions of the larynx may be the best method of improving patient quality of life and survival rates. New in-vivo technologies may be of great clinical relevance in improving the accuracy of sampling during microlaryngeal surgery. Optical coherence tomography (OCT) is an optical imaging technique that clearly identifies basement membrane violation caused by laryngeal cancer. With a microscope-based spectral domain OCT (SD-OCT) we reached in vivo a fairly accurate assessment of benign and dysplastic laryngeal lesions. Recent improvements in OCT technology have led to the development of high-speed OCT systems displaying millions of pixels per second. These systems allow non-contact real-time imaging of large sections of laryngeal tissue. Polarization contrast OCT (PS-OCT) may provide additional information about the lamina propria of the true vocal cord because of the birefringence of connective tissue. We present microscope-based high-speed SD-OCT images with and without polarization contrast and 3D volumes of selected laryngeal pathologies in order to demonstrate our current concepts for the intended intraoperative application. High-speed SD-OCT and polarization contrast can also be complemented by our recently developed rigid confocal endoscopic system to obtain cellular and sub-cellular information about the tissue. Further perspectives will be presented.

  15. Toolbox of assessment tools of technical skills in otolaryngology-head and neck surgery: A systematic review.

    PubMed

    Labbé, Mathilde; Young, Meredith; Nguyen, Lily H P

    2017-10-08

    To support the development of programs of assessment of technical skills in the operating room (OR), we systematically reviewed the literature to identify assessment tools specific to otolaryngology-head and neck surgery (OTL-HNS) core procedures and summarized their characteristics. We systematically searched Embase, MEDLINE, PubMed, and Cochrane to identify and report on assessment tools that can be used to assess residents' technical surgical skills in the operating room for OTL-HNS core procedures. Of the 736 unique titles retrieved, 16 articles met inclusion criteria, covering 11 different procedures (in otology, rhinology, laryngology, head and neck, and general otolaryngology). The tools were composed of a task-specific checklist and/or global rating scale and were developed in the OR, on human cadavers, or in a simulation setting. Our study reports on published tools for assessing technical skills for OTL-HNS residents during core procedures conducted in the OR. These assessment tools could facilitate the provision of timely feedback to trainees including specific goals for improvement. However, the paucity of publications suggests little agreement on how to best perform work-based direct-observation assessment for core surgical procedures in OTL-HNS. The sparsity of tools specific to OTL-HNS may become a barrier to a fluid transition to competency-based medical education. Laryngoscope, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

  16. Beyond strong and weak: rethinking postdictatorship civil societies.

    PubMed

    Riley, Dylan; Fernández, Juan J

    2014-09-01

    What is the impact of dictatorships on postdictatorial civil societies? Bottom-up theories suggest that totalitarian dictatorships destroy civil society while authoritarian ones allow for its development. Top-down theories of civil society suggest that totalitarianism can create civil societies while authoritarianism is unlikely to. This article argues that both these perspectives suffer from a one-dimensional understanding of civil society that conflates strength and autonomy. Accordingly we distinguish these two dimensions and argue that totalitarian dictatorships tend to create organizationally strong but heteronomous civil societies, while authoritarian ones tend to create relatively autonomous but organizationally weak civil societies. We then test this conceptualization by closely examining the historical connection between dictatorship and civil society development in Italy (a posttotalitarian case) and Spain (a postauthoritarian one). Our article concludes by reflecting on the implications of our argument for democratic theory, civil society theory, and theories of regime variation.

  17. Implementation of study results in guidelines and adherence to guidelines in clinical practice

    PubMed Central

    Waldfahrer, Frank

    2016-01-01

    Guidelines were introduced in hospital- and practice-based otorhinolaryngology in the 1990ies, and have been undergoing further development ever since. There are currently 20 guidelines on file at the German Society of Oto-Rhino-Laryngology, Head & Neck Surgery. The society has cooperated in further 34 guidelines. The quality of the guidelines has been continuously improved by concrete specifications put forward by the Association of the Scientific Medical Societies in Germany (Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e.V., AWMF). Since increasing digitalization has made access to scientific publications quicker and simpler, relevant study results can be incorporated in guidelines more easily today than in the analog world. S2e and S3 guidelines must be based on a formal literature search with subsequent evaluation of the evidence. The consensus procedure for S2k guidelines is also regulated. However, the implementation of guidelines in routine medical practice must still be considered inadequate, and there is still a considerable need for improvement in adherence to these guidelines. PMID:28025601

  18. The Knowledge Society: Refounding the Socius

    NASA Astrophysics Data System (ADS)

    de Beer, Carel S.

    The theme 'knowledge society' can have many meanings depending on who defines it. But can knowledge really define society since there are many other qualifying adjectives for society as well. What one should be preferred? Is knowledge a better qualifying term than risk, information, technology, or any other one? These questions need answers. There are many dreams and counter dreams regarding the ideal society. Some dreams, like Unesco's dream, focus on the self-evident issues in the knowledge society, or what people consider to be self-evident, or what is taken for granted, as if no exploration is required: issues like access to knowledge, knowledge management, knowledge sharing, etc. These dreams contain a threat despite promises of a future that cannot be achieved. Other dreams, like those of Ars Industrialis, dig deeper and look for founding possibilities, take nothing for granted, search for the original, the defining principles. These dreams bring hope and light, a future to live for.

  19. Does gender bias influence awards given by societies?

    NASA Astrophysics Data System (ADS)

    Holmes, Mary Anne; Asher, Pranoti; Farrington, John; Fine, Rana; Leinen, Margaret S.; LeBoy, Phoebe

    2011-11-01

    AGU is a participant in a U.S. National Science Foundation (NSF)-funded project called Advancing Ways of Awarding Recognition in Disciplinary Societies (AWARDS), which seeks to examine whether gender bias affects selection of recipients of society awards. AGU is interested in learning why there is a higher proportion of female recipients of service and education awards over the past 2 decades. Combined with a lower rate of receipt of research awards, these results suggest that implicit (subconscious) bias in favor of male candidates still influences awardee selection. Six other professional societies (American Chemical Society, American Mathematical Society, American Society of Anesthesiologists, Mathematical Association of America, Society for Neuroscience, and Society for Industrial and Applied Mathematics) are participating in the project. Volunteers from each participant society attended an Association for Women in Science (AWIS)-sponsored workshop in May 2010 to examine data and review literature on best practices for fair selection of society awardees. A draft proposal for implementing these practices will be brought before the AGU Council and the Honors and Recognition Committee at their upcoming meetings.

  20. History society launches journal

    NASA Astrophysics Data System (ADS)

    Richman, Barbara T.

    A fledgling international organization plans to launch, in the next few months, a journal devoted to the study of the history of the earth sciences. The journal, to be published by the History of Earth Sciences Society (HESS), will be edited by Gerald M. Friedman ot the Rensselaer Polytechnic Institute.HESS will promote interest and scholarship in the history of the earth sciences by publishing the semiannual journal, by organizing meetings about the history of earth sciences, and by supporting the efforts of other associations displaying similar interests, according to the society's draft constitution. An organizational meeting to ratify the constitution and to elect officers will be held in conjunction with the annual meeting of the Geological Society of America in October. The interim officers and the proposed slate for 1983 include David B. Kitts (University of Oklahoma, Norman), president; Albert V. Carrozi (University of Illinois, Urbana), president-elect; and Ellis L. Yochelson (U.S. Geological Survey, National Museum of Natural History), secretary.

  1. Tsunami Science for Society

    NASA Astrophysics Data System (ADS)

    Bernard, E. N.

    2014-12-01

    As the decade of mega-tsunamis has unfolded with new data, the science of tsunami has advanced at an unprecedented pace. Our responsibility to society should guide the use of these new scientific discoveries to better prepare society for the next tsunami. This presentation will focus on the impacts of the 2004 and 2011 tsunamis and new societal expectations accompanying enhanced funding for tsunami research. A list of scientific products, including tsunami hazard maps, tsunami energy scale, real-time tsunami flooding estimates, and real-time current velocities in harbors will be presented to illustrate society's need for relevant, easy to understand tsunami information. Appropriate use of these tsunami scientific products will be presented to demonstrate greater tsunami resilience for tsunami threatened coastlines. Finally, a scientific infrastructure is proposed to ensure that these products are both scientifically sound and represent today's best practices to protect the scientific integrity of the products as well as the safety of coastal residents.

  2. The Learning Society: Two Justifications

    ERIC Educational Resources Information Center

    Su, Ya-hui

    2010-01-01

    This article examines the view that has long been fashionable in related policies and literature that the establishment of the learning society is a necessary response to changing times. This article suggests that the association between the learning society and current change may be defensible but is limited. The justification of the learning…

  3. Ontogeny of prosocial behavior across diverse societies.

    PubMed

    House, Bailey R; Silk, Joan B; Henrich, Joseph; Barrett, H Clark; Scelza, Brooke A; Boyette, Adam H; Hewlett, Barry S; McElreath, Richard; Laurence, Stephen

    2013-09-03

    Humans are an exceptionally cooperative species, but there is substantial variation in the extent of cooperation across societies. Understanding the sources of this variability may provide insights about the forces that sustain cooperation. We examined the ontogeny of prosocial behavior by studying 326 children 3-14 y of age and 120 adults from six societies (age distributions varied across societies). These six societies span a wide range of extant human variation in culture, geography, and subsistence strategies, including foragers, herders, horticulturalists, and urban dwellers across the Americas, Oceania, and Africa. When delivering benefits to others was personally costly, rates of prosocial behavior dropped across all six societies as children approached middle childhood and then rates of prosociality diverged as children tracked toward the behavior of adults in their own societies. When prosocial acts did not require personal sacrifice, prosocial responses increased steadily as children matured with little variation in behavior across societies. Our results are consistent with theories emphasizing the importance of acquired cultural norms in shaping costly forms of cooperation and creating cross-cultural diversity.

  4. [Gender equality activity in the Bioimaging Society].

    PubMed

    Suzaki, Etsuko

    2013-09-01

    Gender equality activity in the Bioimaging Society was initiated in 2005 when it joined the Japan Inter-Society Liaison Association Committee for Promoting Equal Participation of Men and Women in Science and Engineering (EPMEWSE). The Gender Equality Committee of the Bioimaging Society is acting on this issue by following the policy of the EPMEWSE, and has also been planning and conducting lectures at annual meetings of the society to gain the understanding, consents, and cooperation of the members of the society to become conscious of gender equality. Women's participation in the society has been promoted through the activities of the Gender Equality Committee, and the number of women officers in the society has since increased from two women out of 40 members in 2005 to five out of 44 in 2013. The activities of the Gender Equality Committee of the Japanese Association of Anatomists (JAA) have just started. There are more than 400 women belonging to the JAA. When these women members join together and collaborate, women's participation in the JAA will increase.

  5. Ontogeny of prosocial behavior across diverse societies

    PubMed Central

    House, Bailey R.; Silk, Joan B.; Henrich, Joseph; Barrett, H. Clark; Scelza, Brooke A.; Boyette, Adam H.; Hewlett, Barry S.; McElreath, Richard; Laurence, Stephen

    2013-01-01

    Humans are an exceptionally cooperative species, but there is substantial variation in the extent of cooperation across societies. Understanding the sources of this variability may provide insights about the forces that sustain cooperation. We examined the ontogeny of prosocial behavior by studying 326 children 3–14 y of age and 120 adults from six societies (age distributions varied across societies). These six societies span a wide range of extant human variation in culture, geography, and subsistence strategies, including foragers, herders, horticulturalists, and urban dwellers across the Americas, Oceania, and Africa. When delivering benefits to others was personally costly, rates of prosocial behavior dropped across all six societies as children approached middle childhood and then rates of prosociality diverged as children tracked toward the behavior of adults in their own societies. When prosocial acts did not require personal sacrifice, prosocial responses increased steadily as children matured with little variation in behavior across societies. Our results are consistent with theories emphasizing the importance of acquired cultural norms in shaping costly forms of cooperation and creating cross-cultural diversity. PMID:23959869

  6. Sustainable Society Formed by Unselfish Agents

    NASA Astrophysics Data System (ADS)

    Kikuchi, Toshiko

    It has been pointed out that if the social configuration of the three relations (market, communal and obligatory relations) is not balanced, a market based society as a total system fails. Using multi-agent simulations, this paper shows that a sustainable society is formed when all three relations are integrated and function respectively. When agent trades are based on the market mechanism (i.e., agents act in their own interest and thus only market relations exist), weak agents who cannot perform transactions die. If a compulsory tax is imposed to enable all weak agents to survive (i.e., obligatory relations exist), then the fiscal deficit increases. On the other hand, if agents who have excess income undertake the unselfish action of distributing their surplus to the weak agents (i.e., communal relations exist), then trade volume increases. It is shown that the existence of unselfish agents is necessary for the realization of a sustainable society. However, the survival of all agents is difficult in a communal society. In an artificial society, for all agents survive and fiscal balance to be maintained, all three social relations need to be fully integrated. These results show that adjusting the balance of the three social relations well lead to the realization of a sustainable society.

  7. Can the Ni classification of vessels predict neoplasia? A systematic review and meta-analysis.

    PubMed

    Mehlum, Camilla S; Rosenberg, Tine; Dyrvig, Anne-Kirstine; Groentved, Aagot Moeller; Kjaergaard, Thomas; Godballe, Christian

    2018-01-01

    The Ni classification of vascular change from 2011 is well documented for evaluating pharyngeal and laryngeal lesions, primarily focusing on cancer. In the planning of surgery it may be more relevant to differentiate neoplasia from non-neoplasia. We aimed to evaluate the ability of the Ni classification to predict laryngeal or hypopharyngeal neoplasia and to investigate if a changed cutoff value would support the recent European Laryngological Society (ELS) proposal of perpendicular vascular changes as indicative of neoplasia. PubMed, Embase, Cochrane, and Scopus databases. A systematic review and meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement. We systematically searched for publications from 2011 until 2016. All retrieved studies were reviewed and qualitatively assessed. The pooled sensitivity and specificity of the Ni classification with two different cutoffs were calculated, and bubble and summary receiver operating characteristics plots were created. The combined sensitivity of five studies (n = 687) with Ni type IV-V defined as test-positive was 0.89 (95% confidence interval [CI]: 0.76-0.95), and specificity was 0.82 (95% CI: 0.72-0.89). The equivalent combined sensitivity of four studies (n = 624) with Ni type V defined as test-positive was 0.82 (95% CI: 0.75-0.87), and specificity was 0.93 (95% CI: 0.82-0.97). The diagnostic accuracy of the Ni classification in predicting neoplasia was high, without significant difference between the two analyzed cutoff values. Implementation of the proposed ELS classification of vascular changes seems reasonable from a clinical perspective, with comparable accuracy. Attention must be drawn to the accompanying risk of exposing patients to unnecessary surgery. Laryngoscope, 128:168-176, 2018. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

  8. 75 FR 21212 - Approval of Classification Societies

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-23

    ...-AB35 Approval of Classification Societies AGENCY: Coast Guard, DHS. ACTION: Notice of proposed rulemaking. SUMMARY: Congress requires that classification societies conducting certain work in the United States must either be full members of International Association of Classification Societies (IACS) or...

  9. Education for a Learning Society.

    ERIC Educational Resources Information Center

    Tempero, Howard E., Ed.

    The essays contained in this booklet are 1) "Education for a 'Learning Society': The Challenge" by Ernest Bayles in which he calls for focus on learning to live, developing skills of reflection and judgment applicable to vital issues, and reflective teaching; 2) "Teacher Education in a Learning Society" in which David Turney demands teacher…

  10. Asset Inequality and Economic Activity in Artificial Societies

    NASA Astrophysics Data System (ADS)

    Kikuchi, Toshiko

    In this paper, using multi-agent simulations, the effect asset inequality has on an artificial society is analyzed. It is shown that it is possible for a sustainable society to decrease in asset inequality and at the same time increase economic activity. In sustainable societies, the asset inequality increases as the consumption tax rate is raised, and in artificial societies where the tax rate is the same, inequality increases in the society in which agents with even small a surplus undertake unselfish actions. In sustainable societies which employ both income and consumption tax, an increase in asset inequalities leads to an increase economic activity. But, in sustainable societies which levy only the income tax, this result does not necessarily hold. These results show that if economic activity is increased in sustainable societies where the consumption tax rate is raised for the fiscal stability, an inequality expansion is an acceptable consequence. However, the sustainable society with the highest economic activity is realized when only the income tax is levied. In sustainable societies which levy only the income tax, it is possible to decrease inequality while simultaneously increasing economic activity.

  11. 46 CFR 90.10-35 - Recognized classification society.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 4 2011-10-01 2011-10-01 false Recognized classification society. 90.10-35 Section 90... classification society. The term recognized classification society means the American Bureau of Shipping or other classification society recognized by the Commandant. ...

  12. Human identity and the evolution of societies.

    PubMed

    Moffett, Mark W

    2013-09-01

    Human societies are examined as distinct and coherent groups. This trait is most parsimoniously considered a deeply rooted part of our ancestry rather than a recent cultural invention. Our species is the only vertebrate with society memberships of significantly more than 200. We accomplish this by using society-specific labels to identify members, in what I call an anonymous society. I propose that the human brain has evolved to permit not only the close relationships described by the social brain hypothesis, but also, at little mental cost, the anonymous societies within which such alliances are built. The human compulsion to discover or invent labels to "mark" group memberships may originally have been expressed in hominins as vocally learned greetings only slightly different in function from chimpanzee pant hoots (now known to be society-specific). The weight of evidence suggests that at some point, conceivably early in the hominin line, the distinct groups composed of several bands that were typical of our ancestors came to be distinguished by their members on the basis of multiple labels that were socially acquired in this way, the earliest of which would leave no trace in the archaeological record. Often overlooked as research subjects, these sizable fission-fusion communities, in recent egalitarian hunter-gatherers sometimes 2,000 strong, should consistently be accorded the status of societies, in the same sense that this word is used to describe tribes, chiefdoms, and other cultures arising later in our history. The capacity of hunter-gatherer societies to grow sufficiently populous that not all members necessarily recognize one another would make the transition to larger agricultural societies straightforward. Humans differ from chimpanzees in that societal labels are essential to the maintenance of societies and the processes giving birth to new ones. I propose that anonymous societies of all kinds can expand only so far as their labels can remain

  13. Making the Good Society Work

    ERIC Educational Resources Information Center

    Field, John

    2010-01-01

    Everyone is talking about civil society. Perhaps it's the election, and the shock of seeing more voters at the polling booths than anyone had expected. Now David Cameron's idea of a "big society" is being translated into some early policy measures. Does today's debate have anything to do with adult learning? The author believes that the…

  14. 1987 Salaries: Society Membership Survey.

    ERIC Educational Resources Information Center

    Kellman, Dawn; Skelton, W. Keith

    Nationwide data are provided on the 1987 salaries of members of each of the American Institute of Physics' 10 member societies. Of the approximately 13,600 society members who were mailed a questionnaire, 61% responded. Data are presented by: degree level, type of employer, gender, salaries for PhDs by geographic location, PhD salaries by…

  15. Education for an Open Society.

    ERIC Educational Resources Information Center

    Della-Dora, Delmo, Ed.; House, James E., Ed.

    This yearbook focuses on the issue of opening the society for all people, particularly for those who have not been properly represented heretofore. Part 1 reviews some of the progress made toward an open society during the past two decades. It delineates the exasperatingly slow but important gains that have been registered since the Supreme Court…

  16. Trajectories of development in Third World societies.

    PubMed

    Lenski, G

    1985-01-01

    A test of ecological-evolutionary theory shows that historic differences in the modes of production of Third World countries have important consequences for these countries today. Those with an agrarian heritage are more highly developed and enjoy higher rates of economic growth than those with a horticultural heritage. Horticultural societies are less developed than agrarian ones. Horticultural societies are ones in which the basic farming implements are the hoe and the digging stick, tools less powerful than the plow, which is the basic farming tool of agrarian societies. The authors examine 30 socioeconomic indicators for 77 Third World countries, of which 32 were classified as industrializing horticultural and 45 as industrializing agrarian. Industrializing agrarian societies have been much more successful in controlling their population growth than have industrializing horticultural societies. The data suggest that the 2 types of societies not only started out differently, but are still diverging, in both rates of population growth and in gross national product per capita. Most of the sample of horticultural societies were recently colonies, and many of the agrarian ones were not. Almost all of the horticultural societies are in sub-Saharan Africa, which gives rise to the question of whether these findings only reflect geographic factors. However, Papua-New Guinea and Haiti also show the same pattern of results. It may be that such material factors as climate, soil, and disease express themselves in different modes of production, showing that the past is not dead history but living material that influences the life of societies in later centuries.

  17. 77 FR 47544 - Approval of Classification Societies

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-09

    ...-AB35 Approval of Classification Societies AGENCY: Coast Guard, DHS. ACTION: Final rule. SUMMARY: Federal law requires that classification societies conducting certain work in the United States be... that classification societies must meet in order to obtain approval by the Coast Guard. Through this...

  18. Management of hemodynamically unstable pelvic trauma: results of the first Italian consensus conference (cooperative guidelines of the Italian Society of Surgery, the Italian Association of Hospital Surgeons, the Multi-specialist Italian Society of Young Surgeons, the Italian Society of Emergency Surgery and Trauma, the Italian Society of Anesthesia, Analgesia, Resuscitation and Intensive Care, the Italian Society of Orthopaedics and Traumatology, the Italian Society of Emergency Medicine, the Italian Society of Medical Radiology -Section of Vascular and Interventional Radiology- and the World Society of Emergency Surgery)

    PubMed Central

    2014-01-01

    Hemodynamically Unstable Pelvic Trauma is a major problem in blunt traumatic injury. No cosensus has been reached in literature on the optimal treatment of this condition. We present the results of the First Italian Consensus Conference on Pelvic Trauma which took place in Bergamo on April 13 2013. An extensive review of the literature has been undertaken by the Organizing Committee (OC) and forwarded to the Scientific Committee (SC) and the Panel (JP). Members of them were appointed by surgery, critical care, radiology, emergency medicine and orthopedics Italian and International societies: the Italian Society of Surgery, the Italian Association of Hospital Surgeons, the Multi-specialist Italian Society of Young Surgeons, the Italian Society of Emergency Surgery and Trauma, the Italian Society of Anesthesia, Analgesia, Resuscitation and Intensive Care, the Italian Society of Orthopaedics and Traumatology, the Italian Society of Emergency Medicine, the Italian Society of Medical Radiology, Section of Vascular and Interventional Radiology and the World Society of Emergency Surgery. From November 2012 to January 2013 the SC undertook the critical revision and prepared the presentation to the audience and the Panel on the day of the Conference. Then 3 recommendations were presented according to the 3 submitted questions. The Panel voted the recommendations after discussion and amendments with the audience. Later on a email debate took place until December 2013 to reach a unanimous consent. We present results on the 3 following questions: which hemodynamically unstable patient needs an extraperitoneal pelvic packing? Which hemodynamically unstable patient needs an external fixation? Which hemodynamically unstable patient needs emergent angiography? No longer angiography is considered the first therapeutic maneuver in such a patient. Preperitoneal pelvic packing and external fixation, preceded by pelvic binder have a pivotal role in the management of these patients

  19. Social Value Orientation and Capitalism in Societies.

    PubMed

    Shahrier, Shibly; Kotani, Koji; Kakinaka, Makoto

    2016-01-01

    Cooperation and competition are core issues in various fields, since they are claimed to affect the evolution of human societies and ecological organizations. A long-standing debate has existed on how social behaviors and preferences are shaped with culture. Considering the economic environment as part of culture, this study examines whether the ongoing modernization of competitive societies, called "capitalism," affects the evolution of people's social preferences and behaviors. To test this argument, we implemented field experiments of social value orientation and surveys with 1002 respondents for three different areas of Bangladesh: (i) rural, (ii) transitional and (iii) capitalistic societies. The main result reveals that with the evolution from rural to capitalistic societies, people are likely to be less prosocial and more likely to be competitive. In a transitional society, there is a considerable proportion of "unidentified" people, neither proself nor prosocial, implying the potential existence of unstable states during a transformation period from rural to capitalistic societies. We also find that people become more proself with increasing age, education and number of children. These results suggest that important environmental, climate change or sustainability problems, which require cooperation rather than competition, will pose more danger as societies become capitalistic.

  20. Wound botulism presenting as a deep neck space infection.

    PubMed

    Gouveia, Christopher; Mookherjee, Somnath; Russell, Matthew S

    2012-12-01

    Otolaryngologists commonly evaluate patients with findings suspicious for deep space soft tissue infections of the neck. In this case, a woman with a history of injection drug use (IDU) presented with dysphagia, odynophagia, and neck pain. Multiple neck abscesses, too small to drain, were seen on imaging. Despite broad-spectrum intravenous antibiotics, she unexpectedly and rapidly developed respiratory failure requiring intubation. Further work-up diagnosed wound botulism (WB). To our knowledge, this is the first report of WB presenting as a deep neck space infection, and illustrates the importance of considering this deadly diagnosis in patients with IDU history and bulbar symptoms. Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.

