Sample records for glaxo smith kline

  1. GW-501516 GlaxoSmithKline/Ligand.

    PubMed

    Pelton, Patricia

    2006-04-01

    GlaxoSmithKline and Ligand are developing GW-501516, a peroxisome proliferator-activator receptor-delta agonist for the potential treatment of dyslipidemia. Phase II clinical trials of this compound are ongoing.

  2. Scientists in Sport, the 2012-Inspired GlaxoSmithKline Schools Outreach Programme

    ERIC Educational Resources Information Center

    Gadd, Mark

    2012-01-01

    The GlaxoSmithKline Scientists in Sport team have worked with 4science to provide resources and offer activities for use by schools to show the relevance of science in sport. Much of the content looks at anti-doping and the science involved with detecting the misuse of banned substances. Through the development of a website, this work can continue…

  3. Impact of study outcome on submission and acceptance metrics for peer reviewed medical journals: six year retrospective review of all completed GlaxoSmithKline human drug research studies.

    PubMed

    Evoniuk, Gary; Mansi, Bernadette; DeCastro, Barbara; Sykes, Jennie

    2017-04-21

    Objectives  To determine whether the outcome of drug studies influenced submission and/or acceptance rates for publication in peer reviewed medical journals. Design  A six year retrospective review of publication status by study outcome for all human drug research studies conducted by a single industry sponsor (GlaxoSmithKline) that completed from 1 January 2009 to 30 June 2014 and were therefore due for manuscript submission (per the sponsor's policy) to peer reviewed journals within 18 months of study completion-that is, 31 December 2015. In addition, manuscripts from studies completing after 30 June 2014 were included irrespective of outcome if they were submitted before 31 December 2015. Setting  Studies conducted by a single industry sponsor (GlaxoSmithKline) Studies reviewed  1064 human drug research studies. Main outcome measures  All studies were assigned a publication status at 26 February 2016 including (as applicable): study completion date, date of first primary manuscript submission, number of submissions, journal decision(s), and publication date. All studies were also classified with assessors blinded to publication status as "positive" (perceived favorable outcome for the drug under study), "negative" (perceived unfavorable outcome for the drug under study), mixed, or non-comparative based on the presence and outcome of the primary outcome measure(s) for each study. "Negative" studies included safety studies in which the primary outcome was achieved but was adverse for the drug under study. For the total cohort and each of the four study outcomes, measures included descriptive statistics for study phase, time from study completion to submission and publication, and number and outcome (accepted/rejected) of publication submissions. Results  Of the 1064 studies (phase I-IV, interventional and non-interventional) included, 321 had study outcomes classified as positive, 155 as negative, 52 as mixed, and 536 as non-comparative. At the time of

  4. 76 FR 6456 - Intent To Grant an Exclusive License for a U.S. Government-Owned Invention

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-04

    ..., revocable license, to U.S. Patent No. 6,254,873, issued July 3, 2001, entitled ``Inactivated Dengue Virus... against Dengue virus for human use. The intended licensee is GlaxoSmithKline Bio, with its principal place...

  5. Supercomputers Join the Fight against Cancer – U.S. Department of Energy

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

    None

    The Department of Energy has some of the best supercomputers in the world. Now, they’re joining the fight against cancer. Learn about our new partnership with the National Cancer Institute and GlaxoSmithKline Pharmaceuticals.

  6. Niacin

    MedlinePlus

    ... syndrome. Taking the niacin along with a prescription omega-3 fatty acid seems to work even better. Alzheimer's ... this dosage along with 4 grams of prescription omega-3 ethyl esters (Lovaza, GlaxoSmithKline Pharmaceuticals) BY IV: For ...

  7. Tech Transfer Award Hails FNL's Role in Ebola Response | Frederick National Laboratory for Cancer Research

    Cancer.gov

    For speeding the delivery of an effective candidate vaccine during the largest Ebola outbreak in history, the Frederick National Lab (as Leidos Biomed) was cited along with National Institute of Allergy and Infectious Diseases and GlaxoSmithKline in

  8. Tech Transfer Award Hails FNL's Role in Ebola Response | FNLCR Staging

    Cancer.gov

    For speeding the delivery of an effective candidate vaccine during the largest Ebola outbreak in history, the Frederick National Lab (as Leidos Biomed) was cited along with National Institute of Allergy and Infectious Diseases and GlaxoSmithKline in

  9. New Drugs for Anemia Treatment Based on a New Understanding of the Mechanisms of Stress Erythropoiesis

    DTIC Science & Technology

    2015-11-01

    but the most effective was the PPARα receptor agonist GW7647 originally developed by GlaxoSmithKline for dyslipidemia . It is a potent and highly...3- fold the output of human red cells in culture. These PPARα receptor agonists, fenofibrate and GW7647, originally developed by for dyslipidemia

  10. 76 FR 1181 - Oncologic Drugs Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-07

    ... lymphoblastic leukemia (ALL) whose disease has not responded to or has relapsed following treatment with at..., application submitted by GlaxoSmithKline, indicated for the treatment of patients with types of leukemia or lymphoma known as T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma whose disease has...

  11. New Drugs for Anemia Treatment Based on a New Understanding of the Mechanisms of Stress Erythropoiesis

    DTIC Science & Technology

    2014-09-01

    GlaxoSmithKline for dyslipidemia . It is a potent and highly selective PPARα agonist (EC50 values are 6, 1100 and 6200 nM for human PPARα, PPARγ and PPARδ...red cells in culture. These PPARα receptor agonists, fenofibrate and GW7647, originally developed by for dyslipidemia , can be used in clinical trials

  12. Disconnected Youth in the Research Triangle Region: An Ominous Problem Hidden in Plain Sight

    ERIC Educational Resources Information Center

    Dodson, David; Guillory, Ferrel; Lipsitz, Joan; Raper, Noah; Rausch, Christina

    2008-01-01

    In September 2006, the North Carolina GlaxoSmithKline Foundation commissioned MDC, Inc. of Chapel Hill to analyze the problem of "disconnected youth" in the Research Triangle region, determine the current state of the region's responses to the challenge, and recommend steps to deepen and accelerate action on the issue. The research process was…

  13. Abstracts of the 24th international isotope society (UK group) symposium: synthesis and applications of labelled compounds 2015.

    PubMed

    Aigbirhio, F I; Allwein, S; Anwar, A; Atzrodt, J; Audisio, D; Badman, G; Bakale, R; Berthon, F; Bragg, R; Brindle, K M; Bushby, N; Campos, S; Cant, A A; Chan, M Y T; Colbon, P; Cornelissen, B; Czarny, B; Derdau, V; Dive, V; Dunscombe, M; Eggleston, I; Ellis-Sawyer, K; Elmore, C S; Engstrom, P; Ericsson, C; Fairlamb, I J S; Georgin, D; Godfrey, S P; He, L; Hickey, M J; Huscroft, I T; Kerr, W J; Lashford, A; Lenz, E; Lewinton, S; L'Hermite, M M; Lindelöf, Å; Little, G; Lockley, W J S; Loreau, O; Maddocks, S; Marguerit, M; Mirabello, V; Mudd, R J; Nilsson, G N; Owens, P K; Pascu, S I; Patriarche, G; Pimlott, S L; Pinault, M; Plastow, G; Racys, D T; Reif, J; Rossi, J; Ruan, J; Sarpaki, S; Sephton, S M; Simonsson, R; Speed, D J; Sumal, K; Sutherland, A; Taran, F; Thuleau, A; Wang, Y; Waring, M; Watters, W H; Wu, J; Xiao, J

    2016-04-01

    The 24th annual symposium of the International Isotope Society's United Kingdom Group took place at the Møller Centre, Churchill College, Cambridge, UK on Friday 6th November 2015. The meeting was attended by 77 delegates from academia and industry, the life sciences, chemical, radiochemical and scientific instrument suppliers. Delegates were welcomed by Dr Ken Lawrie (GlaxoSmithKline, UK, chair of the IIS UK group). The subsequent scientific programme consisted of oral presentations, short 'flash' presentations in association with particular posters and poster presentations. The scientific areas covered included isotopic synthesis, regulatory issues, applications of labelled compounds in imaging, isotopic separation and novel chemistry with potential implications for isotopic synthesis. Both short-lived and long-lived isotopes were represented, as were stable isotopes. The symposium was divided into a morning session chaired by Dr Rebekka Hueting (University of Oxford, UK) and afternoon sessions chaired by Dr Sofia Pascu (University of Bath, UK) and by Dr Alan Dowling (Syngenta, UK). The UK meeting concluded with remarks from Dr Ken Lawrie (GlaxoSmithKline, UK). Copyright © 2016 John Wiley & Sons, Ltd.

  14. An Invitation to Open Innovation in Malaria Drug Discovery: 47 Quality Starting Points from the TCAMS.

    PubMed

    Calderón, Félix; Barros, David; Bueno, José María; Coterón, José Miguel; Fernández, Esther; Gamo, Francisco Javier; Lavandera, José Luís; León, María Luisa; Macdonald, Simon J F; Mallo, Araceli; Manzano, Pilar; Porras, Esther; Fiandor, José María; Castro, Julia

    2011-10-13

    In 2010, GlaxoSmithKline published the structures of 13533 chemical starting points for antimalarial lead identification. By using an agglomerative structural clustering technique followed by computational filters such as antimalarial activity, physicochemical properties, and dissimilarity to known antimalarial structures, we have identified 47 starting points for lead optimization. Their structures are provided. We invite potential collaborators to work with us to discover new clinical candidates.

  15. Computational Tools and Resources for Metabolism-Related Property Predictions. 1. Overview of Publicly Available (Free and Commercial) Databases and Software

    DTIC Science & Technology

    2012-01-01

    pathway inhibitor Smoothened GPCR Basal cell carcinoma Ivacaftor Kalydeco™ Vertex 203188 31 January 2012 CFTR potentiator CFTR chloride channel ...inhibitor Platelet P2Y 12 ADP-receptor Acute coronary syndrome Ezogabine Potiga™ GlaxoSmithKline/ Valeant 022345 10 June 2011 Potassium channel opener...KCNQ/ Kv7 Epilepsy Linagliptin Tradjenta® Boehringer Ingelheim 201280 2 May 2011 Peptidase inhibitor DPP-4 Type 2 diabetes Abiraterone Zytiga® Janssen

  16. Investor Outlook: Rising from the Ashes; GSK's European Approval of Strimvelis for ADA-SCID.

    PubMed

    Schimmer, Joshua; Breazzano, Steven

    2016-06-01

    GlaxoSmithKline's (GSK) and partner San Raffaele Telethon Institute for Gene Therapy's recent positive European approval for Strimvelis for treatment of severe combined immunodeficiency due to adenosine deaminase deficiency (ADA-SCID) represents the second EU-approved gene therapy and the first γ-retrovirus and first ex vivo gene therapy. In this article we discuss the significance and implications of this historic approval for the broader gene therapy field.

  17. International Drug Discovery Science and Technology--BIT's Seventh Annual Congress.

    PubMed

    Bodovitz, Steven

    2010-01-01

    BIT's Seventh Annual International Drug Discovery Science and Technology Congress, held in Shanghai, included topics covering new therapeutic and technological developments in the field of drug discovery. This conference report highlights selected presentations on open-access approaches to R&D, novel and multifactorial targets, and technologies that assist drug discovery. Investigational drugs discussed include the anticancer agents astuprotimut-r (GlaxoSmithKline plc) and AS-1411 (Antisoma plc).

  18. NIC23

    PubMed Central

    Baxter, David; Guppy, Martin J.

    2013-01-01

    The 23rd National Immunization Conference for Health Care Workers was held on December 7th, 2012 at the Manchester Conference Centre. There were over 220 delegates for this event sponsored by educational grants from Crucell, Glaxo Smith Kline, Pfizer Vaccines and Sanofi Pasteur. A number of speakers took the opportunity kindly afforded by Human Vaccines and Immunotherapeutics to write up their conference presentation as a paper for this special supplement. PMID:23857271

  19. Lasting immune memory against hepatitis B following challenge 10-11 years after primary vaccination with either three doses of hexavalent DTPa-HBV-IPV/Hib or monovalent hepatitis B vaccine at 3, 5 and 11-12 months of age.

    PubMed

    Avdicova, Mária; Crasta, Priya D; Hardt, Karin; Kovac, Martina

    2015-05-28

    The combined hexavalent diphtheria-tetanus-pertussis-hepatitis B-inactivated poliomyelitis - Haemophilus influenzae type b conjugate vaccine (Infanrix hexa™; DTPa-HBV-IPV/Hib: GlaxoSmithKline Vaccines) induces robust responses to the HBV component when administered at 3, 5 and 11-12 months of age. We assessed long term HBV antibody persistence 10-11 years after primary vaccination in infancy. Antibody persistence and immune memory were assessed post-primary vaccination at 3, 5, 11-12 months with DTPa-HBV-IPV/Hib, or monovalent HBV vaccine (Engerix™ B, GlaxoSmithKline Vaccines) co-administered with DTPa-IPV/Hib (Infanrix™-IPV/Hib, GlaxoSmithKline Vaccines) in 185 children aged 11-12 years. Blood samples were collected before and 1 month after a challenge dose of Engerix™ B (10μg dose). 10-11 years after primary vaccination the percentage of subjects with persisting anti-HBs antibody concentrations ≥10mIU/ml was 48.4% in the DTPa-HBV-IPV/Hib group and 58.4% in the DTPa-IPV/Hib+HBV group. After the HBV challenge dose, the percentage with anti-HBs ≥100mIU/ml increased from 14.7% to 93.6% in the DTPa-HBV-IPV/Hib group and 19.1% to 94.4% in the DTPa-IPV/Hib+HBV group. Anti-HBs GMCs increased by at least 187-fold in each group. An anamnestic response (≥4-fold increase in initially seropositive or anti-HBs concentration ≥10mIU/ml in initially seronegative subjects) was observed in 96.8% and 96.6% of subjects in the DTPa-HBV-IPV/Hib and DTPa-IPV/Hib+HBV groups, respectively. No serious adverse events occurred that were considered related to challenge vaccination. Administration of HBV as part of a combination vaccine or as a monovalent vaccine induced long lasting immune memory against HBV in children primed at 3, 5 and 11 months of age. Antibody persistence and immune memory were similar, suggesting that protection afforded by DTPa-HBV-IPV/Hib and monovalent HBV vaccines, is likely to be of similar duration. The administration of HBV challenge dose 10

  20. An interlaboratory transfer of a multi-analyte assay between continents.

    PubMed

    Georgiou, Alexandra; Dong, Kelly; Hughes, Stephen; Barfield, Matthew

    2015-01-01

    Alex has worked at GlaxoSmithKline for the past 15 years and currently works within the bioanalytical and toxicokinetic group in the United Kingdom. Alex's role in previous years has been the in-house support of preclinical and clinical bioanalysis, from method development through to sample analysis activities as well as acting as PI for GLP bioanalysis and toxicokinetics. For the past two years, Alex has applied this analytical and regulatory experience to focus on the outsourcing of preclinical bioanalysis, toxicokinetics and clinical bioanalysis, working closely with multiple bioanalytical and in-life CRO partners worldwide. Alex works to support DMPK and Safety Assessment outsourcing activities for GSK across multiple therapeutic areas, from the first GLP study through to late stage clinical PK studies. Transfer and cross-validation of an existing analytical assay between a laboratory providing current analytical support, and a laboratory needed for new or additional support, can present the bioanalyst with numerous challenges. These challenges can be technical or logistical in nature and may prove to be significant when transferring an assay between laboratories in different continents. Part of GlaxoSmithKline's strategy to improve confidence in providing quality data, is to cross-validate between laboratories. If the cross-validation fails predefined acceptance criteria, then a subsequent investigation would follow. This may also prove to be challenging. The importance of thorough planning and good communication throughout assay transfer, cross-validation and any subsequent investigations is illustrated in this case study.

  1. Mechanistic insights into influenza vaccine-associated narcolepsy.

    PubMed

    Ahmed, S Sohail; Steinman, Lawrence

    2016-12-01

    We previously reported an increased frequency of antibodies to hypocretin (HCRT) receptor 2 in sera obtained from narcoleptic patients who received the European AS03-adjuvanted vaccine Pandemrix (GlaxoSmithKline Biologicals, s.a.) for the global influenza A H1N1 pandemic in 2009 [A(H1N1)pdm09]. These antibodies cross-reacted with a particular fragment of influenza nucleoprotein (NP) - one of the proteins naturally contained in the virus used to make seasonal influenza vaccine and pandemic influenza vaccines. The purpose of this commentary is to provide additional insights and interpretations of the findings and share additional data not presented in the original paper to help the reader appreciate the key messages of that publication. First, a brief background to narcolepsy and vaccine-induced narcolepsy will be provided. Then, additional insights and clarification will be provided on the following topics: 1) the critical difference identified in the adjuvanted A(H1N1)pdm09 vaccines, 2) the contributing factor likely for the discordant association of narcolepsy between the AS03-adjuvanted pandemic vaccines Pandemrix and Arepanrix (GlaxoSmithKline Biologicals, s.a.), 3) the significance of detecting HCRT receptor 2 (HCRTr2) antibodies in some Finnish control subjects, 4) the approach used for the detection of HCRTr2 antibodies in vaccine-associated narcolepsy, and 5) the plausibility of the proposed mechanism involving HCRTr2 modulation in vaccine-associated narcolepsy.

  2. 32nd National Medicinal Chemistry Symposium--medicinal chemistry developments for neurodegeneration, diabetes and cancer.

    PubMed

    Gater, Deborah

    2010-08-01

    The 32nd National Medicinal Chemistry Symposium, held in Minneapolis, MN, USA, included topics covering new developments in the field of medicinal chemistry. This conference report highlights selected presentations on NR2B subtype-selective NMDA receptor antagonists from Merck; selective neuronal nitric oxide synthase inhibitors from Northwestern University; novel GPR119 agonists, suchas GSK-1292263A (GlaxoSmithKline plc), PSN-821 ((OSI) Prosidion) and MBX-2982 (Metabolex Inc); a small-molecule Bcl inhibitor,navitoclax (Abbott Laboratories); and p53-targeting agents from sanofi-aventis and Ascenta Therapeutics Inc, including AT-219.

  3. A randomised, partially observer blind, multicentre, head-to-head comparison of a two-dose regimen of Baxter and GlaxoSmithKline H1N1 pandemic vaccines, administered 21 days apart.

    PubMed

    Nicholson, K G; Abrams, K R; Batham, S; Clark, T W; Hoschler, K; Lim, W S; Medina, M; Nguyen-Van-Tam, J S; Read, R C; Warren, F C; Zambon, M

    2010-12-01

    To evaluate the immunogenicity of a two-dose schedule of Baxter cell-cultured, non-adjuvanted, whole-virion H1N1 vaccine, and GlaxoSmithKline AS03(A)-adjuvanted split-virion H1N1 vaccine with respect to the EU Committee for Medicinal Products for Human Use (CHMP) and the US Food and Drug Administration (FDA) licensing criteria. An age-stratified, randomised, observer-blind, parallel-group, multicentre controlled trial was carried out in volunteers aged ≥ 18-44, ≥ 45-64 and ≥ 65 years. Three teaching hospitals in the UK (Leicester Royal Infirmary, Leicester; Nottingham City Hospital, Nottingham; and Royal Hallamshire Hospital, Sheffield). Three hundred and forty-seven subjects were identified and randomised to AS03(A)-adjuvanted split-virion H1N1 vaccine or whole-virion (WV) vaccine in age groups [≥ 18-44 years (n = 140), ≥ 45-64 years (n = 136) and ≥ 65 years (n = 71)]. Vaccine was administered by intramuscular injection into the deltoid muscle of the non-dominant arm. One hundred and seventy-five randomised subjects were allocated AS03(A)-adjuvanted split H1N1 vaccine; one hundred and sixty-nine subjects had a second dose of the same vaccine 21 days later. One hundred and seventy-two subjects were allocated WV vaccine; one hundred and seventy-one subjects had a second dose of the same vaccine 21 days later. Serum samples for antibody measurements were collected on days 0 (before the first vaccination), 7, 14, 21 (before the second vaccination), 28, 35, 42 and 180. Subjects were observed for local and systemic reactions for 30 minutes after each injection, and for the next 7 days they recorded, in self-completed diaries, the severity of solicited local (pain, bruising, erythema and swelling) and systemic symptoms (chills, malaise, muscle aches, nausea and headache), oral temperature and use of analgesic medications. Vaccine immunogenicity using the CHMP and the FDA licensing criteria. Antibody titres were measured using haemagglutination inhibition (HI

  4. Development and clinical testing of multivalent vaccines based on a diphtheria-tetanus-acellular pertussis vaccine: difficulties encountered and lessons learned.