  1. Trauma-induced schwannoma of the recurrent laryngeal nerve after thyroidectomy.

    PubMed

    Kennedy, William P; Brody, Robert M; LiVolsi, Virginia A; Wang, Amber R; Mirza, Natasha A

    2016-06-01

    Laryngeal schwannomas are rare, benign tumors, most often arising from the superior laryngeal nerve. We describe a case of a 68-year-old female with a laryngeal schwannoma of the recurrent laryngeal nerve after traumatic injury. We postulate that trauma to the recurrent laryngeal nerve during thyroidectomy or thyroplasty incited growth of a nerve sheath tumor. This is the first reported case of a trauma-induced schwannoma of the recurrent laryngeal nerve and second case of a recurrent laryngeal nerve schwannoma. Although rare, this case demonstrates that these tumors should be considered during workup of vocal cord paresis after surgery or failed thyroplasty. Laryngoscope, 126:1408-1410, 2016. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

  2. Ossicular fusion and cholesteatoma in auriculo-condylar syndrome: in vivo evidence of arrest of embryogenesis.

    PubMed

    Propst, Evan J; Ngan, Bo Y; Mount, Richard J; Martin-Munoz, Daniel; Blaser, Susan; Harrison, Robert V; Cushing, Sharon L; Papsin, Blake C

    2013-02-01

    Auriculo-condylar syndrome (ACS) is a rare condition affecting first branchial arch structures. The types of hearing loss and temporal bone findings in ACS have not been reported. We describe a 14-year-old male with constricted pinnae, mandibular dysostosis, glossoptosis, a high-arched palate, hearing loss, and cholesteatoma. Computed tomography imaging demonstrated malleoincudal joint ankylosis. The fused malleoincudal complex was removed during mastoidectomy for cholesteatoma. Electron microscopy and histopathology of the joint suggested the fusion was congenital. This is the first report of ossicular fusion and cholesteatoma in ACS and the most detailed in vivo evidence of disruption of embryogenesis during malleoincudal joint formation. Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.

  3. Canadian Cardiovascular Society/Canadian Society of Cardiac Surgeons/Canadian Society for Vascular Surgery Joint Position Statement on Open and Endovascular Surgery for Thoracic Aortic Disease.

    PubMed

    Appoo, Jehangir J; Bozinovski, John; Chu, Michael W A; El-Hamamsy, Ismail; Forbes, Thomas L; Moon, Michael; Ouzounian, Maral; Peterson, Mark D; Tittley, Jacques; Boodhwani, Munir

    2016-06-01

    In 2014, the Canadian Cardiovascular Society (CCS) published a position statement on the management of thoracic aortic disease addressing size thresholds for surgery, imaging modalities, medical therapy, and genetics. It did not address issues related to surgical intervention. This joint Position Statement on behalf of the CCS, Canadian Society of Cardiac Surgeons, and the Canadian Society for Vascular Surgery provides recommendations about thoracic aortic disease interventions, including: aortic valve repair, perfusion strategies for arch repair, extended arch hybrid reconstruction for acute type A dissection, endovascular management of arch and descending aortic aneurysms, and type B dissection. The position statement is constructed using Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology, and has been approved by the primary panel, an international secondary panel, and the CCS Guidelines Committee. Advent of endovascular technology has improved aortic surgery safety and extended the indications of minimally invasive thoracic aortic surgery. The combination of safer open surgery with endovascular treatment has improved patient outcomes in this rapidly evolving subspecialty field of cardiovascular surgery. Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

  4. American Society of Gene & Cell Therapy

    MedlinePlus

    ... Learn More Close The American Society of Gene & Cell Therapy ASGCT is the primary membership organization for ... Official Journal of the American Society of Gene & Cell Therapy Molecular Therapy is the leading journal for ...

  5. American Epilepsy Society

    MedlinePlus

    ... Epilepsy Society CLINICAL RESOURCES FAQs GUIDELINES IOM EPILEPSY MEDICAL MARIJUANA SUDEP SURGERY DEVICES GENETICS TREATMENTS Drug Alerts and ... RESOURCES Navigation CLINICAL RESOURCES FAQs GUIDELINES IOM EPILEPSY MEDICAL MARIJUANA SUDEP SURGERY DEVICES GENETICS TREATMENTS Drug Alerts and ...

  6. Interrogating an insect society

    PubMed Central

    Gadagkar, Raghavendra

    2009-01-01

    Insect societies such as those of ants, bees, and wasps consist of 1 or a small number of fertile queens and a large number of sterile or nearly sterile workers. While the queens engage in laying eggs, workers perform all other tasks such as nest building, acquisition and processing of food, and brood care. How do such societies function in a coordinated and efficient manner? What are the rules that individuals follow? How are these rules made and enforced? These questions are of obvious interest to us as fellow social animals but how do we interrogate an insect society and seek answers to these questions? In this article I will describe my research that was designed to seek answers from an insect society to a series of questions of obvious interest to us. I have chosen the Indian paper wasp Ropalidia marginata for this purpose, a species that is abundantly distributed in peninsular India and serves as an excellent model system. An important feature of this species is that queens and workers are morphologically identical and physiologically nearly so. How then does an individual become a queen? How does the queen suppress worker reproduction? How does the queen regulate the nonreproductive activities of the workers? What is the function of aggression shown by different individuals? How and when is the queen's heir decided? I will show how such questions can indeed be investigated and will emphasize the need for a whole range of different techniques of observation and experimentation. PMID:19487678

  7. Social Value Orientation and Capitalism in Societies

    PubMed Central

    Shahrier, Shibly; Kakinaka, Makoto

    2016-01-01

    Cooperation and competition are core issues in various fields, since they are claimed to affect the evolution of human societies and ecological organizations. A long-standing debate has existed on how social behaviors and preferences are shaped with culture. Considering the economic environment as part of culture, this study examines whether the ongoing modernization of competitive societies, called “capitalism,” affects the evolution of people’s social preferences and behaviors. To test this argument, we implemented field experiments of social value orientation and surveys with 1002 respondents for three different areas of Bangladesh: (i) rural, (ii) transitional and (iii) capitalistic societies. The main result reveals that with the evolution from rural to capitalistic societies, people are likely to be less prosocial and more likely to be competitive. In a transitional society, there is a considerable proportion of “unidentified” people, neither proself nor prosocial, implying the potential existence of unstable states during a transformation period from rural to capitalistic societies. We also find that people become more proself with increasing age, education and number of children. These results suggest that important environmental, climate change or sustainability problems, which require cooperation rather than competition, will pose more danger as societies become capitalistic. PMID:27792756

  8. Conflict of interest between professional medical societies and industry: a cross-sectional study of Italian medical societies' websites.

    PubMed

    Fabbri, Alice; Gregoraci, Giorgia; Tedesco, Dario; Ferretti, Filippo; Gilardi, Francesco; Iemmi, Diego; Lisi, Cosima; Lorusso, Angelo; Natali, Francesca; Shahi, Edit; Rinaldi, Alessandro

    2016-06-01

    To describe how Italian medical societies interact with pharmaceutical and medical device industries through an analysis of the information available on their websites. Cross sectional study. Italy. 154 medical societies registered with the Italian Federation of Medical-Scientific Societies. Indicators of industry sponsorship (presence of industry sponsorship in the programme of the last medical societies' annual conference; presence of manufacturers' logos on the homepage; presence of industry sponsorship of satellite symposia during the last annual conference). 131 Italian medical societies were considered. Of these, 4.6% had an ethical code covering relationships with industry on their websites, while 45.6% had a statute that mentioned the issue of conflict of interest and 6.1% published the annual financial report. With regard to industry sponsorship, 64.9% received private sponsorship for their last conference, 29.0% had manufacturers' logos on their webpage, while 35.9% had industry-sponsored satellite symposia at their last conference. The presence of an ethical code on the societies' websites was associated with both an increased risk of industry sponsorship of the last conference (relative risk (RR) 1.22, 95% CIs 1.01 to 1.48 after adjustment) and of conferences and/or satellite symposia (RR 1.22, 95% CIs 1.02 to 1.48 after adjustment) but not with the presence of manufacturers' logos on the websites (RR 1.79, 95% CIs 0.66 to 4.82 after adjustment). No association was observed with the other indicators of governance and transparency. This survey shows that industry sponsorship of Italian medical societies' conferences is common, while the presence of a structured regulatory system is not. Disclosure of the amount of industry funding to medical societies is scarce. The level of transparency therefore needs to be improved and the whole relationship between medical societies and industry should be further disciplined in order to avoid any potential for

  9. The Impact of Science on Society

    NASA Technical Reports Server (NTRS)

    Burke, J.; Bergman, J.; Asimov, I.

    1985-01-01

    Four speeches delivered as part of a public lecture series to assess the impact of science on society are presented. The computerization of society, space exploration and habitation, the mechanisms of technological change, and cultural responses are addressed.

  10. Protection of quality and innovation in radiation oncology: the prospective multicenter trial the German Society of Radiation Oncology (DEGRO-QUIRO study). Evaluation of time, attendance of medical staff, and resources during radiotherapy with IMRT.

    PubMed

    Vorwerk, H; Zink, K; Schiller, R; Budach, V; Böhmer, D; Kampfer, S; Popp, W; Sack, H; Engenhart-Cabillic, R

    2014-05-01

    A number of national and international societies published recommendations regarding the required equipment and manpower assumed to be necessary to treat a number of patients with radiotherapy. None of these recommendations were based on actual time measurements needed for specific radiotherapy procedures. The German Society of Radiation Oncology (DEGRO) was interested in substantiating these recommendations by prospective evaluations of all important core procedures of radiotherapy in the most frequent cancers treated by radiotherapy. The results of the examinations of radiotherapy with intensity-modulated radiation therapy (IMRT) in patients with different tumor entities are presented in this manuscript. Four radiation therapy centers [University Hospital of Marburg, University Hospital of Giessen, University Hospital of Berlin (Charité), Klinikum rechts der Isar der Technischen Universität München] participated in this prospective study. The workload of the different occupational groups and room occupancies for the core procedures of radiotherapy were prospectively documented during a 2-month period per center and subsequently statistically analyzed. The time needed per patient varied considerably between individual patients and between centers for all the evaluated procedures. The technical preparation (contouring of target volume and organs at risk, treatment planning, and approval of treatment plan) was the most time-consuming process taking 3 h 54 min on average. The time taken by the medical physicists for this procedure amounted to about 57%. The training part of the preparation time was 87% of the measured time for the senior physician and resident. The total workload for all involved personnel comprised 74.9 min of manpower for the first treatment, 39.7 min for a routine treatment with image guidance, and 22.8 min without image guidance. The mean room occupancy varied between 10.6 min (routine treatment without image guidance) and 23.7 min (first

  11. The contribution of the Estonian Soil Sciences Society to the science, society and education

    NASA Astrophysics Data System (ADS)

    Rossner, Helis; Reintam, Endla; Astover, Alar; Shanskiy, Merrit

    2015-04-01

    Predecessor of todays Estonian Soil Science Society was Estonian Branch of All-Union Soil Society of Soil Scientist which acted from 1957 to 1991. In 1957-1964 Estonian Branch was leaded by prof. Osvald Hallik and in 1964-1991 by prof. Loit Reintam. After re-independence of Estonia in 1991 the society acted in informal way and was leaded by prof. L. Reintam. Non-profit organization "Estonian Soil Science Society" was officially (re)established in 10.23.2009. Estonian Soil Science Society (ESSS) is aimed to: • coordinate collaboration between institutions and individuals intrested of soil science, conservation and sustainable use of soils; • promoting soil science education and research, raising awareness of publicity on topics relating to soils in Estonia; • cooperation between local and foreign unions and associations. In recent years the ESSS had managed to reunite the number of soil scientist from different research institutions of Estonia and of related institutions. Also, the ESSS had provided numerous of materials based on later scientific findings. One of most important activity leaded by ESSS is the organizing Soil Day in Estonia with relevant seminar, where the speakers are sharing latest information with target group (researchers, teachers, policy makers, farmers, students etc.). In a frames of Soil Day the Soil of the Year is selected for Estonia. In 2015, the soil of the year is Leptosol. For current, International Year of the Soil ESSS had planned numerous activities to introduce the importance of soils to wider audience. In current presentation we would like to share the soil science researchers experience through- out the decades of soil science research in Estonia, show our latest findings and designed activities for the International Year of SOIL.

  12. The society of thoracic surgeons.

    PubMed

    Alley, R D

    1976-11-01

    The opportunity to discuss evolving socioeconomic issues affecting the medical profession as a whole was rejected in favor of personalizing The Society of Thoracic Surgeons for a membership that has grown to almost 1,500 persons. Drawing on historical insights gained through participation in the origin, growth, and development of The Society, I take readers behind the scenes and introduce to them the many people and vast resources that serve our membership. Particular attention is focused on the services of The Society's headquarters office, which is housed and managed by Smith, Bucklin and Associates, Inc, of Chicago, a multiple-association management firm that serves 60 national organizations; on our prestigious publisher, Little, Brown and Company of Boston; and on its link with our Editorial Office in Ann Arbor.

  13. [History of the Strasbourg Society of Biology].

    PubMed

    Antony, Pierre; Romier, Christophe; Mantz, Jean-Marie

    2017-01-01

    The Society of Biology of Strasbourg (SBS) is a learned society that was created in 1919 based on the model of the Society of Biology of which it is a subsidiary. Like its Parisian colleague, SBS aims at diffusing and promoting scientific knowledge in biology. To achieve this goal, SBS initiated since its creation a dialogue interface between researchers in biology and physicians, and more recently with other scientific disciplines, industry and the civil society. At the dawn of its first century, the Society of Biology of Strasbourg must continue to reinvent itself to pursue its development and to fulfil its mission of sharing scientific knowledge. This work continues in strong collaboration with our partners that share with SBS the willingness to foster excellence in biological research in Strasbourg, its region and beyond. © Société de Biologie, 2017.

  14. Civil Society, Health, and Social Exclusion in Bangladesh

    PubMed Central

    Mahmud, Simeen

    2009-01-01

    Civil society has the potential to have a positive impact on social exclusion and health equity through active monitoring and increased accountability. This paper examines the role of civil society in Bangladesh to understand why this potential has not been realized. Looking at two models of civil society action—participation in decentralized public-sector service provision and academic think-tank data analysis—this analysis examines the barriers to positive civil society input into public policy decision-making. The role of non-governmental organizations, political, cultural and economic factors, and the influence of foreign bilateral and multilateral donors are considered. The paper concludes that, with a few exceptions, civil society in Bangladesh replicates the structural inequalities of society at large. PMID:19761087

  15. History of Japanese Society of Toxicology.

    PubMed

    Satoh, Tetsuo

    2016-01-01

    Founded in 1981, the Japanese Society of Toxicology (JSOT) has grown into an organization of nearly 3,000 members working together to advance the nation's scientific knowledge and understanding of toxicology through the implementation of planning that ensures a systematic and efficient expenditure of energies and resources, and is closely aligned with a strategy for accomplishing the Society's long-range plans. To promote public education in toxicology, the Society organizes public lectures during each year's annual meeting. Other activities include hosting scientific conferences, promoting continuing education, and facilitating international collaboration. Internally, the JSOT operates five standing committees: General Affairs, Educational, Editorial, Finance, and Science and Publicity to handle its necessary relationships. To bestow official recognition, the Society established its Toxicologist Certification Program in 1997, and has certified 536 members as Diplomat Toxicologists (DJSOT) as of May 1, 2016. Furthermore, on the same date, 43 JSOT members were certified as Emeritus Diplomats of the JSOT (EDJSOT). The Society has launched two official journals, the "Journal of Toxicological Sciences (JTS)" in 1981 and "Fundamental Toxicological Sciences (Fundam. Toxicol. Sci.)" in 2014. As for participation in the international organizations, the JSOT (then known as the Toxicological Research Group) joined the International Union of Toxicology as a charter member in 1980, and became a founding member of the Asian Society of Toxicology at its inauguration in 1994. Into the future, the JSOT will continue working diligently to advance knowledge and understanding of toxicology and secure its place among the interdisciplinary fields of science, humane studies, and ethics.

  16. Civil society in a divided society: Linking legitimacy and ethnicness of civil society organizations in Bosnia-Herzegovina

    PubMed Central

    Puljek-Shank, Randall; Verkoren, Willemijn

    2016-01-01

    Civil society (CS) strengthening is central to peacebuilding policies for divided, post-war societies. However, it has been criticized for creating internationalized organizations without local backing, unable to represent citizens’ interests. Based on in-depth empirical research in Bosnia-Herzegovina, this article focuses on the legitimacy of CS organizations (CSOs). It explores why legitimacy for donors rarely accompanies legitimacy for local actors. We hypothesized that whilst donors avoid supporting mono-ethnic organizations, seen as problematic for peacebuilding, ‘ethnicness’ may provide local legitimacy. However, our analysis of CSOs’ ethnicness nuances research characterizing organizations as either inclusive or divisive. Moreover, local legitimacy is not based on ethnicness per se, but CSOs’ ability to skilfully interact with ethnically divided constituencies and political structures. In addition, we offer novel explanations why few organizations enjoy both donor and local legitimacy, including local mistrust of donors’ normative frameworks and perceived lack of results. However, we also show that a combination of local and donor legitimacy is possible, and explore this rare but interesting category of organizations. PMID:28546640

  17. Civil society in a divided society: Linking legitimacy and ethnicness of civil society organizations in Bosnia-Herzegovina.

    PubMed

    Puljek-Shank, Randall; Verkoren, Willemijn

    2017-06-01

    Civil society (CS) strengthening is central to peacebuilding policies for divided, post-war societies. However, it has been criticized for creating internationalized organizations without local backing, unable to represent citizens' interests. Based on in-depth empirical research in Bosnia-Herzegovina, this article focuses on the legitimacy of CS organizations (CSOs). It explores why legitimacy for donors rarely accompanies legitimacy for local actors. We hypothesized that whilst donors avoid supporting mono-ethnic organizations, seen as problematic for peacebuilding, 'ethnicness' may provide local legitimacy. However, our analysis of CSOs' ethnicness nuances research characterizing organizations as either inclusive or divisive. Moreover, local legitimacy is not based on ethnicness per se, but CSOs' ability to skilfully interact with ethnically divided constituencies and political structures. In addition, we offer novel explanations why few organizations enjoy both donor and local legitimacy, including local mistrust of donors' normative frameworks and perceived lack of results. However, we also show that a combination of local and donor legitimacy is possible, and explore this rare but interesting category of organizations.

  18. The School, The Scholar, And Society.

    ERIC Educational Resources Information Center

    Wilson, O. Meredith

    Traditionally, universities have independently sought and preserved knowledge and prepared students for professional careers, although society has influenced and supported their objectives. Today's universities, challenged by the increasingly complex needs of society, are responding with educational innovations that are usually profitable to both.…

  19. Science and Society Colloquium

    ScienceCinema

    None

    2017-12-09

    Mr. Randi will give an update of his lecture to the American Physical Society on the occasion of his award of the 1989 Forum Prize. The citation said: "for his unique defense of Science and the scientific method in many disciplines, including physics, against pseudoscience, frauds and charlatans. His use of scientific techniques has contributed to refuting suspicious and fraudulent claims of paranormal results. He has contributed significantly to public understanding of important issues where science and society interact". He is a professional magician and author of many books. He worked with John Maddox, the Editor of Nature to investigate the claims of "water with memory".

  20. Science and Society Colloquium

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    None

    Mr. Randi will give an update of his lecture to the American Physical Society on the occasion of his award of the 1989 Forum Prize. The citation said: "for his unique defense of Science and the scientific method in many disciplines, including physics, against pseudoscience, frauds and charlatans. His use of scientific techniques has contributed to refuting suspicious and fraudulent claims of paranormal results. He has contributed significantly to public understanding of important issues where science and society interact". He is a professional magician and author of many books. He worked with John Maddox, the Editor of Nature to investigatemore » the claims of "water with memory".« less

  1. Advanced information society(7)

    NASA Astrophysics Data System (ADS)

    Chiba, Toshihiro

    Various threats are hiding in advanced informationalized society. As we see car accident problems in motorization society light aspects necessarily accompy shady ones. Under the changing circumstances of advanced informationalization added values of information has become much higher. It causes computer crime, hacker, computer virus to come to the surface. In addition it can be said that infringement of intellectual property and privacy are threats brought by advanced information. Against these threats legal, institutional and insurance measures have been progressed, and newly security industry has been established. However, they are not adequate individually or totally. The future vision should be clarified, and countermeasures according to the visions have to be considered.

  2. Impacting Society through Astronomy Undergraduate Courses

    NASA Astrophysics Data System (ADS)

    Schleigh, Sharon

    2015-04-01

    A high percentage of non-science majors enroll in undergraduate, introductory astronomy courses across the country. The perception of the astronomy course as being easier than the ``hard sciences'' and the idea that the course will focus on ``pretty pictures'', influences the interests of the non-science majors. Often the students that enroll in these courses will not take other science courses, resulting in the only opportunity to teach college students about basic scientific concepts that impact their lives. Vast misconceptions about the nature of science, the role of science and scientists in society, and social issues embedded in scientific information, impact the decisions that individuals make about every day events. In turn, these decisions influence the policies that construct our society. This talk will provide an overview of the common misconceptions and discuss how they impact our society as a whole. The research presented provides evidence of the impact that introductory college astronomy courses have on changing these everyday misconceptions and influencing non-science majors' ideas about science in society. The research suggests that introductory courses designed for non-science majors are extremely important in impacting our society, and begs for a stronger understanding and implementation of best practices for teaching and learning in the college classroom environment.

  3. History of the Congenital Heart Surgeons' Society.

    PubMed

    Mavroudis, Constantine; Williams, William G

    2015-10-01

    The Congenital Heart Surgeons' Society is a group of over 100 pediatric heart surgeons representing 72 institutions that specialize in the treatment of patients with congenital heart defects. The Society began in 1972 and incorporated as a not-for-profit charitable organization in 2004. It has become the face and voice of congenital heart surgery in North America. In 1985, the Society established a data center for multicenter clinical research studies to encourage congenital heart professionals to participate in improving outcomes for our patients. The goals of the Congenital Heart Surgeons' Society are to stimulate the study of congenital cardiac physiology, pathology, and management options which are instantiated in data collection, multi-institutional studies, and scientific meetings. Honest and open discussion of problems with possible solutions to the challenges facing congenital heart professionals have been the strength of the Congenital Heart Surgeons' Society. It is imperative for the growth of an organization to know from where it came in order to know to where it is going. The purpose of this article is to review the history of the Congenital Heart Surgeons' Society. © The Author(s) 2015.

  4. Maintaining Life-saving Testing for Patients With Infectious Diseases: Infectious Diseases Society of America, American Society for Microbiology, and Pan American Society for Clinical Virology Recommendations on the Regulation of Laboratory-developed Tests.

    PubMed

    Caliendo, Angela M; Couturier, Marc R; Ginocchio, Christine C; Hanson, Kimberly E; Miller, Melissa B; Walker, Kimberly E; Frank, Gregory M

    2016-07-15

    In 2014, the US Food and Drug Administration (FDA) proposed to regulate laboratory-developed tests (LDTs)-diagnostics designed, manufactured, and used within a single laboratory. The Infectious Diseases Society of America, the American Society for Microbiology, and the Pan American Society for Clinical Virology recognize that the FDA is committed to protecting patients. However, our societies are concerned that the proposed regulations will limit access to testing and negatively impact infectious diseases (ID) LDTs. In this joint commentary, our societies discuss why LDTs are critical for ID patient care, hospital infection control, and public health responses. We also highlight how the FDA's proposed regulation of LDTs could impair patient access to life-saving tests and stifle innovation in ID diagnostics. Finally, our societies make specific recommendations for the FDA's consideration to reduce the burden of the proposed new rules on clinical laboratories and protect patients' access to state-of-the art, quality LDTs. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  5. Efficacy of Vesicular Stomatitis Virus-Ebola Virus Postexposure Treatment in Rhesus Macaques Infected With Ebola Virus Makona.

    PubMed

    Marzi, Andrea; Hanley, Patrick W; Haddock, Elaine; Martellaro, Cynthia; Kobinger, Gary; Feldmann, Heinz

    2016-10-15

    The Ebola virus (EBOV) epidemic in West Africa increased the focus on vaccine development against this hemorrhagic fever-causing pathogen, and as a consequence human clinical trials for a few selected platforms were accelerated. One of these vaccines is vesicular stomatitis virus (VSV)-EBOV, also known as rVSV-ZEBOV, a fast-acting vaccine against EBOV and so far the only vaccine with reported efficacy against EBOV infections in humans in phase III clinical trials. In this study, we analyzed the potential of VSV-EBOV for postexposure treatment of rhesus macaques infected with EBOV-Makona. We treated groups of animals with 1 dose of VSV-EBOV either in a single injection at 1 or 24 hours after EBOV exposure or with 2 injections, half the dose at each time point; 1 control group received the same dose of the VSV-based Marburg virus vaccine at both time points; another group remained untreated. Although all untreated animals succumbed to EBOV infection, 33%-67% of the animals in each treatment group survived the infection, including the group treated with the VSV-based Marburg virus vaccine. This result suggests that protection from postexposure vaccination may be antigen unspecific and due rather to an early activation of the innate immune system. In conclusion, VSV-EBOV remains a potent and fast-acting prophylactic vaccine but demonstrates only limited efficacy in postexposure treatment. Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  6. Science Serves Society.

    ERIC Educational Resources Information Center

    Sneed, G. C.

    This book discusses how some of the topics taught in a conventional physics course have been used to solve interesting technical problems in industry, medicine, agriculture, transportation, and other areas of society. The topics include heat, optics, magnetism and electricity, nuclear physics, and sound. (MLH)

  7. Margaret Cavendish and the Royal Society.

    PubMed

    Wilkins, Emma

    2014-09-20

    It is often claimed that Margaret Cavendish was an anti-experimentalist who was deeply hostile to the activities of the early Royal Society--particularly in relation to Robert Hooke's experiments with microscopes. Some scholars have argued that her views were odd or even childish, while others have claimed that they were shaped by her gender-based status as a scientific 'outsider'. In this paper I examine Cavendish's views in contemporary context, arguing that her relationship with the Royal Society was more nuanced than previous accounts have suggested. This contextualized approach reveals two points: first, that Cavendish's views were not isolated or odd when compared with those of her contemporaries, and second, that the early Royal Society was less intellectually homogeneous than is sometimes thought. I also show that, although hostile to some aspects of experimentalism, Cavendish nevertheless shared many of the Royal Society's ambitions for natural philosophy, especially in relation to its usefulness and the importance of plain language as a means to disseminate new ideas.

  8. The Society of Thoracic Surgeons, The Society of Cardiovascular Anesthesiologists, and The American Society of ExtraCorporeal Technology: Clinical Practice Guidelines for Cardiopulmonary Bypass--Temperature Management During Cardiopulmonary Bypass.

    PubMed

    Engelman, Richard; Baker, Robert A; Likosky, Donald S; Grigore, Alina; Dickinson, Timothy A; Shore-Lesserson, Linda; Hammon, John W

    2015-08-01

    In order to improve our understanding of the evidence-based literature supporting temperature management during adult cardiopulmonary bypass, The Society of Thoracic Surgeons, the Society of Cardiovascular Anesthesiology and the American Society of ExtraCorporeal Technology tasked the authors to conduct a review of the peer-reviewed literature, including: 1) optimal site for temperature monitoring, 2) avoidance of hyperthermia, 3) peak cooling temperature gradient and cooling rate, and 4) peak warming temperature gradient and rewarming rate. Authors adopted the American College of Cardiology/American Heart Association method for development clinical practice guidelines, and arrived at the following recommendations: No Recommendation No recommendation for a guideline is provided concerning optimal temperature for weaning from CPB due to insufficient published evidence. Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  9. The History of the Soil Science Society of Nigeria

    NASA Astrophysics Data System (ADS)

    Okechukwu Chude, Victor

    2013-04-01

    The Soil Science Society of Nigeria (SSSN) founded in 1968, is a registered member of the African Soil Science Association, International Union of Soil Science and the Global Soil Partnership. The Society aims at promoting and fostering better understanding of basic and applied Soil Science in Nigeria. The society also strives to enhance the dissemination of knowledge in all aspects of Soil science and shares ideas with National and International Societies through conferences, symposium, lectures, seminars and journal publications. The numerical strength of the society is 600 members (student, ordinary ,life and corporate). The soil science society of Nigeria has provided invaluable services in the formulation of agricultural land and fertilizer use strategies and policies of the country. The existing reconnaissance soil map of Nigeria typifies one of the major professional services rendered to the country by the society and its members. Despite the numerous contributions the society has made to the advancement of soil science in the country, the larger society is not aware of the its existence. This is largely because of our limited soil extension activities to land users due to lack of funds. If the society can attract donor funds, this will go a long way in enhancing the capacity and capability of the society.

  10. [From the French Society of Plastic and Reconstructive Surgery to the French Society of Plastic Reconstructive and Aesthetic Surgery].

    PubMed

    Glicenstein, J

    2004-04-01

    (The) 3rd December 1952, 11 surgeons and other specialists found the French Society of Plastic and Reconstructive Surgery (SFCPR) which was officially published on (the) 28 September 1953. The first congress was during October 1953 and the first president as Maurice Aubry. The first secretary was Daniel Morel Fatio. The symposiums were after about three of four times each year and the thematic subjects were initially according the reconstructive surgery. The review "Annales de chirurgie plastique" was free in 1956. The members of the Society were about 30 initially, but their plastic surgery in the big hospitals at Paris and other big towns in France. The "specialty" of plastic surgery was created in 1971. On "syndicate", one French board of plastic reconstructive and aesthetic surgery, the increasing of departments of plastic surgery were the front of increasing of the plastic surgery in French and of the number of the French Society of Plastic Reconstructive surgery (580 in 2003). The French Society organized the International Congress of Plastic Surgery in 1975. The society SFCPR became the French Society of plastic reconstruction and Aesthetic Surgery (SFCPRE) in 1983 and the "logo" (front view) was in the 1994 SOF.CPRE.

  11. Some Questions for the Information Society.

    ERIC Educational Resources Information Center

    Marien, Michael

    1983-01-01

    Though frequently forecasted and referred to, the so-called information society is likely but not necessarily inevitable. Questions are raised about such a society, including its impact on work, commerce, health, education, entertainment, politics, intergroup relations, families, and the impact of anticipated changes on the quality of life.…

  12. Teacher Education in a Global Society

    ERIC Educational Resources Information Center

    Jenlink, Patrick M.

    2008-01-01

    These are strange times for teacher education in a democratic society because globalization dominates economic, political, and technological interfaces among social institutions, nation-states, and the world. These are also dangerous times for teacher education in a democratic society because the expansion of neoliberalism as form of contemporary…

  13. Life Science Professional Societies Expand Undergraduate Education Efforts.

    PubMed

    Matyas, Marsha Lakes; Ruedi, Elizabeth A; Engen, Katie; Chang, Amy L

    2017-01-01

    The Vision and Change in Undergraduate Biology Education reports cite the critical role of professional societies in undergraduate life science education and, since 2008, have called for the increased involvement of professional societies in support of undergraduate education. Our study explored the level of support being provided by societies for undergraduate education and documented changes in support during the Vision and Change era. Society representatives responded to a survey on programs, awards, meetings, membership, teaching resources, publications, staffing, finances, evaluation, and collaborations that address undergraduate faculty and students. A longitudinal comparison group of societies responded to surveys in both 2008 and 2014. Results indicate that life science professional societies are extensively engaged in undergraduate education in their fields, setting standards for their discipline, providing vetted education resources, engaging students in both research and education, and enhancing professional development and recognition/status for educators. Societies are devoting funding and staff to these efforts and engaging volunteer leadership. Longitudinal comparison group responses indicate there have been significant and quantifiable expansions of undergraduate efforts in many areas since 2008. These indicators can serve as a baseline for defining, aligning, and measuring how professional societies can promote sustainable, evidence-based support of undergraduate education initiatives. © 2017 M. L. Matyas et al. CBE—Life Sciences Education © 2017 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  14. A Single-Vector, Single-Injection Trivalent Filovirus Vaccine: Proof of Concept Study in Outbred Guinea Pigs.

    PubMed

    Mire, Chad E; Geisbert, Joan B; Versteeg, Krista M; Mamaeva, Natalia; Agans, Krystle N; Geisbert, Thomas W; Connor, John H

    2015-10-01

    The filoviruses, Marburg marburgvirus (MARV), Zaire ebolavirus (ZEBOV), and Sudan ebolavirus (SEBOV), cause severe and often fatal hemorrhagic fever in humans and nonhuman primates (NHPs). Monovalent recombinant vesicular stomatitis virus (rVSV)-based vaccine vectors, which encode a filovirus glycoprotein (GP) in place of the VSV glycoprotein, have shown 100% efficacy against homologous filovirus challenge in rodent and NHP studies. Here, we examined the utility of a single-vector, single-injection trivalent rVSV vector expressing MARV, ZEBOV, and SEBOV GPs to protect against MARV-, ZEBOV-, and SEBOV-induced disease in outbred Hartley guinea pigs where we observed protection from effects of all 3 filoviruses. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  15. Life Science Professional Societies Expand Undergraduate Education Efforts

    PubMed Central

    Matyas, Marsha Lakes; Ruedi, Elizabeth A.; Engen, Katie; Chang, Amy L.

    2017-01-01

    The Vision and Change in Undergraduate Biology Education reports cite the critical role of professional societies in undergraduate life science education and, since 2008, have called for the increased involvement of professional societies in support of undergraduate education. Our study explored the level of support being provided by societies for undergraduate education and documented changes in support during the Vision and Change era. Society representatives responded to a survey on programs, awards, meetings, membership, teaching resources, publications, staffing, finances, evaluation, and collaborations that address undergraduate faculty and students. A longitudinal comparison group of societies responded to surveys in both 2008 and 2014. Results indicate that life science professional societies are extensively engaged in undergraduate education in their fields, setting standards for their discipline, providing vetted education resources, engaging students in both research and education, and enhancing professional development and recognition/status for educators. Societies are devoting funding and staff to these efforts and engaging volunteer leadership. Longitudinal comparison group responses indicate there have been significant and quantifiable expansions of undergraduate efforts in many areas since 2008. These indicators can serve as a baseline for defining, aligning, and measuring how professional societies can promote sustainable, evidence-based support of undergraduate education initiatives. PMID:28130272

  16. Inequality in nature and society

    PubMed Central

    Scheffer, Marten; van Bavel, Bas; van de Leemput, Ingrid A.; van Nes, Egbert H.

    2017-01-01

    Most societies are economically dominated by a small elite, and similarly, natural communities are typically dominated by a small fraction of the species. Here we reveal a strong similarity between patterns of inequality in nature and society, hinting at fundamental unifying mechanisms. We show that chance alone will drive 1% or less of the community to dominate 50% of all resources in situations where gains and losses are multiplicative, as in returns on assets or growth rates of populations. Key mechanisms that counteract such hyperdominance include natural enemies in nature and wealth-equalizing institutions in society. However, historical research of European developments over the past millennium suggests that such institutions become ineffective in times of societal upscaling. A corollary is that in a globalizing world, wealth will inevitably be appropriated by a very small fraction of the population unless effective wealth-equalizing institutions emerge at the global level. PMID:29183971

  17. The Economic and Social Impacts of the Transition from the Industrial Society to a Computer Literate, High Technology, Information Society.

    ERIC Educational Resources Information Center

    Groff, Warren H.

    As our society evolves from an industrial society to a computer literate, high technology, information society, educational planners must reexamine the role of postsecondary education in economic development and in intellectual capital formation. In response to this need, a task force on high technology was established to examine the following…

  18. Tolerance and Education in Multicultural Societies

    ERIC Educational Resources Information Center

    Wiater, Werner, Ed.; Manschke, Doris, Ed.

    2011-01-01

    This book examines the concepts of tolerance and education in multicultural societies. It focuses on different aspects of multiculturalism in these societies and considers possible conflicts and tensions as well as best-practice examples of co-existence among different cultural groups. Special emphasis is placed on educational issues and schools.…

  19. Network-Based Community Brings forth Sustainable Society

    NASA Astrophysics Data System (ADS)

    Kikuchi, Toshiko

    It has already been shown that an artificial society based on the three relations of social configuration (market, communal, and obligatory relations) functioning in balance with each other formed a sustainable society which the social reproduction is possible. In this artificial society model, communal relations exist in a network-based community with alternating members rather than a conventional community with cooperative mutual assistance practiced in some agricultural communities. In this paper, using the comparison between network-based communities with alternating members and conventional communities with fixed members, the significance of a network-based community is considered. In concrete terms, the difference in appearance rate for sustainable society, economic activity and asset inequality between network-based communities and conventional communities is analyzed. The appearance rate for a sustainable society of network-based community is higher than that of conventional community. Moreover, most of network-based communities had a larger total number of trade volume than conventional communities. But, the value of Gini coefficient in conventional community is smaller than that of network-based community. These results show that communal relations based on a network-based community is significant for the social reproduction and economic efficiency. However, in such an artificial society, the inequality is sacrificed.

  20. Man and Society

    ERIC Educational Resources Information Center

    Lyons, Thomas T.

    1972-01-01

    Description of three years' experience with an interdisciplinary, field experience course, Man & Society," instituted at the Phillips Academy in 1970. It involved comparative societal study with a nine-week working and living experience in Boston and Mexico, a combination of student, teacher, and joint leadership, group discussion, and joint…

  1. 46 CFR 8.260 - Revocation of classification society recognition.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 1 2010-10-01 2010-10-01 false Revocation of classification society recognition. 8.260... VESSEL INSPECTION ALTERNATIVES Recognition of a Classification Society § 8.260 Revocation of classification society recognition. A recognized classification society which fails to maintain the minimum...

  2. 46 CFR 8.260 - Revocation of classification society recognition.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 1 2011-10-01 2011-10-01 false Revocation of classification society recognition. 8.260... VESSEL INSPECTION ALTERNATIVES Recognition of a Classification Society § 8.260 Revocation of classification society recognition. A recognized classification society which fails to maintain the minimum...

  3. Asia Society's Ongoing Chinese Language Initiatives

    ERIC Educational Resources Information Center

    Livaccari, Chris; Wang, Jeff

    2009-01-01

    Asia Society remains committed to promoting the teaching and learning of Chinese in American schools as an integral part of the broader agenda of building students' global competency, the key goal of its Partnership for Global Learning. Under the leadership of Asia Society's new Vice President for Education Tony Jackson and with continuing…

  4. The Impact of Science on Society.

    ERIC Educational Resources Information Center

    Burke, James; And Others

    The impact of science on society is examined in this publication's coverage of a series of public lectures that commemorated the 25th anniversary of the National Aeronautics and Space Administration. Edited versions of four speeches are presented which address the impact of science on society from the time of humanity's first significant…

  5. Geoethics and the Role of Professional Geoscience Societies

    NASA Astrophysics Data System (ADS)

    Kieffer, S. W.; Palka, J. M.; Geissman, J. W.; Mogk, D. W.

    2014-12-01

    Codes of Ethics (Conduct) for geoscientists are formulated primarily by professional societies and the codes must be viewed in the context of the Goals (Missions, Values) of the societies. Our survey of the codes of approximately twenty-five societies reveals that most codes enumerate principles centered on practical issues regarding professional conduct of individuals such as plagiarism, fabrication, and falsification, and the obligation of individuals to the profession and society at large. With the exception of statements regarding the ethics of peer review, there is relatively little regarding the ethical obligations of the societies themselves. In essence, the codes call for traditionally honorable behavior of individual members. It is striking, given that the geosciences are largely relevant to the future of Earth, most current codes of societies fail to address our immediate obligations to the environment and Earth itself. We challenge professional organizations to consider the ethical obligations to Earth in both their statements of goals and in their codes of ethics. Actions by societies could enhance the efforts of individual geoscientists to serve society, especially in matters related to hazards, resources and planetary stewardship. Actions we suggest to be considered include: (1) Issue timely position statements on topics in which there is expertise and consensus (some professional societies such as AGU, GSA, AAAS, and the AMS, do this regularly, yet others not at all.); (2) Build databases of case studies regarding geoethics that can be used in university classes; (3) Hold interdisciplinary panel discussions with ethicists, scientists, and policy makers at annual meetings; (4) Foster publication in society journals of contributions relating to ethical questions; and (5) Aggressively pursue the incorporation of geoethical issues in undergraduate and graduate curricula and in continuing professional development.

  6. 46 CFR 188.10-59 - Recognized classification society.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Recognized classification society. 188.10-59 Section 188.10-59 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH... classification society. This term means the American Bureau of Shipping or other classification society...

  7. 46 CFR 188.10-59 - Recognized classification society.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Recognized classification society. 188.10-59 Section 188.10-59 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH... classification society. This term means the American Bureau of Shipping or other classification society...

  8. 46 CFR 8.330 - Termination of classification society authority.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 1 2010-10-01 2010-10-01 false Termination of classification society authority. 8.330... classification society authority. (a) The Coast Guard may terminate an authorization agreement with a classification society if: (1) The Commandant revokes the classification society's recognition, as specified in...

  9. 46 CFR 8.330 - Termination of classification society authority.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 1 2011-10-01 2011-10-01 false Termination of classification society authority. 8.330... classification society authority. (a) The Coast Guard may terminate an authorization agreement with a classification society if: (1) The Commandant revokes the classification society's recognition, as specified in...

  10. Towards E-Society Policy Interoperability

    NASA Astrophysics Data System (ADS)

    Iannella, Renato

    The move towards the Policy-Oriented Web is destined to provide support for policy expression and management in the core web layers. One of the most promising areas that can drive this new technology adoption is e-Society communities. With so much user-generated content being shared by these social networks, there is the real danger that the implicit sharing rules that communities have developed over time will be lost in translation in the new digital communities. This will lead to a corresponding loss in confidence in e-Society sites. The Policy-Oriented Web attempts to turn the implicit into the explicit with a common framework for policy language interoperability and awareness. This paper reports on the policy driving factors from the Social Networks experiences using real-world use cases and scenarios. In particular, the key functions of policy-awareness - for privacy, rights, and identity - will be the driving force that enables the e-Society to appreciate new interoperable policy regimes.

  11. Welcome - Construction History Society of America

    Science.gov Websites

    Construction History Society of America Menu About CHSA Membership Join CHSA Sponsorship Construction History CHSA Biennial Meeting 5th International Congress on Construction History Past Events 2016 Construction History Society of America (CHSA) is dedicated to the study of the history and evolution of all

  12. Remaking Public Spaces for Civil Society

    ERIC Educational Resources Information Center

    Ranson, Stewart

    2012-01-01

    The collective action predicaments of the time require citizens to participate in remaking the governance of civil society so that they can become engaged and cooperate together. Can citizens become makers of civil society? This article draws upon Hannah Arendt's "On Revolution" to provide a theory of remaking in which citizens come together to…

  13. The Duplex Society.

    ERIC Educational Resources Information Center

    Schorr, Alvin L.

    1984-01-01

    The duplex society, in which the poor live in close proximity to others but in a separate compartment, is already with us. Unless something deeply changes about family income, more than one-third of future generations will come to adulthood having spent a portion of their childhood in official poverty. (RM)

  14. S3-guideline "helicobacter pylori and gastroduodenal ulcer disease" of the German society for digestive and metabolic diseases (DGVS) in cooperation with the German society for hygiene and microbiology, society for pediatric gastroenterology and nutrition e. V., German society for rheumatology, AWMF-registration-no. 021 / 001.

    PubMed

    Fischbach, W; Malfertheiner, P; Hoffmann, J C; Bolten, W; Bornschein, J; Götze, O; Höhne, W; Kist, M; Koletzko, S; Labenz, J; Layer, P; Miehlke, St; Morgner, A; Peitz, U; Preiss, J; Prinz, C; Rosien, U; Schmidt, W; Schwarzer, A; Suerbaum, St; Timmer, A; Treiber, G; Vieth, M

    2009-12-01

    This guideline updates a prior consensus recommendation of the German Society for Digestive and Metabolic Diseases (DGVS) from 1996. It was developed by an interdisciplinary cooperation with representatives of the German Society for Hygiene and Microbiology, the Society for Pediatric Gastroenterology and Nutrition (GPGE), and the German Society for Rheumatology. The guideline is methodologically based on recommendations of the Association of the Scientific Medical Societies in Germany (AWMF) for providing a systematic evidence-based S 3 level consensus guideline and has also implemented grading criteria according to the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) process. Clinical applicability of study results as well as specifics for Germany in terms of epidemiology, antibiotic resistance status, diagnostics, and therapy were taken into account.

  15. Identification of a coumarin-based antihistamine-like small molecule as an anti-filoviral entry inhibitor.

    PubMed

    Cheng, Han; Schafer, Adam; Soloveva, Veronica; Gharaibeh, Dima; Kenny, Tara; Retterer, Cary; Zamani, Rouzbeh; Bavari, Sina; Peet, Norton P; Rong, Lijun

    2017-09-01

    Filoviruses, consisting of Ebola virus, Marburg virus and Cuevavirus, cause severe hemorrhagic fevers in humans with high mortality rates up to 90%. Currently, there is no approved vaccine or therapy available for the prevention and treatment of filovirus infection in humans. The recent 2013-2015 West African Ebola epidemic underscores the urgency to develop antiviral therapeutics against these infectious diseases. Our previous study showed that GPCR antagonists, particularly histamine receptor antagonists (antihistamines) inhibit Ebola and Marburg virus entry. In this study, we screened a library of 1220 small molecules with predicted antihistamine activity, identified multiple compounds with potent inhibitory activity against entry of both Ebola and Marburg viruses in human cancer cell lines, and confirmed their anti-Ebola activity in human primary cells. These small molecules target a late-stage of Ebola virus entry. Further structure-activity relationship studies around one compound (cp19) reveal the importance of the coumarin fused ring structure, especially the hydrophobic substituents at positions 3 and/or 4, for its antiviral activity, and this identified scaffold represents a favorable starting point for the rapid development of anti-filovirus therapeutic agents. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Pittsburgh Science Technology Society Project: Instruction Modules. Interrelationships Science--Technology--Society.

    ERIC Educational Resources Information Center

    O'Brien, George, Ed.

    This collection of instruction modules studies the interactions of science, technology, and society (STS) using five activity sets. The introduction module includes activities which show students the STS relationships in their world, develop good organizational skills, develop an understanding of who and what a scientist is, develop graphing…

  17. 46 CFR 8.220 - Recognition of a classification society.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 1 2010-10-01 2010-10-01 false Recognition of a classification society. 8.220 Section 8... INSPECTION ALTERNATIVES Recognition of a Classification Society § 8.220 Recognition of a classification society. (a) A classification society must be recognized by the Commandant before it may receive statutory...

  18. 46 CFR 8.220 - Recognition of a classification society.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 1 2011-10-01 2011-10-01 false Recognition of a classification society. 8.220 Section 8... INSPECTION ALTERNATIVES Recognition of a Classification Society § 8.220 Recognition of a classification society. (a) A classification society must be recognized by the Commandant before it may receive statutory...

  19. The Black Man in American Society.

    ERIC Educational Resources Information Center

    Framingham Public Schools, MA.

    GRADE OR AGES: Junior high school. SUBJECT MATTER: The black man in American society. ORGANIZATION AND PHYSICAL APPEARANCE: There are four major parts each with an overview. The four parts concern a) the African heritage of the black man, b) the American exploitation of the black man, c) the black man's contribution to American society, d) the…

  20. Naming and Address in Afghan Society.

    ERIC Educational Resources Information Center

    Miran, M. Alam

    Forms of address in Afghan society reflect the relationships between the speakers as well as the society's structure. In Afghan Persian, or Dari, first, second, and last names have different semantic dimensions. Boys' first names usually consist of two parts or morphemes, of which one may be part of the father's name. Girls' names usually consist…

  1. 46 CFR 42.05-60 - Recognized classification society.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 2 2011-10-01 2011-10-01 false Recognized classification society. 42.05-60 Section 42... FOREIGN VOYAGES BY SEA Definition of Terms Used in This Subchapter § 42.05-60 Recognized classification society. The term recognized classification society means the American Bureau of Shipping or other...

  2. 46 CFR 42.05-60 - Recognized classification society.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 2 2010-10-01 2010-10-01 false Recognized classification society. 42.05-60 Section 42... FOREIGN VOYAGES BY SEA Definition of Terms Used in This Subchapter § 42.05-60 Recognized classification society. The term recognized classification society means the American Bureau of Shipping or other...

  3. 46 CFR 42.05-60 - Recognized classification society.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 2 2013-10-01 2013-10-01 false Recognized classification society. 42.05-60 Section 42... FOREIGN VOYAGES BY SEA Definition of Terms Used in This Subchapter § 42.05-60 Recognized classification society. The term recognized classification society means the American Bureau of Shipping or other...

  4. 46 CFR 42.05-60 - Recognized classification society.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 2 2012-10-01 2012-10-01 false Recognized classification society. 42.05-60 Section 42... FOREIGN VOYAGES BY SEA Definition of Terms Used in This Subchapter § 42.05-60 Recognized classification society. The term recognized classification society means the American Bureau of Shipping or other...

  5. 46 CFR 90.10-35 - Recognized classification society.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 4 2010-10-01 2010-10-01 false Recognized classification society. 90.10-35 Section 90... VESSELS GENERAL PROVISIONS Definition of Terms Used in This Subchapter § 90.10-35 Recognized classification society. The term recognized classification society means the American Bureau of Shipping or other...

  6. Environmental Design for a Structured Network Learning Society

    ERIC Educational Resources Information Center

    Chang, Ben; Cheng, Nien-Heng; Deng, Yi-Chan; Chan, Tak-Wai

    2007-01-01

    Social interactions profoundly impact the learning processes of learners in traditional societies. The rapid rise of the Internet using population has been the establishment of numerous different styles of network communities. Network societies form when more Internet communities are established, but the basic form of a network society, especially…

  7. The Society of Thoracic Surgeons, The Society of Cardiovascular Anesthesiologists, and The American Society of ExtraCorporeal Technology: Clinical Practice Guidelines for Cardiopulmonary Bypass--Temperature Management during Cardiopulmonary Bypass.

    PubMed

    Engelman, Richard; Baker, Robert A; Likosky, Donald S; Grigore, Alina; Dickinson, Timothy A; Shore-Lesserson, Linda; Hammon, John W

    2015-09-01

    To improve our understanding of the evidence-based literature supporting temperature management during adult cardiopulmonary bypass, The Society of Thoracic Surgeons, the Society of Cardiovascular Anesthesiology and the American Society of ExtraCorporeal Technology tasked the authors to conduct a review of the peer-reviewed literature, including 1) optimal site for temperature monitoring, 2) avoidance of hyperthermia, 3) peak cooling temperature gradient and cooling rate, and 4) peak warming temperature gradient and rewarming rate. Authors adopted the American College of Cardiology/American Heart Association method for development clinical practice guidelines, and arrived at the following recommendation.

  8. A history of the Teratology Society.

    PubMed

    Shepard, T H; Barr, M; Brent, R L; Hendrickx, A; Kochhar, D; Oakley, G; Scott, W J

    2000-11-01

    The 39-year history of the Teratology Society is reviewed. An abbreviated history is outlined in table form, along with listings of the Warkany Lectures, the postgraduate courses, and officers of the Society. A year-by-year description of the events, including the scientific and social content of the annual meetings and changes in the business of the Society, is given, in many cases using comments from the past presidents. The valuable and unique diversity of the members is discussed and illustrated, presenting the disciplines and main research area of the presidents. The number of submitted abstracts and the various categories are tabulated, averaging the number and type over four periods. Within the past 10 years, a significant increase in the number of abstracts dealing with epidemiology and developmental biology is evident. The Society's development is compared with that of a human, and the question is asked: Have we reached the maturational stage of old age or senescence, or is the Society still maturing gracefully? This question needs further discussion by all the members. During the past 40 years, we have developed the scientific basis to prevent birth defects caused by rubella, alcoholism, and folate deficiency, as well as many other prenatal exposures. We must now engage in the political battles to obtain the resources needed to conduct further research and to implement the prevention programs, as well as to provide care and rehabilitation for persons with birth defects. Copyright 2000 Wiley-Liss, Inc.