    PubMed

    Capiau, Carine; Poolman, Jan; Hoet, Bernard; Bogaerts, Hugues; Andre, Francis

    2003-06-02

    The widespread use of whole-cell pertussis vaccines in the second half of the 20th century have reduced the incidence of the disease significantly. However, in some countries, concerns about the reactogenicity and potential neurological damage associated with whole-cell vaccines led to a decrease in vaccine acceptance and an increase in morbidity and mortality of pertussis in several countries. This prompted the development of less reactogenic acellular pertussis vaccines combined with diphtheria and tetanus toxoids, initially in Japan and later in other countries. In Europe, the improved diphtheria, tetanus and acellular pertussis (DTPa) vaccine was first introduced in March 1994. The pertussis component of this DTPa vaccine, developed by Glaxo SmithKline, consists of pertussis toxoid, filamentous haemagglutinin and pertactin. The vaccine is well tolerated, with a lower incidence of adverse reactions than after administration of whole-cell vaccines. The long-lasting efficacy and effectiveness of DTPa vaccines have been extensively documented and these are now the cornerstone of a large range of combined vaccines including DTPa-hepatitis B (HBV), DTPa-inactivated polio (IPV) and DTPa-HBV-IPV. A lyophilised Haemophilus influenzae type b (Hib) vaccine can be reconstituted with all of these liquid combinations. The introduction of well-tolerated and efficacious DTPa vaccines and their more polyvalent combinations has improved the acceptance and simplified the implementation of childhood immunisation. This paper is a review of the technical and scientific difficulties encountered and the lessons learned over the 10-year period that it took to develop and introduce six multivalent vaccines using the Glaxo SmithKline DTPa as a building block.

  5. Recommendations of the Advisory Committee on Immunization Practices for Use of Herpes Zoster Vaccines.

    PubMed

    Dooling, Kathleen L; Guo, Angela; Patel, Manisha; Lee, Grace M; Moore, Kelly; Belongia, Edward A; Harpaz, Rafael

    2018-01-26

    On October 20, 2017, Zoster Vaccine Recombinant, Adjuvanted (Shingrix, GlaxoSmithKline, [GSK] Research Triangle Park, North Carolina), a 2-dose, subunit vaccine containing recombinant glycoprotein E in combination with a novel adjuvant (AS01 B ), was approved by the Food and Drug Administration for the prevention of herpes zoster in adults aged ≥50 years. The vaccine consists of 2 doses (0.5 mL each), administered intramuscularly, 2-6 months apart (1). On October 25, 2017, the Advisory Committee on Immunization Practices (ACIP) recommended the recombinant zoster vaccine (RZV) for use in immunocompetent adults aged ≥50 years.

  6. Technology evaluation: C242-DM1, ImmunoGen Inc.

    PubMed

    Smith, S

    2001-04-01

    C242-DM1 is a tumor-activated immunotoxin under development by GlaxoSmithKline plc (formerly SmithKline Beecham plc), under licence from ImmunoGen Inc, as a potential treatment for colon tumor. It consists of a colon cancer-specific humanized antibody, C242, conjugated to the maytansine derivative DM1. In preclinical studies, C242-DM1 caused complete tumor regression in animal models of both human pancreatic and non-small cell lung cancer (NSCLC) at non-toxic doses. C242-DM1 has also been evaluated in an immunoconjugate combination with J-591 (Cornell University). The J591-DM1 immunoconjugate demonstrated effective, antigen-specific delivery of a highly cytotoxic drug to PSMA-positive Pca cells in vitro and in vivo with low systemic toxicity. Results from studies in monkeys showed that C242-DM1 had no significant toxicity or side effects, when administered at doses higher than those that were previously shown to completely eradicate human colon tumors in mice [271420]. ImmunoGen acquired the right to evaluate, and an option to license, technology related to maytansines from Takeda. In February 1999, ImmunoGen and SmithKline Beecham signed a US $45 million development and commercialization agreement for C242-DM1 [313493]. In August 1997, Immunogen received an SBIR grant to advance development of huC242-DM1 [258356]. EP-00425235, held by ImmunoGen, covers conjugated forms of ansamitocin (maytansine) derivatives. Takeda holds several patents for the production of ansamitocin and its analogs, the first one being JP-53124692.

  7. Scanner K-line photometry of Orion stars

    NASA Technical Reports Server (NTRS)

    Hesser, J. E.; Mcclintock, W.; Henry, R. C.

    1977-01-01

    Results are presented for two-channel scanner measurements of calcium K-line strengths in 39 Orion sword and belt stars. Values of the calcium k index and its associated standard error are given for each observed star, and the K-line strengths are compared with those of K-line standard stars and Hyades stars. Plots of k index against reddening-corrected color and of k-index deviation against metal-strength index deviation are provided which show that the Orion sword and belt stars do not differ significantly in their calcium and metal abundances from general field stars.

  8. The FEBS Journal in 2018 - putting a bit of color in your life, and your figures.

    PubMed

    Martin, Seamus J

    2018-01-01

    Seamus Martin holds the Smurfit Chair of Medical Genetics at the Smurfit Institute of Genetics, Trinity College Dublin, Ireland. He works on all aspects of cell death control and is especially interested in the links between cell death, cell stress and inflammation. He received the GlaxoSmithKline Award of The Biochemical Society (2006) and The RDS-Irish Times Boyle Medal (2015) for his work on the role of caspases in apoptosis and was elected to the Royal Irish Academy in 2006 and EMBO in 2009. He is the Editor-in-Chief of The FEBS Journal since 2014. © 2018 Federation of European Biochemical Societies.

  9. Efficacy and Safety of Fluticasone Furoate/Vilanterol Compared With Fluticasone Propionate/Salmeterol Combination in Adult and Adolescent Patients With Persistent Asthma

    PubMed Central

    Bleecker, Eugene R.; Lötvall, Jan; O’Byrne, Paul M.; Bateman, Eric D.; Medley, Hilary; Ellsworth, Anna; Jacques, Loretta; Busse, William W.

    2013-01-01

    Background: The combination of fluticasone furoate (FF), a novel inhaled corticosteroid (ICS), and vilanterol (VI), a long-acting β2 agonist, is under development as a once-daily treatment of asthma and COPD. The aim of this study was to compare the efficacy of FF/VI with fluticasone propionate (FP)/salmeterol (SAL) in patients with persistent asthma uncontrolled on a medium dose of ICS. Methods: In a randomized, double-blind, double-dummy, parallel group study, 806 patients received FF/VI (100/25 μg, n = 403) once daily in the evening delivered through ELLIPTA (GlaxoSmithKline) dry powder inhaler, or FP/SAL (250/50 μg, n = 403) bid through DISKUS/ACCUHALER (GlaxoSmithKline). The primary efficacy measure was 0- to 24-h serial weighted mean (wm) FEV1 after 24 weeks of treatment. Results: Improvements from baseline in 0- to 24-h wmFEV1 were observed with both FF/VI (341 mL) and FP/SAL (377 mL); the adjusted mean treatment difference was not statistically significant (−37 mL; 95% CI, −88 to 15, P = 0.162). There were no differences between 0- to 4-h serial wmFEV1, trough FEV1, and asthma control and quality-of-life questionnaire scores. There was no difference in reported exacerbations between treatments. Both treatments were well tolerated, with no clinically relevant effect on urinary cortisol excretion or vital signs and no treatment-related serious adverse events. Conclusions: The efficacy of once-daily FF/VI was similar to bid FP/SAL in improving lung function in patients with persistent asthma. No safety issues were identified. Trial registry: ClinicalTrials.gov; No.: NCT01147848; URL: www.clinicaltrials.gov PMID:23846316

  10. Pharmacological inhibition of myostatin protects against skeletal muscle atrophy and weakness after anterior cruciate ligament tear.

    PubMed

    Wurtzel, Caroline Nw; Gumucio, Jonathan P; Grekin, Jeremy A; Khouri, Roger K; Russell, Alan J; Bedi, Asheesh; Mendias, Christopher L

    2017-11-01

    Anterior cruciate ligament (ACL) tears are among the most frequent knee injuries in sports medicine, with tear rates in the US up to 250,000 per year. Many patients who suffer from ACL tears have persistent atrophy and weakness even after considerable rehabilitation. Myostatin is a cytokine that directly induces muscle atrophy, and previous studies rodent models and patients have demonstrated an upregulation of myostatin after ACL tear. Using a preclinical rat model, our objective was to determine if the use of a bioneutralizing antibody against myostatin could prevent muscle atrophy and weakness after ACL tear. Rats underwent a surgically induced ACL tear and were treated with either a bioneutralizing antibody against myostatin (10B3, GlaxoSmithKline) or a sham antibody (E1-82.15, GlaxoSmithKline). Muscles were harvested at either 7 or 21 days after induction of a tear to measure changes in contractile function, fiber size, and genes involved in muscle atrophy and hypertrophy. These time points were selected to evaluate early and later changes in muscle structure and function. Compared to the sham antibody group, 7 days after ACL tear, myostatin inhibition reduced the expression of proteolytic genes and induced the expression of hypertrophy genes. These early changes in gene expression lead to a 22% increase in muscle fiber cross-sectional area and a 10% improvement in maximum isometric force production that were observed 21 days after ACL tear. Overall, myostatin inhibition lead to several favorable, although modest, changes in molecular biomarkers of muscle regeneration and reduced muscle atrophy and weakness following ACL tear. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2499-2505, 2017. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  11. Serological response following re-vaccination with Salmonella typhi Vi-capsular polysaccharide vaccines in healthy adult travellers.

    PubMed

    Roggelin, Louise; Vinnemeier, Christof D; Fischer-Herr, Johanna; Johnson-Weaver, Brandi T; Rolling, Thierry; Burchard, Gerd D; Staats, Herman F; Cramer, Jakob P

    2015-08-07

    An injectable Vi-capsular polysaccharide vaccine against typhoid fever is available but vaccine-induced immunity tends to wane over time. The phenomenon of immunotolerance or hyporesponsiveness has earlier been described for polysaccharide vaccines such as pneumococcal capsular polysaccharide vaccine and some publications also suggest a possible immunotolerance after revaccination with Vi-capsular polysaccharide vaccines. In this study, post-immunisation antibody concentrations in adult travellers first vaccinated with a Salmonella typhi Vi-capsular polysaccharide vaccine (primary vaccination group) were compared with those having received one or more vaccinations previously (multiple vaccinations group). Vaccines administered were Typherix(®) (GlaxoSmithKline), Typhim Vi(®) (Sanofi Pasteur MSD) or Hepatyrix(®) (GlaxoSmithKline). Blood samples were obtained prior to vaccination (day 0) and on day 28 (-1/+14) after vaccination. Serum Vi-Antigen IgG concentrations were measured by ELISA. Of the 85 subjects included in the per protocol data set, 45 (53%) belonged to the multiple vaccinations group. In both groups, geometric mean antibody concentrations (GMCs) were significantly higher after vaccination than before vaccination. Pre-vaccination GMCs were lower in the primary vaccination group than in the multiple vaccinations group (3.40 μg/ml versus 6.13 μg/ml, P=0.005), while there was no significant difference in the post vaccination GMCs between groups (11.34 μg/ml versus 14.58 μg/ml, P=0.4). In the multiple vaccinations group, vaccination was performed 18 to 57 months after the last vaccination (median 38 months) and there was a negative correlation between time since last vaccination and antibody concentration on day 0. In conclusion, we were not able to demonstrate a relevant immunotolerance after multiple versus primary vaccination with S. typhi Vi-capsular polysaccharide vaccines. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. 78 FR 63226 - GlaxoSmithKline LLC; Withdrawal of Approval of the Indication for Treatment of Patients With...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-23

    ... have not received prior rituximab, for BEXXAR (tositumomab and iodine I 131 tositumomab) Injection held... withdraw the rituximab-na[iuml]ve indication for BEXXAR (tositumomab and iodine I 131 tositumomab... indication for BEXXAR (tositumomab and iodine I 131 tositumomab) Injection from the package insert. In the...

  13. Acellular pertussis vaccine boosters combined with diphtheria and tetanus toxoid boosters for adolescents: safety and immunogenicity assessment when preceded by different 5-dose DTaP/DTwP schedules.

    PubMed

    Pichichero, Michael E; Casey, Janet R; Francis, Anne B; Marsocci, Steven M; Murphy, Marie; Hoeger, William; Cleary, Carolyn

    2006-09-01

    A sixth dose of tetanus, diphtheria, acellular pertussis (Tdap) vaccine in adolescents might produce a differing reactogenicity and/or immunogenicity response depending on the composition of the 5 prior doses of DTaP or DT-whole cell pertussis (DTwP) vaccine. Reactions and immune responses following receipt of the Sanofi Pasteur (Adacel) and GlaxoSmithKline (Boostrix) Tdap vaccines were assessed in 229 adolescents. No differences were observed for reactions to either Tdap vaccine regardless of the prior DTaP/DTwP vaccination history. Seroprotective levels and antibody concentrations were comparable regardless of prior DTaP/DTwP vaccine history. A sixth sequential dose of Tdap after 5 doses of DTaP appears safe and immunogenic.

  14. A Divergent SAR Study Allows Optimization of a Potent 5-HT2c Inhibitor to a Promising Antimalarial Scaffold.

    PubMed

    Calderón, Félix; Vidal-Mas, Jaume; Burrows, Jeremy; de la Rosa, Juan Carlos; Jiménez-Díaz, María Belén; Mulet, Teresa; Prats, Sara; Solana, Jorge; Witty, Michael; Gamo, Francisco Javier; Fernández, Esther

    2012-05-10

    From the 13 533 chemical structures published by GlaxoSmithKline in 2010, we identified 47 quality starting points for lead optimization. One of the most promising hits was the TCMDC-139046, a molecule presenting an indoline core, which is well-known for its anxiolytic properties by interacting with serotonin antagonist receptors 5-HT2. The inhibition of this target will complicate the clinical development of these compounds as antimalarials. Herein, we present the antimalarial profile of this series and our efforts to avoid interaction with this receptor, while maintaining a good antiparasitic potency. By using a double-divergent structure-activity relationship analysis, we have obtained a novel lead compound harboring an indoline core.

  15. Variability of Solar UV Irradiance Related to Bright Magnetic Features Observed in Call K-Line: Relationship between Lyman alpha and K-line Report for UARS funding agency

    NASA Technical Reports Server (NTRS)

    Zirin, Harold; Cameron, Robert

    1999-01-01

    In this report we comment on the relationship between the Lyman alpha and Calcium K-line emission from the Sun. We firstly examine resolved Lyman alpha images (from TRACE) and resolved K-line images. We find that the Lyman alpha emission is consistent with a linear dependence on the K-line emission. As this is in conflict with the analysis of Johannesson et al.(1995, 1998) we proceed by comparing the disk integrated Lyman alpha flux as a function of ratio between the disk integrated Mg II core and wing fluxes (Johannesson et al (1998) having previously found a linear dependence between this index and the BBSO K-line index). We find that a reasonably good fit can be obtained, however note the discrepancies which lead Johannesson et al to consider the square root relationship. We suggest an alternative interpretation of the discrepancy.

  16. Micro-shear bond strength of resin cement to dentin after application of desensitizing toothpastes.

    PubMed

    Bavbek, Andac Barkin; Goktas, Baris; Cekic-Nagas, Isil; Egilmez, Ferhan; Ergun, Gulfem; Eskitascioglu, Gurcan

    2013-01-01

    The aim of the study was to evaluate the effect of three desensitizing toothpastes on bonding of resin cements to dentin. The occlusal surfaces of 72 maxillary third molars were ground to obtain flat dentin surfaces and then divided into three groups according to three desensitizing toothpastes used: Sensodyne Rapid Relief (GlaxoSmithKline, SmithKline Beecham Ltd., Slough, UK), Signal Sensitive Expert (Unilever Sanayi ve Ticaret Türk A.Ş., Ümraniye, İstanbul, Turkey) and Colgate Sensitive Pro-Relief (Colgate Palmolive, New York, NY). Following bonding of the resin cement (Clearfil™ SA Cement, Kuraray Co, Osaka, Japan) to dentin, the specimens were light cured for 40 s with a LED (Elipar S10, 3M Espe, St. Paul, MN). The strength measurements were accomplished with a micro-shear testing machine (Bisco, Schaumburg, IL) at a cross-head speed of 0.5 mm/min until the failure occurs. Failure modes were examined using a stereomicroscope and scanning electron microscope. The data were analyzed with one-way analysis of variance (ANOVA) and Tukey HSD test (α = 0.05). ANOVA revealed that the application of desensitizing toothpastes had significant effects on bond strength of the resin cement tested to dentin (p < 0.05). Mixed failures were observed in all of the groups. The use of a desensitizing toothpaste before cementation might alter the bond strength of adhesively luted restorations.

  17. Novel 1,2-dihydroquinazolin-2-ones: Design, synthesis, and biological evaluation against Trypanosoma brucei.

    PubMed

    Pham, ThanhTruc; Walden, Madeline; Butler, Christopher; Diaz-Gonzalez, Rosario; Pérez-Moreno, Guiomar; Ceballos-Pérez, Gloria; Gomez-Pérez, Veronica; García-Hernández, Raquel; Zecca, Henry; Krakoff, Emma; Kopec, Brian; Ichire, Ogar; Mackenzie, Caden; Pitot, Marika; Ruiz, Luis Miguel; Gamarro, Francisco; González-Pacanowska, Dolores; Navarro, Miguel; Dounay, Amy B

    2017-08-15

    In 2014, a published report of the high-throughput screen of>42,000 kinase inhibitors from GlaxoSmithKline against T. brucei identified 797 potent and selective hits. From this rich data set, we selected NEU-0001101 (1) for hit-to-lead optimization. Through our preliminary compound synthesis and SAR studies, we have confirmed the previously reported activity of 1 in a T. brucei cell proliferation assay and have identified alternative groups to replace the pyridyl ring in 1. Pyrazole 24 achieves improvements in both potency and lipophilicity relative to 1, while also showing good in vitro metabolic stability. The SAR developed on 24 provides new directions for further optimization of this novel scaffold for anti-trypanosomal drug discovery. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Antibody engineering and therapeutics conference. The annual meeting of the antibody society, Huntington Beach, CA, December 7-11, 2014.

    PubMed

    Larrick, James W; Parren, Paul W H I; Huston, James S; Plückthun, Andreas; Bradbury, Andrew; Tomlinson, Ian M; Chester, Kerry A; Burton, Dennis R; Adams, Gregory P; Weiner, Louis M; Scott, Jamie K; Alfenito, Mark R; Veldman, Trudi; Reichert, Janice M

    2014-01-01

    The 25th anniversary of the Antibody Engineering & Therapeutics Conference, the Annual Meeting of The Antibody Society, will be held in Huntington Beach, CA, December 7-11, 2014. Organized by IBC Life Sciences, the event will celebrate past successes, educate participants on current activities and offer a vision of future progress in the field. Keynote addresses will be given by academic and industry experts Douglas Lauffenburger (Massachusetts Institute of Technology), Ira Pastan (National Cancer Institute), James Wells (University of California, San Francisco), Ian Tomlinson (GlaxoSmithKline) and Anthony Rees (Rees Consulting AB and Emeritus Professor, University of Bath). These speakers will provide updates of their work, placed in the context of the substantial growth of the industry over the past 25 years.

  19. Obtaining real-world evidence: the Salford Lung Study

    PubMed Central

    New, John P; Bakerly, Nawar Diar; Leather, David; Woodcock, Ashley

    2014-01-01

    We need to assess clinical treatments in real-life settings outside of randomised controlled trials (RCTs). Pragmatic RCT (pRCT) data can supplement RCTs by providing effectiveness information to support healthcare decisions. Electronic health records can facilitate concurrent safety monitoring and data collection without direct patient contact for large randomised study populations in pRCTs. The Salford Lung Study is the world's first phase III pRCT in asthma and chronic obstructive pulmonary disease (COPD), which aims to randomise over 7000 patients. This paper describes the hurdles overcome and the enormous effort and resource required to establish this comparative effectiveness study of a prelicence intervention. GlaxoSmithKline protocol HZC115151 Asthma study clinicaltrials.gov registration NCT01706198 COPD study clinicaltrials.gov registration NCT01551758 PMID:24603195

  20. Stability of seasonal influenza vaccines investigated by spectroscopy and microscopy methods.

    PubMed

    Patois, E; Capelle, M A H; Gurny, R; Arvinte, T

    2011-10-06

    The stability of different seasonal influenza vaccines was investigated by spectroscopy and microscopy methods before and after the following stress-conditions: (i) 2 and 4 weeks storage at 25°C, (ii) 1 day storage at 37°C and (iii) one freeze-thaw cycle. The subunit vaccine Influvac (Solvay Pharma) and the split vaccine Mutagrip (Sanofi Pasteur) were affected by all stresses. The split vaccine Fluarix (GlaxoSmithKline) was affected only by storage at 25°C. The virosomal vaccine Inflexal V (Berna Biotech) was stable after the temperature stresses but aggregated after one freeze-thaw cycle. This study provides new insights into commercial vaccines of low antigen concentration and highlights the importance of using multiple techniques to assess vaccine stability. Copyright © 2011 Elsevier Ltd. All rights reserved.