  9. Oropharyngeal trauma mimicking a first branchial cleft anomaly.

    PubMed

    Larem, Aisha; Sheikh, Rashid; Al Qahtani, Abdulsalam; Khais, Frat; Ganesan, Shanmugam; Haidar, Hassan

    2016-06-01

    We present a unique and challenging case of a remnant foreign body that presented to us in a child disguised as a strongly suspected congenital branchial cleft anomaly. This case entailed oropharyngeal trauma, with a delayed presentation as a retroauricular cyst accompanied by otorrhea that mimicked the classic presentation of an infected first branchial cleft anomaly. During surgical excision of the presumed branchial anomaly, a large wooden stick was found in the tract. The diagnostic and therapeutic obstacles in the management of such cases are highlighted. In addition to exploring the existing literature, we retrospectively analyzed a plausible explanation of the findings of this case. Laryngoscope, 126:E224-E226, 2016. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

  10. Health economic evaluation: important principles and methodology.

    PubMed

    Rudmik, Luke; Drummond, Michael

    2013-06-01

    To discuss health economic evaluation and improve the understanding of common methodology. This article discusses the methodology for the following types of economic evaluations: cost-minimization, cost-effectiveness, cost-utility, cost-benefit, and economic modeling. Topics include health-state utility measures, the quality-adjusted life year (QALY), uncertainty analysis, discounting, decision tree analysis, and Markov modeling. Economic evaluation is the comparative analysis of alternative courses of action in terms of both their costs and consequences. With increasing health care expenditure and limited resources, it is important for physicians to consider the economic impact of their interventions. Understanding common methodology involved in health economic evaluation will improve critical appraisal of the literature and optimize future economic evaluations. Copyright © 2012 The American Laryngological, Rhinological and Otological Society, Inc.

  11. Taste disorders after tonsillectomy: a long-term follow-up.

    PubMed

    Heiser, Clemens; Landis, Basile N; Giger, Roland; Cao Van, Helene; Guinand, Nils; Hörmann, Karl; Stuck, Boris A

    2012-06-01

    In a former study, taste disturbances after tonsillectomy seemed to be more frequent than expected. Eight percent of patients reported subjective taste disorders 6 months after tonsillectomy. Fifteen patients from the initial trial, who reported taste disorders after tonsillectomy, were contacted again for this long-term follow-up. A telephone interview using the same questionnaire addressing the current self-estimate of taste function was performed. At 32 ± 10 months following surgery, two (0.9%) patients still reported suffering from taste disturbance. This long-term follow-up study shows that dysgeusia following tonsillectomy occurs in approximately 1% of patients. These data should be considered when patients are informed about complications after tonsillectomy. Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.

  12. Facial nerve hemangioma: a rare case involving the vertical segment.

    PubMed

    Ahmadi, Neda; Newkirk, Kenneth; Kim, H Jeffrey

    2013-02-01

    This case report and literature review reports on a rare case of facial nerve hemangioma (FNH) involving the vertical facial nerve (FN) segment, and discusses the clinical presentation, imaging, pathogenesis, and management of these rare lesions. A 53-year-old male presented with a 10-year history of right hemifacial twitching and progressive facial paresis (House-Brackmann grading score V/VI). The computed tomography and magnetic resonance imaging studies confirmed an expansile lesion along the vertical FN segment. Excision and histopathologic examination demonstrated FNH. FNHs involving the vertical FN segment are extremely rare. Despite being rare lesions, we believe that familiarity with the presentation and management of FNHs are imperative. Laryngoscope, 2012. Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.

  13. Digital Literacy: Tools and Methodologies for Information Society

    ERIC Educational Resources Information Center

    Rivoltella, Pier Cesare, Ed.

    2008-01-01

    Currently in a state of cultural transition, global society is moving from a literary society to digital one, adopting widespread use of advanced technologies such as the Internet and mobile devices. Digital media has an extraordinary impact on society's formative processes, forcing a pragmatic shift in their management and organization. This…

  14. Parent-teacher agreement on children's problems in 21 societies.

    PubMed

    Rescorla, Leslie A; Bochicchio, Lauren; Achenbach, Thomas M; Ivanova, Masha Y; Almqvist, Fredrik; Begovac, Ivan; Bilenberg, Niels; Bird, Hector; Dobrean, Anca; Erol, Nese; Fombonne, Eric; Fonseca, Antonio; Frigerio, Alessandra; Fung, Daniel S S; Lambert, Michael C; Leung, Patrick W L; Liu, Xianchen; Marković, Ivica; Markovic, Jasminka; Minaei, Asghar; Ooi, Yoon Phaik; Roussos, Alexandra; Rudan, Vlasta; Simsek, Zeynep; van der Ende, Jan; Weintraub, Sheila; Wolanczyk, Tomasz; Woo, Bernardine; Weiss, Bahr; Weisz, John; Zukauskiene, Rita; Verhulst, Frank C

    2014-01-01

    Parent-teacher cross-informant agreement, although usually modest, may provide important clinical information. Using data for 27,962 children from 21 societies, we asked the following: (a) Do parents report more problems than teachers, and does this vary by society, age, gender, or type of problem? (b) Does parent-teacher agreement vary across different problem scales or across societies? (c) How well do parents and teachers in different societies agree on problem item ratings? (d) How much do parent-teacher dyads in different societies vary in within-dyad agreement on problem items? (e) How well do parents and teachers in 21 societies agree on whether the child's problem level exceeds a deviance threshold? We used five methods to test agreement for Child Behavior Checklist (CBCL) and Teacher's Report Form (TRF) ratings. CBCL scores were higher than TRF scores on most scales, but the informant differences varied in magnitude across the societies studied. Cross-informant correlations for problem scale scores varied moderately across societies studied and were significantly higher for Externalizing than Internalizing problems. Parents and teachers tended to rate the same items as low, medium, or high, but within-dyad item agreement varied widely in every society studied. In all societies studied, both parental noncorroboration of teacher-reported deviance and teacher noncorroboration of parent-reported deviance were common. Our findings underscore the importance of obtaining information from parents and teachers when evaluating and treating children, highlight the need to use multiple methods of quantifying cross-informant agreement, and provide comprehensive baselines for patterns of parent-teacher agreement across 21 societies.

  15. Testing the Teacher's Report Form Syndromes in 20 Societies

    ERIC Educational Resources Information Center

    Ivanova, Masha Y.; Achenbach, Thomas M.; Rescorla, Leslie A.; Dumenci, Levent; Almqvist, Fredrik; Bathiche, Marie; Bilenberg, Niels; Bird, Hector; Domuta, Anca; Erol, Nese; Fombonne, Eric; Fonseca, Antonio; Frigerio, Alessandra; Kanbayashi, Yasuko; Lambert, Michael C.; Leung, Patrick; Liu, Xianchen; Minaei, Asghar; Roussos, Alexandra; Simsek, Zeynep; Weintraub, Sheila; Wolanczyk, Tomasz; Zubrick, Stephen; Zukauskiene, Rita; Verhulst, Frank C.

    2007-01-01

    Standardized assessment instruments developed in one society are often used in other societies. However, it is important to determine empirically how assessment instruments developed in one society function in others. The present study tested the fit of the Teacher's Report Form syndrome structures in 20 diverse societies using data for 30,030 6-…

  16. Longevity suppresses conflict in animal societies

    PubMed Central

    Port, Markus; Cant, Michael A.

    2013-01-01

    Models of social conflict in animal societies generally assume that within-group conflict reduces the value of a communal resource. For many animals, however, the primary cost of conflict is increased mortality. We develop a simple inclusive fitness model of social conflict that takes this cost into account. We show that longevity substantially reduces the level of within-group conflict, which can lead to the evolution of peaceful animal societies if relatedness among group members is high. By contrast, peaceful outcomes are never possible in models where the primary cost of social conflict is resource depletion. Incorporating mortality costs into models of social conflict can explain why many animal societies are so remarkably peaceful despite great potential for conflict. PMID:24088564

  17. The first President of the Royal Society.

    PubMed

    Fara, Patricia

    2003-12-01

    Few people know the name of the Royal Society's first President, even though he features prominently in Thomas Sprat's famous allegorical frontispiece. In promotional images, his individual identity is irrelevant for proclaiming the Society's allegiance to Francis Bacon and commitment to experimental investigation. By contrast, William Brouncker's name does appear on Peter Lely's large portrait, which hung at the Royal Society. Brouncker was a gifted mathematician as well as a conscientious administrator, and Lely's portrait reproduces the diagram of one of his innovative algebraic proofs.

  18. Medical "publishing societies" in eighteenth-century Britain.

    PubMed Central

    Kronick, D A

    1994-01-01

    This article reviews the relationship between medical journals and publishing societies in eighteenth-century Great Britain. The importance of the perception that these journals were being issued under the auspices of societies is revealed by the number of times this kind of sponsorship was invoked by new medical journals. This kind of endorsement was projected even when a society so designated exercised only a nominal responsibility for the journal and, even when, in some instances, no organization can be said to have existed. PMID:7920337

  19. A Learned Society's Perspective on Publishing.

    PubMed

    Suzuki, Kunihiko; Edelson, Alan; Iversen, Leslie L; Hausmann, Laura; Schulz, Jörg B; Turner, Anthony J

    2016-10-01

    Scientific journals that are owned by a learned society, like the Journal of Neurochemistry (JNC), which is owned by the International Society for Neurochemistry (ISN), benefit the scientific community in that a large proportion of the income is returned to support the scientific mission of the Society. The income generated by the JNC enables the ISN to organize conferences as a platform for members and non-members alike to share their research, supporting researchers particularly in developing countries by travel grants and other funds, and promoting education in student schools. These direct benefits and initiatives for ISN members and non-members distinguish a society journal from pure commerce. However, the world of scholarly publishing is changing rapidly. Open access models have challenged the business model of traditional journal subscription and hence provided free access to publicly funded scientific research. In these models, the manuscript authors pay a publication cost after peer review and acceptance of the manuscript. Over the last decade, numerous new open access journals have been launched and traditional subscription journals have started to offer open access (hybrid journals). However, open access journals follow the general scheme that, of all participating parties, the publisher receives the highest financial benefit. The income is generated by researchers whose positions and research are mostly financed by taxpayers' or funders' money, and by reviewers and editors, who frequently are not reimbursed. Last but not least, the authors pay for the publication of their work after a rigorous and sometimes painful review process. JNC itself has an open access option, at a significantly reduced cost for Society members as an additional benefit. This article provides first-hand insights from two former Editors-in-Chief, Kunihiko Suzuki and Leslie Iversen, about the history of JNC's ownership and about the difficulties and battles fought along the way to

  20. Is Society Capable of Learning? Beyond a Metaphysical Foundation

    ERIC Educational Resources Information Center

    Su, Ya-hui

    2016-01-01

    There is an assumption that any contemporary society should become a learning society to maintain stability in the face of change. Although proponents and policymakers take for granted that a society has the ability to learn, can this idea be defended? There is a problem in determining exactly what is meant by a learning society that learns. One…

  1. Society 3.0: How Technology Is Reshaping Education, Work and Society

    ERIC Educational Resources Information Center

    Wilen-Daugenti, Tracey

    2012-01-01

    Higher education in the U.S. has traditionally prepared students for work and social success, but with families, work, and society itself undergoing revolutionary change, is this preparation sufficient to develop the 21st-century workforce? This book explores how evolving family structures, new ways of balancing work and personal lives, and rapid…

  2. Foundation and progress of Japanese society of toxicologic pathology*.

    PubMed

    Konishi, Yoichi; Enomoto, Makoto; Hayashi, Yuzo

    2011-03-01

    The Japanese Society of Toxicologic Pathology (JSTP) has a differing conceptual framework from the Japanese Society of Pathology (JSP) and Japanese Society of Toxicology (JST) and was founded in 1985 by the leadership of late Dr. Yasukazu Nishiyama with the cooperation of several founding members and the support of JSP. The aim of the JSTP is to improve the human and animal health using an interdisciplinary scientific approach based on pathology and toxicology. In its development as a professional society, the JSTP has established society rules and activities. The JSTP has grown in terms of membership and financial aspects and is now recognized not only domestically but also internationally as a well-organized scientific society. To maintain the high professional standard and visibility of JSTP, we here provide the historical background of the society as a basis for current members to contribute to the continued improvement of our scientific organization.

  3. ACC/AATS/AHA/ASE/ASNC/HRS/SCAI/SCCT/SCMR/STS 2017 Appropriate Use Criteria for Multimodality Imaging in Valvular Heart Disease : A Report of the American College of Cardiology Appropriate Use Criteria Task Force, American Association for Thoracic Surgery, American Heart Association, American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Computed Tomography, Society for Cardiovascular Magnetic Resonance, and Society of Thoracic Surgeons.

    PubMed

    Doherty, John U; Kort, Smadar; Mehran, Roxana; Schoenhagen, Paul; Soman, Prem

    2017-12-01

    This document is 1 of 2 companion appropriate use criteria (AUC) documents developed by the American College of Cardiology, American Association for Thoracic Surgery, American Heart Association, American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Computed Tomography, Society for Cardiovascular Magnetic Resonance, and Society of Thoracic Surgeons. This document addresses the evaluation and use of multimodality imaging in the diagnosis and management of valvular heart disease, whereas the second, companion document addresses this topic with regard to structural heart disease. Although there is clinical overlap, the documents addressing valvular and structural heart disease are published separately, albeit with a common structure. The goal of the companion AUC documents is to provide a comprehensive resource for multimodality imaging in the context of valvular and structural heart disease, encompassing multiple imaging modalities.Using standardized methodology, the clinical scenarios (indications) were developed by a diverse writing group to represent patient presentations encountered in everyday practice and included common applications and anticipated uses. Where appropriate, the scenarios were developed on the basis of the most current American College of Cardiology/American Heart Association guidelines.A separate, independent rating panel scored the 92 clinical scenarios in this document on a scale of 1 to 9. Scores of 7 to 9 indicate that a modality is considered appropriate for the clinical scenario presented. Midrange scores of 4 to 6 indicate that a modality may be appropriate for the clinical scenario, and scores of 1 to 3 indicate that a modality is considered rarely appropriate for the clinical scenario.The primary objective of the AUC is to provide a framework for the assessment of these scenarios by practices that will

  4. An updated history of the Teratology Society.

    PubMed

    Shepard, Thomas H; Barr, Mason; Brent, Robert L; Hendrickx, Andrew; Kochhar, Devendra; Oakley, Godfrey; Scott, William J; Rogers, John M

    2010-05-01

    The 49-year history of the Teratology Society is reviewed. An abbreviated history is outlined in table form, with listings of the Warkany Lectures, the Continuing Education Courses, and officers of the society. The original article was updated to include the years 2000 to 2010. A year-by-year description of the events is given, including the scientific and social content of the annual meetings and changes in the business of the society, in many cases using comments from the past presidents. The valuable and unique diversity of the members is discussed and illustrated, presenting the disciplines and main research areas of the presidents. The number of submitted abstracts and the various categories are tabulated, averaging the number and type over successive periods. A significant increase in the number of abstracts dealing with epidemiology and developmental biology is evident. The society's development is compared to that of a human, and the question was asked by Shephard et al. (2000): Have we reached the maturational stage of old age or senescence, or is the society still maturing gracefully? This question needs further discussion by all the members. By 2010, many positive changes are happening to revitalize the society. During the past 50 years, we have developed the scientific basis to prevent birth defects caused by rubella, alcoholism, and folate deficiency, as well as other prenatal exposures. We are now taking advantage of advances in many fields to begin shaping the Teratology Society of the 21st century. We must now engage in political battles to obtain the resources needed to conduct further research and to implement prevention programs, as well as to provide care and rehabilitation for persons with birth defects. 2010 Wiley-Liss, Inc.

  5. Therapeutic methods for psychosomatic disorders in oto-rhino-laryngology

    PubMed Central

    Decot, Elke

    2005-01-01

    Psychosomatic disorders such as tinnitus, acute hearing loss, attacks of dizziness, globus syndrome, dysphagias, voice disorders and many more are quite common in ear, nose and throat medicine. They are mostly caused by a number of factors, although the bio-psycho-social model does play an important role. Initial contact with a psychosomatically ill patient and compiling a first case history are important steps to psychosomatic oriented therapy. This contribution will sum up the most important otorhinolaryngological diseases with psychosomatic comorbidity and scientifically evaluated methods of treatment. The contribution will also introduce the reader to important psychosomatic treatment methods from psychotherapeutic relaxation techniques to talk therapy. To conclude, the contribution will discuss the criteria for outpatient as well as inpatient treatment and look at the advantages of psychosomatically oriented therapy, both for the patient and for the doctor. PMID:22073069

  6. Prejudice and Society.

    ERIC Educational Resources Information Center

    Raab, Earl; Lipset, Seymour M.

    This monograph consists of six chapters which discuss the problem of prejudice in our society. Chapter I looks at "Prejudice as a Social Problem." As a social problem prejudice can be defined exclusively in terms of human behavior which denies or attempts to deny equality of opportunity or status to certain racial, religious, or ethnic groups.…

  7. Values and Society.

    ERIC Educational Resources Information Center

    Nelson, Jack L.

    The idea of a democratic society based on human rights and social justice is the social issue examined in this book which is one of a series on challenges and choices in American values. The format followed in the series includes the following for secondary students: case studies illustrating the issue by focusing on human institutions, factual…

  8. Changing anthropology, changing society.

    PubMed

    Varughese, Heather

    2009-12-01

    Fifty years after the founding of the field of medical anthropology, the Society for Medical Anthropology of the American Anthropological Association held its first independent meeting on September 24-27, 2009, at Yale University.

  9. Teaching the Intersection of Climate and Society

    NASA Astrophysics Data System (ADS)

    Thomson, C.; Ting, M.; Orlove, B. S.

    2014-12-01

    As the first program of its kind, the M.A. in Climate and Society at Columbia University educates students on how climate affects society and vice versa. The 12-month interdisciplinary Master's program is designed to allow students from a wide variety of backgrounds to gain knowledge in climate science and a deep understanding of social sciences and how they related to climate. There are currently more than 250 alumni applying their skills in fields including energy, economics, disaster mitigation, journalism and climate research in more than a dozen countries worldwide. The presentation will highlight three key components of the program that have contributed to its growth and helped alumni become brokers that can effectively put climate science in the hands of the public and policymakers for the benefit of society. Those components include working with other academic departments at Columbia to successfully integrate social science classes into the curriculum; the development of the course Applications in Climate and Society to help students make an overt link between climate and its impacts on society; and providing students with hands-on activities with practitioners in climate-related fields.

  10. Coevolution of nutrigenomics and society: ethical considerations.

    PubMed

    Korthals, Michiel

    2011-12-01

    To optimize the coevolution of nutrigenomics and society (ie, the reciprocal stimulation of both developments), I analyzed chances for a fruitful match between normative concepts and strategies of both developments. Nutrigenomics embodies ≥ 3 normative concepts. First, food is exclusively interpreted in terms of disease prevention. Second, striving for health is interpreted as the quantification of risks and prevention of diseases through positive food-gene interactions. The third normative idea is that disease prevention by the minimization of risks is an individual's task. My thesis was that these concepts of nutrigenomics would not easily match with concepts of food and health of various food styles in Western societies, which, for instance, parents in the case of metabolic programming endorse and with a philosophical view of the relation between food, health, and the meaning of life. Next, I reflected on the nonsynchronized coevolution of nutrigenomics and society because of this mismatch and introduced the concept of the fair representation of food styles in nutrigenomic developments. To synchronize and optimize the coevolution of nutrigenomics and society, I propose that the research policy of nutrigenomics should change to a research partnership with society on the basis of fair representation.

  11. The beginnings of the Southern Child/Pediatric Neurology Society.

    PubMed

    Dyken, Paul Richard; Bodensteiner, John B

    2015-04-01

    The founding and early development of the Southern Pediatric Neurology Society was in many ways parallel to that of the Child Neurology Society. The organization started out as the Southern Child Neurology Society but the name was changed at the time of incorporation so as to avoid confusion of identity and purpose with the larger Child Neurology Society. Although there are archives of early days and the later development of the Southern Pediatric Neurology Society, the details have never been set down in a narrative explaining the events that led to the development of the organization. In this paper, we try to produce a written record of the history of the founding and early development of the Southern Pediatric Neurology Society. © The Author(s) 2014.

  12. Neurosurgery certification in member societies of the World Federation of Neurosurgical Societies: Asia.

    PubMed

    Gasco, Jaime; Braun, Jonathan D; McCutcheon, Ian E; Black, Peter M

    2011-01-01

    To objectively compare the complexity and diversity of the certification process in neurological surgery in member societies of the World Federation of Neurosurgical Societies. This study centers in continental Asia. We provide here an analysis based on the responses provided to a 13-item survey. The data received were analyzed, and three Regional Complexity Scores (RCS) were designed. To compare national board experience, eligibility requirements for access to the certification process, and the obligatory nature of the examinations, an RCS-Organizational score was created (20 points maximum). To analyze the complexity of the examination, an RCS-Components score was designed (20 points maximum). The sum of both is presented in a Global RCS score. Only those countries that responded to the survey and presented nationwide homogeneity in the conduction of neurosurgery examinations could be included within the scoring system. In addition, a descriptive summary of the certification process per responding society is also provided. On the basis of the data provided by our RCS system, the highest global RCS was achieved by South Korea and Malaysia (21/40 points) followed by the joint examination of Singapore and Hong-Kong (FRCS-Ed) (20/40 points), Japan (17/40 points), the Philippines (15/40 points), and Taiwan (13 points). The experience from these leading countries should be of value to all countries within Asia. Copyright © 2011 Elsevier Inc. All rights reserved.

  13. Introduction to Ageing: science, medicine, and society

    PubMed Central

    Klug, A.

    1997-01-01

    Introduction to Ageing: science, medicine, and society, the proceedings of a Discussion held at The Royal Society on 7 and 8 May 1997. Organized and edited by J. Grimley Evans, R. Holliday, T. B. L. Kirkwood, P. Laslett and L. Tyler.

  14. The focus of women in The American Fertility Society.

    PubMed

    Haseltine, F P; Wentz, A C

    1984-09-01

    This article reports survey responses from 71 female members of the American Fertility Society during the Society's 1984 annual meeting. Survey questions concern 1) demographic factors such as rank, degree, title, address, and number of children, 2) field of specialization and research interests, and 3) what the Society can do for its meeting participants. The typical respondent is a physician living in the Eastern United States and employed as an assistant professor in an academic setting. In vitro fertilization is the greatest area of interest, followed by general practice, endocrine and male infertility, contraception, and fertility surgery. Survey responses show that women are interested in 1) networking, 2) increased visibility at professional meetings, 3) information about research possibilities and grants, 4) child care provision at Society meetings, and 5) more basic science and physiology oriented presentions in the program. In response to networking interests, the Society will make available information from the surveyed members. Since 16% of respondents have a PH.D., and 77% are employed in academics, the Society should consider more basic presentations. The need for day care indicates changes in Society membership. The Society plans to conduct similar surveys on a regular basis.

  15. Changing Anthropology, Changing Society

    PubMed Central

    Varughese, Heather

    2009-01-01

    Fifty years after the founding of the field of medical anthropology, the Society for Medical Anthropology of the American Anthropological Association held its first independent meeting on September 24-27, 2009, at Yale University. PMID:20027281

  16. Literature, Society and the Writer in Tripartite Unity

    ERIC Educational Resources Information Center

    Anaso, George Nworah; Nwabudike, Christopher Eziafa

    2014-01-01

    The proactive unity of purpose between Literature, society and the writer is the main focus of this paper. Writers use Literature to address various important themes or the goings on in the society, with the purpose of edifying its virtues and condemning the vices so as to adulate the good deeds or correct the society where it goes wrong. However,…

  17. The history of three scientific societies: the Society for the Study of Fertility (now the Society for Reproduction and Fertility) (Britain), the Société Française pour l'Etude de la Fertilité, and the Society for the Study of Reproduction (USA).

    PubMed

    Clarke, John

    2007-06-01

    Three scientific societies devoted to the study of reproduction were established in Britain, France and USA in the middle of the twentieth century by clinical, veterinary and agricultural scientists. The principal motivation for their establishment had been the study of sterility and fertility of people and livestock. There was also a wider perspective embracing other biologists interested in reproduction more generally. Knowledge disseminated through the societies' scientific meetings and publications would bear upon human and animal population problems as well as basic reproductive physiology and its applications. New journals dealing with reproductive physiology, having worldwide appeal, were established in Britain and USA. The financial resources of at least one of the societies and its journal are directed towards charitable functions, including financial support for travel to scientific meetings, for visits to particular laboratories, and for research in the short term, including that of undergraduates. Perhaps the example of the British society has given rise to others having a more specialised focus, as well as to the formation of the European Society for the Study of Human Reproduction and Embryology.

  18. American Cancer Society, American Society for Colposcopy and Cervical Pathology, and American Society for Clinical Pathology Screening Guidelines for the Prevention and Early Detection of Cervical Cancer

    PubMed Central

    Saslow, Debbie; Solomon, Diane; Lawson, Herschel W.; Killackey, Maureen; Kulasingam, Shalini; Cain, Joanna; Garcia, Francisco A. R.; Moriarty, Ann; Waxman, Alan; Wilbur, David; Wentzensen, Nicolas; Downs, Levi; Spitzer, Mark; Moscicki, Anna-Barbara; Saraiya, Mona; Franco, Eduardo L.; Stoler, Mark H.; Schiffman, Mark; Castle, Philip E.; Myers, Evan R.

    2013-01-01

    An update to the American Cancer Society (ACS) guideline regarding screening for the early detection of cervical precancerous lesions and cancer is presented. The guidelines are based on a systematic evidence review, contributions from six working groups, and a recent symposium co-sponsored by the ACS, American Society for Colposcopy and Cervical Pathology (ASCCP), and American Society for Clinical Pathology (ASCP), which was attended by 25 organizations. The new screening recommendations address age-appropriate screening strategies, including the use of cytology and high-risk human papillomavirus (HPV) testing, follow-up (e.g., management of screen positives and screening interval for screen negatives) of women after screening, age at which to exit screening, future considerations regarding HPV testing alone as a primary screening approach, and screening strategies for women vaccinated against HPV16 and HPV18 infections. PMID:22418039

  19. American Cancer Society, American Society for Colposcopy and Cervical Pathology, and American Society for Clinical Pathology Screening Guidelines for the Prevention and Early Detection of Cervical Cancer

    PubMed Central

    Saslow, Debbie; Solomon, Diane; Lawson, Herschel W.; Killackey, Maureen; Kulasingam, Shalini; Cain, Joanna; Garcia, Francisco A. R.; Moriarty, Ann; Waxman, Alan; Wilbur, David; Wentzensen, Nicolas; Downs, Levi; Spitzer, Mark; Moscicki, Anna-Barbara; Franco, Eduardo L.; Stoler, Mark H.; Schiffman, Mark; Castle, Philip E.; Myers, Evan R.

    2013-01-01

    An update to the American Cancer Society (ACS) guideline regarding screening for the early detection of cervical precancerous lesions and cancer is presented. The guidelines are based on a systematic evidence review, contributions from six working groups, and a recent symposium cosponsored by the ACS, American Society for Colposcopy and Cervical Pathology (ASCCP), and American Society for Clinical Pathology (ASCP), which was attended by 25 organizations. The new screening recommendations address age-appropriate screening strategies, including the use of cytology and high-risk human papillomavirus (HPV) testing, follow-up (e.g., management of screen positives and screening interval for screen negatives) of women after screening, age at which to exit screening, future considerations regarding HPV testing alone as a primary screening approach, and screening strategies for women vaccinated against HPV16 and HPV18 infections. PMID:22422631

  20. Asian Radiology Forum 2016 for Promoting Radiology Together in the Asian-Oceanian Region: Roles of the Asian-Oceanian Society of Radiology and Its Member Societies

    PubMed Central

    Kim, Ho Sung; Choi, Jung-Ah

    2018-01-01

    According to the reports presented at the second Asian Radiology Forum (ARF) 2016, organized by the Korean Society of Radiology (KSR) during the Korean Congress of Radiology (KCR) in September 2016 in Seoul, there is an increasing need for the Asian-Oceanian Society of Radiology (AOSR) and its member societies to promote radiology together in the Asian-Oceanian region. In ARF 2016, the national delegates of the Asian-Oceanian radiological partner societies primarily discussed their societies' activities and contributions in international and regional societies including AOSR, expectations for AOSR, recommendations and suggestions for AOSR, and their societies' support of AOSR. PMID:29520175

  1. Cryptozoology Society

    NASA Astrophysics Data System (ADS)

    Richman, Barbara T.

    Reports of Loch Ness monsters, Bigfoot, and the Yeti spring u p from time to time, sparking scientific controversy about the veracity of these observations. Now an organization has been established to help cull, analyze, and disseminate information on the alleged creatures. The International Society of Cryptozoology, formed at a January meeting at the U.S. National Museum of Natural History of the Smithsonian Institution, will serve as the focal point for the investigation, analysis, publication, and discussion of animals of unexpected form or size or of unexpected occurrences in time or space.

  2. An official American Thoracic Society/European Respiratory Society policy statement: disparities in respiratory health.

    PubMed

    Schraufnagel, Dean E; Blasi, Francesco; Kraft, Monica; Gaga, Mina; Finn, Patricia W; Rabe, Klaus F

    2013-10-01

    Health disparities, defined as a significant difference in health between populations, are more common for diseases of the respiratory system than for those of other organ systems, because of the environmental influence on breathing and the variation of the environment among different segments of the population. The lowest social groups are up to 14 times more likely to have respiratory diseases than are the highest. Tobacco smoke, air pollution, environmental exposures, and occupational hazards affect the lungs more than other organs, and occur disproportionately in ethnic minorities and those with lower socioeconomic status. Lack of access to quality health care contributes to disparities. The executive committees of the American Thoracic Society (ATS) and European Respiratory Society (ERS) established a writing committee to develop a policy on health disparities. The document was reviewed, edited, and approved by the full executive committees and boards of directors of the societies. This document expresses a policy to address health disparities by promoting scientific inquiry and training, disseminating medical information and best practices, and monitoring and advocating for public respiratory health. ERS and ATS have strong international commitments, and work with leaders from governments, academia, and organizations to address and reduce avoidable health inequalities. Their training initiatives improve the function of health care systems and health equality. Both the ATS and ERS support all aspects of this document, confer regularly, and act together when possible, but the activities to bring about change may vary because of the differences in the continents where the two organizations carry out most of their activities. The ATS and ERS pledge to frame their actions to reduce respiratory health disparities. The vision of the ATS and ERS is that all persons attain better and sustained respiratory health. They call on all their members and other societies to

  3. Support Science by Publishing in Scientific Society Journals.

    PubMed

    Schloss, Patrick D; Johnston, Mark; Casadevall, Arturo

    2017-09-26

    Scientific societies provide numerous services to the scientific enterprise, including convening meetings, publishing journals, developing scientific programs, advocating for science, promoting education, providing cohesion and direction for the discipline, and more. For most scientific societies, publishing provides revenues that support these important activities. In recent decades, the proportion of papers on microbiology published in scientific society journals has declined. This is largely due to two competing pressures: authors' drive to publish in "glam journals"-those with high journal impact factors-and the availability of "mega journals," which offer speedy publication of articles regardless of their potential impact. The decline in submissions to scientific society journals and the lack of enthusiasm on the part of many scientists to publish in them should be matters of serious concern to all scientists because they impact the service that scientific societies can provide to their members and to science. Copyright © 2017 Schloss et al.

  4. Society of Thoracic Surgeons

    MedlinePlus

    ... Society of Thoracic Surgeons Facebook Twitter LinkedIn YouTube Instagram Flickr About STS Governance and Leadership Bylaws Policies ... Tweets by @STS_CTsurgery Facebook Twitter LinkedIn YouTube Instagram Flickr Footer menu Home Contact Us CT Surgery ...

  5. A brief history of the British Pharmacological Society

    PubMed Central

    Cuthbert, Alan W

    2006-01-01

    The article traces the history of the BPS since its inception in 1931 until the present day. Details are given about the size and nature of the membership and how the governance of the Society has changed during the last 75 years. The emergence of the Clinical Section from within the main Society and the growth of the Society's publications are described. PMID:16402105

  6. [Cooperation between professional association and scientific society].

    PubMed

    Schroeder, A; Hakenberg, O W

    2013-08-01

    Developments in health economics, urological sciences and social as well as demographic conditions pose numerous problems for the field of urology. In order to solve these problems a close cooperation between the professional association and the scientific society are needed which at first sight seem to have very different interests. The increasing complexity and interdependency in all areas of the healthcare system make a simple separation of interests between the scientific society and the professional association impossible. The Professional Association of German Urologists and the German Society of Urology have acknowledged this situation for many years and have intensified their close collaboration.

  7. Sexism and gender inequality across 57 societies.

    PubMed

    Brandt, Mark J

    2011-11-01

    Theory predicts that individuals' sexism serves to exacerbate inequality in their society's gender hierarchy. Past research, however, has provided only correlational evidence to support this hypothesis. In this study, I analyzed a large longitudinal data set that included representative data from 57 societies. Multilevel modeling showed that sexism directly predicted increases in gender inequality. This study provides the first evidence that sexist ideologies can create gender inequality within societies, and this finding suggests that sexism not only legitimizes the societal status quo, but also actively enhances the severity of the gender hierarchy. Three potential mechanisms for this effect are discussed briefly.

  8. Who's making global civil society: philanthropy and US empire in world society.

    PubMed

    Vogel, Ann

    2006-12-01

    Theories of US hegemony commonly ignore the role of American philanthropy in the contemporary transformations of world society and the globalization of capitalism. In this essay, I suggest that the philanthropic foundation, and with it the institution of philanthropy, is being invigorated by the expansion of its domestic role to foreign activities and to globally framed activities within the USA. I propose that US philanthropy exports American understandings of democracy and simultaneously organizes global reflexivity through citizenship education for the US populace. I offer a preliminary theoretical interpretation of the empirical patterns of international grant-making activities by US foundations, considering John W. Meyer's concept of 'instrumental culture' and some arguments made by Foucauldian 'governmentality' scholars. I emphasize the need to conceptualize the cultural-symbolic and organizational dimensions of hegemony and suggest further sociological analysis of philanthropic activities as integral to current politically and economically led transformations of societies around the globe.

  9. Management of patients with refractory angina: Canadian Cardiovascular Society/Canadian Pain Society joint guidelines.

    PubMed

    McGillion, Michael; Arthur, Heather M; Cook, Allison; Carroll, Sandra L; Victor, J Charles; L'allier, Philippe L; Jolicoeur, E Marc; Svorkdal, Nelson; Niznick, Joel; Teoh, Kevin; Cosman, Tammy; Sessle, Barry; Watt-Watson, Judy; Clark, Alexander; Taenzer, Paul; Coyte, Peter; Malysh, Louise; Galte, Carol; Stone, James

    2012-01-01

    Refractory angina (RFA) is a debilitating disease characterized by cardiac pain resistant to conventional treatments for coronary artery disease including nitrates, calcium-channel and β-adrenoceptor blockade, vasculoprotective agents, percutaneous coronary interventions, and coronary artery bypass grafting. The mortality rate of patients living with RFA is not known but is thought to be in the range of approximately 3%. These individuals suffer severely impaired health-related quality of life with recurrent and sustained pain, poor general health status, psychological distress, impaired role functioning, and activity restriction. Effective care for RFA sufferers in Canada is critically underdeveloped. These guidelines are predicated upon a 2009 Canadian Cardiovascular Society (CCS) Position Statement which identified that underlying the problem of RFA management is the lack of a formalized, coordinated, interprofessional strategy between the cardiovascular and pain science/clinical communities. The guidelines are therefore a joint initiative of the CCS and the Canadian Pain Society (CPS) and make practice recommendations about treatment options for RFA that are based on the best available evidence. Concluding summary recommendations are also made, giving direction to future clinical practice and research on RFA management in Canada. Copyright © 2012 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

  10. Sir Ronald A. Fisher and the International Biometric Society.

    PubMed

    Billard, Lynne

    2014-06-01

    The year 2012 marks the 50th anniversary of the death of Sir Ronald A. Fisher, one of the two Fathers of Statistics and a Founder of the International Biometric Society (the "Society"). To celebrate the extraordinary genius of Fisher and the far-sighted vision of Fisher and Chester Bliss in organizing and promoting the formation of the Society, this article looks at the origins and growth of the Society, some of the key players and events, and especially the roles played by Fisher himself as the First President. A fresh look at Fisher, the man rather than the scientific genius is also presented. © 2014, The International Biometric Society.

  11. 46 CFR 108.109 - Classification society standards.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 4 2011-10-01 2011-10-01 false Classification society standards. 108.109 Section 108.109 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) A-MOBILE OFFSHORE DRILLING UNITS DESIGN AND EQUIPMENT General § 108.109 Classification society standards. (a) Any person who desires to...

  12. 46 CFR 108.109 - Classification society standards.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 4 2012-10-01 2012-10-01 false Classification society standards. 108.109 Section 108.109 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) A-MOBILE OFFSHORE DRILLING UNITS DESIGN AND EQUIPMENT General § 108.109 Classification society standards. (a) Any person who desires to...

  13. 46 CFR 108.109 - Classification society standards.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 4 2010-10-01 2010-10-01 false Classification society standards. 108.109 Section 108.109 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) A-MOBILE OFFSHORE DRILLING UNITS DESIGN AND EQUIPMENT General § 108.109 Classification society standards. (a) Any person who desires to...

  14. 46 CFR 108.109 - Classification society standards.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 4 2014-10-01 2014-10-01 false Classification society standards. 108.109 Section 108.109 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) A-MOBILE OFFSHORE DRILLING UNITS DESIGN AND EQUIPMENT General § 108.109 Classification society standards. (a) Any person who desires to...

  15. 46 CFR 108.109 - Classification society standards.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 4 2013-10-01 2013-10-01 false Classification society standards. 108.109 Section 108.109 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) A-MOBILE OFFSHORE DRILLING UNITS DESIGN AND EQUIPMENT General § 108.109 Classification society standards. (a) Any person who desires to...

  16. Professionalism and medicine's social contract with society.

    PubMed

    Cruess, Sylvia R

    2006-08-01

    Medicine's relationship with society has been described as a social contract: an "as if" contract with obligations and expectations on the part of both society and medicine, "each of the other". The term is often used without elaboration by those writing on professionalism in medicine. Based on the literature, society's expectations of medicine are: the services of the healer, assured competence, altruistic service, morality and integrity, accountability, transparency, objective advice, and promotion of the public good. Medicine's expectations of society are: trust, autonomy, self-regulation, a health care system that is value-driven and adequately funded, participation in public policy, shared responsibility for health, a monopoly, and both non-financial and financial rewards. The recognition of these expectations is important as they serve as the basis of a series of obligations which are necessary for the maintenance of medicine as a profession. Mutual trust and reasonable demands are required of both parties to the contract.

  17. Acromegaly: an endocrine society clinical practice guideline.

    PubMed

    Katznelson, Laurence; Laws, Edward R; Melmed, Shlomo; Molitch, Mark E; Murad, Mohammad Hassan; Utz, Andrea; Wass, John A H

    2014-11-01

    The aim was to formulate clinical practice guidelines for acromegaly. The Task Force included a chair selected by the Endocrine Society Clinical Guidelines Subcommittee (CGS), five experts in the field, and a methodologist. The authors received no corporate funding or remuneration. This guideline is cosponsored by the European Society of Endocrinology. This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe both the strength of recommendations and the quality of evidence. The Task Force reviewed primary evidence and commissioned two additional systematic reviews. One group meeting, several conference calls, and e-mail communications enabled consensus. Committees and members of the Endocrine Society and the European Society of Endocrinology reviewed drafts of the guidelines. Using an evidence-based approach, this acromegaly guideline addresses important clinical issues regarding the evaluation and management of acromegaly, including the appropriate biochemical assessment, a therapeutic algorithm, including use of medical monotherapy or combination therapy, and management during pregnancy.

  18. Ad35 and Ad26 Vaccine Vectors Induce Potent and Cross-Reactive Antibody and T-Cell Responses to Multiple Filovirus Species

    PubMed Central

    Zahn, Roland; Gillisen, Gert; Roos, Anna; Koning, Marina; van der Helm, Esmeralda; Spek, Dirk; Weijtens, Mo; Grazia Pau, Maria; Radošević, Katarina; Weverling, Gerrit Jan; Custers, Jerome; Vellinga, Jort; Schuitemaker, Hanneke; Goudsmit, Jaap; Rodríguez, Ariane

    2012-01-01

    Filoviruses cause sporadic but highly lethal outbreaks of hemorrhagic fever in Africa in the human population. Currently, no drug or vaccine is available for treatment or prevention. A previous study with a vaccine candidate based on the low seroprevalent adenoviruses 26 and 35 (Ad26 and Ad35) was shown to provide protection against homologous Ebola Zaire challenge in non human primates (NHP) if applied in a prime-boost regimen. Here we have aimed to expand this principle to construct and evaluate Ad26 and Ad35 vectors for development of a vaccine to provide universal filovirus protection against all highly lethal strains that have caused major outbreaks in the past. We have therefore performed a phylogenetic analysis of filovirus glycoproteins to select the glycoproteins from two Ebola species (Ebola Zaire and Ebola Sudan/Gulu,), two Marburg strains (Marburg Angola and Marburg Ravn) and added the more distant non-lethal Ebola Ivory Coast species for broadest coverage. Ad26 and Ad35 vectors expressing these five filovirus glycoproteins were evaluated to induce a potent cellular and humoral immune response in mice. All adenoviral vectors induced a humoral immune response after single vaccination in a dose dependent manner that was cross-reactive within the Ebola and Marburg lineages. In addition, both strain-specific as well as cross-reactive T cell responses could be detected. A heterologous Ad26–Ad35 prime-boost regime enhanced mainly the humoral and to a lower extend the cellular immune response against the transgene. Combination of the five selected filovirus glycoproteins in one multivalent vaccine potentially elicits protective immunity in man against all major filovirus strains that have caused lethal outbreaks in the last 20 years. PMID:23236343

  19. The Society of Thoracic Surgeons, The Society of Cardiovascular Anesthesiologists, and The American Society of ExtraCorporeal Technology: Clinical Practice Guidelines-Anticoagulation During Cardiopulmonary Bypass.

    PubMed

    Shore-Lesserson, Linda; Baker, Robert A; Ferraris, Victor A; Greilich, Philip E; Fitzgerald, David; Roman, Philip; Hammon, John W

    2018-02-01

    Despite more than a half century of "safe" cardiopulmonary bypass (CPB), the evidence base surrounding the conduct of anticoagulation therapy for CPB has not been organized into a succinct guideline. For this and other reasons, there is enormous practice variability relating to the use and dosing of heparin, monitoring heparin anticoagulation, reversal of anticoagulation, and the use of alternative anticoagulants. To address this and other gaps, The Society of Thoracic Surgeons, the Society of Cardiovascular Anesthesiologists, and the American Society of Extracorporeal Technology developed an Evidence Based Workgroup. This was a group of interdisciplinary professionals gathered to summarize the evidence and create practice recommendations for various aspects of CPB. To date, anticoagulation practices in CPB have not been standardized in accordance with the evidence base. This clinical practice guideline was written with the intent to fill the evidence gap and to establish best practices in anticoagulation therapy for CPB using the available evidence. To identify relevant evidence, a systematic review was outlined and literature searches were conducted in PubMed using standardized medical subject heading (MeSH) terms from the National Library of Medicine list of search terms. Search dates were inclusive of January 2000 to December 2015. The search yielded 833 abstracts, which were reviewed by two independent reviewers. Once accepted into the full manuscript review stage, two members of the writing group evaluated each of 286 full papers for inclusion eligibility into the guideline document. Ninety-six manuscripts were included in the final review. In addition, 17 manuscripts published before 2000 were included to provide method, context, or additional supporting evidence for the recommendations as these papers were considered sentinel publications. Members of the writing group wrote and developed recommendations based on review of the articles obtained and achieved

  20. Support Science by Publishing in Scientific Society Journals

    PubMed Central

    Johnston, Mark

    2017-01-01

    ABSTRACT Scientific societies provide numerous services to the scientific enterprise, including convening meetings, publishing journals, developing scientific programs, advocating for science, promoting education, providing cohesion and direction for the discipline, and more. For most scientific societies, publishing provides revenues that support these important activities. In recent decades, the proportion of papers on microbiology published in scientific society journals has declined. This is largely due to two competing pressures: authors’ drive to publish in “glam journals”—those with high journal impact factors—and the availability of “mega journals,” which offer speedy publication of articles regardless of their potential impact. The decline in submissions to scientific society journals and the lack of enthusiasm on the part of many scientists to publish in them should be matters of serious concern to all scientists because they impact the service that scientific societies can provide to their members and to science. PMID:28951482

  1. Science-Technology-Society or Technology-Society-Science? Insights from an Ancient Technology

    ERIC Educational Resources Information Center

    Lee, Yeung Chung

    2010-01-01

    Current approaches to science-technology-society (STS) education focus primarily on the controversial socio-scientific issues that arise from the application of science in modern technology. This paper argues for an interdisciplinary approach to STS education that embraces science, technology, history, and social and cultural studies. By employing…

  2. Structure of glycosylated NPC1 luminal domain C reveals insights into NPC2 and Ebola virus interactions.

    PubMed

    Zhao, Yuguang; Ren, Jingshan; Harlos, Karl; Stuart, David I

    2016-03-01

    Niemann-pick type C1 (NPC1) is an endo/lysosomal membrane protein involved in intracellular cholesterol trafficking, and its luminal domain C is an essential endosomal receptor for Ebola and Marburg viruses. We have determined the crystal structure of glycosylated NPC1 luminal domain C and find all seven possible sites are glycosylated. Mapping the disease mutations onto the glycosylated structure reveals a potential binding face for NPC2. Knowledge-based docking of NPC1 onto Ebola viral glycoprotein and sequence analysis of filovirus susceptible and refractory species reveals four critical residues, H418, Q421, F502 and F504, some or all of which are likely responsible for the species-specific susceptibility to the virus infection. © 2016 The Authors. FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

  3. Emerging Information Societies in an Interdependent World.

    ERIC Educational Resources Information Center

    Bernasconi, F. A.

    Commenting on the trends toward the interlocking of emerging information societies and the growing interdependence of countries, this paper suggests the role that "informatics" (the rational and systematic use of information for planning and decision making) may play in the transition of societies into the information age. Two paradoxes…

  4. Engineering equations for characterizing non-linear laser intensity propagation in air with loss.

    PubMed

    Karr, Thomas; Stotts, Larry B; Tellez, Jason A; Schmidt, Jason D; Mansell, Justin D

    2018-02-19

    The propagation of high peak-power laser beams in real atmospheres will be affected at long range by both linear and nonlinear effects contained therein. Arguably, J. H. Marburger is associated with the mathematical characterization of this phenomenon. This paper provides a validated set of engineering equations for characterizing the self-focusing distance from a laser beam propagating through non-turbulent air with, and without, loss as well as three source configurations: (1) no lens, (2) converging lens and (3) diverging lens. The validation was done against wave-optics simulation results. Some validated equations follow Marburger completely, but others do not, requiring modification of the original theory. Our results can provide a guide for numerical simulations and field experiments.

  5. 7 CFR 795.10 - Club, society, fraternal or religious organization.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 7 2010-01-01 2010-01-01 false Club, society, fraternal or religious organization... General § 795.10 Club, society, fraternal or religious organization. Each individual club, society..., society, fraternal or religious organization is engaged in the production of crops as a separate producer...

  6. 7 CFR 795.10 - Club, society, fraternal or religious organization.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 7 2011-01-01 2011-01-01 false Club, society, fraternal or religious organization... General § 795.10 Club, society, fraternal or religious organization. Each individual club, society..., society, fraternal or religious organization is engaged in the production of crops as a separate producer...

  7. 46 CFR 8.450 - Termination of classification society authority.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 1 2010-10-01 2010-10-01 false Termination of classification society authority. 8.450... VESSEL INSPECTION ALTERNATIVES Alternate Compliance Program § 8.450 Termination of classification society authority. (a) The Coast Guard may terminate an authorization agreement with a classification society to...

  8. 46 CFR 8.450 - Termination of classification society authority.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 1 2011-10-01 2011-10-01 false Termination of classification society authority. 8.450... VESSEL INSPECTION ALTERNATIVES Alternate Compliance Program § 8.450 Termination of classification society authority. (a) The Coast Guard may terminate an authorization agreement with a classification society to...

  9. International Federation of Head Neck Oncology Society 5(th) World Congress/American Head Neck Society 2014 update.

    PubMed

    Sharma, Shilpi; Chaukar, Devendra A

    2014-07-01

    Head neck cancer is an important health problem with high morbidity and mortality. Early detection and adequate treatment improve prognosis significantly. Thus creating awareness among clinicians is an important step toward control of head neck cancer and reducing its overall burden. We here provide an update on the International Federation of Head Neck Oncology Society/American Head Neck Society 2014 held between July 26, 2014 and July 30, 2014 in New York.

  10. Just Say Know? Schooling the Knowledge Society

    ERIC Educational Resources Information Center

    Willinsky, John

    2005-01-01

    This review essay challenges the practice of rooting educational theory in the economic assumptions that underlie the current championing of a knowledge society. It examines the approaches of three recent works: one book, Andy Hargreaves's Teaching in a Knowledge Society, and two edited collections, Barry Smith's Liberal Education in a Knowledge…

  11. Autonomy and Liberalism in a Multicultural Society

    ERIC Educational Resources Information Center

    Jewell, Paul

    2005-01-01

    That children should be educated to be ideal citizens, capable of making rational and informed decisions, has been proposed in cultures ranging from Ancient Greece to current societies. In particular, societies that favour liberalism preach the primacy of the individual autonomous citizen and a concomitant tolerance for others. In modern…

  12. Sex Role Socialization Patterns in Selected Societies.

    ERIC Educational Resources Information Center

    Safilios-Rothschild, Constantina

    This document evolved because studies concerning sex role socialization patterns were available from only a limited number of societies. In addition to examining available research findings, the author develops a number of relevant hypotheses with respect to several selected societies--the United States, Russia, Greece, India, and Eastern Europe.…

  13. Mineral resources of Peru's ancient societies

    USGS Publications Warehouse

    Brooks, W.E.

    2003-01-01

    Northern Peru has an exceptionally rich archaeological heritage that includes metalwork, ceramics and textiles. The success of at least a half-dozen pre-Columbian societies dating back 3,000 years and subsequent Spanish colonization in the 1400s has rested on the effective use of northern Peru's abundant resources. In the summer of 2000, my son Matt and I learned about that connection firsthand by volunteering at the Santa Rita B archaeological site in the Chao Valley near Trujillo in northern Peru. Riding donkey-back through the Andes and talking with local people, we got our hands dirty in the rich archaeology and geology of the area. We were able to correlate mineral occurrences to their various roles in society - opening a window into the region's fascinating past. From construction to metallurgy, pre-Columbian societies flourished and advanced because of their understanding and use of the available mineral resources.