  1. The FEBS Journal in 2016: read, reflect and don't feed the wolves.

    PubMed

    Martin, Seamus J

    2016-01-01

    Seamus Martin holds the Smurfit Chair of Medical Genetics at the Smurfit Institute of Genetics, Trinity College Dublin, Ireland. He obtained his PhD with Tom Cotter at the National University of Ireland, followed by post-doctoral fellowships with Ivan Roitt at UCL, London, UK, and Doug Green at The La Jolla Institute for Allergy and Immunology, California, USA. He works on all aspects of cell death control and is especially interested in the links between apoptosis, necrosis and inflammation. He received the GlaxoSmithKline Award of The Biochemical Society for his work on unravelling the caspase activation cascade and was elected to the Royal Irish Academy in 2006 and EMBO in 2009. He has been the Editor-in-Chief of The FEBS Journal since 2014. © 2015 FEBS.

  2. Postoperative K-line conversion from negative to positive is independently associated with a better surgical outcome after posterior decompression with instrumented fusion for K-line negative cervical ossification of the posterior ligament.

    PubMed

    Koda, Masao; Furuya, Takeo; Saito, Junya; Ijima, Yasushi; Kitamura, Mitsuhiro; Ohtori, Seiji; Orita, Sumihisa; Inage, Kazuhide; Abe, Tetsuya; Noguchi, Hiroshi; Funayama, Toru; Kumagai, Hiroshi; Miura, Kosei; Nagashima, Katsuya; Yamazaki, Masashi

    2018-06-01

    Addition of posterior instrumented fusion to laminoplasty (posterior decompression with instrumented fusion: PDF) can improve the surgical outcome of patients with K-line (-) cervical ossification of the longitudinal ligament (OPLL) compared with laminoplasty alone. We sought to elucidate the factors that are significantly associated with a better outcome after PDF for K-line (-) OPLL. The present study included 38 patients who underwent PDF for K-line (-) OPLL and were followed up for at least 1 year after surgery. Clinical outcome was assessed using Japanese Orthopedic Association (JOA) scores for cervical myelopathy and the recovery rate was calculated. Patients who belonged to the upper quartile of all the patients according to rank order of the JOA score recovery rate were considered to have a good outcome. The correlations between good outcome, patient factors and imaging assessments were analyzed statistically. Univariate analyses showed that postoperative conversion of K-line from (-) to (+) (p = 0.004), no increase in the sagittal vertical axis from the center of gravity of the head to C7 (p = 0.07), and a lower grade of preoperative intramedullary T2-signal intensity (p = 0.03) were candidates for the association. Stepwise logistic regression analysis revealed that postoperative K-line conversion from (-) to (+) is an independent factor that is significantly associated with a better surgical outcome (p = 0.04). Postoperative K-line conversion from (-) to (+) is a factor independently associated with a better surgical outcome. These slides can be retrieved under Electronic Supplementary material.

  3. The Need for Understanding and Engaging the Patient as Consumer of Products Developed by Neural Engineering.

    PubMed

    French, Jennifer; Lujan, J Luis; Bardot, Dawn; Graczyk, Emily Lauren; Hess-Dunning, Allison; Triolo, Ronald J; Moynahan, Megan; Tan, Winny; Zbrzeski, Adeline

    2018-05-21

    Neural Engineering is a discipline at the intersection of neuroscience, engineering, and clinical care. Recent major efforts by government and industry aimed at bringing forth personalized therapies, increasing the potential of the neural engineering industry for future growth, eg. the National Institutes of Health (NIH) Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative and Stimulating Peripheral Activity to Relieve Conditions (SPARC) Common Fund Program, the Defense Advanced Research Projects Agency (DARPA) Electrical Prescriptions (ElectRx) and Systems-Based Neurotechnology for Emerging Therapies (SUBNETS) Programs, and the GlaxoSmithKline Bioelectric Medicines Initiative. However, the incremental development of neural technologies can easily become a case of advancing technology for its own sake. This mindset can lead to a solution looking for a problem, without taking into consideration the patient/consumer point of view. Creative Commons Attribution license.

  4. Rapid and Reliable Binding Affinity Prediction of Bromodomain Inhibitors: A Computational Study

    PubMed Central

    2016-01-01

    Binding free energies of bromodomain inhibitors are calculated with recently formulated approaches, namely ESMACS (enhanced sampling of molecular dynamics with approximation of continuum solvent) and TIES (thermodynamic integration with enhanced sampling). A set of compounds is provided by GlaxoSmithKline, which represents a range of chemical functionality and binding affinities. The predicted binding free energies exhibit a good Spearman correlation of 0.78 with the experimental data from the 3-trajectory ESMACS, and an excellent correlation of 0.92 from the TIES approach where applicable. Given access to suitable high end computing resources and a high degree of automation, we can compute individual binding affinities in a few hours with precisions no greater than 0.2 kcal/mol for TIES, and no larger than 0.34 and 1.71 kcal/mol for the 1- and 3-trajectory ESMACS approaches. PMID:28005370

  5. Analysis of neighborhood behavior in lead optimization and array design.

    PubMed

    Papadatos, George; Cooper, Anthony W J; Kadirkamanathan, Visakan; Macdonald, Simon J F; McLay, Iain M; Pickett, Stephen D; Pritchard, John M; Willett, Peter; Gillet, Valerie J

    2009-02-01

    Neighborhood behavior describes the extent to which small structural changes defined by a molecular descriptor are likely to lead to small property changes. This study evaluates two methods for the quantification of neighborhood behavior: the optimal diagonal method of Patterson et al. and the optimality criterion method of Horvath and Jeandenans. The methods are evaluated using twelve different types of fingerprint (both 2D and 3D) with screening data derived from several lead optimization projects at GlaxoSmithKline. The principal focus of the work is the design of chemical arrays during lead optimization, and the study hence considers not only biological activity but also important drug properties such as metabolic stability, permeability, and lipophilicity. Evidence is provided to suggest that the optimality criterion method may provide a better quantitative description of neighborhood behavior than the optimal diagonal method.

  6. Personalized medicine--trends in molecular diagnostics: exponential growth expected in the next ten years.

    PubMed

    Hoggatt, Julie

    2011-02-01

    Companion diagnostics and stratified medicines will be increasingly used over the next ten years. Current market leaders who have created diagnostic divisions with a focus on biomarker identification will benefit, notably Abbott, AstraZeneca, Novartis, and GlaxoSmithKline. Pricing incentives and improvement in efficacy will drive this market. The US FDA is not likely to mandate stratification of medications, but cost containment for clinical trials will be sufficient incentive for companies to pursue this approach. The next area expected to produce stratified medicines is infectious disease, expanding from HIV to hepatitis C and hepatitis B. Celera is likely to be first to market with diagnostics for genetic variations in hepatitis C and hepatitis B. Metabolic disorders, especially diabetes, are also fertile ground for stratified medicine, likely to catch up to oncology and infectious disease over the next decade.

  7. Strategies for continuous evaluation of the benefit-risk profile of HPV-16/18-AS04-adjuvanted vaccine.

    PubMed

    Angelo, Maria-Genalin; Taylor, Sylvia; Struyf, Frank; Tavares Da Silva, Fernanda; Arellano, Felix; David, Marie-Pierre; Dubin, Gary; Rosillon, Dominique; Baril, Laurence

    2014-11-01

    The HPV types 16/18-AS04-adjuvanted cervical cancer vaccine, Cervarix(®) (HPV-16/18-vaccine, GlaxoSmithKline, Belgium) was first approved in 2007 and is licensed in 134 countries for the prevention of persistent infection, premalignant cervical lesions and cervical cancer caused by oncogenic HPV. Benefit-risk status requires continual re-evaluation as vaccine uptake increases, as the epidemiology of the disease evolves and as new information becomes available. This paper provides an example of benefit-risk considerations and risk-management planning. Evaluation of the benefit-risk of HPV-16/18-vaccine post-licensure includes studies with a range of designs in many countries and in collaboration with national public agencies and regulatory authorities. The strategy to assess benefit versus risk will continue to evolve and adapt to the changing HPV-16/18-vaccine market.

  8. FDA approval of expanded age indication for a tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine.

    PubMed

    2011-09-23

    On July 8, 2011, the Food and Drug Administration (FDA) approved an expanded age indication for the tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine (Tdap) Boostrix (GlaxoSmithKline Biologicals, Rixensart, Belgium). Originally, Boostrix was licensed in 2005 for persons aged 10 through 18 years, but in 2008, FDA approved an expanded age indication for Boostrix to include persons aged 19 through 64 years. FDA has now expanded the age indication to include persons aged 65 years and older. Boostrix is now licensed for use in persons aged 10 years and older as a single-dose booster vaccination. This notice summarizes the indications for use of Boostrix. Recommendations of the Advisory Committee on Immunization Practices (ACIP) for Tdap vaccines have been published previously. Publication of revised Tdap recommendations within the next year is anticipated.

  9. Presence of human papillomavirus in semen in relation to semen quality.

    PubMed

    Luttmer, Roosmarijn; Dijkstra, Maaike G; Snijders, Peter J F; Hompes, Peter G A; Pronk, Divera T M; Hubeek, Isabelle; Berkhof, Johannes; Heideman, Daniëlle A M; Meijer, Chris J L M

    2016-02-01

    on the speakers bureau of Qiagen and has been a consultant for Roche, DDL Diagnostic Laboratory, GlaxoSmithKline and Merck. D.A.M.H. has been member of the scientific advisory boards of Amgen and Pfizer, and has been on the speakers bureau of Hologic/Gen-Probe. C.J.L.M.M. has been on the speakers bureau of GlaxoSmithKline, Qiagen, Merck, Roche, Menarini and Seegene, has served occasionally on the scientific advisory board of GlaxoSmithKline, Qiagen, Merck, Roche and Genticel, and has occasionally been a consultant for Qiagen. Formerly, C.J.L.M.M. was a minority shareholder of Delphi Biosciences, which bankrupted in 2014. C.J.L.M.M. is a minority shareholder of Diassay B.V. P.J.F.S., D.A.M.H. and C.J.L.M.M. have minority stake in Self-Screen B.V., a spin-off company of VU University Medical Center. R.L., M.G.D., P.G.A.H., D.T.M.P., and I.H. do not have any conflicts of interest to disclose. Not applicable. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  10. An industry update: the latest news in therapeutic delivery.

    PubMed

    Harris, Elaine

    2017-11-01

    The present industry update covers the period 1-31 July 2017. Information was sourced primarily from company press releases, regulatory and patent agencies, scientific literature and various news websites. There was positive approval news this month for GlaxoSmithKline for its new self-injecting treatment for systemic lupus erythematosus but less positive news for Ocular Therapeutix, a new drug application for its treatment for postoperative ocular pain, DEXTENZA™ was rejected for a second time. Endo Pharmaceuticals agreed to withdraw its opioid formulation Opana ® Er due to abuse concerns. Collaborations for novel therapeutic delivery research were announced this month by Takeda and BioSurfaces, Catelent and Rutgers University, Lilly and Purdue University and Titan Pharmaceuticals with Walter Reed and the Southwest Research Institute. A number of companies announced significant financing deals to allow for the clinical development of products with enhanced delivery options including Sebacia and Diasome.

  11. Nuisance Compounds, PAINS Filters, and Dark Chemical Matter in the GSK HTS Collection.

    PubMed

    Chakravorty, Subhas J; Chan, James; Greenwood, Marie Nicole; Popa-Burke, Ioana; Remlinger, Katja S; Pickett, Stephen D; Green, Darren V S; Fillmore, Martin C; Dean, Tony W; Luengo, Juan I; Macarrón, Ricardo

    2018-07-01

    High-throughput screening (HTS) hits include compounds with undesirable properties. Many filters have been described to identify such hits. Notably, pan-assay interference compounds (PAINS) has been adopted by the community as the standard term to refer to such filters, and very useful guidelines have been adopted by the American Chemical Society (ACS) and subsequently triggered a healthy scientific debate about the pitfalls of draconian use of filters. Using an inhibitory frequency index, we have analyzed in detail the promiscuity profile of the whole GlaxoSmithKline (GSK) HTS collection comprising more than 2 million unique compounds that have been tested in hundreds of screening assays. We provide a comprehensive analysis of many previously published filters and newly described classes of nuisance structures that may serve as a useful source of empirical information to guide the design or growth of HTS collections and hit triaging strategies.

  12. Making British cortisone: Glaxo and the development of corticosteroids in Britain in the 1950s-1960s.

    PubMed

    Quirke, Viviane

    2005-12-01

    Following the announcement in 1949 in the USA that cortisone offered rheumatoid arthritis sufferers effective treatment for their crippling disease, the Ministry of Health came under considerable pressure from the medical profession and the public to make cortisone available in Britain. The Ministry, therefore, urged British companies to start manufacturing cortisone. Among the several pharmaceutical firms responding to the Ministry's request, Glaxo's expertise in the field of vitamins gave them a head start. This paper describes the varied and flexible strategy that enabled Glaxo to maintain this head start, and the scientific and technical capabilities which the company subsequently built up, enabling them to dominate the market for corticosteroids in Britain. Among the drugs to emerge out of the Glaxo project to manufacture cortisone, which began in 1950 and later became a wider R&D programme on steroids, was the topical steroid Betnovate, launched in 1963, which remains a best-seller today. However, although it led to successful new products, Glaxo's programme had limitations. The paper identifies a missed opportunity, in the shape of the biosynthetic route to steroid drugs, often considered as a milestone in the development of the new biotechnology. Whether or not this missed opportunity proved costly to the company is uncertain. However, it illustrates the role of technological path-dependence, and the importance of the integration between different scientific disciplines, in this case chemistry and biology, in pharmaceutical innovation.

  13. OOMMPPAA: A Tool To Aid Directed Synthesis by the Combined Analysis of Activity and Structural Data

    PubMed Central

    2014-01-01

    There is an ever increasing resource in terms of both structural information and activity data for many protein targets. In this paper we describe OOMMPPAA, a novel computational tool designed to inform compound design by combining such data. OOMMPPAA uses 3D matched molecular pairs to generate 3D ligand conformations. It then identifies pharmacophoric transformations between pairs of compounds and associates them with their relevant activity changes. OOMMPPAA presents this data in an interactive application providing the user with a visual summary of important interaction regions in the context of the binding site. We present validation of the tool using openly available data for CDK2 and a GlaxoSmithKline data set for a SAM-dependent methyl-transferase. We demonstrate OOMMPPAA’s application in optimizing both potency and cell permeability and use OOMMPPAA to highlight nuanced and cross-series SAR. OOMMPPAA is freely available to download at http://oommppaa.sgc.ox.ac.uk/OOMMPPAA/. PMID:25244105

  14. Updated recommendations for use of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine in adults aged 65 years and older - Advisory Committee on Immunization Practices (ACIP), 2012.

    PubMed

    2012-06-29

    Since 2005, the Advisory Committee on Immunization Practices (ACIP) has recommended a tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine booster dose for all adolescents aged 11 through 18 years (preferred at 11 through 12 years) and for those adults aged 19 through 64 years who have not yet received a dose. In October 2010, despite the lack of an approved Tdap vaccine for adults aged 65 years and older, ACIP recommended that unvaccinated adults aged 65 years and older be vaccinated with Tdap if in close contact with an infant, and that other adults aged 65 years and older may receive Tdap. In July 2011, the Food and Drug Administration (FDA) approved expanding the age indication for Boostrix (GlaxoSmithKline Biologicals, Rixensart, Belgium) to aged 65 years and older. In February 2012, ACIP recommended Tdap for all adults aged 65 years and older. This recommendation supersedes previous Tdap recommendations regarding adults aged 65 years and older.

  15. Use of MenACWY-CRM in adolescents in the United States.

    PubMed

    Black, Steven; Block, Stan L

    2013-03-01

    Adolescents constitute a high-risk group for invasive meningococcal disease. MenACWY-CRM (Menveo, Novartis Vaccines, Cambridge, MA) is a quadrivalent meningococcal conjugate vaccine indicated to prevent invasive meningococcal disease caused by Neisseria meningitidis serogroups A, C, W-135, and Y. It has been approved for use in persons age 2-55 years. The tolerability and immunogenicity of MenACWY-CRM in adolescents have been ascertained in phase 2 and 3 trials against MPSV4 (Menomune, sanofi pasteur, Swiftwater, PA), an unconjugated quadrivalent meningococcal vaccine, and MenACWY-D (Menactra, sanofi pasteur), another conjugated quadrivalent meningococcal vaccine. Clinical trials also have demonstrated that MenACWY-CRM is well tolerated and immunogenic when administered to adolescents concomitantly with the combined tetanus, diphtheria, and acellular pertussis vaccine (Boostrix, GlaxoSmithKline Biologicals, Rixensart, Belgium) and the quadrivalent human papillomavirus vaccine (Gardasil, Merck & Co., Inc., Whitehouse Station, NJ). Copyright © 2013 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

  16. Resource based view of the firm: measures of reputation among health service-sector businesses.

    PubMed

    Smith, Alan D

    2008-01-01

    Application of the strategic leverage of Resource Based View of the Firm (RBV) directly advocates that a company's competitive advantage is derived from its ability to assemble and exploit an appropriate combination of resources (both tangible and intangible assets). The three companies that were selected were Pittsburgh-based companies that were within relatively easy access, representing healthcare service-related industries, and can be reviewed for the principles of the RBV. The particular firms represented a variety of establishments and included Baptist Homes (a long-term care facility), University of Pittsburgh Medical Center (UPMC)(a provider of hospital and other health services), and GlaxoSmithKline, Consumer Healthcare, North America (GSK-CHNA)(a global provider of healthcare products and services). Through the case studies, it was found that not all intangible assets are strategic, and by extension, not all measures of reputation are strategic either. For an intangible asset to be considered strategic, in this case reputation, it must be valuable, rare, imperfectly imitable, and non-substitutable.

  17. Interscience Conference on Antimicrobial Agents and Chemotherapy--49th annual meeting. Part 1. 11-15 September 2009, San Francisco, CA, USA.

    PubMed

    Turner, Ben; Murch, Lisa

    2009-11-01

    The Interscience Conference on Antimicrobial Agents and Chemotherapy held in San Francisco included topics covering new therapeutic developments for the treatment of infectious diseases. This conference report highlights selected presentations on a beta-cyclodextrin derivative for the treatment of Staphylococcus aureus infections, a type 3 secretion system inhibitor for the treatment of Pseudomonas aeruginosa infections, a small-molecule inhibitor of the fungal Hos2 HDAC, a TLR9 agonist used as an adjuvant, a CMV vaccine, a glycopeptide-cephalosporin heterodimer antibiotic, a topical quinolone for the treatment of complicated skin and skin structure infections, a broad-spectrum glycylcycline antibiotic and an HCV RNA replication inhibitor. Investigational drugs discussed include IB-201 (Innovative Biologics Inc), MBX-1641 (Microbiotix Inc), MGCD-290 (MethylGene Inc), agatolimod (Coley Pharmaceutical Group Inc/Pfizer Inc/GlaxoSmithKline plc/Merck & Co Inc/Dynavax Technologies Corp/Novartis AG/Emergent BioSolutions Inc), TD-1792 (Theravance Inc), ozenoxacin (Ferrer Internacional SA/Maruho Co Ltd/Toyama Chemical Co Ltd) and ATI-0810 (Arisyn Therapeutics Inc).

  18. Public health impact of accelerated immunization against rotavirus infection among children aged less than 6 months in the United States

    PubMed Central

    Weycker, Derek; Atwood, Mark Andrew; Standaert, Baudouin; Krishnarajah, Girishanthy

    2014-01-01

    We developed a cohort model to evaluate the expected public health impact of accelerated regimens for immunization against rotavirus gastroenteritis (RVGE). Alternative strategies for vaccination with the pentavalent human-bovine reassortant vaccine, Rotateq® (RV5, Merck) and the oral live attenuated human rotavirus vaccine, Rotarix® (RV1, GlaxoSmithKline Vaccines) were considered, including acceleration of the 1st dose only (by 2 weeks) as well as acceleration of the 1st (by 2 weeks) and subsequent doses (by up to 10 weeks). Assuming vaccine coverage levels consistent with current US clinical practice, accelerated regimens would be expected to reduce annual numbers of RVGE-related hospitalizations by 300–400, emergency department visits by 3000–4000, and outpatient visits by 3000–4000 (i.e., by 9–14%) among US children aged <6 months. Accordingly, accelerating the immunization of children against RVGE may yield substantive reductions in the number of RV-related encounters in US clinical practice. PMID:25424813

  19. Accepting the Invitation to Open Innovation in Malaria Drug Discovery: Synthesis, Biological Evaluation, and Investigation on the Structure-Activity Relationships of Benzo[b]thiophene-2-carboxamides as Antimalarial Agents.

    PubMed

    Pieroni, Marco; Azzali, Elisa; Basilico, Nicoletta; Parapini, Silvia; Zolkiewski, Michal; Beato, Claudia; Annunziato, Giannamaria; Bruno, Agostino; Vacondio, Federica; Costantino, Gabriele

    2017-03-09

    Malaria eradication is a global health priority, but current therapies are not always suitable for providing a radical cure. Artemisinin has paved the way for the current malaria treatment, the so-called Artemisinin-based Combination Therapy (ACT). However, with the detection of resistance to ACT, innovative compounds active against multiple parasite species and at multiple life stages are needed. GlaxoSmithKline has recently disclosed the results of a phenotypic screening of an internal library, publishing a collection of 400 antimalarial chemotypes, termed the "Malaria Box". After analysis of the data set, we have carried out a medicinal chemistry campaign in order to define the structure-activity relationships for one of the released compounds, which embodies a benzothiophene-2-carboxamide core. Thirty-five compounds were prepared, and a description of the structural features responsible for the in vitro activity against different strains of P. falciparum, the toxicity, and the metabolic stability is herein reported.

  20. The Safety of Adjuvanted Vaccines Revisited: Vaccine-Induced Narcolepsy.

    PubMed

    Ahmed, S Sohail; Montomoli, Emanuele; Pasini, Franco Laghi; Steinman, Lawrence

    2016-01-01

    Despite the very high benefit-to-risk ratio of vaccines, the fear of negative side effects has discouraged many people from getting vaccinated, resulting in the reemergence of previously controlled diseases such as measles, pertussis and diphtheria. This fear has been amplified more recently by multiple epidemiologic studies that confirmed the link of an AS03-adjuvanted pandemic influenza vaccine (Pandemrix, GlaxoSmithKline Biologicals, Germany) used in Europe during the 2009 H1N1 influenza pandemic [A(H1N1) pdm09] with the development of narcolepsy, a chronic sleep disorder, in children and adolescents. However, public misperceptions of what adjuvants are and why they are used in vaccines has created in some individuals a closed "black box" attitude towards all vaccines. The focus of this review article is to revisit this "black box" using the example of narcolepsy associated with the European AS03-adjuvanted pandemic influenza vaccine.

  1. Identification of Novel Anti-mycobacterial Compounds by Screening a Pharmaceutical Small-Molecule Library against Nonreplicating Mycobacterium tuberculosis.

    PubMed

    Warrier, Thulasi; Martinez-Hoyos, Maria; Marin-Amieva, Manuel; Colmenarejo, Gonzalo; Porras-De Francisco, Esther; Alvarez-Pedraglio, Ana Isabel; Fraile-Gabaldon, Maria Teresa; Torres-Gomez, Pedro Alfonso; Lopez-Quezada, Landys; Gold, Ben; Roberts, Julia; Ling, Yan; Somersan-Karakaya, Selin; Little, David; Cammack, Nicholas; Nathan, Carl; Mendoza-Losana, Alfonso

    2015-12-11

    Identification of compounds that target metabolically diverse subpopulations of Mycobacterium tuberculosis (Mtb) may contribute to shortening the course of treatment for tuberculosis. This study screened 270,000 compounds from GlaxoSmithKline's collection against Mtb in a nonreplicating (NR) state imposed in vitro by a combination of four host-relevant stresses. Evaluation of 166 confirmed hits led to detailed characterization of 19 compounds for potency, specificity, cytotoxicity, and stability. Compounds representing five scaffolds depended on reactive nitrogen species for selective activity against NR Mtb, and two were stable in the assay conditions. Four novel scaffolds with activity against replicating (R) Mtb were also identified. However, none of the 19 compounds was active against Mtb in both NR and R states. There was minimal overlap between compounds found active against NR Mtb and those previously identified as active against R Mtb, supporting the hypothesis that NR Mtb depends on distinct metabolic pathways for survival.

  2. Comparison of clinical outcomes between laminoplasty, posterior decompression with instrumented fusion, and anterior decompression with fusion for K-line (-) cervical ossification of the posterior longitudinal ligament.

    PubMed

    Koda, Masao; Mochizuki, Makondo; Konishi, Hiroaki; Aiba, Atsuomi; Kadota, Ryo; Inada, Taigo; Kamiya, Koshiro; Ota, Mitsutoshi; Maki, Satoshi; Takahashi, Kazuhisa; Yamazaki, Masashi; Mannoji, Chikato; Furuya, Takeo

    2016-07-01

    The K-line, which is a virtual line that connects the midpoints of the anteroposterior diameter of the spinal canal at C2 and C7 in a plain lateral radiogram, is a useful preoperative predictive indicator for sufficient decompression by laminoplasty (LMP) for ossification of the posterior longitudinal ligament (OPLL). K-line is defined as (+) when the peak of OPLL does not exceed the K-line, and is defined as (-) when the peak of OPLL exceeds the K-line. For patients with K-line (-) OPLL, LMP often results in poor outcome. The aim of the present study was to compare the clinical outcome of LMP, posterior decompression with instrumented fusion (PDF) and anterior decompression and fusion (ADF) for patients with K-line (-) OPLL. The present study included patients who underwent surgical treatment including LMP, PDF and ADF for K-line (-) cervical OPLL. We retrospectively compared the clinical outcome of those patients in terms of Japanese Orthopedic Association score (JOA score) recovery rate. JOA score recovery rate was significantly higher in the ADF group compared with that in the LMP group and the PDF group. The JOA score recovery rate in the PDF group was significantly higher than that in the LMP group. LMP should not be used for K-line (-) cervical OPLL. ADF is one of the suitable surgical treatments for K-line (-) OPLL. Both ADF and PDF are applicable for K-line (-) OPLL according to indications set by each institute and surgical decisions.

  3. Outcome of posterior decompression with instrumented fusion surgery for K-line (-) cervical ossification of the longitudinal ligament.

    PubMed

    Saito, Junya; Maki, Satoshi; Kamiya, Koshiro; Furuya, Takeo; Inada, Taigo; Ota, Mitsutoshi; Iijima, Yasushi; Takahashi, Kazuhisa; Yamazaki, Masashi; Aramomi, Masaaki; Mannoji, Chikato; Koda, Masao

    2016-10-01

    We investigated the outcome of posterior decompression and instrumented fusion (PDF) surgery for patients with K-line (-) ossification of the posterior longitudinal ligament (OPLL) of the cervical spine, who may have a poor surgical prognosis. We retrospectively analyzed the outcome of a series of 27 patients who underwent PDF without correction of cervical alignment for K-line (-) OPLL and were followed-up for at least 1 year after surgery. We had performed double-door laminoplasty followed by posterior instrumented fusion without excessive correction of cervical spine alignment. The preoperative Japanese Orthopedic Association (JOA) score for cervical myelopathy was 8.0 points and postoperative JOA score was 11.9 points on average. The mean JOA score recovery rate was 43.6%. The average C2-C7 angle was 2.2° preoperatively and 3.1° postoperatively. The average maximum occupation ratio of OPLL was 56.7%. In conclusion, PDF without correcting cervical alignment for patients with K-line (-) OPLL showed moderate neurological recovery, which was acceptable considering K-line (-) predicts poor surgical outcomes. Thus, PDF is a surgical option for such patients with OPLL. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Protective Effect of Contemporary Pertussis Vaccines: A Systematic Review and Meta-analysis.

    PubMed

    Fulton, T Roice; Phadke, Varun K; Orenstein, Walter A; Hinman, Alan R; Johnson, Wayne D; Omer, Saad B

    2016-05-01

    Acellular pertussis (aP) and whole-cell (wP) pertussis vaccines are presumed to have similar short-term (<3 years after completion of the primary series) efficacy. However, vaccine effect varies between individual pertussis vaccine formulations, and many originally studied formulations are now unavailable. An updated analysis of the short-term protective effect of pertussis vaccines limited to formulations currently on the market in developed countries is needed. We conducted a systematic review and meta-analysis of published studies that evaluated pertussis vaccine efficacy or effectiveness within 3 years after completion (>3 doses) of a primary series of a currently available aP or wP vaccine formulation. The primary outcome was based on the World Health Organization (WHO) clinical case definitions for pertussis. Study quality was assessed using the approach developed by the Child Health Epidemiology Research Group. We determined overall effect sizes using random-effects meta-analyses, stratified by vaccine (aP or wP) and study (efficacy or effectiveness) type. Meta-analysis of 2 aP vaccine efficacy studies (assessing the 3-component GlaxoSmithKline and 5-component Sanofi-Pasteur formulations) yielded an overall aP vaccine efficacy of 84% (95% confidence interval [CI], 81%-87%). Meta-analysis of 3 wP vaccine effectiveness studies (assessing the Behringwerke, Pasteur/Mérieux, and SmithKline Beecham formulations) yielded an overall wP vaccine effectiveness of 94% (95% CI, 88%-97%) (bothI(2)= 0%). Although all contemporary aP and wP formulations protect against pertussis disease, in this meta-analysis the point estimate for short-term protective effect against WHO-defined pertussis in young children was lower for currently available aP vaccines than wP vaccines. © 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. Ketamine: stimulating antidepressant treatment?

    PubMed

    Malhi, Gin S; Byrow, Yulisha; Cassidy, Frederick; Cipriani, Andrea; Demyttenaere, Koen; Frye, Mark A; Gitlin, Michael; Kennedy, Sidney H; Ketter, Terence A; Lam, Raymond W; McShane, Rupert; Mitchell, Alex J; Ostacher, Michael J; Rizvi, Sakina J; Thase, Michael E; Tohen, Mauricio

    2016-05-01

    The appeal of ketamine - in promptly ameliorating depressive symptoms even in those with non-response - has led to a dramatic increase in its off-label use. Initial promising results await robust corroboration and key questions remain, particularly concerning its long-term administration. It is, therefore, timely to review the opinions of mood disorder experts worldwide pertaining to ketamine's potential as an option for treating depression and provide a synthesis of perspectives - derived from evidence and clinical experience - and to consider strategies for future investigations. G.S.M. Grant/research support: National Health Medical Research Council, NSW Health, Ramsay Health, American Foundation for Suicide Prevention, AstraZeneca, Eli Lilly & Co, Organon, Pfizer, Servier, and Wyeth; has been a speaker for Abbott, AstraZeneca, Eli Lilly & Co, Janssen Cilag, Lundbeck, Pfizer, Ranbaxy, Servier, and Wyeth; consultant: AstraZeneca, Eli Lilly & Co, Janssen Cilag, Lundbeck, and Servier. M.A.F. Grant support: AssureRx, Janssen Research & Development, Mayo Foundation, Myriad, National Institute of Alcohol Abuse and Alcoholism (NIAAA), National Institute of Mental Health (NIMH), Pfizer. Consultant (Mayo): Janssen Research & Development, LLC, Mitsubishi Tanabe Pharma Corporation, Myriad Genetics, Neuralstem Inc., Sunovion, Supernus Pharmaceuticals, Teva Pharmaceuticals. CME/travel support: American Physician Institute, CME Outfitters. Financial interest/Mayo Clinic 2016: AssureRx. S.H.K. Grant/research support: Brain Canada, Bristol Meyer Squibb, CIHR, Janssen, Johnson & Johnson, Lundbeck, Ontario Brain Institute, Pfizer, Servier, St. Jude Medical, Sunovion. T.A.K. Grant/research support (through Stanford University): Sunovion Pharmaceuticals and Merck & Co., Inc.; consultant/advisory board bember: Allergan, Inc., Janssen Pharmaceuticals, Myriad Genetic Laboratories, Inc., and Sunovion Pharmaceuticals; lecture honoraria (not Speaker's Bureau payments): GlaxoSmithKline

  6. Haemophilus influenzae type b-Neisseria meningitidis serogroups C and Y tetanus toxoid conjugate vaccine for infants and toddlers.

    PubMed

    Bryant, Kristina A; Marshall, Gary S

    2011-07-01

    The highest rates of invasive meningococcal disease occur in children under 2 years of age, yet as of early 2011 no vaccine was licensed for the youngest infants. However, a novel vaccine consisting of capsular polysaccharides from Haemophilus influenzae type b (Hib) and Neisseria meningitidis serogroups C and Y conjugated to tetanus toxoid (HibMenCY-TT; MenHibrix, GlaxoSmithKline) is in the late stages of development. In clinical trials involving more than 7800 children, HibMenCY-TT was shown to be safe and immunogenic when administered at 2, 4, 6 and 12-15 months of age. Anti-polyribosylribitol phosphate antibody responses were noninferior to those elicited by licensed monovalent Hib vaccines, and most vaccinees developed bactericidal antibodies against N. meningitidis serogroups C and Y. The majority of subjects retained antibody responses as far as 3 years after vaccination. If licensed, HibMenCY-TT not only represents an incremental option for protection against invasive Hib, but also has the potential to prevent invasive meningococcal disease without increasing the number of injections.

  7. Is PDE4 too difficult a drug target?

    PubMed

    Higgs, Gerry

    2010-05-01

    The search for selective inhibitors of PDE4 as novel anti-inflammatory drugs has continued for more than 30 years. Although several compounds have demonstrated therapeutic effects in diseases such as asthma, COPD, atopic dermatitis and psoriasis, none have reached the market. A persistent challenge in the development of PDE4 inhibitors has been drug-induced gastrointestinal adverse effects, such as nausea. However, extensive clinical trials with well-tolerated doses of roflumilast (Daxas; Nycomed/Mitsubishi Tanabe Pharma Corp/Forest Laboratories Inc) in COPD, a disease that is generally unresponsive to existing therapies, have demonstrated significant therapeutic improvements. In addition, GlaxoSmithKline plc is developing 256066, an inhaled formulation of a PDE4 inhibitor that has demonstrated efficacy in trials in asthma, and apremilast from Celgene Corp has been reported to be effective for the treatment of psoriasis. Despite the challenges and complications that have been encountered during the development of PDE4 inhibitors, these drugs may provide a genuinely novel class of anti-inflammatory agents, and there are several compounds in development that could fulfill that promise.

  8. Predicting the quality of powders for inhalation from surface energy and area.

    PubMed

    Cline, David; Dalby, Richard

    2002-09-01

    To correlate the surface energy of active and carrier components in an aerosol powder to in vitro performance of a passive dry powder inhaler. Inverse gas chromatography (IGC) was used to assess the surface energy of active (albuterol and ipratropium bromide) and carrier (lactose monohydrate, trehalose dihydrate and mannitol) components of a dry powder inhaler formulation. Blends (1%w/w) of drug and carrier were prepared and evaluated for dry powder inhaler performance by cascade impaction. The formulations were tested with either of two passive dry powder inhalers, Rotahaler (GlaxoSmithKline) or Handihaler (Boehringer Ingelheim). In vitro performance of the powder blends was strongly correlated to surface energy interaction between active and carrier components. Plotting fine particle fraction vs. surface energy interaction yielded an R2 value of 0.9283. Increasing surface energy interaction between drug and carrier resulted in greater fine particle fraction of drug. A convincing relationship, potentially useful for rapid formulation design and screening, was found between the surface energy and area parameters derived from IGC and dry powder inhaler performance.

  9. Benchmarks for detecting 'breakthroughs' in clinical trials: empirical assessment of the probability of large treatment effects using kernel density estimation.

    PubMed

    Miladinovic, Branko; Kumar, Ambuj; Mhaskar, Rahul; Djulbegovic, Benjamin

    2014-10-21

    To understand how often 'breakthroughs,' that is, treatments that significantly improve health outcomes, can be developed. We applied weighted adaptive kernel density estimation to construct the probability density function for observed treatment effects from five publicly funded cohorts and one privately funded group. 820 trials involving 1064 comparisons and enrolling 331,004 patients were conducted by five publicly funded cooperative groups. 40 cancer trials involving 50 comparisons and enrolling a total of 19,889 patients were conducted by GlaxoSmithKline. We calculated that the probability of detecting treatment with large effects is 10% (5-25%), and that the probability of detecting treatment with very large treatment effects is 2% (0.3-10%). Researchers themselves judged that they discovered a new, breakthrough intervention in 16% of trials. We propose these figures as the benchmarks against which future development of 'breakthrough' treatments should be measured. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  10. Rotarix in developing countries: paving the way for inclusion in national childhood immunization programs in Africa.

    PubMed

    Pawinski, Robert; Debrus, Serge; Delem, Andrée; Smolenov, Igor; Suryakiran, Pemmaraju V; Han, Htay Htay

    2010-09-01

    Rotavirus gastroenteritis causes more than half a million deaths annually among children aged <5 years, the great majority of which occur in Africa and Asia. Vaccination is considered to be the most effective public health strategy to prevent rotavirus disease and to reduce the significant global burden of rotavirus gastroenteritis. Rotarix (GlaxoSmithKline Biologicals) is an oral, live attenuated rotavirus vaccine derived from a human G1P[8] rotavirus strain. Results of phase III studies in Europe, Latin America, and Asia have shown that Rotarix offers sustained high protection against severe rotavirus gastroenteritis during the first 2 years of life, when disease burden is highest, with broad protection demonstrated against each of the 5 main rotavirus types that circulate globally (G1, G2, G3, G4, and G9). Coupled with the availability of local burden of disease data and promising interim efficacy data from an ongoing study in Malawi and South Africa, this further reinforces the case for introduction of this rotavirus vaccine in national childhood immunization programs in Africa, where rotavirus-related mortality is significant.

  11. The cost-effectiveness of rotavirus vaccination in Malawi.

    PubMed

    Berry, Stephen A; Johns, Benjamin; Shih, Chuck; Berry, Andrea A; Walker, Damian G

    2010-09-01

    Rotarix (GlaxoSmithKline), a newly licensed rotavirus vaccine requiring 2 doses, may have the potential to save hundreds of thousands of lives in Africa. Nations such as Malawi, where Rotarix is currently under phase III investigation, may nevertheless face difficult economic choices in considering vaccine adoption. The cost-effectiveness of implementing a Rotarix vaccine program in Malawi was estimated using published estimates of rotavirus burden, vaccine efficacy, and health care utilization and costs. With 49.5% vaccine efficacy, a Rotarix program could avert 2582 deaths annually. With GAVI Alliance cofinancing, adoption of Rotarix would be associated with a cost of $5.07 per disability-adjusted life-year averted. With market pricing, Rotarix would be associated with a base case cost of $74.73 per disability-adjusted life-year averted. Key variables influencing results were vaccine efficacy, under-2 rotavirus mortality, and program cost of administering each dose. Adopting Rotarix would likely be highly cost-effective for Malawi, particularly with GAVI support. This finding holds true across uncertainty ranges for key variables, including efficacy, for which data are becoming available.

  12. Methods in Clinical Pharmacology Series

    PubMed Central

    Beaumont, Claire; Young, Graeme C; Cavalier, Tom; Young, Malcolm A

    2014-01-01

    Human radiolabel studies are traditionally conducted to provide a definitive understanding of the human absorption, distribution, metabolism and excretion (ADME) properties of a drug. However, advances in technology over the past decade have allowed alternative methods to be employed to obtain both clinical ADME and pharmacokinetic (PK) information. These include microdose and microtracer approaches using accelerator mass spectrometry, and the identification and quantification of metabolites in samples from classical human PK studies using technologies suitable for non-radiolabelled drug molecules, namely liquid chromatography-mass spectrometry and nuclear magnetic resonance spectroscopy. These recently developed approaches are described here together with relevant examples primarily from experiences gained in support of drug development projects at GlaxoSmithKline. The advantages of these study designs together with their limitations are described. We also discuss special considerations which should be made for a successful outcome to these new approaches and also to the more traditional human radiolabel study in order to maximize knowledge around the human ADME properties of drug molecules. PMID:25041729

  13. Brian Smith | NREL

    Science.gov Websites

    Smith Photo of Brian Smith Brian Smith Laboratory Program Manager II - Mechanical Engineering Brian.Smith@nrel.gov | 303-384-6911 Brian Smith is Partnership Manager for the NWTC and focuses on portfolio

  14. Kristin Smith | NREL

    Science.gov Websites

    Smith Photo of Kristin Smith Kristin Smith Thermochemical Process Design Engineer Kristin.Smith @nrel.gov | 303-384-7877 Orcid ID http://orcid.org/0000-0001-6397-031X Research Interests Kristin Smith is a

  15. Can K-Line Predict the Clinical Outcome of Anterior Controllable Antedisplacement and Fusion Surgery for Cervical Myelopathy Caused by Multisegmental Ossification of the Posterior Longitudinal Ligament?