  14. ACC/AATS/AHA/ASE/ASNC/HRS/SCAI/SCCT/SCMR/STS 2017 Appropriate Use Criteria for Multimodality Imaging in Valvular Heart Disease: A Report of the American College of Cardiology Appropriate Use Criteria Task Force, American Association for Thoracic Surgery, American Heart Association, American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Computed Tomography, Society for Cardiovascular Magnetic Resonance, and Society of Thoracic Surgeons.

    PubMed

    Doherty, John U; Kort, Smadar; Mehran, Roxana; Schoenhagen, Paul; Soman, Prem; Dehmer, Greg J; Doherty, John U; Schoenhagen, Paul; Amin, Zahid; Bashore, Thomas M; Boyle, Andrew; Calnon, Dennis A; Carabello, Blase; Cerqueira, Manuel D; Conte, John; Desai, Milind; Edmundowicz, Daniel; Ferrari, Victor A; Ghoshhajra, Brian; Mehrotra, Praveen; Nazarian, Saman; Reece, T Brett; Tamarappoo, Balaji; Tzou, Wendy S; Wong, John B; Doherty, John U; Dehmer, Gregory J; Bailey, Steven R; Bhave, Nicole M; Brown, Alan S; Daugherty, Stacie L; Dean, Larry S; Desai, Milind Y; Duvernoy, Claire S; Gillam, Linda D; Hendel, Robert C; Kramer, Christopher M; Lindsay, Bruce D; Manning, Warren J; Mehrotra, Praveen; Patel, Manesh R; Sachdeva, Ritu; Wann, L Samuel; Winchester, David E; Wolk, Michael J; Allen, Joseph M

    2018-04-01

    This document is 1 of 2 companion appropriate use criteria (AUC) documents developed by the American College of Cardiology, American Association for Thoracic Surgery, American Heart Association, American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Computed Tomography, Society for Cardiovascular Magnetic Resonance, and Society of Thoracic Surgeons. This document addresses the evaluation and use of multimodality imaging in the diagnosis and management of valvular heart disease, whereas the second, companion document addresses this topic with regard to structural heart disease. Although there is clinical overlap, the documents addressing valvular and structural heart disease are published separately, albeit with a common structure. The goal of the companion AUC documents is to provide a comprehensive resource for multimodality imaging in the context of valvular and structural heart disease, encompassing multiple imaging modalities. Using standardized methodology, the clinical scenarios (indications) were developed by a diverse writing group to represent patient presentations encountered in everyday practice and included common applications and anticipated uses. Where appropriate, the scenarios were developed on the basis of the most current American College of Cardiology/American Heart Association guidelines. A separate, independent rating panel scored the 92 clinical scenarios in this document on a scale of 1 to 9. Scores of 7 to 9 indicate that a modality is considered appropriate for the clinical scenario presented. Midrange scores of 4 to 6 indicate that a modality may be appropriate for the clinical scenario, and scores of 1 to 3 indicate that a modality is considered rarely appropriate for the clinical scenario. The primary objective of the AUC is to provide a framework for the assessment of these scenarios by practices that will

  15. A Single Amino Acid Change in the Marburg Virus Matrix Protein VP40 Provides a Replicative Advantage in a Species-Specific Manner

    PubMed Central

    Koehler, Alexander; Kolesnikova, Larissa; Welzel, Ulla; Schudt, Gordian; Herwig, Astrid

    2015-01-01

    ABSTRACT Marburg virus (MARV) induces severe hemorrhagic fever in humans and nonhuman primates but only transient nonlethal disease in rodents. However, sequential passages of MARV in rodents boosts infection leading to lethal disease. Guinea pig-adapted MARV contains one mutation in the viral matrix protein VP40 at position 184 (VP40D184N). The contribution of the D184N mutation to the efficacy of replication in a new host is unknown. In the present study, we demonstrated that recombinant MARV containing the D184N mutation in VP40 [rMARVVP40(D184N)] grew to higher titers than wild-type recombinant MARV (rMARVWT) in guinea pig cells. Moreover, rMARVVP40(D184N) displayed higher infectivity in guinea pig cells. Comparative analysis of VP40 functions indicated that neither the interferon (IFN)-antagonistic function nor the membrane binding capabilities of VP40 were affected by the D184N mutation. However, the production of VP40-induced virus-like particles (VLPs) and the recruitment of other viral proteins to the budding site was improved by the D184N mutation in guinea pig cells, which resulted in the higher infectivity of VP40D184N-induced infectious VLPs (iVLPs) compared to that of VP40-induced iVLPs. In addition, the function of VP40 in suppressing viral RNA synthesis was influenced by the D184N mutation specifically in guinea pig cells, thus allowing greater rates of transcription and replication. Our results showed that the improved viral fitness of rMARVVP40(D184N) in guinea pig cells was due to the better viral assembly function of VP40D184N and its lower inhibitory effect on viral transcription and replication rather than modulation of the VP40-mediated suppression of IFN signaling. IMPORTANCE The increased virulence achieved by virus passaging in a new host was accompanied by mutations in the viral genome. Analyzing how these mutations affect the functions of viral proteins and the ability of the virus to grow within new host cells helps in the understanding

  16. Explaining Society: An Expanded Toolbox for Social Scientists

    PubMed Central

    Bell, David C.; Atkinson-Schnell, Jodie L.; DiBacco, Aron E.

    2012-01-01

    We propose for social scientists a theoretical toolbox containing a set of motivations that neurobiologists have recently validated. We show how these motivations can be used to create a theory of society recognizably similar to existing stable societies (sustainable, self-reproducing, and largely peaceful). Using this toolbox, we describe society in terms of three institutions: economy (a source of sustainability), government (peace), and the family (reproducibility). Conducting a thought experiment in three parts, we begin with a simple theory with only two motivations. We then create successive theories that systematically add motivations, showing that each element in the toolbox makes its own contribution to explain the workings of a stable society and that the family has a critical role in this process. PMID:23082093

  17. Evolutionary Paths to Corrupt Societies of Artificial Agents

    NASA Astrophysics Data System (ADS)

    Nasrallah, Walid

    Virtual corrupt societies can be defined as groups of interacting computer-generated agents who predominantly choose behavior that gives short term personal gain at the expense of a higher aggregate cost to others. This paper focuses on corrupt societies that, unlike published models in which cooperation must evolve in order for the society to continue to survive, do not naturally die out as the corrupt class siphons off the resources. For example, a very computationally simple strategy of avoiding confrontation can allow a majority of "unethical" individuals to survive off the efforts of an "ethical" but productive minority. Analogies are drawn to actual human societies in which similar conditions gave rise to behavior traditionally defined as economic or political corruption.

  18. 45 CFR 73.735-707 - Holding office in professional societies.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Holding office in professional societies. 73.735... STANDARDS OF CONDUCT Outside Activities § 73.735-707 Holding office in professional societies. (a) Employees may be members of professional societies and be elected or appointed to office in such a society...

  19. 45 CFR 73.735-707 - Holding office in professional societies.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 45 Public Welfare 1 2011-10-01 2011-10-01 false Holding office in professional societies. 73.735... STANDARDS OF CONDUCT Outside Activities § 73.735-707 Holding office in professional societies. (a) Employees may be members of professional societies and be elected or appointed to office in such a society...

  20. Experimental Inoculation of Egyptian Rousette Bats (Rousettus aegyptiacus) with Viruses of the Ebolavirus and Marburgvirus Genera.

    PubMed

    Jones, Megan E B; Schuh, Amy J; Amman, Brian R; Sealy, Tara K; Zaki, Sherif R; Nichol, Stuart T; Towner, Jonathan S

    2015-06-25

    The Egyptian rousette bat (Rousettus aegyptiacus) is a natural reservoir for marburgviruses and a consistent source of virus spillover to humans. Cumulative evidence suggests various bat species may also transmit ebolaviruses. We investigated the susceptibility of Egyptian rousettes to each of the five known ebolaviruses (Sudan, Ebola, Bundibugyo, Taï Forest, and Reston), and compared findings with Marburg virus. In a pilot study, groups of four juvenile bats were inoculated with one of the ebolaviruses or Marburg virus. In ebolavirus groups, viral RNA tissue distribution was limited, and no bat became viremic. Sudan viral RNA was slightly more widespread, spurring a second, 15-day Sudan virus serial euthanasia study. Low levels of Sudan viral RNA disseminated to multiple tissues at early time points, but there was no viremia or shedding. In contrast, Marburg virus RNA was widely disseminated, with viremia, oral and rectal shedding, and antigen in spleen and liver. This is the first experimental infection study comparing tissue tropism, viral shedding, and clinical and pathologic effects of six different filoviruses in the Egyptian rousette, a known marburgvirus reservoir. Our results suggest Egyptian rousettes are unlikely sources for ebolaviruses in nature, and support a possible single filovirus-single reservoir host relationship.

  1. Experimental Inoculation of Egyptian Rousette Bats (Rousettus aegyptiacus) with Viruses of the Ebolavirus and Marburgvirus Genera

    PubMed Central

    Jones, Megan E.B.; Schuh, Amy J.; Amman, Brian R.; Sealy, Tara K.; Zaki, Sherif R.; Nichol, Stuart T.; Towner, Jonathan S.

    2015-01-01

    The Egyptian rousette bat (Rousettus aegyptiacus) is a natural reservoir for marburgviruses and a consistent source of virus spillover to humans. Cumulative evidence suggests various bat species may also transmit ebolaviruses. We investigated the susceptibility of Egyptian rousettes to each of the five known ebolaviruses (Sudan, Ebola, Bundibugyo, Taï Forest, and Reston), and compared findings with Marburg virus. In a pilot study, groups of four juvenile bats were inoculated with one of the ebolaviruses or Marburg virus. In ebolavirus groups, viral RNA tissue distribution was limited, and no bat became viremic. Sudan viral RNA was slightly more widespread, spurring a second, 15-day Sudan virus serial euthanasia study. Low levels of Sudan viral RNA disseminated to multiple tissues at early time points, but there was no viremia or shedding. In contrast, Marburg virus RNA was widely disseminated, with viremia, oral and rectal shedding, and antigen in spleen and liver. This is the first experimental infection study comparing tissue tropism, viral shedding, and clinical and pathologic effects of six different filoviruses in the Egyptian rousette, a known marburgvirus reservoir. Our results suggest Egyptian rousettes are unlikely sources for ebolaviruses in nature, and support a possible single filovirus—single reservoir host relationship. PMID:26120867

  2. 5-Fluorouracil-resistant strain of Methanobacterium thermoautotrophicum.

    PubMed

    Nagle, D P; Teal, R; Eisenbraun, A

    1987-09-01

    Growth of Methanobacterium thermoautotrophicum Marburg is inhibited by the pyrimidine, 5-fluorouracil (FU). It was shown previously that methanogenesis is not inhibited to the same extent as growth. A spontaneously occurring FU-resistant strain (RTAE-1) was isolated from a culture of strain Marburg. The growth of both strains was inhibited by 5-fluorodeoxyuridine but not 5-fluorocytosine, and the wild type was more susceptible to inhibition by 5-azauracil and 6-azauracil than was strain RTAE-1. The cellular targets for the pyrimidine analogs are not known. When the accumulation of 14C-labeled uracil or FU by the two strains was compared, the wild type took up 15-fold more radiolabel per cell than did the FU-resistant strain. In the wild type, radiolabel from uracil was incorporated into the soluble pool, RNA, and DNA. The metabolism of uracil appeared to involve a uracil phosphoribosyltransferase activity. Strain Marburg extracts contained this enzyme, whereas FU-resistant strain RTAE-1 extracts had less than 1/10 as much activity. Although it is possible that a change in permeability to the compounds plays a role in the stable resistance of strain RTAE-1, the fact that it lacks the ability to metabolize pyrimidines to nucleotides is sufficient to account for its phenotype.

  3. 5-Fluorouracil-resistant strain of Methanobacterium thermoautotrophicum.

    PubMed Central

    Nagle, D P; Teal, R; Eisenbraun, A

    1987-01-01

    Growth of Methanobacterium thermoautotrophicum Marburg is inhibited by the pyrimidine, 5-fluorouracil (FU). It was shown previously that methanogenesis is not inhibited to the same extent as growth. A spontaneously occurring FU-resistant strain (RTAE-1) was isolated from a culture of strain Marburg. The growth of both strains was inhibited by 5-fluorodeoxyuridine but not 5-fluorocytosine, and the wild type was more susceptible to inhibition by 5-azauracil and 6-azauracil than was strain RTAE-1. The cellular targets for the pyrimidine analogs are not known. When the accumulation of 14C-labeled uracil or FU by the two strains was compared, the wild type took up 15-fold more radiolabel per cell than did the FU-resistant strain. In the wild type, radiolabel from uracil was incorporated into the soluble pool, RNA, and DNA. The metabolism of uracil appeared to involve a uracil phosphoribosyltransferase activity. Strain Marburg extracts contained this enzyme, whereas FU-resistant strain RTAE-1 extracts had less than 1/10 as much activity. Although it is possible that a change in permeability to the compounds plays a role in the stable resistance of strain RTAE-1, the fact that it lacks the ability to metabolize pyrimidines to nucleotides is sufficient to account for its phenotype. PMID:3624203

  4. Behavioral/Emotional Problems of Preschoolers: Caregiver/Teacher Reports From 15 Societies.

    PubMed

    Rescorla, Leslie A; Achenbach, Thomas M; Ivanova, Masha Y; Bilenberg, Niels; Bjarnadottir, Gudrun; Denner, Silvia; Dias, Pedro; Dobrean, Anca; Döpfner, Manfred; Frigerio, Alessandra; Gonçalves, Miguel; Guđmundsson, Halldór; Jusiene, Roma; Kristensen, Solvejg; Lecannelier, Felipe; Leung, Patrick W L; Liu, Jianghong; Löbel, Sofia P; Machado, Bárbara César; Markovic, Jasminka; Mas, Paola A; Esmaeili, Elaheh Mohammad; Montirosso, Rosario; Plück, Julia; Pronaj, Adelina Ahmeti; Rodriguez, Jorge T; Rojas, Pamela O; Schmeck, Klaus; Shahini, Mimoza; Silva, Jaime R; van der Ende, Jan; Verhulst, Frank C

    2012-01-01

    This study tested societal effects on caregiver/teacher ratings of behavioral/emotional problems for 10,521 preschoolers from 15 societies. Many societies had problem scale scores within a relatively narrow range, despite differences in language, culture, and other characteristics. The small age and gender effects were quite similar across societies. The rank orders of mean item ratings were similar across diverse societies. For 7,380 children from 13 societies, ratings were also obtained from a parent. In all 13 societies, mean Total Problems scores derived from parent ratings were significantly higher than mean Total Problems scores derived from caregiver/teacher ratings, although the size of the difference varied somewhat across societies. Mean cross-informant agreement for problem scale scores varied across societies. Societies were very similar with respect to which problem items, on average, received high versus low ratings from parents and caregivers/teachers. Within every society, cross-informant agreement for item ratings varied widely across children. In most respects, results were quite similar across 15 very diverse societies.

  5. Behavioral/Emotional Problems of Preschoolers: Caregiver/Teacher Reports From 15 Societies

    PubMed Central

    Rescorla, Leslie A.; Achenbach, Thomas M.; Ivanova, Masha Y.; Bilenberg, Niels; Bjarnadottir, Gudrun; Denner, Silvia; Dias, Pedro; Dobrean, Anca; Döpfner, Manfred; Frigerio, Alessandra; Gonçalves, Miguel; Guđmundsson, Halldór; Jusiene, Roma; Kristensen, Solvejg; Lecannelier, Felipe; Leung, Patrick W. L.; Liu, Jianghong; Löbel, Sofia P.; Machado, Bárbara César; Markovic, Jasminka; Mas, Paola A.; Esmaeili, Elaheh Mohammad; Montirosso, Rosario; Plück, Julia; Pronaj, Adelina Ahmeti; Rodriguez, Jorge T.; Rojas, Pamela O.; Schmeck, Klaus; Shahini, Mimoza; Silva, Jaime R.; van der Ende, Jan; Verhulst, Frank C.

    2017-01-01

    This study tested societal effects on caregiver/teacher ratings of behavioral/emotional problems for 10,521 preschoolers from 15 societies. Many societies had problem scale scores within a relatively narrow range, despite differences in language, culture, and other characteristics. The small age and gender effects were quite similar across societies. The rank orders of mean item ratings were similar across diverse societies. For 7,380 children from 13 societies, ratings were also obtained from a parent. In all 13 societies, mean Total Problems scores derived from parent ratings were significantly higher than mean Total Problems scores derived from caregiver/teacher ratings, although the size of the difference varied somewhat across societies. Mean cross-informant agreement for problem scale scores varied across societies. Societies were very similar with respect to which problem items, on average, received high versus low ratings from parents and caregivers/teachers. Within every society, cross-informant agreement for item ratings varied widely across children. In most respects, results were quite similar across 15 very diverse societies. PMID:29416292

  6. American Society of Radiologic Technologists

    MedlinePlus

    ... Radiologist Assistant Legislation Career Center Careers in Radiologic Technology Job Bank® Job Search Resources Radiologist ... American Society of Radiologic Technologists ASRT is the premier professional ...

  7. 26 CFR 1.501(c)(8)-1 - Fraternal beneficiary societies.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 7 2011-04-01 2009-04-01 true Fraternal beneficiary societies. 1.501(c)(8)-1... beneficiary societies. (a) A fraternal beneficiary society is exempt from tax only if operated under the lodge... exempt it is also necessary that the society have an established system for the payment to its members or...

  8. 26 CFR 1.501(c)(8)-1 - Fraternal beneficiary societies.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 7 2010-04-01 2010-04-01 true Fraternal beneficiary societies. 1.501(c)(8)-1... beneficiary societies. (a) A fraternal beneficiary society is exempt from tax only if operated under the lodge... exempt it is also necessary that the society have an established system for the payment to its members or...

  9. Functional Hypothalamic Amenorrhea: An Endocrine Society Clinical Practice Guideline.

    PubMed

    Gordon, Catherine M; Ackerman, Kathryn E; Berga, Sarah L; Kaplan, Jay R; Mastorakos, George; Misra, Madhusmita; Murad, M Hassan; Santoro, Nanette F; Warren, Michelle P

    2017-05-01

    The American Society for Reproductive Medicine, the European Society of Endocrinology, and the Pediatric Endocrine Society. This guideline was funded by the Endocrine Society. To formulate clinical practice guidelines for the diagnosis and treatment of functional hypothalamic amenorrhea (FHA). The participants include an Endocrine Society-appointed task force of eight experts, a methodologist, and a medical writer. This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation approach to describe the strength of recommendations and the quality of evidence. The task force commissioned two systematic reviews and used the best available evidence from other published systematic reviews and individual studies. One group meeting, several conference calls, and e-mail communications enabled consensus. Endocrine Society committees and members and cosponsoring organizations reviewed and commented on preliminary drafts of this guideline. FHA is a form of chronic anovulation, not due to identifiable organic causes, but often associated with stress, weight loss, excessive exercise, or a combination thereof. Investigations should include assessment of systemic and endocrinologic etiologies, as FHA is a diagnosis of exclusion. A multidisciplinary treatment approach is necessary, including medical, dietary, and mental health support. Medical complications include, among others, bone loss and infertility, and appropriate therapies are under debate and investigation. Copyright © 2017 Endocrine Society

  10. Active middle ear implant coupled bilaterally to the round window despite bilateral implanted stapes prostheses.

    PubMed

    Coordes, Annekatrin; Jahreiss, Linda; Schönfeld, Uwe; Lenarz, Minoo

    2017-02-01

    After stapes surgery, patients with mixed or moderate hearing loss have limited possibilities for hearing improvement. We are reporting on a patient who underwent stapedotomy bilaterally 20 years ago and had sensorineural and mixed hearing loss. Recurrent otitis externa prevented the use of hearing aids. This patient was treated bilaterally with the Vibrant Soundbridge (Med-El, Innsbruck, Austria) successively. The Schuknecht piston stapes prostheses remained in situ. The Floating Mass Transducer (FMT; Med-El) was coupled to the round window (RW) and provided good acoustic reinforcement bilaterally. In conclusion, for patients with otosclerosis and stapes surgery, the FMT-RW coupling (Bess AG, Berlin, DE) is a safe procedure with good acoustic amplification. Laryngoscope, 2016 127:500-503, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

  11. Skin problems following septorhinoplasty.

    PubMed

    Koc, Eltaf A O; Buyuklu, Fuat; Koç, Bulent; Demirci, Gulsen T

    2015-06-01

    Septorhinoplasty is one of the most commonly performed plastic surgery procedures in the world. Studies on septorhinoplasty in the literature mainly focus on the surgical procedures and their outcomes, but the general appearance of the nose and nasal skin following surgery is also very important. Case-control study examining 30 septorhinoplasty patients and 20 septoplasty patients for postoperative skin conditions. There were significant differences identified between the septorhinoplasty group and the septoplasty group with respect to their mean preoperative Global Acne Grading System, Seborrheic Dermatitis Area Severity Index, and visual analog scores (acne, seborrhea, and ecchymosis). The aim of study was to identify and evaluate postoperative skin conditions among septorhinoplasty patients, as well as the progression and duration of treatment of these conditions. 3b. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

  12. Minocycline-induced hyperpigmentation of tympanic membrane, sclera, teeth, and pinna.

    PubMed

    Reese, Stephen; Grundfast, Kenneth

    2015-11-01

    A 40-year-old woman was referred by her primary care physician for evaluation after a routine physical exam revealed bilateral brownish pigmentation of the tympanic membrane. Head and neck examination in the otolaryngology clinic revealed bluish hue of both sclera, teeth, and portions of her pinnae. A hearing test revealed bilateral mild sensorineural hearing loss. The patient had a history of taking minocycline for 14 years, and the hyperpigmentation that she had is known to be a rare complication of prolonged minocycline use. However, to our knowledge, this is the first case showing photographic evidence of minocycline-induced tympanic membrane hyperpigmentation. Minocycline-induced hyperpigmentation should be considered when a patient presents with brown or blue discoloration of the tympanic membrane. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

  13. Novelty, Creation, and Society.

    ERIC Educational Resources Information Center

    Hattiangadi, Jagdish N.

    1985-01-01

    Individual artistic creativity has no place in the development of art, science, or society. If an intellectual has a thorough understanding of intellectual traditions and appreciation of the situation, s/he needs to be no more than reasonable to produce what have been hitherto considered products of genius. (MT)

  14. Perception and duration of pain after office-based vocal fold injection augmentation.

    PubMed

    Crawley, Brianna K; Dehom, Salem; Kutzner, Emily; Murry, Thomas; Krishna, Priya; Hata, Justin

    2018-04-01

    In-office laryngology procedures are important in the treatment of voice and swallowing disorders. Patient tolerance determines which procedures can be performed without sedation or formal anesthesia. This study examines pain perception during and after in-office vocal fold injection augmentation. Prospective cohort study. Patients scheduled for office-based vocal fold injection augmentation were prospectively enrolled at an academic voice center. The short-form McGill Pain Questionnaire was administered before, during, and after the procedure and on postprocedure days 1, 3, and 7. Pre- and postprocedure vital signs were recorded and heart rate was continuously monitored. Telephone questionnaires were completed on postprocedure days 1 and 3. Forty-five patients consented to participate in our study (24 males, mean age 61 years). Most patients experienced mild to moderate pain with increasing heart rate during the procedure. Pain remained or increased 20 minutes after the procedure and improved but persisted for 1 day. Sensory and affective discomfort was endorsed by the majority. A minority of patients experienced bruising and changes in swallowing with diet modification for 3 days after the procedure. Sixteen percent had discomfort after 1 week. This is the first prospective study examining patient perception of pain during and after in-office injection augmentation using a validated scale and pain descriptors with extended follow-up. The results may offer guidance for patient counseling, consent, and treatment to improve tolerance and success. 4. Laryngoscope, 128:929-934, 2018. © 2018 The American Laryngological, Rhinological and Otological Society, Inc.

  15. Meeting report: Metastasis Research Society-Chinese Tumor Metastasis Society joint conference on metastasis.

    PubMed

    Bankaitis, Katherine; Borriello, Lucia; Cox, Thomas; Lynch, Conor; Zijlstra, Andries; Fingleton, Barbara; Gužvić, Miodrag; Anderson, Robin; Neman, Josh

    2017-04-01

    During September 16th-20th 2016, metastasis experts from around the world convened for the 16th Biennial Congress of the Metastasis Research Society and 12th National Congress of the Chinese Tumor Metastasis Society in Chengdu, China to share most current data covering basic, translational, and clinical metastasis research. Presentations of the more than 40 invited speakers of the main congress and presentations from the associated Young Investigator Satellite Meeting are summarized in this report by session topic. The congress program also included three concurrent short talk sessions, an advocacy forum with Chinese and American metastatic patient advocates, a 'Meet the Professors Roundtable' session for young investigators, and a 'Meet the Editors' session with editors from Cancer Cell and Nature Cell Biology. The goal of integrating expertise and exchanging the latest findings, ideas, and practices in cancer metastasis research was achieved magnificently, thanks to the excellent contributions of many leaders in the field.

  16. Multilevel selection and social evolution of insect societies

    NASA Astrophysics Data System (ADS)

    Korb, Judith; Heinze, Jürgen

    How sterile, altruistic worker castes have evolved in social insects and how they are maintained have long been central topics in evolutionary biology. With the advance of kin selection theory, insect societies, in particular those of haplodiploid bees, ants, and wasps, have become highly suitable model systems for investigating the details of social evolution and recently also how within-group conflicts are resolved. Because insect societies typically do not consist of clones, conflicts among nestmates arise, for example about the partitioning of reproduction and the allocation of resources towards male and female sexuals. Variation in relatedness among group members therefore appears to have a profound influence on the social structure of groups. However, insect societies appear to be remarkably robust against such variation: division of labor and task allocation are often organized in more or less the same way in societies with high as in those with very low nestmate relatedness. To explain the discrepancy between predictions from kin structure and empirical data, it was suggested that constraints-such as the lack of power or information-prevent individuals from pursuing their own selfish interests. Applying a multilevel selection approach shows that these constraints are in fact group-level adaptation preventing or resolving intracolonial conflict. The mechanisms of conflict resolution in insect societies are similar to those at other levels in the biological hierarchy (e.g., in the genome or multicellular organisms): alignment of interests, fair lottery, and social control. Insect societies can thus be regarded as a level of selection with novelties that provide benefits beyond the scope of a solitary life. Therefore, relatedness is less important for the maintenance of insect societies, although it played a fundamental role in their evolution.

  17. Lumbar disc nomenclature: version 2.0: recommendations of the combined task forces of the North American Spine Society, the American Society of Spine Radiology, and the American Society of Neuroradiology.

    PubMed

    Fardon, David F; Williams, Alan L; Dohring, Edward J; Murtagh, F Reed; Gabriel Rothman, Stephen L; Sze, Gordon K

    2014-11-15

    This article comprises a review of the literature pertaining to the normal and pathological lumbar disc and the compilation of a standardized nomenclature. To provide a resource that promotes a clear understanding of lumbar disc terminology among clinicians, radiologists, and researchers. The article "Nomenclature and Classification of Lumbar Disc Pathology. Recommendations of the Combined Task Forces of the North American Spine Society, American Society of Spine Radiology and American Society of Neuroradiology" was published in 2001 in Spine © Lippincott, Williams and Wilkins and formally endorsed by the 3 boards. Its purpose, which it served for well over a decade, was to promote greater clarity and consistency of usage of spine terminology. Since 2001, there has been sufficient evolution in our understanding of the lumbar disc to suggest the need for revision and updating. The document represents the consensus recommendations of the current combined task forces and reflects changes consistent with current concepts in radiological and clinical care. A PubMed search was performed for literature pertaining to the lumbar disc. The task force members individually and collectively reviewed the literature and revised the 2001 document. It was then reviewed by the governing boards of the American Society of Spine Radiology, the American Society of Neuroradiology, and the North American Spine Society. After further revision based on their feedback, the paper was approved for publication. The article provides a discussion of the recommended diagnostic categories and a glossary of terms pertaining to the lumbar disc, a detailed discussion of the terms and their recommended usage, as well as updated illustrations and literature references. We have revised and updated a document that, since 2001, has provided a widely accepted nomenclature that helps maintain consistency and accuracy in the description of the properties of the normal and abnormal lumbar discs and that

  18. Building a MicroSociety

    ERIC Educational Resources Information Center

    Dunton, Sheryl

    2006-01-01

    Talbot Hill Elementary School in Renton, Washington, uses the MicroSociety model to make learning relevant and engaging for its diverse student population. Three afternoons each week, every student participates in a for-profit business, a governmental agency, or a nonprofit organization. Teachers prepare students to participate in the school's…

  19. Researching Society and Culture.

    ERIC Educational Resources Information Center

    Seale, Clive, Ed.

    This book provides theoretically informed guidance to practicing the key research methods for investigating society and culture. It is a text in both methods and methodology, in which the importance of understanding the historical, theoretical and institutional context in which particular methods have developed is stressed. The contributors of the…

  20. Commitment to quality of the Spanish scientific societies.

    PubMed

    García-Alegría, J; Vázquez-Fernández Del Pozo, S; Salcedo-Fernández, F; García-Lechuz Moya, J M; Andrés Zaragoza-Gaynor, G; López-Orive, M; García-San Jose, S; Casado-Durández, P

    2017-05-01

    This article summarises the objectives, methodology and initial conclusions of the project "Commitment to Quality of the Spanish Scientific Societies", coordinated by the Ministry of Health, Social Services and Equality, the Spanish Society of Internal Medicine and the Aragon Institute of Health Sciences, in which 48 scientific societies participate. This project's objectives are to decrease the use of unnecessary medical interventions, which are those that have shown no efficacy, have little or questionable effectiveness or are not cost-effective; decrease variability in clinical practice; promote the commitment among physicians and patients to properly use healthcare resources; and to promote clinical safety. The document includes 135 final recommendations for what not to do, prepared by 30 Spanish scientific societies. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

  1. American Cancer Society/American Society of Clinical Oncology Breast Cancer Survivorship Care Guideline.

    PubMed

    Runowicz, Carolyn D; Leach, Corinne R; Henry, N Lynn; Henry, Karen S; Mackey, Heather T; Cowens-Alvarado, Rebecca L; Cannady, Rachel S; Pratt-Chapman, Mandi L; Edge, Stephen B; Jacobs, Linda A; Hurria, Arti; Marks, Lawrence B; LaMonte, Samuel J; Warner, Ellen; Lyman, Gary H; Ganz, Patricia A

    2016-01-01

    Answer questions and earn CME/CNE The purpose of the American Cancer Society/American Society of Clinical Oncology Breast Cancer Survivorship Care Guideline is to provide recommendations to assist primary care and other clinicians in the care of female adult survivors of breast cancer. A systematic review of the literature was conducted using PubMed through April 2015. A multidisciplinary expert workgroup with expertise in primary care, gynecology, surgical oncology, medical oncology, radiation oncology, and nursing was formed and tasked with drafting the Breast Cancer Survivorship Care Guideline. A total of 1073 articles met inclusion criteria; and, after full text review, 237 were included as the evidence base. Patients should undergo regular surveillance for breast cancer recurrence, including evaluation with a cancer-related history and physical examination, and should be screened for new primary breast cancer. Data do not support performing routine laboratory tests or imaging tests in asymptomatic patients to evaluate for breast cancer recurrence. Primary care clinicians should counsel patients about the importance of maintaining a healthy lifestyle, monitor for post-treatment symptoms that can adversely affect quality of life, and monitor for adherence to endocrine therapy. Recommendations provided in this guideline are based on current evidence in the literature and expert consensus opinion. Most of the evidence is not sufficient to warrant a strong evidence-based recommendation. Recommendations on surveillance for breast cancer recurrence, screening for second primary cancers, assessment and management of physical and psychosocial long-term and late effects of breast cancer and its treatment, health promotion, and care coordination/practice implications are made. © 2015 American Cancer Society.

  2. A short history of the Australian Society of Soil Science

    NASA Astrophysics Data System (ADS)

    Bennison, Linda

    2013-04-01

    In 1955 a resolution, "that the Australian Society of Soil Science be inaugurated as from this meeting" was recorded in Melbourne Australia. The following year in Queensland, the first official meeting of the Society took place with a Federal Executive and Presidents from the Australian Capital Territory, New South Wales, Queensland, South Australian and Victorian branches forming the Federal Council. In later years the executive expanded with the addition of the Western Australia branch in 1957, the Riverina Branch in 1962 and most recently the Tasmania Branch in 2008. The objects of the Society were 1) the advancement of soil science and studies therein with particular reference to Australia and 2) to provide a link between soil scientists and kindred bodies within Australia and between them and other similar organisations in other countries. Membership was restricted to persons engaged in the scientific study of the soil and has grown steadily from to 147 members in 1957 to 875 members in 2012. The first issue of the Society newsletter, Soils News, was published in January 1957 and continued to be published twice yearly until 1996. A name change to Profile and an increase to quarterly publication occurred in 1997; circulation remained restricted to members. The Publications Committee in 1968 determined the Publication Series would be the medium for occasional technical papers, reviews and reports but not research papers and in 1962 the Australian Journal of Soil Research was established by CSIRO in response to continued representations from the Society. By 1960 a draft constitution was circulated to, and adopted by members. The first honorary life membership of the Society was awarded to Dr. J A Prescott. Honorary memberships are still awarded for service to the Society and to soil science and are capped at 25. In 1964 the ISSS awarded honorary membership to Dr. Prescott. Now known as IUSS Honorary members other Australians recognised have been EG Hallsworth

  3. Margaret Cavendish and the Royal Society

    PubMed Central

    Wilkins, Emma

    2014-01-01

    It is often claimed that Margaret Cavendish was an anti-experimentalist who was deeply hostile to the activities of the early Royal Society—particularly in relation to Robert Hooke's experiments with microscopes. Some scholars have argued that her views were odd or even childish, while others have claimed that they were shaped by her gender-based status as a scientific ‘outsider’. In this paper I examine Cavendish's views in contemporary context, arguing that her relationship with the Royal Society was more nuanced than previous accounts have suggested. This contextualized approach reveals two points: first, that Cavendish's views were not isolated or odd when compared with those of her contemporaries, and second, that the early Royal Society was less intellectually homogeneous than is sometimes thought. I also show that, although hostile to some aspects of experimentalism, Cavendish nevertheless shared many of the Royal Society's ambitions for natural philosophy, especially in relation to its usefulness and the importance of plain language as a means to disseminate new ideas. PMID:25254278

  4. Fitness consequences of spousal relatedness in 46 small-scale societies.

    PubMed

    Bailey, Drew H; Hill, Kim R; Walker, Robert S

    2014-05-01

    Social norms that regulate reproductive and marital decisions generate impressive cross-cultural variation in the prevalence of kin marriages. In some societies, marriages among kin are the norm and this inbreeding creates intensive kinship networks concentrated within communities. In others, especially forager societies, most marriages are between more genealogically and geographically distant individuals, which generates a larger number of kin and affines of lesser relatedness in more extensive kinship networks spread out over multiple communities. Here, we investigate the fitness consequence of kin marriages across a sample of 46 small-scale societies (12,439 marriages). Results show that some non-forager societies (including horticulturalists, agriculturalists and pastoralists), but not foragers, have intensive kinship societies where fitness outcomes (measured as the number of surviving children in genealogies) peak at commonly high levels of spousal relatedness. By contrast, the extensive kinship systems of foragers have worse fitness outcomes at high levels of spousal relatedness. Overall, societies with greater levels of inbreeding showed a more positive relationship between fitness and spousal relatedness. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

  5. Olympic and world sport: making transnational society?

    PubMed

    Giulianotti, Richard; Brownell, Susan

    2012-06-01

    This paper introduces the special issue of the British Journal of Sociology on the subject of the transnational aspects of Olympic and world sport. The special issue is underpinned by the perspective that because sport provides a space for the forging of transnational connections and global consciousness, it is increasingly significant within contemporary processes of globalization and the making of transnational society. In this article, we examine in turn eight social scientific themes or problems that are prominent within the special issue: globalization, glocalization, neo-liberal ideologies and policies, transnational society, securitization, global civil society, transnational/global public sphere, and fantasy/imagination. We conclude by highlighting five 'circles' of future research inquiry within world sport that should be explored by social scientists. © London School of Economics and Political Science 2012.

  6. Applied Computational Electromagnetics Society Journal. Volume 13, No. 1

    DTIC Science & Technology

    1998-03-01

    APPLIED COMPUTATIONAL ELECTROMAGNETICS SOCIETY JOURNAL March 1998 Vol. 13 No. 1 ISSN 1054-4887 MBTMBUTION BTATCICEHt 1 ’ | Appcofd for...public rdtooMf DUrtrlbnttoo Unlimited 1 19980709 083 GENERAL PURPOSE AND SCOPE. The Applied Computational Electromagnetics Society Journal...SOCIETY Journal March 1998 Vol. 13 No. 1 ISSN 1054-4887 The ACES Journal is abstracted in INSPEC, in Engineering Index, and in DTIC. The second

  7. Ebola Virus and Marburg Virus

    MedlinePlus

    ... chimps and fruit bats in Africa. Transmission from animals to humans Experts suspect that both viruses are transmitted to humans through an infected animal's bodily fluids. Examples include: Blood. Butchering or eating ...

  8. Science, Technology, Society: Opportunities.

    ERIC Educational Resources Information Center

    Lux, Donald G., Ed.

    1992-01-01

    Recognizing the potential pitfalls resulting from a lack of human foresight lies at the heart of the science-technology-society (STS) movement. This issue of "Theory Into Practice" is the second part of a two-part series that examines the educational opportunities arising as educators attempt to develop student understanding of STS. In the first…

  9. Science, Sex, and Society.

    ERIC Educational Resources Information Center

    Kammer, Ann E.; And Others

    This manual is a compilation of articles about women who pursue careers in science and the multiple sources and forms of discouragement they encounter. It is intended as a guide when developing courses that explore career opportunities and pressures for women in science and a resource in understanding the interaction between science, society, and…

  10. Huntington's Disease Society of America

    MedlinePlus

    ... Donald A. King Summer Research Fellowship HD Human Biology Project Scientific Advisory Board Further Reading HD Insights ... Disease Society of America Awards Four HD Human Biology Project Fellowships for 2017 10.12.17 HDBUZZ: ...

  11. Human cloning and 'posthuman' society.

    PubMed

    Blackford, Russell

    2005-01-01

    Since early 1997, when the creation of Dolly the sheep by somatic cell nuclear transfer was announced in Nature, numerous government reports, essays, articles and books have considered the ethical problems and policy issues surrounding human reproductive cloning. In this article, I consider what response a modern liberal society should give to the prospect of human cloning, if it became safe and practical. Some opponents of human cloning have argued that permitting it would place us on a slippery slope to a repugnant future society, comparable to that portrayed in Aldous Huxley's novel, Brave New World. I conclude that, leaving aside concerns about safety, none of the psychological or social considerations discussed in this article provides an adequate policy justification for invoking the state's coercive powers to prevent human cloning.

  12. Society for Academic Emergency Medicine Statement on Plagiarism.

    PubMed

    Asher, Shellie L; Iserson, Kenneth V; Merck, Lisa H

    2017-10-01

    The integrity of the research enterprise is of the utmost importance for the advancement of safe and effective medical practice for patients and for maintaining the public trust in health care. Academic societies and editors of journals are key participants in guarding scientific integrity. Avoiding and preventing plagiarism helps to preserve the scientific integrity of professional presentations and publications. The Society for Academic Emergency Medicine (SAEM) Ethics Committee discusses current issues in scientific publishing integrity and provides a guideline to avoid plagiarism in SAEM presentations and publications. © 2017 by the Society for Academic Emergency Medicine.

  13. A brief history of the Japan Society for Cell Biology.

    PubMed

    Tashiro, Y; Okigaki, T

    2001-02-01

    The Japan Society for Cell Biology (JSCB) was first founded in 1950 as the Japan Society for Cellular Chemistry under the vigorous leadership of Seizo Katsunuma, in collaboration with Shigeyasu Amano and Satimaru Seno. The Society was provisionally named as above simply because cell biology had not yet been coined at that time in Japan, although in prospect and reality the Society was in fact for the purpose of pursuing cell biology. Later in 1964, the Society was properly renamed as the Japan Society for Cell Biology. After this renaming, the JSCB made great efforts to adapt itself to the rapid progress being made in cell biology. For this purpose the Society's constitution was created in 1966 and revised in 1969. According to the revised constitution, the President, Executive Committee and Councils were to be determined by ballot vote. The style of the annual meetings was gradually modified to incorporate general oral and poster presentations in addition to Symposia (1969-1974). The publication of annual periodicals in Japanese called Symposia of the Japan Society for Cellular Chemistry (1951-1967) and later Symposia of the Japan Society for Cell Biology (1968-1974) was replaced by a new international journal called Cell Structure and Function initiated in 1975. This reformation made it possible for the Society to participate in the Science Council of Japan in 1975 and finally in 1993 to acquire its own study section of Cell Biology with grants-in-aid from the Ministry of Education and Science, Japan. The JSCB hosted the 3rd International Congress on Cell Biology (ICCB) in 1984 and the 3rd Asian-Pacific Organization for Cell Biology (APOCB) Congress in 1998, thus contributing to the international advancement of cell biology. Now the membership of JSCB stands at approximately 1,800 and the number of presentations per meeting is 300 to 400 annually. Although a good number of interesting and important findings in cell biology have been reported from Japan, the

  14. Popularizing dissent: A civil society perspective.

    PubMed

    Motion, Judy; Leitch, Shirley; Weaver, C Kay

    2015-05-01

    This article theorizes civil society groups' attempts to popularize opposition to genetic modification in New Zealand as deliberative interventions that seek to open up public participation in science-society governance. In this case, the popularization strategies were designed to intensify concerns about social justice and democratic incursions, mobilize dissent and offer meaningful mechanisms for navigating and participating in public protest. Such civic popularization efforts, we argue, are more likely to succeed when popularity and politicization strategies are judiciously integrated to escalate controversy, re-negotiate power relations and provoke agency and action. © The Author(s) 2014.

  15. Artificial Exo-Society Modeling: a New Tool for SETI Research

    NASA Astrophysics Data System (ADS)

    Gardner, James N.

    2002-01-01

    One of the newest fields of complexity research is artificial society modeling. Methodologically related to artificial life research, artificial society modeling utilizes agent-based computer simulation tools like SWARM and SUGARSCAPE developed by the Santa Fe Institute, Los Alamos National Laboratory and the Bookings Institution in an effort to introduce an unprecedented degree of rigor and quantitative sophistication into social science research. The broad aim of artificial society modeling is to begin the development of a more unified social science that embeds cultural evolutionary processes in a computational environment that simulates demographics, the transmission of culture, conflict, economics, disease, the emergence of groups and coadaptation with an environment in a bottom-up fashion. When an artificial society computer model is run, artificial societal patterns emerge from the interaction of autonomous software agents (the "inhabitants" of the artificial society). Artificial society modeling invites the interpretation of society as a distributed computational system and the interpretation of social dynamics as a specialized category of computation. Artificial society modeling techniques offer the potential of computational simulation of hypothetical alien societies in much the same way that artificial life modeling techniques offer the potential to model hypothetical exobiological phenomena. NASA recently announced its intention to begin exploring the possibility of including artificial life research within the broad portfolio of scientific fields comprised by the interdisciplinary astrobiology research endeavor. It may be appropriate for SETI researchers to likewise commence an exploration of the possible inclusion of artificial exo-society modeling within the SETI research endeavor. Artificial exo-society modeling might be particularly useful in a post-detection environment by (1) coherently organizing the set of data points derived from a detected

  16. A history of the American Society for Clinical Investigation

    PubMed Central

    Howell, Joel D.

    2009-01-01

    One hundred years ago, in 1909, the American Society for Clinical Investigation (ASCI) held its first annual meeting. The founding members based this new society on a revolutionary approach to research that emphasized newer physiological methods. In 1924 the ASCI started a new journal, the Journal of Clinical Investigation. The ASCI has also held an annual meeting almost every year. The society has long debated who could be a member, with discussions about whether members must be physicians, what sorts of research they could do, and the role of women within the society. The ASCI has also grappled with what else the society should do, especially whether it ought to take a stand on policy issues. ASCI history has reflected changing social, political, and economic contexts, including several wars, concerns about the ethics of biomedical research, massive increases in federal research funding, and an increasingly large and specialized medical environment. PMID:19348041

  17. [Foundation of the science and society alliance in France. Towards a conscious and recognised collaboration between actors of research and civil society].

    PubMed

    Fellini, Nadia; Faroult, Elie

    2015-01-01

    In the last two decades, the debate on the meaning of science in relation to societies that create it, nourish it, and benefit from it, focused on civil society's ability to produce knowledge. This yielded first the concept of participatory science and later the wider concept of participatory research. Throughout Europe, numerous collective experimentations have generated countless interactions, and new interfaces between the world of research and civil society are constantly being created. But in spite of the proliferation of these experiences, a paradox slows down their acknowledgment and legitimation. On the one hand, these interactions often go unseen and unrecognized by the institutions, public policies, and even at times their very creators. On the other hand, scientists, are still overwhelmingly wary of civil society and, perceiving only its intellectual deficit and lack of comprehension, they fail to consider the study and development of these interactions as being of primary importance. The Sciences and Society Alliance, which was recently founded in France, provides a platform where these collaborative experiences can be collected, studied, supported, communicated, and institutionally acknowledged. The launch of this process,which is soon to be European in scope, answers the need to bring science into the democratic path tread by the societies that create it. In its ability to compose diversity, this process is an example of deep democracy.

  18. An Astrosociological Perspective on Space-Capable vs. Spacefaring Societies

    NASA Astrophysics Data System (ADS)

    Pass, J.

    As with any academic field, astrosociology allows for an endless number of competing theoretical models and hypotheses. One possible theoretical model is presented here that starts with the premise that even the most advanced societies today are extremely far from achieving a spacefaring status. The most advanced nation states are, in fact, space-capable societies because they have the capacity to send cargo and humans into low Earth orbit and beyond. However, their social structures and cultures lack fundamental characteristics that would allow for their designation as spacefaring societies. This article describes the characteristics of a theoretical spacefaring society and argues that getting there from our current status as space-capable societies is a long and arduous process, and it is not a definite outcome whatsoever. While a continuum is offered, it represents an imprecise path that can retrograde or fall apart at any time. Thus, this theoretical model provides one possible series of an unfolding of events that result in the creation of characteristics of the social fabric that may result in movement along the continuum toward a spacefaring society. Movement along the continuum results in an accumulation of coordinated spacefaring characteristics for a given society. Simultaneously, strictly terrestrial characteristics disappear or transform themselves into hybrid forms that include spacefaring features. This exercise demonstrates that this theoretical exercise has a number of benefits for astrosociologists conducting research in the area of spacefaring theory. Moreover, it makes the case for the idea that the study of the theoretical transformation from a space-capable to a spacefaring society includes implications for current and future 1) space policy in the public sector and 2) corporate decision-making related to space in the private sector.

  19. Education for Jobless Society

    ERIC Educational Resources Information Center

    Sidorkin, Alexander M.

    2017-01-01

    The advent of societies with low employment rates will present a challenge to education. Education must move away from the discourse of skills and towards the discourse of meaning and motivation. The paper considers three kinds of non-waged optional labor that may form the basis of the future economy: prosumption, volunteering, and self-design.…

  20. The Politics, Roles, and Future of Professional Societies

    ERIC Educational Resources Information Center

    Feingold, Ronald S.; Estes, Steven G.

    2016-01-01

    This article analyzes various issues related to a professional society's having greater influence on governmental, societal, and global issues. Analysis of association/society missions and goals, support for enhanced connections with other groups and collaboration to other disciplines through scholarly research projects, plus greater relevance and…

  1. 33 CFR 157.04 - Authorization of classification societies.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 2 2011-07-01 2011-07-01 false Authorization of classification... CARRYING OIL IN BULK General § 157.04 Authorization of classification societies. (a) The Coast Guard may authorize any classification society (CS) to perform certain plan reviews, certifications, and inspections...

  2. 33 CFR 157.04 - Authorization of classification societies.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Authorization of classification... CARRYING OIL IN BULK General § 157.04 Authorization of classification societies. (a) The Coast Guard may authorize any classification society (CS) to perform certain plan reviews, certifications, and inspections...

  3. Social penalty promotes cooperation in a cooperative society.

    PubMed

    Ito, Hiromu; Yoshimura, Jin

    2015-08-04

    Why cooperation is well developed in human society is an unsolved question in biological and human sciences. Vast studies in game theory have revealed that in non-cooperative games selfish behavior generally dominates over cooperation and cooperation can be evolved only under very limited conditions. These studies ask the origin of cooperation; whether cooperation can evolve in a group of selfish individuals. In this paper, instead of asking the origin of cooperation, we consider the enhancement of cooperation in a small already cooperative society. We ask whether cooperative behavior is further promoted in a small cooperative society in which social penalty is devised. We analyze hawk-dove game and prisoner's dilemma introducing social penalty. We then expand it for non-cooperative games in general. The results indicate that cooperation is universally favored if penalty is further imposed. We discuss the current result in terms of the moral, laws, rules and regulations in a society, e.g., criminology and traffic violation.

  4. A molecular concept of caste in insect societies.

    PubMed

    Sumner, Seirian; Bell, Emily; Taylor, Daisy

    2018-02-01

    The term 'caste' is used to describe the division of reproductive labour that defines eusocial insect societies. The definition of 'caste' has been debated over the last 50 years, specifically with respect to the simplest insect societies; this raises the question of whether a simple categorisation of social behaviour by reproductive state alone is helpful. Gene-level analyses of behaviours of individuals in hymenopteran social insect societies now provide a new empirical base-line for defining caste and understanding the evolution and maintenance of a reproductive division of labour. We review this literature to identify a set of potential molecular signatures that, combined with behavioural, morphological and physiological data, help define caste more precisely; these signatures vary with the type of society, and are likely to be influenced by ecology, life-history, and stage in the colony cycle. We conclude that genomic approaches provide us with additional ways to help quantify and categorise caste, and behaviour in general. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Social penalty promotes cooperation in a cooperative society

    PubMed Central

    Ito, Hiromu; Yoshimura, Jin

    2015-01-01

    Why cooperation is well developed in human society is an unsolved question in biological and human sciences. Vast studies in game theory have revealed that in non-cooperative games selfish behavior generally dominates over cooperation and cooperation can be evolved only under very limited conditions. These studies ask the origin of cooperation; whether cooperation can evolve in a group of selfish individuals. In this paper, instead of asking the origin of cooperation, we consider the enhancement of cooperation in a small already cooperative society. We ask whether cooperative behavior is further promoted in a small cooperative society in which social penalty is devised. We analyze hawk-dove game and prisoner’s dilemma introducing social penalty. We then expand it for non-cooperative games in general. The results indicate that cooperation is universally favored if penalty is further imposed. We discuss the current result in terms of the moral, laws, rules and regulations in a society, e.g., criminology and traffic violation. PMID:26238521

  6. Society of Forensic Toxicologists, Inc.

    Science.gov Websites

    you interested in learning more about SOFT? Click here to download and read our brochure. The Society forensic toxicologists and those interested in the discipline for the purpose of promoting and developing

  7. German gynecologic societies investigating their Nazi past.

    PubMed

    Frobenius, Wolfgang; Kinzelbach, Annemarie; Anthuber, Christoph; Dross, Fritz

    2014-11-01

    Research into the activities of German medical specialist associations during the Nazi period is still in its initial stages even today. In the field of gynecology and obstetrics as well, most representatives of the discipline continued to take an attitude based on "concealment and forgetting", even after the turn of the millennium. In order to break with this approach, the Bavarian Society for Obstetrics and Gynecology (Bayerische Gesellschaft für Geburtshilfe und Frauenheilkunde, BGGF) commissioned an interdisciplinary research group to focus on clarifying its Nazi past for the purposes of a history of the institution on the occasion of its centenary. The research was based on the Society's archive. When the files were found to show conspicuous gaps for the Nazi period, the investigation was extended into the role of BGGF representatives and members who were active at the time. In some cases, it was possible to draw on existing studies and to supplement the available information from additional archival sources. It was found that the BGGF started at a very early stage to marginalize and ignore its "non-Aryan" members. No official decision to exclude such members was apparently taken, however. Many representatives and honorary members of the society were involved in promoting and carrying out eugenic sterilizations, simultaneously conducting abortions on some victims, and they at least shared responsibility for forced abortions among Ostarbeiterinnen ("Eastern workers", forced laborers from Eastern Europe). Accompanying unethical research that was mainly intended to garner academic prestige for the physicians involved was never discussed at the Society's conferences. Representatives of the Society who were substantially incriminated were able to continue their careers almost without interruption after 1945.