    PubMed

    Sun, Jing Chuan; Zhang, Bin; Shi, Jiangang; Sun, Kai Qiang; Huan, Le; Sun, Xiao Fei; Liu, Ning; Zheng, Bing; Wang, Hai Bo

    2018-04-27

    To analyze the correlation between the K-line-based classification of patients with ossification of the posterior longitudinal ligament (OPLL) and their outcome after anterior controllable antedisplacement and fusion (ACAF) surgery. A series of 24 patients with multisegmental OPLL were enrolled. All patients underwent ACAF surgery. First, the patients were classified into 2 groups according to their K-line classification. Then, we separated the patients into subgroups according to their OPLL thickness. The Japanese Orthopaedic Association scores before and 6 months after surgery were studied, and the recovery rate (RR) was calculated. The preoperative and postoperative radiologic parameters were also investigated. Clinical and radiographic assessments showed no significant correlation between the K-line-based classification of patients with OPLL and their outcome of ACAF surgery (P > 0.05). When the OPLL was ≤6 mm thick, K-line-based classification groups had a similar change of occupation ratio and RR (P > 0.05). However, when the OPLL was >6 mm thick, the mean RR was 61.8% ± 14.0% in the K-line (+) group and 78.3% ± 9.7% in the K-line (-) group (P < 0.05), and the mean was 16.0% ± 4.2% in the K-line (+) group and 28.0% ± 7.1% in the K-line (-) group (P < 0.05). This study shows that K-line can predict the clinical outcome of ACAF surgery for multisegmental OPLL in a different way from posterior decompression surgery. When the OPLL was thin, the outcome was satisfactory and there was no correlation with K-line-based classification of patients with OPLL. When the OPLL was >6 mm thick, the K-line (-) group patients had a better outcome than did K-line (+) group patients. Copyright © 2018 Elsevier Inc. All rights reserved.

  16. Summary of the EMA Joint Regulators/Industry QbD workshop (London, UK; 28-29 January 2014).

    PubMed

    Cook, Graham; France, Georges; Holte, Øyvind; Lorenti, Giampiero; Tainsh, David

    2016-01-01

    This paper summarizes the discussions and insights gained from the key themes that emerged during the Quality by Design (QbD) Workshop held at the European Medicines Agency (EMA) offices in London, UK, on 28-29 January 2014. Industry and regulators shared practical experiences from six case studies (five approved small molecule products and one phase 3 biotechnological product) based on QbD submissions by five companies (AstraZeneca, GlaxoSmithKline, Novartis, NovoNordisk, and Pfizer).The case studies covered a range of different development, regulatory submission, and post-approval aspects of QbD and were developed through confidential discussions between the company representatives and regulators. Key themes that emerged from the workshop discussions were: 1. presentation of information in submissions (development story and the presentation of information in marketing authorization applications; risk assessment and criticality); 2. development aspects (design space; use of models; control strategy); and 3. post-approval aspects (lifecycle management; dossier-quality system interactions; handling of deviations). Many aspects of QbD for biotechnological products are similar to small molecules, but there are some important differences highlighted in this paper.The final section of the paper discusses some proposals for future developments to address the issues that were identified. This paper summarizes the discussions and insights gained from the key themes that emerged during the Quality by Design (QbD) Workshop held at the European Medicines Agency offices in London, UK, on 28-29 January 2014. Industry and regulators shared practical experiences from six case studies (five approved small-molecule products and one phase 3 biotechnological product) based on QbD submissions by five companies (AstraZeneca, GlaxoSmithKline, Novartis, NovoNordisk, and Pfizer).The case studies covered a range of different development, regulatory submission, and post-approval aspects of

  17. Circulating rotavirus genotypes in the Irish paediatric population prior to the introduction of the vaccination programme.

    PubMed

    Yandle, Z; Coughlan, S; Drew, R J; O'Flaherty, N; O'Gorman, J; De Gascun, C

    2017-11-01

    Rotavirus is the leading cause of viral gastroenteritis in children, and it is anticipated that the introduction of the Rotarix™ vaccine (GlaxoSmithKline Biologicals S.A., Rixensart, Belgium) into the Irish immunisation schedule will result in a significant reduction of rotavirus-associated disease. In the pre- and post-vaccination eras, it is important to determine circulating strains of rotavirus to assess vaccine effectiveness, to monitor vaccine failures, and to detect potential emerging strains. This study was a collaboration between the Temple Street Children's University Hospital (TSCUH), Dublin, and the National Virus Reference Laboratory (NVRL), Dublin, to determine the then circulating rotavirus strains in a paediatric hospital. In the 2015/2016 period (July 2015-June 2016) 89 faecal samples from paediatric patients (53 from TSCUH, 36 from other hospitals) were characterised. The results showed G1P[8] to be the predominant genotype (57%), followed by G9P[8] (34%), G4P[8] (6%), G2P[4] (2%), and G12P[8] (1%). This distribution of genotypes is comparable to those found in other European countries prior to vaccination suggesting that the vaccine should be highly efficacious in the Irish population.

  18. Epidemiological trends for hospital admissions for acute rotavirus gastroenteritis in Belgium following the introduction of routine rotavirus vaccination and the subsequent switch from lyophilized to liquid formulation of Rotarix™.

    PubMed

    Raes, M; Strens, D; Kleintjens, J; Biundo, E; Morel, T; Vyse, A

    2016-10-01

    This study describes epidemiological trends for acute rotavirus gastroenteritis (RVGE) in Belgium in children aged ⩽5 years during the period June 2007 to May 2014 after the introduction of routine rotavirus (RV) vaccination. This period encompassed the switch from lyophilized to the liquid formulation of Rotarix™ (GlaxoSmithKline, Belgium) in August 2011. Uptake of RV vaccine remained consistently high throughout the study period with Rotarix the brand most often used. RV was present in 9% (1139/12 511) of hospitalized cases with acute gastroenteritis included in the study. Epidemiological trends for hospital admissions for RVGE remained consistent throughout the study period, with no evidence of any change associated with the switch from lyophilized to liquid formulation of Rotarix. This suggests both formulations perform similarly, with the liquid formulation not inferior regarding ability to reduce hospital admissions for acute RVGE in children aged ⩽5 years. A strong seasonal effect was observed with most RVGE occurring in the winter months but with some variability in intensity, with highest incidence found in those aged 6-24 months. The main observation was the decreased number of hospital admissions for RVGE in Belgium that occurred during winter 2013/2014.

  19. Effects of a denture adhesive in edentulous patients after maxillectomy.

    PubMed

    Sumita, Yuka I; Otomaru, Takafumi; Taniguchi, Hisashi

    2012-06-01

    The objective of this study is to evaluate the usefulness of a denture adhesive in edentulous patients after maxillectomy. Maxillectomy patients suffer from functional impairments. Denture adhesives (DAs) are the solution in such patients. However, little is known about DAs in maxillectomy patients. Eight edentulous patients who had undergone maxillectomy were included and divided into three groups. Group 1 (half ≤ remaining residual maxilla), Group 2 (quarter < remaining residual maxilla < half) and Group 3 (remaining residual maxilla ≤ quarter). They were evaluated by a speech intelligibility test and a mixing ability test, respectively. A cream-type DA called New Poligrip(®) (GlaxoSmithKline, Tokyo, Japan) was used. Applying the DA, speech intelligibility showed a higher score than the data without DA. The effects of using a DA depend on the amount of the remaining residual maxilla. Our study showed that if the remaining residual maxilla is less than a quarter (Group 3), it is difficult to have confidence in the effectiveness of the DA to improve masticatory function. On the other hand, the use a DA showed improved speech intelligibility test values in all groups. © 2011 The Gerodontology Society and John Wiley & Sons A/S.

  20. Augmentin duo™ in the treatment of childhood blepharokeratoconjunctivitis.

    PubMed

    Cehajic-Kapetanovic, Jasmina; Kwartz, Jeff

    2010-01-01

    To report the use of Augmentin Duo 400/57 (GlaxoSmithKline, Middlesex, UK) in the treatment of childhood blepharokeratoconjunctivitis (BKC). This is a retrospective interventional case series. The case notes of 7 consecutive patients treated with Augmentin Duo 400/57 for BKC during 18 months were reviewed. Diagnostic criteria for BKC were blepharitis including recurrent chalazia and meibomian gland dysfunction, eyelid margin telangiectasia and facial rosacea, recurrent episodes of chronic red eye, photophobia, watering, punctate superficial keratopathy, corneal neovascularization, and corneal ulcers. Seven children (age range: 6 to 14 years) were diagnosed as having BKC. All children received systemic Augmentin Duo 400/57 and showed considerable improvement within the first month of therapy. Six children had no recurrences during a mean follow-up of 6 months. No patients experienced any side effects from this treatment. Augmentin Duo 400/57 has not previously been reported in the treatment of BKC in children. In this case series, Augmentin Duo 400/57 proved to be at least as effective as current treatments with systemic erythromycin or doxycycline with the advantage of a twice-daily dosage and a superior side-effect profile. Copyright 2010, SLACK Incorporated.

  1. Current safety issues with quadrivalent meningococcal conjugate vaccines.

    PubMed

    Myers, Tanya R; McNeil, Michael M

    2018-05-04

    Invasive meningococcal disease, although rare, can present as sudden, life-threatening disease with high risk of mortality or severe long-term sequelae. The main prevention strategy for invasive meningococcal disease in the United States is the routine vaccination of adolescents and other persons at increased risk of meningococcal disease with quadrivalent meningococcal conjugate vaccines. Two such vaccines are currently licensed and available in the United States, Menactra® (Sanofi Pasteur) and Menveo® (GlaxoSmithKline), and usage in the adolescent population has steadily increased since their introduction. Although early reports raised concerns about a possible association of Menactra with Guillain-Barré syndrome, a comprehensive safety review determined that if such risk existed it was no more than 0.66 cases per 1 million vaccinations. More recently, a study found an elevated risk of Bell's palsy when Menveo was administered concomitantly with other vaccines but no association was found when the vaccine was administered alone. In this commentary, we describe the current state of knowledge with respect to the safety of quadrivalent meningococcal conjugate vaccines, and we identify potential areas for safety research for these vaccines.

  2. [Narcolepsy with cataplexy: an autoimmune disease?].

    PubMed

    Jacob, Louis; Dauvilliers, Yves

    2014-12-01

    Narcolepsy type 1 (also named narcolepsy-cataplexy or hypocretin deficiency syndrome) is a rare sleep disorder characterized by excessive daytime sleepiness and cataplexy, plus frequently hypnagogic hallucinations, sleep paralysis and nocturnal sleep disturbances. Narcolepsy type 1 is an immune system-associated disease linked with the destruction of 70.000-90.000 hypocretin neurons notably involved in wakefulness. Among narcoleptic patients, 98% are positive for HLA-DQB1*06:02, a HLA class II allele, against 20-25% in general population. Individuals carrying HLA-DQB1*06:02 have an extraordinary risk to develop narcolepsy (odd ratio: 251). Other genes involved in CD4+ T cells and immune system activation as T-cell receptor α are also associated with narcolepsy. The development of the disease is linked with environmental factors such as influenza and streptococcal infections. Narcolepsy type 1 incidence also increased in Europe following the use of Pandemrix, a 2009 H1N1 AS03-adjuvanted vaccine manufactured by GlaxoSmithKline. Interestingly, such increase was not observed with Arepanrix, another vaccine developed by GSK very similar to Pandemrix. © 2014 médecine/sciences – Inserm.

  3. Essential health care package for children--the 'Fit for School' program in the Philippines.

    PubMed

    Monse, Bella; Naliponguit, Ella; Belizario, Vincente; Benzian, Habib; van Helderman, Wim Palenstein

    2010-04-01

    High prevalence of poverty diseases such as diarrhoea, respiratory tract infection, parasitic infections and dental caries among children in the developing world calls for a return to primary health care principles with a focus on prevention. The 'Fit for School' program in the Philippines is based on international recommendations and offers a feasible, low-cost and realistic strategy using the principles of health promotion outlined in the Ottawa Charter. The cornerstone of the programme is the use of school structures for the implementation of preventive health strategies. 'Fit for School' consists of simple, evidence-based interventions like hand washing with soap, tooth brushing with fluoride toothpaste and other high impact interventions such as bi-annual de-worming as a routine school activity for all children visiting public elementary schools. The programme has been successfully rolled-out in the Philippines covering 630,000 children in 22 provinces and it is planned to reach 6 million children in the next three years. The programme is a partnership project between the Philippine Department of Education and the Local Government Units with support for capacity development activities from the German Development Cooperation and GlaxoSmithKline.

  4. Interview: partnering with the industry: the Olympic laboratory model.

    PubMed

    Cowan, David A; Barker, Campbell P

    2012-07-01

    Centre undertook the sample analysis during the 2002 Manchester Commonwealth Games and Cowan was Co-Director of the laboratory for the Commonwealth Games in Kuala Lumpur in 1998. Cowan, who has directed the laboratory at King's College London for many years, was a member of the bid team making the presentation to the International Olympic Committee in February 2005. Campbell P Barker has been leading GlaxoSmithKline's delivery of the London 2012 laboratory services since September 2009. Prior to that time he was Director of Global Strategic Projects in GlaxoSmithKline's Consumer Healthcare business from 2006, and from 1994 to 2006 he worked in R&D for Procter & Gamble. Barker holds a PhD in chemistry from the University of Durham.

  5. Blood eosinophil count and pneumonia risk in patients with chronic obstructive pulmonary disease: a patient-level meta-analysis.

    PubMed

    Pavord, Ian D; Lettis, Sally; Anzueto, Antonio; Barnes, Neil

    2016-09-01

    Inhaled corticosteroids are important in the management of chronic obstructive pulmonary disease (COPD), but can slightly increase the risk of pneumonia in patients with moderate-to-severe COPD. Patients with circulating eosinophil counts of 2% or more of blood leucocytes respond better to inhaled corticosteroids than do those with counts of less than 2% and it was therefore postulated that blood eosinophil count might also have an effect on the risk of pneumonia in patients with COPD. In this post-hoc meta-analysis, we investigate whether a 2% threshold can identify patients who differ in their risk of pneumonia, irrespective of inhaled corticosteroid treatment. From the GlaxoSmithKline trial registry, we selected randomised, double-blind, clinical trials of patients with COPD that had: inhaled corticosteroid arms (fluticasone propionate and salmeterol or fluticasone furoate and vilanterol); a control arm (not given inhaled fluticasone); and pre-randomisation measurements of blood eosinophil counts and were of at least 24 weeks in duration. With use of specified terms from the Medical Dictionary for Regulatory Activities we identified pneumonia adverse events in patient-level data. We calculated number of patients with pneumonia events, stratified by baseline blood eosinophil count (<2% vs ≥2% of blood leucocytes) and whether or not patients had received inhaled corticosteroids. We identified ten trials (conducted between 1998 and 2011), with eosinophil count data available for 10 861 patients with COPD. 4043 patients had baseline blood eosinophil counts of less than 2% and 6818 patients had baseline blood eosinophil counts of 2% or more. 149 (3·7%) patients with counts less than 2% had one or more pneumonia adverse events compared with 215 (3·2%) with counts of 2% or more (hazard ratio [HR] 1·31; 95% CI 1·06-1·62). In patients not treated with inhaled corticosteroids, 40 (3·8%) patients with less than 2% blood eosinophil counts had a pneumonia event

  6. Carrington Maps of Ca II K-Line Emission for the Years 1915-1985

    DTIC Science & Technology

    2011-03-03

    contained relatively large numbers of faculae (Sheeley 2008) 6 The Astrophysical Journal, 730:51 (17pp), 2011 March 20 Sheeley, Cooper, & Anderson...The Astrophysical Journal, 730:51 (17pp), 2011 March 20 doi:10.1088/0004-637X/730/1/51 Copyright is not claimed for this article. All rights reserved... Astrophysical Journal, 730:51 (17pp), 2011 March 20 14. ABSTRACT We have used Mount Wilson Observatory calcium K-line images, digitized and flat fielded by the

  7. A practical derivatization LC/MS approach for determination of trace level alkyl sulfonates and dialkyl sulfates genotoxic impurities in drug substances.

    PubMed

    An, Jianguo; Sun, Mingjiang; Bai, Lin; Chen, Ted; Liu, David Q; Kord, Alireza

    2008-11-04

    Derivatization LC/MS methodology has been developed for the determination of a group of commonly encountered alkyl esters of sulfonates or sulfates in drug substances at low ppm levels. This general method uses trimethylamine as the derivatizing reagent for ethyl/propyl/isopropyl esters and triethylamine for methyl esters. The resulting quaternary ammonium derivatization products are highly polar (ionic) and can be retained by a hydrophilic interaction liquid chromatography (HILIC) column and readily separated from the main interfering active pharmaceutical ingredient (API) peak that is usually present at very high concentration. The method gives excellent sensitivity for all the alkyl esters at typical target analyte level of 1-2 ppm when the API samples were prepared at 5mg/mL. The recoveries at 1-2 ppm were generally above 85% for all the alkyl esters in the various APIs tested. The injection precisions of the lowest concentration standards were excellent with R.S.D.=0.4-4%. A linear range for concentrations from 0.2 to 20 ppm has been established with R(2)>or=0.99. This general method has been tested in a number of API matrices and used successfully for determination of alkyl sulfonates or dialkyl sulfates in support of API batch releases at GlaxoSmithKline.

  8. Use of MenACWY-CRM vaccine in children aged 2 through 23 months at increased risk for meningococcal disease: recommendations of the Advisory Committee on Immunization Practices, 2013.

    PubMed

    MacNeil, Jessica R; Rubin, Lorry; McNamara, Lucy; Briere, Elizabeth C; Clark, Thomas A; Cohn, Amanda C

    2014-06-20

    During its October 2013 meeting, the Advisory Committee on Immunization Practices (ACIP) recommended use of a third meningococcal conjugate vaccine, MenACWY-CRM (Menveo, Novartis), as an additional option for vaccinating infants aged 2 through 23 months at increased risk for meningococcal disease. MenACWY-CRM is the first quadrivalent meningococcal conjugate vaccine licensed for use in children aged 2 through 8 months. MenACWY-D (Menactra, Sanofi Pasteur) is recommended for use in children aged 9 through 23 months who are at increased risk for meningococcal disease, and Hib-MenCY-TT (MenHibrix, GlaxoSmithKline) is recommended for use in children aged 6 weeks through 18 months at increased risk. This report summarizes information on MenACWY-CRM administration in infants and provides recommendations for vaccine use in infants aged 2 through 23 months who are at increased risk for meningococcal disease. Because the burden of meningococcal disease in infants is low in the United States and the majority of cases that do occur are caused by serogroup B, which is not included in any vaccine licensed in the United States, only those infants who are at increased risk for meningococcal disease are recommended to receive a meningococcal vaccine.

  9. Implementation of Rotavirus Surveillance and Vaccine Introduction - World Health Organization African Region, 2007-2016.

    PubMed

    Mwenda, Jason M; Burke, Rachel M; Shaba, Keith; Mihigo, Richard; Tevi-Benissan, Mable Carole; Mumba, Mutale; Biey, Joseph Nsiari-Muzeyi; Cheikh, Dah; Poy MSc, Alain; Zawaira, Felicitas R; Aliabadi, Negar; Tate, Jacqueline E; Hyde, Terri; Cohen, Adam L; Parashar, Umesh D

    2017-11-03

    Rotavirus is a leading cause of severe pediatric diarrhea globally, estimated to have caused 120,000 deaths among children aged <5 years in sub-Saharan Africa in 2013 (1). In 2009, the World Health Organization (WHO) recommended rotavirus vaccination for all infants worldwide (2). Two rotavirus vaccines are currently licensed globally: the monovalent Rotarix vaccine (RV1, GlaxoSmithKline; 2-dose series) and the pentavalent RotaTeq vaccine (RV5, Merck; 3-dose series). This report describes progress of rotavirus vaccine introduction (3), coverage (using estimates from WHO and the United Nations Children's Fund [UNICEF]) (4), and impact on pediatric diarrhea hospitalizations in the WHO African Region. By December 2016, 31 (66%) of 47 countries in the WHO African Region had introduced rotavirus vaccine, including 26 that introduced RV1 and five that introduced RV5. Among these countries, rotavirus vaccination coverage (completed series) was 77%, according to WHO/UNICEF population-weighted estimates. In 12 countries with surveillance data available before and after vaccine introduction, the proportion of pediatric diarrhea hospitalizations that were rotavirus-positive declined 33%, from 39% preintroduction to 26% following rotavirus vaccine introduction. These results support introduction of rotavirus vaccine in the remaining countries in the region and continuation of rotavirus surveillance to monitor impact.

  10. Development of a high-throughput screen to detect inhibitors of TRPS1 sumoylation.

    PubMed

    Brandt, Martin; Szewczuk, Lawrence M; Zhang, Hong; Hong, Xuan; McCormick, Patricia M; Lewis, Tia S; Graham, Taylor I; Hung, Sunny T; Harper-Jones, Amber D; Kerrigan, John J; Wang, Da-Yuan; Dul, Edward; Hou, Wangfang; Ho, Thau F; Meek, Thomas D; Cheung, Mui H; Johanson, Kyung O; Jones, Christopher S; Schwartz, Benjamin; Kumar, Sanjay; Oliff, Allen I; Kirkpatrick, Robert B

    2013-06-01

    Small ubiquitin-like modifier (SUMO) belongs to the family of ubiquitin-like proteins (Ubls) that can be reversibly conjugated to target-specific lysines on substrate proteins. Although covalently sumoylated products are readily detectible in gel-based assays, there has been little progress toward the development of robust quantitative sumoylation assay formats for the evaluation of large compound libraries. In an effort to identify inhibitors of ubiquitin carrier protein 9 (Ubc9)-dependent sumoylation, a high-throughput fluorescence polarization assay was developed, which allows detection of Lys-1201 sumoylation, corresponding to the major site of functional sumoylation within the transcriptional repressor trichorhino-phalangeal syndrome type I protein (TRPS1). A minimal hexapeptide substrate peptide, TMR-VVK₁₂₀₁TEK, was used in this assay format to afford high-throughput screening of the GlaxoSmithKline diversity compound collection. A total of 728 hits were confirmed but no specific noncovalent inhibitors of Ubc9 dependent trans-sumoylation were found. However, several diaminopyrimidine compounds were identified as inhibitors in the assay with IC₅₀ values of 12.5 μM. These were further characterized to be competent substrates which were subject to sumoylation by SUMO-Ubc9 and which were competitive with the sumoylation of the TRPS1 peptide substrates.

  11. A malaria vaccine for travelers and military personnel: Requirements and top candidates.

    PubMed

    Teneza-Mora, Nimfa; Lumsden, Joanne; Villasante, Eileen

    2015-12-22

    Malaria remains an important health threat to non-immune travelers with the explosive growth of global travel. Populations at high risk of acquiring malaria infections include once semi-immune travelers who visit friends and relatives, military forces, business travelers and international tourists with destinations to sub-Saharan Africa, where malaria transmission intensity is high. Most malaria cases have been associated with poor compliance with existing preventive measures, including chemoprophylaxis. High risk groups would benefit immensely from an efficacious vaccine to protect them against malaria infection and together make up a sizable market for such a vaccine. The attributes of an ideal malaria vaccine for non-immune travelers and military personnel include a protective efficacy of 80% or greater, durability for at least 6 months, an acceptable safety profile and compatibility with existing preventive measures. It is very likely that a malaria vaccine designed to effectively prevent infection and clinical disease in the non-immune traveler and military personnel will also protect semi-immune residents of malaria-endemic areas and contribute to malaria elimination by reducing or blocking malaria transmission. The RTS,S vaccine (GlaxoSmithKline) and the PfSPZ Vaccine (Sanaria Inc) are the leading products that would make excellent vaccine candidates for these vulnerable populations. Published by Elsevier Ltd.

  12. Rational design of HIV vaccine and microbicides: report of the EUROPRISE annual conference.

    PubMed

    Wahren, Britta; Biswas, Priscilla; Borggren, Marie; Coleman, Adam; Da Costa, Kelly; De Haes, Winni; Dieltjens, Tessa; Dispinseri, Stefania; Grupping, Katrijn; Hallengärd, David; Hornig, Julia; Klein, Katja; Mainetti, Lara; Palma, Paolo; Reudelsterz, Marc; Seifried, Janna; Selhorst, Philippe; Sköld, Annette; Uchtenhagen, Hannes; van Gils, Marit J; Weber, Caroline; Shattock, Robin; Scarlatti, Gabriella

    2010-07-26

    EUROPRISE is a Network of Excellence sponsored from 2007 to 2011 by the European Commission within the 6th Framework Program. The Network encompasses a wide portfolio of activities ranging from an integrated research program in the field of HIV vaccines and microbicides to training, dissemination and advocacy. The research program covers the whole pipeline of vaccine and microbicide development from discovery to early clinical trials. The Network is composed of 58 partners representing more than 65 institutions from 13 European countries; it also includes three major pharmaceutical companies (GlaxoSmithKline, Novartis and Sanofi-Pasteur) involved in HIV microbicide and vaccine research. The Network displays a dedicated and informative web page: http://www.europrise.org. Finally, a distinguishing trait of EUROPRISE is its PhD School of students from across Europe, a unique example in the world of science aimed at spreading excellence through training. EUROPRISE held its second annual conference in Budapest in November, 2009. The conference had 143 participants and their presentations covered aspects of vaccine and microbicide research, development and discovery. Since training is a major task of the Network, the students of the EUROPRISE PhD program summarized certain presentations and their view of the conference in this paper.

  13. Rational design of HIV vaccine and microbicides: report of the EUROPRISE annual conference

    PubMed Central

    2010-01-01

    EUROPRISE is a Network of Excellence sponsored from 2007 to 2011 by the European Commission within the 6th Framework Program. The Network encompasses a wide portfolio of activities ranging from an integrated research program in the field of HIV vaccines and microbicides to training, dissemination and advocacy. The research program covers the whole pipeline of vaccine and microbicide development from discovery to early clinical trials. The Network is composed of 58 partners representing more than 65 institutions from 13 European countries; it also includes three major pharmaceutical companies (GlaxoSmithKline, Novartis and Sanofi-Pasteur) involved in HIV microbicide and vaccine research. The Network displays a dedicated and informative web page: http://www.europrise.org. Finally, a distinguishing trait of EUROPRISE is its PhD School of students from across Europe, a unique example in the world of science aimed at spreading excellence through training. EUROPRISE held its second annual conference in Budapest in November, 2009. The conference had 143 participants and their presentations covered aspects of vaccine and microbicide research, development and discovery. Since training is a major task of the Network, the students of the EUROPRISE PhD program summarized certain presentations and their view of the conference in this paper. PMID:20659333

  14. Application of simple mathematical expressions to relate the half-lives of xenobiotics in rats to values in humans.

    PubMed

    Ward, Keith W; Erhardt, Paul; Bachmann, Kenneth

    2005-01-01

    Previous publications from GlaxoSmithKline and University of Toledo laboratories convey our independent attempts to predict the half-lives of xenobiotics in humans using data obtained from rats. The present investigation was conducted to compare the performance of our published models against a common dataset obtained by merging the two sets of rat versus human half-life (hHL) data previously used by each laboratory. After combining data, mathematical analyses were undertaken by deploying both of our previous models, namely the use of an empirical algorithm based on a best-fit model and the use of rat-to-human liver blood flow ratios as a half-life correction factor. Both qualitative and quantitative analyses were performed, as well as evaluation of the impact of molecular properties on predictability. The merged dataset was remarkably diverse with respect to physiochemical and pharmacokinetic (PK) properties. Application of both models revealed similar predictability, depending upon the measure of stipulated accuracy. Certain molecular features, particularly rotatable bond count and pK(a), appeared to influence the accuracy of prediction. This collaborative effort has resulted in an improved understanding and appreciation of the value of rats to serve as a surrogate for the prediction of xenobiotic half-lives in humans when clinical pharmacokinetic studies are not possible or practicable.

  15. Innovations for the future of pharmacovigilance.

    PubMed

    Almenoff, June S

    2007-01-01

    Post-marketing pharmacovigilance involves the review and management of safety information from many sources. Among these sources, spontaneous adverse event reporting systems are among the most challenging and resource-intensive to manage. Traditionally, efforts to monitor spontaneous adverse event reporting systems have focused on review of individual case reports. The science of pharmacovigilance could be enhanced with the availability of systems-based tools that facilitate analysis of aggregate data for purposes of signal detection, signal evaluation and knowledge management. GlaxoSmithKline (GSK) recently implemented Online Signal Management (OSM) as a data-driven framework for managing the pharmacovigilance of marketed products. This pioneering work builds upon the strong history GSK has of innovation in this area. OSM is a software application co-developed by GSK and Lincoln Technologies that integrates traditional pharmacovigilance methods with modern quantitative statistical methods and data visualisation tools. OSM enables the rapid identification of trends from the individual adverse event reports received by GSK. OSM also provides knowledge-management tools to ensure the successful tracking of emerging safety issues. GSK has developed standard procedures and 'best practices' around the use of OSM to ensure the systematic evaluation of complex safety datasets. In summary, the implementation of OSM provides new tools and efficient processes to advance the science of pharmacovigilance.

  16. Persistence of T-cell immune response induced by two acellular pertussis vaccines in children five years after primary vaccination.

    PubMed

    Palazzo, Raffaella; Carollo, Maria; Bianco, Manuela; Fedele, Giorgio; Schiavoni, Ilaria; Pandolfi, Elisabetta; Villani, Alberto; Tozzi, Alberto E; Mascart, Françoise; Ausiello, Clara M

    2016-01-01

    The resurgence of pertussis suggests the need for greater efforts to understand the long-lasting protective responses induced by vaccination. In this paper we dissect the persistence of T memory responses induced by primary vaccination with two different acellular pertussis (aP) vaccines, hexavalent Hexavac® vaccine (Hexavac) (Sanofi Pasteur MSD) and Infanrix hexa® (Infanrix) (Glaxo-SmithKline Biologicals). We evaluated magnitude and duration of T-cell responses to pertussis toxin (PT) by measuring T-cell proliferation, cytokines (IL-2 and IFNγ) production and memory subsets in two groups of children 5 years after primary vaccination. Some of the enrolled children received only primary vaccination, while others had the pre-school boost dose. Positive T-cell responses to PT were detected in 36% of children. Percentage of responsive children, T-cell proliferation and CD4IL-2+ cells were significantly higher in the children primed with Hexavac than in those who received Infanrix vaccine. No major effects of the boost on PT-specific proliferation were observed. Overall, our data documented a persistence of T-cell memory against PT in a minor fraction of children 5 years after primary vaccination. The different responses induced by Hexavac and Infanrix vaccine could rely on differences in PT inactivation process or excipients/adjuvants formulations.

  17. Associations of centrally acting ACE inhibitors with cognitive decline and survival in Alzheimer's disease.

    PubMed

    Fazal, Karim; Perera, Gayan; Khondoker, Mizanur; Howard, Robert; Stewart, Robert

    2017-07-01

    Cognitive improvement has been reported in patients receiving centrally acting angiotensin-converting enzyme inhibitors (C-ACEIs). To compare cognitive decline and survival after diagnosis of Alzheimer's disease between people receiving C-ACEIs, non-centrally acting angiotensin-converting enzyme inhibitors (NC-ACEIs), and neither. Routine Mini-Mental State Examination (MMSE) scores were extracted in 5260 patients receiving acetylcholinesterase inhibitors and analysed against C-/NC-ACEI exposure at the time of Alzheimer's disease diagnosis. In the 9 months after Alzheimer's disease diagnosis, MMSE scores significantly increased by 0.72 and 0.19 points per year in patients on C-ACEIs and neither respectively, but deteriorated by 0.61 points per year in those on NC-ACEIs. There were no significant group differences in score trajectories from 9 to 36 months and no differences in survival. In people with Alzheimer's disease receiving acetylcholinesterase inhibitors, those also taking C-ACEIs had stronger initial improvement in cognitive function, but there was no evidence of longer-lasting influence on dementia progression. R.S. has received research funding from Pfizer, Lundbeck, Roche, Janssen and GlaxoSmithKline. © The Royal College of Psychiatrists 2017. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license.

  18. Predictors of Appropriate Pharmacotherapy Management of COPD Exacerbations and Impact on 6-Month Readmission.

    PubMed

    Tran, Melody; Xiang, Pin; Rascati, Karen L; Stock, Eileen M; Godley, Paul J; Coleman, Amber; Bogart, Michael R; Stanford, Richard H

    2016-10-01

    %) received PCE-D; and 229 (61%) received both. Patients were more likely to receive PCE with an index inpatient visit as compared with an ED visit (PCE-C: RR = 2.25, 95% CI = 1.21-4.17, P = 0.010; PCE-D: RR = 1.90, 95% CI = 1.01-3.58, P = 0.048). Those with previous use of rescue medication were also more likely to receive PCE (PCE-C: RR = 1.88, 95% CI = 1.12-3.17, P = 0.018; PCE-D: RR = 2.11, 95% CI = 1.16-3.83, P = 0.014). Patients with greater adherence (proportion of days covered [PDC] ≥ 75%) to COPD maintenance medication before admission (RR = 8.67, 95% CI = 1.60-46.78, P = 0.012) were also more likely to receive PCE-D. Older patients were more likely to have a COPD-related readmission (RR = 1.07, 95% CI = 1.01-1.13, P = 0.028), while use of maintenance medication before admission was associated with lower risk of an all-cause readmission (RR = 0.49, 95% CI = 0.30-0.79, P = 0.004). In addition, patients with higher medical and pharmacy costs before the index event were more likely to have all-cause readmission (RR = 1.01, 95% CI = 1.00-1.02, P = 0.013). Receipt of PCE was not shown to be a significant predictor of all-cause or COPD-related readmission. The use of bronchodilators and systemic corticosteroids after a COPD-related inpatient or ED visit may be related to the severity of the index COPD exacerbation or patients' previous pattern of bronchodilator use. However, the use of maintenance medication before the index event was associated with a significant reduction in all-cause readmission, so proper treatment of the underlying disease may be an effective strategy in reducing readmission. Funding for this study was provided by GlaxoSmithKline (HO-14-15081). Tran was a Fellow at Scott & White Health Plan (SWHP) during year 1 of this study and a Fellow at Novartis during year 2 of this study. Novartis did not have any input in this study nor did it contribute any funding or support for this research. Tran, Xiang, Godley, and Stock were employed by SWHP at the time

  19. The Devil in Mr. Smith: A Conversation with Jonathan Z. Smith

    ERIC Educational Resources Information Center

    Smith, Jonathan Z.; Pearson, Thomas; Gallagher, Eugene V.; Jensen, Tim; Fujiwara, Satoko

    2014-01-01

    This interview was recorded in November 2012 in Jonathan Z. Smith's Hyde Park graystone. Professor Smith offers insights into how he thinks about his classroom teaching and his students' learning through descriptions of various assignments and classroom activities he has developed over more than forty years of teaching. The discussion…

  20. Intravenous zanamivir or oral oseltamivir for hospitalised patients with influenza: an international, randomised, double-blind, double-dummy, phase 3 trial.

    PubMed

    Marty, Francisco M; Vidal-Puigserver, Joan; Clark, Carol; Gupta, Sandeep K; Merino, Esperanza; Garot, Denis; Chapman, Marianne J; Jacobs, Frédérique; Rodriguez-Noriega, Eduardo; Husa, Petr; Shortino, Denise; Watson, Helen A; Yates, Phillip J; Peppercorn, Amanda F

    2017-02-01

    Neuraminidase inhibitors are effective for the treatment of acute uncomplicated influenza. However, there is an unmet need for intravenous treatment for patients admitted to hospital with severe influenza. We studied whether intravenous zanamivir was a suitable treatment in this setting. In this international, randomised, double-blind, double-dummy, phase 3 trial, we recruited patients aged 16 years or older with severe influenza admitted to 97 hospitals from 26 countries. We randomly assigned patients (1:1:1 stratified by symptom onset ≤4 days or 5-6 days) to receive 300 mg or 600 mg intravenous zanamivir, or standard-of-care (75 mg oral oseltamivir) twice a day for 5-10 days; patients were followed up for 28 days. The randomisation schedule, including stratification, was generated using GlaxoSmithKline's RandAll software. Patients, site study staff, and sponsor were masked to study treatment. The primary endpoint was time to clinical response-a composite of vital sign stabilisation and hospital discharge-in the influenza-positive population. The trial was powered to show an improvement of 1·5 days or greater with 600 mg intravenous zanamivir. Pharmacokinetic, safety, and virology endpoints were also assessed. This trial is registered with ClinicalTrials.gov, number NCT01231620. Between Jan 15, 2011, and Feb 12, 2015, 626 patients were randomly assigned to receive 300 mg intravenous zanamivir (n=201), 600 mg intravenous zanamivir (n=209), or 75 mg oral oseltamivir (n=205) twice a day; 11 patients discontinued the study before receiving any study treatment. 488 (78%) of 626 patients had laboratory-confirmed influenza. Compared with a median time to clinical response of 5·14 days in the 600 mg intravenous zanamivir group, the median time to clinical response was 5·87 days (difference of -0·73 days, 95% CI -1·79 to 0·75; p=0·25) in the 300 mg intravenous zanamivir group and 5·63 days (difference of -0·48 days, 95% CI -2·11 to 0·97; p=0·39) in the

  1. Adam Smith and dependency.

    PubMed

    Ozler, Sule

    2012-06-01

    The focus of this paper is the works and life of Adam Smith, who is widely recognized as the father and founder of contemporary economics. Latent content analysis is applied to his seminal text in economics, An Inquiry into the Nature and Causes of the Wealth of Nations (1776). The results reveal that Smith considers dependence on others a problem and sees the solution to this problem in impersonalized interdependence. In addition, his views on social dependency and personal dependency, reflected in his Lectures on Jurisprudence (1963) and The Theory of Moral Sentiments (1759), are analyzed. This analysis suggests a central tension between dependence and independence in Smith's writings. The personal dependency patterns he exhibited in his life, which also suggest a tension between dependence and independence, are identified through a reading of his biographies. Based on insights from psychoanalytic literature, this paper proposes that developing the ideas in the Wealth of Nations was part of Smith's creative solution to this tension. In particular, his solution to one individual's dependence on another was through a system of impersonalized interdependence. In other words, Smith defended against his personal dependence through his economic theorizing.

  2. Aerospace Engineer Lizalyn Smith

    NASA Image and Video Library

    2017-01-09

    Portrait of Orion Service Module Spacecraft Adapter Jettisonable (SAJ) Hardware Lead Engineer Lizalyn Smith. Ms. Smith participated in various 'Hidden Figures to Modern Figures' events sponsored by NASA Glenn Research Center to encourage students to pursue STEM-based careers.

  3. Measurement of X-ray emission efficiency for K-lines.

    PubMed

    Procop, M

    2004-08-01

    Results for the X-ray emission efficiency (counts per C per sr) of K-lines for selected elements (C, Al, Si, Ti, Cu, Ge) and for the first time also for compounds and alloys (SiC, GaP, AlCu, TiAlC) are presented. An energy dispersive X-ray spectrometer (EDS) of known detection efficiency (counts per photon) has been used to record the spectra at a takeoff angle of 25 degrees determined by the geometry of the secondary electron microscope's specimen chamber. Overall uncertainty in measurement could be reduced to 5 to 10% in dependence on the line intensity and energy. Measured emission efficiencies have been compared with calculated efficiencies based on models applied in standardless analysis. The widespread XPP and PROZA models give somewhat too low emission efficiencies. The best agreement between measured and calculated efficiencies could be achieved by replacing in the modular PROZA96 model the original expression for the ionization cross section by the formula given by Casnati et al. (1982) A discrepancy remains for carbon, probably due to the high overvoltage ratio.

  4. Smith Tackles Oakland Unified

    ERIC Educational Resources Information Center

    Mellon, Ericka

    2011-01-01

    As a 20-something, Anthony "Tony" Smith had fulfilled one dream: playing professional football for the Green Bay Packers and the San Francisco 49ers. Next up, he thought, was law school, but a former mentor reminded him that he is a teacher. Smith never became a classroom teacher, but his background in sports--where he learned the power…

  5. Genetics Home Reference: Smith-Lemli-Opitz syndrome

    MedlinePlus

    ... Twitter Home Health Conditions Smith-Lemli-Opitz syndrome Smith-Lemli-Opitz syndrome Printable PDF Open All Close ... Javascript to view the expand/collapse boxes. Description Smith-Lemli-Opitz syndrome is a developmental disorder that ...

  6. Infanrix hexa and sudden death: a review of the periodic safety update reports submitted to the European Medicines Agency.

    PubMed

    Puliyel, Jacob; Sathyamala, C

    2018-01-01

    There have been a number of spontaneous reports of sudden unexpected death soon after the administration of Infanrix hexa (combined diphtheria, tetanus, acellular pertussis, hepatitis B, inactivated poliomyelitis and Haemophilus influenza type B vaccine). The manufacturer, GlaxoSmithKline (GSK), submits confidential periodic safety update reports (PSURs) on Infanrix hexa to the European Medicines Agency (EMA). The latest is the PSUR 19. Each PSUR contains an analysis of observed/expected sudden deaths, which shows that the number of observed deaths soon after immunisation is lower than that expected by chance. This commentary focuses on that aspect of the PSUR which has a bearing on policy decisions. We analysed the data provided in the PSURs. It is apparent that the deaths acknowledged in the PSUR 16 were deleted from the PSUR 19. The number of observed deaths soon after vaccination among children older than one year was significantly higher than that expected by chance once the deleted deaths were restored and included in the analysis. The manufacturer must explain the figures that have been submitted to the regulatory authorities. The procedures undertaken by the EMA to evaluate the manufacturer's claims in the PSUR need to be reviewed. The Drugs Controller General of India nearly automatically accepts drugs and vaccines approved by the EMA. There is a need to reappraise the reliance on due diligence by the EMA.