  8. History of Publications from the American Otological Society: A Celebration of the 150-Year History of the American Otological Society.

    PubMed

    Lustig, Lawrence R

    2018-04-01

    : The American Otological Society (AOS) has been on the forefront of advancing the science of auditory and vestibular physiology, and art of ear medicine since its founding in 1868. For 150 years, through its publications, the AOS has provided a critical forum to debate these advances, highlighting treatment successes and failures, and served a place to celebrate its history. This historical review provides an overview of the publications of the AOS since its founding: the Transactions of the annual meeting from 1868 through 2006, Treatises on Otosclerosis (1928-1935), the History of the Society from the 100 and 125th anniversary, and the sponsored Society journals-American Journal of Otology (1879-1883, 1979-2000) and Otology & Neurotology (2001-present).

  9. Matrilocal residence is ancestral in Austronesian societies

    PubMed Central

    Jordan, Fiona M.; Gray, Russell D.; Greenhill, Simon J.; Mace, Ruth

    2009-01-01

    The nature of social life in human prehistory is elusive, yet knowing how kinship systems evolve is critical for understanding population history and cultural diversity. Post-marital residence rules specify sex-specific dispersal and kin association, influencing the pattern of genetic markers across populations. Cultural phylogenetics allows us to practise ‘virtual archaeology’ on these aspects of social life that leave no trace in the archaeological record. Here we show that early Austronesian societies practised matrilocal post-marital residence. Using a Markov-chain Monte Carlo comparative method implemented in a Bayesian phylogenetic framework, we estimated the type of residence at each ancestral node in a sample of Austronesian language trees spanning 135 Pacific societies. Matrilocal residence has been hypothesized for proto-Oceanic society (ca 3500 BP), but we find strong evidence that matrilocality was predominant in earlier Austronesian societies ca 5000–4500 BP, at the root of the language family and its early branches. Our results illuminate the divergent patterns of mtDNA and Y-chromosome markers seen in the Pacific. The analysis of present-day cross-cultural data in this way allows us to directly address cultural evolutionary and life-history processes in prehistory. PMID:19324748

  10. Birth of the Angle Society of Europe.

    PubMed

    Jacquin, Michel

    2006-01-01

    The history of the Angle Society of Europe began in 1971 with the meeting of two men: Juan Canut from Spain and Ernst Hösl from Germany. They decided to launch the idea of an association to get ready for the emergence of a new wave of Orthodontics in Europe. The first step was the creation of a Society with small groups of fourteen Orthodontists. The very first principle to be followed was "the plaster on the table" demonstration together with presentations on clinical or general interest subjects. The First Official Meeting took place in Zurich. 32 initial members were in attendance trying to set up the requirements for the development of a high quality Society. The second meeting focused on a scientific program centered on Treatment Timing Topic and the emergence of a new set of Bylaws. The third meeting was devoted to the display of 215 treated cases presented by temporary members to be evaluated by a Scientific Committee under the presidency of Dr. Alton Moore as official representative of the USA Edward H. Angle Society of Orthodontists. The following meetings demonstrated a constant and well monitored increase of new candidates and active members motivated to reach the required excellence level.

  11. 7 CFR 795.10 - Club, society, fraternal or religious organization.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 7 2013-01-01 2013-01-01 false Club, society, fraternal or religious organization... SERVICE AGENCY, DEPARTMENT OF AGRICULTURE PROVISIONS COMMON TO MORE THAN ONE PROGRAM PAYMENT LIMITATION General § 795.10 Club, society, fraternal or religious organization. Each individual club, society...

  12. 7 CFR 795.10 - Club, society, fraternal or religious organization.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 7 2014-01-01 2014-01-01 false Club, society, fraternal or religious organization... SERVICE AGENCY, DEPARTMENT OF AGRICULTURE PROVISIONS COMMON TO MORE THAN ONE PROGRAM PAYMENT LIMITATION General § 795.10 Club, society, fraternal or religious organization. Each individual club, society...

  13. 7 CFR 795.10 - Club, society, fraternal or religious organization.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 7 2012-01-01 2012-01-01 false Club, society, fraternal or religious organization... SERVICE AGENCY, DEPARTMENT OF AGRICULTURE PROVISIONS COMMON TO MORE THAN ONE PROGRAM PAYMENT LIMITATION General § 795.10 Club, society, fraternal or religious organization. Each individual club, society...

  14. Analysis of the readability of patient education materials from surgical subspecialties.

    PubMed

    Hansberry, David R; Agarwal, Nitin; Shah, Ravi; Schmitt, Paul J; Baredes, Soly; Setzen, Michael; Carmel, Peter W; Prestigiacomo, Charles J; Liu, James K; Eloy, Jean Anderson

    2014-02-01

    Patients are increasingly using the Internet as a source of information on medical conditions. Because the average American adult reads at a 7th- to 8th-grade level, the National Institutes of Health recommend that patient education material be written between a 4th- and 6th-grade level. In this study, we assess and compare the readability of patient education materials on major surgical subspecialty Web sites relative to otolaryngology. Descriptive and correlational design. Patient education materials from 14 major surgical subspecialty Web sites (American Society of Colon and Rectal Surgeons, American Association of Endocrine Surgeons, American Society of General Surgeons, American Society for Metabolic and Bariatric Surgery, American Association of Neurological Surgeons, American Congress of Obstetricians and Gynecologists, American Academy of Ophthalmology, American Academy of Orthopedic Surgeons, American Academy of Otolaryngology-Head and Neck Surgery, American Pediatric Surgical Association, American Society of Plastic Surgeons, Society for Thoracic Surgeons, and American Urological Association) were downloaded and assessed for their level of readability using 10 widely accepted readability scales. The readability level of patient education material from all surgical subspecialties was uniformly too high. Average readability levels across all subspecialties ranged from the 10th- to 15th-grade level. Otolaryngology and other surgical subspecialties Web sites have patient education material written at an education level that the average American may not be able to understand. To reach a broader population of patients, it might be necessary to rewrite patient education material at a more appropriate level. N/A. © 2013 The American Laryngological, Rhinological and Otological Society, Inc.

  15. HPAC Info-dex 5: Locating engineering societies, associations

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    NONE

    1995-06-01

    This is the 1995/1996 listing of heating, ventilation, air conditioning and refrigeration systems engineering societies, trade associations, and government organizations that have established performance standards for mechanical systems and components. The societies and associations are listed alphabetically along with their complete addresses and telephone and FAX numbers.

  16. Society Membership Profile: The Pattern of Subfield Associations.

    ERIC Educational Resources Information Center

    Czujko, Roman; And Others

    An overview of the membership of nine societies that comprise the American Institute of Physics is presented, with attention to demographic characteristics, employers, work activity, salaries, physics subfields, and differences among the societies. Comparisons are made to surveys since 1979, and highlights on 1983 salaries are included. One…

  17. Women and the Information Society: Barriers and Participation.

    ERIC Educational Resources Information Center

    Goulding, Anne; Spacey, Rachel

    The development and use of communication and information technologies, notably the Internet, have stimulated huge changes in the organization of work and daily life in Europe, leading to a process of transition from the "Industrial" to the "Information" society. The ultimate aim of the Information Society should be the…

  18. The Changing Role of a Professional Society Library.

    ERIC Educational Resources Information Center

    Lees, Nigel

    1997-01-01

    Describes developments in the United Kingdom's Royal Society of Chemistry's Library and Information Centre that has changed from a professional and learned society library into a business center. Development of a priced information service, electronic sources of information including online databases and the Internet, and marketing and promotion…

  19. Indigenous Models of Therapy in Traditional Asian Societies.

    ERIC Educational Resources Information Center

    Das, Ajit K.

    1987-01-01

    Presents an overview of some indigenous ways of understanding and dealing with psychological disorders in the traditional societies of Asia. Indigenous approaches to healing and psychotherapy existing in India, China, and Japan are included. Models of healing in these three societies are classified as folk traditions, mystical traditions, and…

  20. Life Science Professional Societies Expand Undergraduate Education Efforts

    ERIC Educational Resources Information Center

    Matyas, Marsha Lakes; Ruedi, Elizabeth A.; Engen, Katie; Chang, Amy L.

    2017-01-01

    The "Vision and Change in Undergraduate Biology Education" reports cite the critical role of professional societies in undergraduate life science education and, since 2008, have called for the increased involvement of professional societies in support of undergraduate education. Our study explored the level of support being provided by…

  1. 46 CFR 30.10-57 - Recognized classification society-TB/ALL.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 1 2010-10-01 2010-10-01 false Recognized classification society-TB/ALL. 30.10-57... Definitions § 30.10-57 Recognized classification society—TB/ALL. The term recognized classification society means the American Bureau of Shipping or other classification society recognized by the Commandant. ...

  2. 46 CFR 30.10-57 - Recognized classification society-TB/ALL.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 1 2011-10-01 2011-10-01 false Recognized classification society-TB/ALL. 30.10-57... Definitions § 30.10-57 Recognized classification society—TB/ALL. The term recognized classification society means the American Bureau of Shipping or other classification society recognized by the Commandant. ...

  3. Successful linking of the Society of Thoracic Surgeons Database to Social Security data to examine the accuracy of Society of Thoracic Surgeons mortality data.

    PubMed

    Jacobs, Jeffrey P; O'Brien, Sean M; Shahian, David M; Edwards, Fred H; Badhwar, Vinay; Dokholyan, Rachel S; Sanchez, Juan A; Morales, David L; Prager, Richard L; Wright, Cameron D; Puskas, John D; Gammie, James S; Haan, Constance K; George, Kristopher M; Sheng, Shubin; Peterson, Eric D; Shewan, Cynthia M; Han, Jane M; Bongiorno, Phillip A; Yohe, Courtney; Williams, William G; Mayer, John E; Grover, Frederick L

    2013-04-01

    The Society of Thoracic Surgeons Adult Cardiac Surgery Database has been linked to the Social Security Death Master File to verify "life status" and evaluate long-term surgical outcomes. The objective of this study is explore practical applications of the linkage of the Society of Thoracic Surgeons Adult Cardiac Surgery Database to Social Securtiy Death Master File, including the use of the Social Securtiy Death Master File to examine the accuracy of the Society of Thoracic Surgeons 30-day mortality data. On January 1, 2008, the Society of Thoracic Surgeons Adult Cardiac Surgery Database began collecting Social Security numbers in its new version 2.61. This study includes all Society of Thoracic Surgeons Adult Cardiac Surgery Database records for operations with nonmissing Social Security numbers between January 1, 2008, and December 31, 2010, inclusive. To match records between the Society of Thoracic Surgeons Adult Cardiac Surgery Database and the Social Security Death Master File, we used a combined probabilistic and deterministic matching rule with reported high sensitivity and nearly perfect specificity. Between January 1, 2008, and December 31, 2010, the Society of Thoracic Surgeons Adult Cardiac Surgery Database collected data for 870,406 operations. Social Security numbers were available for 541,953 operations and unavailable for 328,453 operations. According to the Society of Thoracic Surgeons Adult Cardiac Surgery Database, the 30-day mortality rate was 17,757/541,953 = 3.3%. Linkage to the Social Security Death Master File identified 16,565 cases of suspected 30-day deaths (3.1%). Of these, 14,983 were recorded as 30-day deaths in the Society of Thoracic Surgeons database (relative sensitivity = 90.4%). Relative sensitivity was 98.8% (12,863/13,014) for suspected 30-day deaths occurring before discharge and 59.7% (2120/3551) for suspected 30-day deaths occurring after discharge. Linkage to the Social Security Death Master File confirms the accuracy of

  4. The Engineering Societies & Continuing Education.

    ERIC Educational Resources Information Center

    Professional Engineer, 1979

    1979-01-01

    Gives a description of what the major engineering societies (ASCE, ASME, AICHE, and IEEE) are doing in the area of continuing education. The description includes the short courses, their costs, duration, type and scope of the content. (GA)

  5. Higher Education and Civil Society: Compatibility Re-Examined

    ERIC Educational Resources Information Center

    Khatun, Mahmuda

    2012-01-01

    Last couple of decades, some developed countries emphasized to develop civil society in developing countries. The main goals were to promote democratic norms and values among citizens who will not be thinking about democratic society otherwise. To establish democratic norms and values, many view that higher education is necessary. The relationship…

  6. An Assessment of the Academic Impact of Shock Society Members.

    PubMed

    Milgrom, Daniel P; Koniaris, Leonidas G; Valsangkar, Nakul P; Lad, Neha; Bell, Teresa M; Wojcik, Brandon; Zimmers, Teresa A

    2018-05-01

    Professional society membership enhances career development and productivity by offering opportunities for networking and learning about recent advances in the field. The quality and contribution of such societies can be measured in part through the academic productivity, career status, and funding success rates of their members. Here, using Scopus, NIH RePORTER, and departmental websites, we compare characteristics of the Shock Society membership to those of the top 55 NIH-funded American university and hospital-based departments of surgery. Shock Society members' mean number of publications, citations and H-indices were all significantly higher than those of non-members in surgery departments (P < 0.001). A higher percentage of members also have received funding from the NIH (42.5% vs. 18.5%, P < 0.001). Regression analysis indicated that members were more likely to have NIH funding compared with non-members (OR 1.46, 95% CI 1.12-1.916). Trauma surgeons belonging to the Shock Society had a higher number of publications and greater NIH funding than those who did not (130.4 vs. 42.7, P < 0.001; 40.4% vs. 8.5%, P < 0.001). Aggregate academic metrics from the Shock Society were superior to those of the Association for Academic Surgery and generally for the Society of University Surgeons as well. These data indicate that the Shock Society represents a highly academic and productive group of investigators. For surgery faculty, membership is associated with greater academic productivity and career advancement. While it is difficult to ascribe causation, certainly the Shock Society might positively influence careers for its members.

  7. Big Society, Big Deal?

    ERIC Educational Resources Information Center

    Thomson, Alastair

    2011-01-01

    Political leaders like to put forward guiding ideas or themes which pull their individual decisions into a broader narrative. For John Major it was Back to Basics, for Tony Blair it was the Third Way and for David Cameron it is the Big Society. While Mr. Blair relied on Lord Giddens to add intellectual weight to his idea, Mr. Cameron's legacy idea…

  8. Applying Andragogical Concepts in Creating a Sustainable Lifelong Learning Society

    ERIC Educational Resources Information Center

    Charungkaittikul, Suwithida; Henschke, John A.

    2017-01-01

    Today, the world is changing, re-establishing the role of education to have a developed society. This article aims to explore the practical application of Andragogy as a key element for creating a sustainable lifelong learning society, to propose strategies for developing a lifelong learning society using andragogical concepts, to enhance…

  9. "Science in Society, Omnibus Pack, Readers M-P."

    ERIC Educational Resources Information Center

    Association for Science Education, Cambridge (England).

    Four additional readers have been written for use in the Science in Society general studies project. Three of the readers discuss the applications and importance of engineering in the world. They include: Engineering 1 (Reader M), which discusses such topics as the role of engineering in society, structural design and engineering, the engineering…

  10. Changing roles of academic societies due to globalization.

    PubMed

    Ehara, Shigeru; Aoki, Shigeki; Honda, Hiroshi

    2016-10-01

    Because of the globalization of environment around the academic society, the expected roles have changed significantly. In this short communication, we present the current situation in our international activities of the Japan Radiological Society, particularly in the academic activities and clinical practice. Establishing and reinforcing international network is one process of their promotion.

  11. College Students' Science Societies and Special-Interest Circles

    ERIC Educational Resources Information Center

    Ivanov, A.

    2005-01-01

    From the point of view of their age, student science societies and special-interest circles are among the most venerable forms of corporate association among students in colleges and universities. In this article, the author traces the formation of different societies and special-interest circles by college students in different universities in…

  12. The Role of Military Myth in Society

    DTIC Science & Technology

    2012-04-01

    the face of adversity and contribute significantly to the war effort. The cause they served is portrayed as admirable and worthy, despite the racism ...most cases, fosters the belief that the nation’s cause is worthy and should be supported by the members of the society. The paper reviews elements of...are worthy of praise, and that their cause is a worthy cause - that is, society is intended to support the men and their cause . Negative military

  13. American Society of Nuclear Cardiology

    MedlinePlus

    ... Society of Nuclear Cardiology Career Center Search for jobs. Post a resume or job. Member Login Enter Forgot your password? Meetings & Events ... Extended! Missed ASNC2017? Save $100 -Order Meeting On Demand by Oct. 31 Wednesday, October 25, 2017 admin ...

  14. Laryngeal Manifestations of Neurofibromatosis.

    PubMed

    Naunheim, Matthew R; Plotkin, Scott R; Franco, Ramon A; Song, Phillip C

    2016-03-01

    To describe the range of findings in patients with neurofibromatosis (NF) presenting to a laryngology clinic and to analyze the etiologic factors of vocal fold dysfunction in this cohort. Case series with chart review. Tertiary laryngology practice. All cases of NF presenting to an academic laryngology practice were retrospectively reviewed (August 2005 to May 2014), with a total of 34 cases. Demographic data, symptoms, and endoscopic examination findings were reviewed. Etiologic factors of laryngeal complaints were analyzed with reference to NF-associated pathologies and surgical history. Thirty-four patients with NF-1 or NF-2 were evaluated, and 28 of these patients (6 NF-1 and 22 NF-2) had laryngeal pathology. The most common presenting symptoms were vocal weakness (n = 21), dysphagia (n = 5), and globus (n = 4). Three patients had NF-related vocal fold masses on examination, including 2 neurofibromas and 1 schwannoma. Unilateral vocal cord paralysis was seen in 17 patients; bilateral paralysis was observed in 5 patients. Of patients with unilateral or bilateral paralysis, 20 had intracranial masses (vestibular schwannoma, meningioma, or skull base tumors), and 16 had previously undergone surgery for these lesions. Of the patients with NF-associated intracranial tumors, 87.0% presented with vocal cord paralysis, whereas only 40.0% of those without intracranial masses had paralysis (P = .0560). Seven patients underwent medialization procedures. Neurofibromatosis patients may present to laryngology clinic with primary laryngeal tumors or, more commonly, unilateral or bilateral paralysis. Otolaryngologists should be keenly aware of vocal fold paralysis caused by the NF-associated tumors, with particular attention to bilateral paralysis in NF-2. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2016.

  15. Diversity in the American Society of Anesthesiologists Leadership.

    PubMed

    Toledo, Paloma; Duce, Lorent; Adams, Jerome; Ross, Vernon H; Thompson, Kelli M; Wong, Cynthia A

    2017-05-01

    Women and minorities are underrepresented in US academic medicine. The Sullivan Commission on Diversity in the Healthcare Workforce emphasized the importance of diverse leadership for reducing health care disparities. The objective of this study was to evaluate the demographics of the American Society of Anesthesiologists leadership. We hypothesized that the percentage of women and underrepresented minorities is less than that of their respective proportions in the general physician workforce. An electronic survey was developed by the authors and mailed to 595 members of the American Society of Anesthesiologists leadership who had valid email addresses, including the members of the 2014 House of Delegates and state society leaders who were not the members of the House of Delegates. Univariate statistics were used to characterize survey responses and the probability distributions were estimated using the binomial distribution. A one-sample t test was used to compare the percentage of women and minorities in the survey pool to that of the corresponding percentages in the general physician workforce (38.0% women and 8.9% minorities), and the US population (51.0% women and 32.0% minorities). The survey response rate was 54%. A total of 21.1% (95% confidence interval: 16.4%-25.7%) of respondents were women and 6.0% (95% confidence interval: 3.3%-8.7%) were minorities. The proportion of women in the American Society of Anesthesiologist leadership was lower than the general medical workforce and the US population (P < .001 for both); the proportion of underrepresented minorities was lower than the US population (P < .001). Women and minorities are underrepresented in the leadership of the American Society of Anesthesiologists. Efforts should be made to increase the diversity of the American Society of Anesthesiologists leadership with the goal of reducing overall anesthesia workforce disparities.

  16. A Swedish Mutual Support Society of Problem Gamblers

    ERIC Educational Resources Information Center

    Binde, Per

    2012-01-01

    Mutual support societies for problem gamblers have existed in Sweden for 20 years. They have helped more people with gambling problems than any other institution inside or outside the Swedish health care system. This paper outlines the background of these societies and describes the meetings of one of them. Data come from interviews with members…

  17. Preservice Science Teachers' Views on Science-Technology-Society

    ERIC Educational Resources Information Center

    Dikmentepe, Emel; Yakar, Zeha

    2016-01-01

    The aim of this study is to investigate the views of pre-service science teachers on Science-Technology-Society (STS). In the research, a descriptive research method was used and data were collected using the Views on Science-Technology-Society (VOSTS) Questionnaire. In general, the results of this study revealed that pre-service science teachers…

  18. The Mass Media and Modern Society. Second Edition.

    ERIC Educational Resources Information Center

    Rivers, William L.; And Others

    The focus throughout this second edition is on the 1970's and the impact of mass communication on contemporary society. Analyzing the ways in which communication affects and is, in turn, affected by society, the book examines the social, economic, and intellectual environments in which the media operate. Two intellectual factors which have had the…

  19. Expression of an immunogenic Ebola immune complex in Nicotiana benthamiana.

    PubMed

    Phoolcharoen, Waranyoo; Bhoo, Seong H; Lai, Huafang; Ma, Julian; Arntzen, Charles J; Chen, Qiang; Mason, Hugh S

    2011-09-01

    Filoviruses (Ebola and Marburg viruses) cause severe and often fatal haemorrhagic fever in humans and non-human primates. The US Centers for Disease Control identifies Ebola and Marburg viruses as 'category A' pathogens (defined as posing a risk to national security as bioterrorism agents), which has lead to a search for vaccines that could prevent the disease. Because the use of such vaccines would be in the service of public health, the cost of production is an important component of their development. The use of plant biotechnology is one possible way to cost-effectively produce subunit vaccines. In this work, a geminiviral replicon system was used to produce an Ebola immune complex (EIC) in Nicotiana benthamiana. Ebola glycoprotein (GP1) was fused at the C-terminus of the heavy chain of humanized 6D8 IgG monoclonal antibody, which specifically binds to a linear epitope on GP1. Co-expression of the GP1-heavy chain fusion and the 6D8 light chain using a geminiviral vector in leaves of N. benthamiana produced assembled immunoglobulin, which was purified by ammonium sulphate precipitation and protein G affinity chromatography. Immune complex formation was confirmed by assays to show that the recombinant protein bound the complement factor C1q. Size measurements of purified recombinant protein by dynamic light scattering and size-exclusion chromatography also indicated complex formation. Subcutaneous immunization of BALB/C mice with purified EIC resulted in anti-Ebola virus antibody production at levels comparable to those obtained with a GP1 virus-like particle. These results show excellent potential for a plant-expressed EIC as a human vaccine. © 2011 The Authors. Plant Biotechnology Journal © 2011 Society for Experimental Biology, Association of Applied Biologists and Blackwell Publishing Ltd.

  20. Forum on Physics and Society Special Recognition

    NASA Astrophysics Data System (ADS)

    Post-Zwicker, Andrew

    2009-05-01

    This year we wish to use the FPS awards session to recognize those individuals who have made special contributions to issues at the interface of physics and society. Twelve years ago, Al Saperstein became the editor of Physics and Society, with Jeff Marque as the news editor. The two have been functioning as co-editors for the past five years. They have conscientiously brought us all a newsletter that informs and challenges. Thanks to the tireless efforts of these two men, the FPS ``newsletter'' is in reality a high-quality quarterly journal that is always thought-provoking and sometimes controversial. The typical issue contains a number of substantive articles, stimulating commentary and letters, informative news and interesting book reviews. The editors have had to exert considerable effort to assemble such interesting material on a range of relevant topics, often laboring with little additional help - and without benefit of a peer review system - to fill out the newsletter. With their retirement, the FPS Executive Committee wishes to express our deep appreciation to each of them for their many years of tireless service. Each year, the Forum on Physics and Society has the privilege of nominating APS members that have made outstanding contributions to the rank of Fellow. This year, we will introduce our newly elected Fellows during this Forum on Physics and Society Awards session.