  7. Antibody for the prevention of neonatal noscocomial staphylococcal infection: a review of the literature.

    PubMed

    Weisman, L E

    2007-09-01

    Staphylococci, especially coagulase negative staphylococci (CONS), are responsible for over 75 % of late-onset infections in very low birth weight infants. These infections cause increased length of hospital stay, need for antibiotics, and cost of medical care. Several drug companies have developed and evaluated hyperimmune polyclonal and monoclonal antibodies for the prevention of neonatal staphylococcal infection including 1) Altastaph by North American Biologics Inc., 2) Veronate by Inhibitex Inc., and 3) Pagibaximab by Biosynexus Inc, and Glaxo Smith Kline Inc. We will review the development and status of these potential products. Altastaph is a S. aureus serotype 5 and 8 vaccine induced hyperimmune polyclonal antibody whose development has been placed on hold due to its failure to demonstrate any trend toward efficacy in a recently completed Phase II study. Veronate is a polyclonal antibody obtained by plasmapheresis from donors with high titers of MSCRAMM (microbial surface components recognizing adhesion matrix molecules) activity against CONS whose development has been placed on hold due to its failure to demonstrate effectiveness in a recently completed Phase III study. Pagibaximab is a humanized mouse chimeric monoclonal antibody (previously known as BSYX-A110) directed against lipoteichoic acid (LTA), a major cell wall component of gram-positive bacteria, that has recently completed a Phase II study suggesting efficacy and is being developed further for clinical investigation.

  8. Satisfaction in complete denture wearers with and without adhesives: A randomized, crossover, double-blind clinical trial

    PubMed Central

    Torres-Sánchez, Carlos; Montoya-Salazar, Vanessa; Gutierrez-Pérez, Jose-Luis; Jimenez-Castellanos, Emilio

    2018-01-01

    Background The purpose of this study was to compare the satisfaction of patients regarding retention, stability and accumulation of particles with a randomized, double-blind crossed method in users with complete dentures with and without adhesive. Material and Methods Seventeen edentulous individuals were randomized and received new upper and lower complete dentures. After a period of adaptation, they participated in some masticatory tests and clinical revisions, after use the protheses with and without the use of two denture adhesives: Adhesive A (Fittydent, Fittydent International GmbH) and adhesive B (Corega, GlaxoSmithKline) at 0, 7 and 14 days. Satisfaction was measured immediately after each test through a survey using a VAS scale (0-10) and data were analyzed with McNemar’s test with Bonferroni correction. Results The results showed significant differences (p<.01) between the study groups with adhesive A - B and the group without adhesive, but no significant differences were found between the two stickers for any of the variables studied. Conclusions Complete denture adhesives significantly improved the satisfaction of patients because a better retention, stability and less accumulation of particles of the food substitute between the denture and the mucosa is obtained compared with non-use of complete denture adhesives. Key words:Complete dentures, patient satisfaction, denture adhesives, clinical trials. PMID:29946414

  9. Retinal pathology is associated with increased blood-retina barrier permeability in a diabetic and hypercholesterolaemic pig model: Beneficial effects of the LpPLA2 inhibitor Darapladib.

    PubMed

    Acharya, Nimish K; Qi, Xin; Goldwaser, Eric L; Godsey, George A; Wu, Hao; Kosciuk, Mary C; Freeman, Theresa A; Macphee, Colin H; Wilensky, Robert L; Venkataraman, Venkat; Nagele, Robert G

    2017-05-01

    Using a porcine model of diabetes mellitus and hypercholesterolaemia, we previously showed that diabetes mellitus and hypercholesterolaemia is associated with a chronic increase in blood-brain barrier permeability in the cerebral cortex, leading to selective binding of immunoglobulin G and deposition of amyloid-beta 1-42 peptide in pyramidal neurons. Treatment with Darapladib (GlaxoSmithKline, SB480848), an inhibitor of lipoprotein-associated phospholipase-A2, alleviated these effects. Here, investigation of the effects of chronic diabetes mellitus and hypercholesterolaemia on the pig retina revealed a corresponding increased permeability of the blood-retina barrier coupled with a leak of plasma components into the retina, alterations in retinal architecture, selective IgG binding to neurons in the ganglion cell layer, thinning of retinal layers due to cell loss and increased glial fibrillary acidic protein expression in Müller cells, all of which were curtailed by treatment with Darapladib. These findings suggest that chronic diabetes mellitus and hypercholesterolaemia induces increased blood-retina barrier permeability that may be linked to altered expression of blood-retina barrier-associated tight junction proteins, claudin and occludin, leading to structural changes in the retina consistent with diabetic retinopathy. Additionally, results suggest that drugs with vascular anti-inflammatory properties, such as Darapladib, may have beneficial effects on eye diseases strongly linked to vascular abnormalities such as diabetic retinopathy and age-related macular degeneration.

  10. A critical review on a globally-licensed, live, orally-administrable, monovalent human rotavirus vaccine: Rotarix.

    PubMed

    Nakagomi, Toyoko; Nakagomi, Osamu

    2009-08-01

    Rotavirus is the major cause of severe gastroenteritis in children worldwide, and two, live, orally-administrable vaccines are licensed globally. They are Rotarix, a monovalent, human rotavirus-based vaccine (GlaxoSmithKline), and RotaTeq, a pentavalent, bovine-human reassortant vaccine (Merck). The RIX4414 strain, a G1P[8] virus, is contained in the Rotarix vaccine. It grows efficiently in the human intestine, as evidenced by vaccine virus shedding into faeces. Efficient multiplication of RIX4414 in the intestines may play a role in stimulating immune effectors other than neutralizing antibodies that may explain the protective immunity against fully heterotypic G2P[4] strains. The protective efficacy against severe rotavirus gastroenteritis afforded by Rotarix is consistently better against strains that share with RIX4414 both G and P serotypes (i.e., G1P[8]), or only P serotype (i.e., G3P[8], G4P[8] and G9P[8]). The Rotarix vaccine is safe regarding intussusception if its first dose is administered between 6 and 12 weeks of age and the last dose by 24 weeks of age with a minimum interval of 4 weeks between the two doses. The expansion by Advisory Committee on Immunization Practices, USA, of the age limit for the first dose to age <15 weeks, and the last dose by 8 months requires close monitoring.

  11. Impact of rotavirus vaccination in Australian children below 5 years of age

    PubMed Central

    Pendleton, Annmarie; Galic, Maja; Clarke, Christopher; Ng, Su Peing; Ledesma, Emilio; Ramakrishnan, Gunasekaran; Liu, Yanfang

    2013-01-01

    This study was conducted to assess the impact of administration of two-dose rotavirus (RV) vaccine (RIX4414; GlaxoSmithKline Vaccines) among children aged less than 5 y in three states/territories of Australia. Aggregated and de-identified data on rotavirus gastroenteritis (RVGE) and all-cause gastroenteritis (AGE) from July 1998–June 2009 were obtained from the Australian Institute of Health and Welfare database. The baseline incidence (July 1998–June 2006) of RVGE hospitalizations before RV vaccine introduction in New South Wales (NSW), the Australian Capital Territory (ACT) and the Northern Territory (NT) were 33.75, 42.93 and 288.67 per 10 000 child-years, respectively among children aged 0–11 mo. Following RV vaccine introduction in NSW, the ACT and the NT, incidence of RVGE hospitalizations reduced to 13.06, 17.35 and 47.52 per 10 000 child-years, respectively, during July 2007–June 2008 and 3.87, 8.40 and 122.79 per 10,000 child-years, respectively, during July 2008–June 2009 among children aged 0–11 mo. Reductions in RVGE and AGE were also observed in all children below 5 y of age in NSW and the ACT. Overall reduction in hospitalizations due to RVGE and AGE was observed following RV vaccine introduction into the NIP in Australia. PMID:23733041

  12. Amoxicillin/clavulanate potassium extended release tablets: a new antimicrobial for the treatment of acute bacterial sinusitis and community-acquired pneumonia.

    PubMed

    Benninger, Michael S

    2003-10-01

    Community-acquired bacterial respiratory tract infections are among the most common health disorders requiring medical care and are associated with substantial morbidity, mortality, and direct and indirect costs. Recent increases in the prevalence of antimicrobial resistance have resulted in reduced susceptibility of the most common respiratory tract bacterial pathogens to a number of antimicrobials. Amoxicillin/clavulanate potassium extended release (ER) tablets (Augmentin XR, GlaxoSmithKline) is a new formulation of amoxicillin/clavulanate that retains activity against betalactamase-producing organisms whilst increasing the activity against Streptococcus pneumoniae through elevated and sustained plasma amoxicillin concentrations. The bilayer tablet provides immediate release of clavulanate and both immediate and sustained release of amoxicillin to maintain therapeutic concentrations of amoxicillin over longer periods of the dosing interval. In clinical trials of acute bacterial sinusitis (ABS) and community-acquired pneumonia (CAP), amoxicillin/clavulanate ER was shown to have excellent bacteriological and clinical success rates, even in patients infected with antimicrobial-resistant pathogens, and was found to be generally well tolerated. Amoxicillin/clavulanate ER is approved in the US for the treatment of patients with ABS or CAP caused by beta-lactamase-producing pathogens (ie, Haemophilus influenzae, Moraxella catarrhalis, Haemophilus parainfluenzae, Klebsiella pneumoniae, or methicillin-susceptible Staphylococcus aureus) and S. pneumoniae with reduced susceptibility to penicillin (penicillin minimum inhibitory concentration = 2.0 microg/ml).

  13. Straight talk with...Joseph Schwartz.

    PubMed

    Ratner, Mark

    2012-06-06

    On 17 May, Human Genome Sciences (HGS) formally rejected a $2.6 billion unsolicited takeover offer by GlaxoSmithKline. The Maryland-based biotech firm had long partnered with the UK drug giant to develop drugs including Benlysta (belimumab), HGS's first drug on the market and the first new medicine approved to fight lupus in 50 years. But, at $13 a share, GSK's bid was deemed "inadequate" by the HGS board. Recent history in the biotech sector shows how high the stakes are in such negotiations. Since last November, six biopharma buyouts have exceeded $1 billion each, with Gilead Sciences' purchase last year of the hepatitis C specialist Pharmasset topping the charts at a whopping $11.2 billion, the highest ever paid for a clinical-stage biotech and an 89% premium to its share price at the time. More recently, in April AstraZeneca paid $1.3 billion for Ardea Biosciences, a company with cancer and gout drugs in the pipeline but nothing on the market.One person watching the upward clime of such deals is biopharma analyst Joseph Schwartz, a managing director at Leerink Swann in Boston. Mark Ratner sought out Schwartz, who was named the top stock picker for pharmaceuticals in the last year's FT/StarMine Analyst Awards, for his views on what's behind the recent buyout spending.

  14. Associations of centrally acting ACE inhibitors with cognitive decline and survival in Alzheimer’s disease

    PubMed Central

    Fazal, Karim; Khondoker, Mizanur; Howard, Robert; Stewart, Robert

    2017-01-01

    Background Cognitive improvement has been reported in patients receiving centrally acting angiotensin-converting enzyme inhibitors (C-ACEIs). Aims To compare cognitive decline and survival after diagnosis of Alzheimer’s disease between people receiving C-ACEIs, non-centrally acting angiotensin-converting enzyme inhibitors (NC-ACEIs), and neither. Method Routine Mini-Mental State Examination (MMSE) scores were extracted in 5260 patients receiving acetylcholinesterase inhibitors and analysed against C-/NC-ACEI exposure at the time of Alzheimer’s disease diagnosis. Results In the 9 months after Alzheimer’s disease diagnosis, MMSE scores significantly increased by 0.72 and 0.19 points per year in patients on C-ACEIs and neither respectively, but deteriorated by 0.61 points per year in those on NC-ACEIs. There were no significant group differences in score trajectories from 9 to 36 months and no differences in survival. Conclusions In people with Alzheimer’s disease receiving acetylcholinesterase inhibitors, those also taking C-ACEIs had stronger initial improvement in cognitive function, but there was no evidence of longer-lasting influence on dementia progression. Declaration of interest R.S. has received research funding from Pfizer, Lundbeck, Roche, Janssen and GlaxoSmithKline. Copyright and usage © The Royal College of Psychiatrists 2017. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license. PMID:28713585

  15. Effect of gastric emptying and entero-hepatic circulation on bioequivalence assessment of ranitidine.

    PubMed

    Chrenova, J; Durisova, M; Mircioiu, C; Dedik, L

    2010-01-01

    The aim of study was to compare the bioavailability of ranitidine obtained from either Ranitidine (300 mg tablet; LPH® S.C. LaborMed Pharma S.A. Romania: the test formulation) and Zantac® (300 mg tablet; GlaxoSmithKline, Austria: the reference formulation). Twelve, Romanian, healthy volunteers were enrolled in the study. An open-label, two-period, crossover, randomized design was used. Plasma levels of ranitidine were determined using the validated, high-pressure liquid chromatography (HPLC) method. The physiologically motivated time-delayed model was used for the data evaluation and a paired Student's t-test and Schuirmann's two one-sided tests were carried out to compare parameters. Nonmodeling parameters (AUC(t), AUC, C(max), T(max)) were tested by the paired Student's t-test and the 90 confidence intervals of the geometric mean ratios were determined by Schuirmann's tests. Paired Student's t-test showed no significant differences between nonmodeling and modeling parameters. The results of the Schuirmann's tests however indicated significant statistical differences with reference to AUC(t), AUC, C(max), T(max) and other modeling parameters, especially MT(c) and τ(c). Schuirmann's tests revealed significant bioequivalence between ranitidine formulations using the modeling parameters MRT and n. The presented model can be useful as an additional tool to assess drug bioequivalence, by screening for disruptive parameters. Copyright 2010 Prous Science, S.A.U. or its licensors. All rights reserved.

  16. Species- and dose-specific pancreatic responses and progression in single- and repeat-dose studies with GI181771X: a novel cholecystokinin 1 receptor agonist in mice, rats, and monkeys.

    PubMed

    Myer, James R; Romach, Elizabeth H; Elangbam, Chandikumar S

    2014-01-01

    Compound-induced pancreatic injury is a serious liability in preclinical toxicity studies. However, its relevance to humans should be cautiously evaluated because of interspecies variations. To highlight such variations, we evaluated the species- and dose-specific pancreatic responses and progression caused by GI181771X, a novel cholecystokinin 1 receptor agonist investigated by GlaxoSmithKline for the treatment of obesity. Acute (up to 2,000 mg/kg GI181771X, as single dose) and repeat-dose studies in mice and/or rats (0.25-250 mg/kg/day for 7 days to 26 weeks) showed wide-ranging morphological changes in the pancreas that were dose and duration dependent, including necrotizing pancreatitis, acinar cell hypertrophy/atrophy, zymogen degranulation, focal acinar cell hyperplasia, and interstitial inflammation. In contrast to rodents, pancreatic changes were not observed in cynomolgus monkeys given GI181771X (1-500 mg/kg/day with higher systemic exposure than rats) for up to 52 weeks. Similarly, no GI181771X treatment-associated abnormalities in pancreatic structure were noted in a 24-week clinical trial with obese patients (body mass index >30 or >27 kg/m(2)) as assessed by abdominal ultrasound or by magnetic resonance imaging. Mechanisms for interspecies variations in the pancreatic response to CCK among rodents, monkeys, and humans and their relevance to human risk are discussed.

  17. Incidence and costs of herpes zoster and postherpetic neuralgia in German adults aged ≥50 years: A prospective study.

    PubMed

    Schmidt-Ott, Ruprecht; Schutter, Ulf; Simon, Jörg; Nautrup, Barbara Poulsen; von Krempelhuber, Alfred; Gopala, Kusuma; Anastassopoulou, Anastassia; Guignard, Adrienne; Curran, Desmond; Matthews, Sean; Espié, Emmanuelle

    2018-05-01

    Herpes zoster (HZ) mainly affects elderly people and immunocompromised individuals. HZ is usually characterized by a unilateral painful skin rash. Its most common complication, postherpetic neuralgia (PHN), may cause chronic debilitating pain. This study aimed to estimate the HZ incidence in individuals aged ≥50 years in Germany, the proportion of PHN and the economic burden. From 2010 to 2014, HZ patients were recruited when consulting physicians in physician networks covering about 157,000 persons aged ≥50 years. PHN was defined as "worst pain" rated ≥3 on the zoster brief pain inventory persisting or appearing over 90 days after rash onset. Costs were calculated based on medical resource utilization and lost working time. HZ incidence was estimated as 6.7/1000 person-years, increasing with age to 9.4/1000 in ≥80 year-olds. Among 513 HZ patients enrolled, the proportion of PHN was 11.9%, rising with age to 14.3% in HZ patients ≥80 years. Estimated total cost per HZ patient was €156 from the healthcare system perspective and €311 from the societal perspective. The study confirmed previous findings that HZ causes a substantial clinical and economic burden in older German adults. It also confirmed the age-related increasing risk of HZ and PHN. Copyright © 2018 GlaxoSmithKline Biologicals SA. Published by Elsevier Ltd.. All rights reserved.

  18. ERP Modulation during Observation of Abstract Paintings by Franz Kline

    PubMed Central

    Sbriscia-Fioretti, Beatrice; Berchio, Cristina; Freedberg, David; Gallese, Vittorio; Umiltà, Maria Alessandra

    2013-01-01

    The aim of this study was to test the involvement of sensorimotor cortical circuits during the beholding of the static consequences of hand gestures devoid of any meaning.In order to verify this hypothesis we performed an EEG experiment presenting to participants images of abstract works of art with marked traces of brushstrokes. The EEG data were analyzed by using Event Related Potentials (ERPs). We aimed to demonstrate a direct involvement of sensorimotor cortical circuits during the beholding of these selected works of abstract art. The stimuli consisted of three different abstract black and white paintings by Franz Kline. Results verified our experimental hypothesis showing the activation of premotor and motor cortical areas during stimuli observation. In addition, abstract works of art observation elicited the activation of reward-related orbitofrontal areas, and cognitive categorization-related prefrontal areas. The cortical sensorimotor activation is a fundamental neurophysiological demonstration of the direct involvement of the cortical motor system in perception of static meaningless images belonging to abstract art. These results support the role of embodied simulation of artist’s gestures in the perception of works of art. PMID:24130693

  19. 33 CFR 117.841 - Smith Creek.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Smith Creek. 117.841 Section 117.841 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES DRAWBRIDGE OPERATION REGULATIONS Specific Requirements North Carolina § 117.841 Smith Creek. The draw of the S117-S133...

  20. Why does the world need another rotavirus vaccine?

    PubMed Central

    Ward, Richard L; McNeal, Monica M; Steele, A Duncan

    2008-01-01

    A “Meeting on Upstream Rotavirus Vaccines and Emerging Vaccine Producers” was held at the World Health Organization in Geneva, Switzerland on March 28–30, 2006. The purpose was to discuss, evaluate, and weigh the importance of additional rotavirus vaccine candidates following the successful international licensure of rotavirus vaccines by two major pharmaceutical companies (GlaxoSmithKline and Merck) that had been in development for many years. Both licensed vaccines are composed of live rotaviruses that are delivered orally as have been all candidate rotavirus vaccines evaluated in humans. Each is built on the experience gained with previous candidates whose development had either been discontinued or, in the case of the previously licensed rhesus rotavirus reassortant vaccine (Rotashield), was withdrawn by its manufacturer after the discovery of a rare association with intussusception. Although which alternative candidate vaccines should be supported for development and where this should be done are controversial topics, there was general agreement expressed at the Geneva meeting that further development of alternative candidates is a high priority. This development will help insure that the most safe, effective and economic vaccines are available to children in Third World nations where the vast majority of the >600,000 deaths due to rotavirus occur each year. This review is intended to provide the history and present status of rotavirus vaccines as well as a perspective on the future development of candidate vaccines as a means of promulgating plans suggested at the Geneva meeting. PMID:18728720

  1. Biochemical Screening of Five Protein Kinases from Plasmodium falciparum against 14,000 Cell-Active Compounds

    PubMed Central

    Crowther, Gregory J.; Hillesland, Heidi K.; Keyloun, Katelyn R.; Reid, Molly C.; Lafuente-Monasterio, Maria Jose; Ghidelli-Disse, Sonja; Leonard, Stephen E.; He, Panqing; Jones, Jackson C.; Krahn, Mallory M.; Mo, Jack S.; Dasari, Kartheek S.; Fox, Anna M. W.; Boesche, Markus; El Bakkouri, Majida; Rivas, Kasey L.; Leroy, Didier; Hui, Raymond; Drewes, Gerard; Maly, Dustin J.; Van Voorhis, Wesley C.; Ojo, Kayode K.

    2016-01-01

    In 2010 the identities of thousands of anti-Plasmodium compounds were released publicly to facilitate malaria drug development. Understanding these compounds’ mechanisms of action—i.e., the specific molecular targets by which they kill the parasite—would further facilitate the drug development process. Given that kinases are promising anti-malaria targets, we screened ~14,000 cell-active compounds for activity against five different protein kinases. Collections of cell-active compounds from GlaxoSmithKline (the ~13,000-compound Tres Cantos Antimalarial Set, or TCAMS), St. Jude Children’s Research Hospital (260 compounds), and the Medicines for Malaria Venture (the 400-compound Malaria Box) were screened in biochemical assays of Plasmodium falciparum calcium-dependent protein kinases 1 and 4 (CDPK1 and CDPK4), mitogen-associated protein kinase 2 (MAPK2/MAP2), protein kinase 6 (PK6), and protein kinase 7 (PK7). Novel potent inhibitors (IC50 < 1 μM) were discovered for three of the kinases: CDPK1, CDPK4, and PK6. The PK6 inhibitors are the most potent yet discovered for this enzyme and deserve further scrutiny. Additionally, kinome-wide competition assays revealed a compound that inhibits CDPK4 with few effects on ~150 human kinases, and several related compounds that inhibit CDPK1 and CDPK4 yet have limited cytotoxicity to human (HepG2) cells. Our data suggest that inhibiting multiple Plasmodium kinase targets without harming human cells is challenging but feasible. PMID:26934697

  2. First Real-World Insights into Belimumab Use and Outcomes in Routine Clinical Care of Systemic Lupus Erythematosus in Germany: Results from the OBSErve Germany Study.

    PubMed

    Schwarting, Andreas; Schroeder, Johann O; Alexander, Tobias; Schmalzing, Marc; Fiehn, Christoph; Specker, Christof; Perna, Alessandra; Cholmakow-Bodechtel, Constanze; Koscielny, Volker B; Carnarius, Heike

    2016-12-01

    OBSErve Germany was the first observational study of belimumab as add-on treatment for systemic lupus erythematosus (SLE) in routine clinical care in Germany, retrospectively collecting data from 102 SLE patients, 6 months before and after belimumab initiation. Most patients had moderate or severe SLE and several SLE manifestations. After 6 months of belimumab treatment, 78% of patients showed an improvement in overall disease activity of at least 20% in their physician's judgment and for 42% of patients the improvement was at least 50%. Similar results were observed for the most common manifestations: arthritis, fatigue, rash, alopecia, increased anti-dsDNA antibody levels, and low complement. The SLE Disease Activity Index (SLEDAI/SELENA-SLEDAI) decreased from 10.6 to 5.6 (n = 65), with other indices also showing improvement. A notable dose reduction was seen for concomitant oral corticosteroids, from 13.7 to 7.6 mg/day overall (n = 91), and from 17.5 to 8.6 mg/day in patients with a high corticosteroid dose at belimumab initiation (≥7.5 mg; n = 63). Six patients discontinued belimumab therapy within 6 months. Overall, belimumab showed promising results for SLE patients in real-world settings. After 6 months of belimumab treatment, disease activity and corticosteroid use were reduced. The discontinuation rate was low and belimumab appeared to be well tolerated. Funding GlaxoSmithKline UK.

  3. Impact of the introduction of the pneumococcal conjugate vaccine in the Brazilian routine childhood national immunization program.

    PubMed

    Moreira, Marta; Cintra, Otavio; Harriague, Julie; Hausdorff, William P; Hoet, Bernard

    2016-05-27

    Brazil introduced the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV, Synflorix™, GSK Vaccines) in the routine childhood immunization program in 2010 with a 3+1 schedule (with catch-up for children <2 years-old). This review represents the first analysis of the overall impact of a second-generation pneumococcal conjugate vaccine on nasopharyngeal carriage and all the major pneumococcal disease manifestations in a single, pneumococcal conjugate vaccine-naïve, developing country. A total of 15 published articles and 13 congress abstracts were included in the analysis. In children <5 years-old, studies showed a positive impact of PHiD-CV on the incidence of vaccine-type and any-type invasive pneumococcal disease (including decreases in pneumococcal meningitis morbidity and mortality), on pneumonia incidence and mortality, and on otitis media. Nasopharyngeal carriage of vaccine-type and any-type pneumococci decreased after the primary doses, with no early signs of replacement with other pathogens. Finally, herd protection against vaccine-type invasive pneumococcal disease and pneumonia in unvaccinated subjects was shown in some studies for some age groups. In conclusion, pneumococcal disease decreased after the introduction of PHiD-CV into the Brazilian national immunization program. Further follow-up is needed to evaluate the long-term overall impact of PHiD-CV in the Brazilian population. Copyright © 2016 GlaxoSmithKline Biologicals SA. Published by Elsevier Ltd.. All rights reserved.

  4. Effects of omega-3 fatty acid supplementation on neurocognitive functioning and mood in deployed U.S. soldiers: a pilot study.

    PubMed

    Dretsch, Michael N; Johnston, Daniel; Bradley, Ryan S; MacRae, Holden; Deuster, Patricia A; Harris, William S

    2014-04-01

    Omega-3 fatty acids (FAs) may have neuroprotective properties for psychological health and cognition. The objective of this study was to evaluate the effectiveness of omega-3 FAs (eicosapentaenoic + docosahexaenoic; Harris-Schacky [HS]-Omega-3 Index) on neuropsychological functioning among U.S. Soldiers deployed to Iraq. This randomized, double-blind, placebo-controlled trial included Soldiers between the ages of 18 and 55 years who were randomly assigned to either the active treatment group (n = 44) or placebo group (n = 34). Active treatment was 2.5 g per day of eicosapentaenoic + docosahexaenoic (Lovaza; GlaxoSmithKline, Research Triangle Park, North Carolina). The placebo was corn oil ethyl esters. HS-Omega-3 Index, a neurocognitive battery (Central Nervous System-Vital Signs, Morrisville, North Carolina), and psychological health scales were assessed at baseline and after 60 days of treatment. Although the results revealed that omega-3 FAs significantly increased the HS-Omega-3 Index (p = 0.001), there were no significant effects on indices psychological health and neurocognitive functioning by treatment group. Nevertheless, there was a significant inverse correlation between the changes in the HS-Omega-3 Index and daytime sleepiness (r = 0.30, p = 0.009). Short-term treatment with 2.5 g of omega-3 FAs did not alter measures of neurocognition or psychological health, but there was evidence of a relationship between omega-3 levels and daytime sleepiness. Reprint & Copyright © 2014 Association of Military Surgeons of the U.S.

  5. Antimycobacterial drug discovery using Mycobacteria-infected amoebae identifies anti-infectives and new molecular targets.

    PubMed

    Trofimov, Valentin; Kicka, Sébastien; Mucaria, Sabrina; Hanna, Nabil; Ramon-Olayo, Fernando; Del Peral, Laura Vela-Gonzalez; Lelièvre, Joël; Ballell, Lluís; Scapozza, Leonardo; Besra, Gurdyal S; Cox, Jonathan A G; Soldati, Thierry

    2018-03-02

    Tuberculosis remains a serious threat to human health world-wide, and improved efficiency of medical treatment requires a better understanding of the pathogenesis and the discovery of new drugs. In the present study, we performed a whole-cell based screen in order to complete the characterization of 168 compounds from the GlaxoSmithKline TB-set. We have established and utilized novel previously unexplored host-model systems to characterize the GSK compounds, i.e. the amoeboid organisms D. discoideum and A. castellanii, as well as a microglial phagocytic cell line, BV2. We infected these host cells with Mycobacterium marinum to monitor and characterize the anti-infective activity of the compounds with quantitative fluorescence measurements and high-content microscopy. In summary, 88.1% of the compounds were confirmed as antibiotics against M. marinum, 11.3% and 4.8% displayed strong anti-infective activity in, respectively, the mammalian and protozoan infection models. Additionally, in the two systems, 13-14% of the compounds displayed pro-infective activity. Our studies underline the relevance of using evolutionarily distant pathogen and host models in order to reveal conserved mechanisms of virulence and defence, respectively, which are potential "universal" targets for intervention. Subsequent mechanism of action studies based on generation of over-expresser M. bovis BCG strains, generation of spontaneous resistant mutants and whole genome sequencing revealed four new molecular targets, including FbpA, MurC, MmpL3 and GlpK.

  6. Environmental health impacts: occurrence, exposure and significance, Lancaster University, UK, 9-10 September 2003.

    PubMed

    Martin, Francis L; Semple, Kirk T

    2004-09-01

    Speakers: John Ashby (Syngenta CTL, UK), Peter A. Behnisch (Eurofins GfA, Germany), Paul L. Carmichael (Unilever Colworth, UK), Curtis C.Harris (National Cancer Institute, USA), Kevin C. Jones (Lancaster University, UK), Andreas Kortenkamp (School of Pharmacy, London, UK), Caroline J. Langdon (Reading University, UK), Anthony M. Lynch (GlaxoSmithKline, UK), Francis L. Martin (Lancaster University, UK), Trevor J. McMillan (Lancaster University, UK), David H. Phillips (Institute of Cancer Research, UK), Huw J. Ricketts (University of Cardiff, UK), Michael N. Routledge (University of Leeds, UK), J. Thomas Sanderson (Utrecht University, The Netherlands) and Kirk T. Semple (Lancaster University, UK) The effects of many environmental exposures to either single contaminants or to mixtures still remain to be properly assessed in ecotoxicological and human toxicological settings. Such assessments need to be carried out using relevant biological assays. On a mechanistic basis, future studies need to be able to extrapolate exposure to disease risk. It is envisaged that such an approach would lead to the development of appropriate strategies to either reduce exposures or to initiate preventative measures in susceptible individuals or populations. To mark the opening of a new Institute, the Lancaster Environmental Centre, an environmental health workshop was held over 2 days (9-10 September 2003) at Lancaster University, UK. The fate, behaviour and movement of chemicals in the environment, together with environmental exposures and human health, biomarkers of such exposures, hormone-like compounds and appropriate genetic toxicology methodologies, were discussed.

  7. Incorporation of a rotavirus vaccine into the national immunisation schedule in the United Kingdom: a review.

    PubMed

    Nakagomi, Osamu; Iturriza-Gomara, Miren; Nakagomi, Toyoko; Cunliffe, Nigel A

    2013-11-01

    Rotavirus, the commonest cause of severe acute gastroenteritis in infants and young children worldwide, imposes a large health and economic burden on the British society, accounting for an estimated 14,300 hospitalisations and 133,000 general practitioner consultations each year among children aged < 5 years in England and Wales alone. Following a tender process, an attenuated human rotavirus vaccine, Rotarix (GlaxoSmithKline Biologicals, Belgium), was introduced into the UK childhood immunisation programme in 2013. This article provides a review of the product profile of the Rotarix vaccine for use in the national immunisation programme in the UK from an expert perspective. This single G1P[8] strain-based human rotavirus vaccine has demonstrated high efficacy in preventing severe rotavirus gastroenteritis in the first 3 years of life in middle- and high-income countries. In countries that have adopted rotavirus vaccine in childhood immunisation programmes, indirect benefits (herd protection) have been observed among older, unvaccinated children and adults. When the first dose is administered between 6 and 14 weeks of age and the last dose by 24 weeks of age, Rotarix carries a small risk of intussusception within the week of vaccination. However, this small risk may at most result in a negligible population attributable risk at the end of the first year of life. Overall, the rotavirus immunisation programme is expected to provide substantial health benefits to the UK population.

  8. Molecular analysis of varicella vaccines and varicella-zoster virus from vaccine-related skin lesions.

    PubMed

    Thiele, Sonja; Borschewski, Aljona; Küchler, Judit; Bieberbach, Marc; Voigt, Sebastian; Ehlers, Bernhard

    2011-07-01

    To prevent complications that might follow an infection with varicella-zoster virus (VZV), the live attenuated Oka strain (V-Oka) is administered to children in many developed countries. Three vaccine brands (Varivax from Sanofi Pasteur MSD; Varilrix and Priorix-Tetra, both from Glaxo-Smith-Kline) are licensed in Germany and have been associated with both different degrees of vaccine effectiveness and adverse effects. To identify genetic variants in the vaccines that might contribute to rash-associated syndromes, single nucleotide polymorphism (SNP) profiles of variants from the three vaccines and rash-associated vaccine-type VZV from German vaccinees were quantitatively compared by PCR-based pyrosequencing (PSQ). The Varivax vaccine contained an estimated 3-fold higher diversity of VZV variants, with 20% more wild-type (wt) SNPs than Varilrix and Priorix-Tetra. These minor VZV variants in the vaccines were identified by analyzing cloned full-length open reading frame (ORF) orf62 sequences by chain termination sequencing and PSQ. Some of these sequences amplified from vaccine VZV were very similar or identical to those of the rash-associated vaccine-type VZV from vaccinees and were almost exclusively detected in Varivax. Therefore, minorities of rash-associated VZV variants are present in varicella vaccine formulations, and it can be concluded that the analysis of a core set of four SNPs is required as a minimum for a firm diagnostic differentiation of vaccine-type VZV from wt VZV.

  9. Evaluating the acute effects of oral, non-combustible potential reduced exposure products marketed to smokers.

    PubMed

    Cobb, C O; Weaver, M F; Eissenberg, T

    2010-10-01

    Non-combustible potential reduced exposure products (PREPs; eg, Star Scientific's Ariva; a variety of other smokeless tobacco products) are marketed to reduce the harm associated with smoking. This marketing occurs despite an absence of objective data concerning the toxicant exposure and effects of these PREPs. Methods used to examine combustible PREPs were adapted to assess the acute effects of non-combustible PREPs for smokers. 28 overnight abstinent cigarette smokers (17 men, 14 non-white) each completed seven, Latin-squared ordered, approximately 2.5 h laboratory sessions that differed by product administered: Ariva, Marlboro Snus (Philip Morris, USA), Camel Snus (RJ Reynolds, Winston-Salem, North Carolina, USA), Commit nicotine lozenge (GlaxoSmithKline; 2 mg), own brand cigarettes, Quest cigarettes (Vector Tobacco; delivers very low levels of nicotine) and sham smoking (ie, puffing on an unlit cigarette). In each session, the product was administered twice (separated by 60 min), and plasma nicotine levels, expired air CO and subjective effects were assessed regularly. Non-combustible products delivered less nicotine than own brand cigarettes, did not expose smokers to CO and failed to suppress tobacco abstinence symptoms as effectively as combustible products. While decreased toxicant exposure is a potential indicator of harm reduction potential, a failure to suppress abstinence symptoms suggests that currently marketed non-combustible PREPs may not be a viable harm reduction strategy for US smokers. This study demonstrates how clinical laboratory methods can be used to evaluate the short-term effects of non-combustible PREPs for smokers.

  10. Young people's comparative recognition and recall of an Australian Government Sexual Health Campaign.

    PubMed

    Lim, Megan S C; Gold, Judy; Bowring, Anna L; Pedrana, Alisa E; Hellard, Margaret E

    2015-05-01

    In 2009, the Australian Government's National Sexually Transmitted Infection Prevention Program launched a multi-million dollar sexual health campaign targeting young people. We assessed campaign recognition among a community sample of young people. Individuals aged 16-29 years self-completed a questionnaire at a music festival. Participants were asked whether they recognised the campaign image and attempted to match the correct campaign message. Recognition of two concurrent campaigns, GlaxoSmithKline's The Facts genital herpes campaign (targeting young women) and the Drama Downunder campaign (targeting gay men) were assessed simultaneously. Among 471 participants, just 29% recognised the National Sexually Transmitted Infection Prevention Program campaign. This compared to 52% recognising The Facts and 27% recognising Drama Downunder. Of 134 who recognised the National Sexually Transmitted Infection Prevention Program campaign, 27% correctly recalled the campaign messages compared to 61% of those recognising the Facts campaign, and 25% of those recognising the Drama Downunder campaign. There was no difference in National Sexually Transmitted Infection Prevention Program campaign recognition by gender or age. Campaign recognition and message recall of the National Sexually Transmitted Infection Prevention Program campaign was comparatively low. Future mass media sexual health campaigns targeting young people can aim for higher recognition and recall rates than that achieved by the National Sexually Transmitted Infection Prevention Program campaign. Alternative distribution channels and message styles should be considered to increase these rates. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  11. The Treatment of Smith's Invisible Hand

    ERIC Educational Resources Information Center

    Wight, Jonathan B.

    2007-01-01

    Adam Smith used the metaphor of an invisible hand to represent the instincts of human nature that direct behavior. Moderated by self-control and guided by proper institutional incentives, actions grounded in instincts can be shown to generate a beneficial social order even if not intended. Smith's concept, however, has been diluted and distorted…

  12. Bringing Sally Smith's Vision to Manayunk

    ERIC Educational Resources Information Center

    Ford, Jackie

    2010-01-01

    In this article, the author narrates her application of what she learned from her internship at Sally Smith's Lab School of Washington to her new school and shares the favorable impact it had brought on her teaching career. The author shares her first exposure to the powerful effects of Smith's "Live It, Learn It" methodology as she…

  13. STS-110 Crew Interviews: Steve Smith

    NASA Technical Reports Server (NTRS)

    2002-01-01

    STS-110 Mission Specialist Steve Smith is seen during this preflight interview, where he gives a quick overview of the mission before answering questions about his inspiration to become an astronaut and his career path. Smith outlines his role in the mission in general, and specifically during the docking and extravehicular activities (EVAs). He describes the payload (S0 Truss and Mobile Transporter) and the dry run installation of the S0 truss that will take place the day before the EVA for the actual installation. Smith discusses the planned EVAs in detail and outlines what supplies will be left for the resident crew of the International Space Station (ISS). He ends with his thoughts on the most valuable aspect of the ISS.

  14. Dialogue of Differences: The Writing of Henry Holmes Smith.

    ERIC Educational Resources Information Center

    Bossen, Howard

    In addition to surveying the writings of Henry Holmes Smith, this paper explains his importance as a theoretician and practitioner of photography. After a discussion of Smith's ideas on "reading photographs" and his concerns with the ethics of photography, particularly of photojournalism, the essays in the book, "Henry Holmes Smith:…

  15. Safety and tolerability of eltrombopag versus placebo for treatment of thrombocytopenia in patients with advanced myelodysplastic syndromes or acute myeloid leukaemia: a multicentre, randomised, placebo-controlled, double-blind, phase 1/2 trial.

    PubMed

    Platzbecker, Uwe; Wong, Raymond S M; Verma, Amit; Abboud, Camille; Araujo, Sergio; Chiou, Tzeon-Jye; Feigert, John; Yeh, Su-Peng; Götze, Katharina; Gorin, Norbert-Claude; Greenberg, Peter; Kambhampati, Suman; Kim, Yoo-Jin; Lee, Je-Hwan; Lyons, Roger; Ruggeri, Marco; Santini, Valeria; Cheng, Gregory; Jang, Jun Ho; Chen, Chien-Yuan; Johnson, Brendan; Bennett, John; Mannino, Frank; Kamel, Yasser Mostafa; Stone, Nicole; Dougherty, Souria; Chan, Geoffrey; Giagounidis, Aristoteles

    2015-10-01

    Patients with myelodysplastic syndrome or acute myeloid leukaemia who are thrombocytopenic and unable to receive disease-modifying therapy have few treatment options. Platelet transfusions provide transient benefit and are limited by alloimmunisation. Eltrombopag, an oral thrombopoietin receptor agonist, increases platelet counts and has preclinical antileukaemic activity. We aimed to assess the safety and tolerability of eltrombopag for the treatment of thrombocytopenia in adult patients with advanced myelodysplastic syndrome, secondary acute myeloid leukaemia after myelodysplastic syndrome, or de-novo acute myeloid leukaemia. We did this multicentre, randomised, placebo-controlled, double-blind, phase 1/2 trial at 37 centres in ten countries in Europe, east Asia, and the Americas. Patients aged 18 years or older who had relapsed or refractory disease or were ineligible for standard treatments; had platelet counts of less than 30 × 10(9) platelets per L; had 10-50% bone-marrow blasts; or were platelet transfusion dependent were randomly assigned (2:1), via a telephone-based interactive voice-response system (GlaxoSmithKline Registration and Medication Ordering System) with a permuted-block randomisation schedule (block size of three), to receive once-daily eltrombopag or matching placebo dose adjusted from 50 mg to a maximum dose of 300 mg. Randomisation was stratified by presence of poor-prognosis (complex) karyotype (presence of at least three abnormalities, or chromosome 7 abnormalities, vs absence) and bone-marrow blast count (<20% vs ≥20%). Patients and study personnel were masked to treatment allocation. The primary endpoint was safety and tolerability, including adverse events, non-haematological laboratory grade 3-4 toxic effects, and changes in bone-marrow blast counts from baseline. Analysis was by intention to treat. This trial is registered at ClinicalTrials.gov, number NCT00903422. Between May 14, 2009, and May 9, 2013, we randomly assigned 98

  16. Efficacy of fewer than three doses of an HPV-16/18 AS04-adjuvanted vaccine: combined analysis of data from the Costa Rica Vaccine and PATRICIA Trials.

    PubMed

    Kreimer, Aimée R; Struyf, Frank; Del Rosario-Raymundo, Maria Rowena; Hildesheim, Allan; Skinner, S Rachel; Wacholder, Sholom; Garland, Suzanne M; Herrero, Rolando; David, Marie-Pierre; Wheeler, Cosette M; González, Paula; Jiménez, Silvia; Lowy, Douglas R; Pinto, Ligia A; Porras, Caroline; Rodriguez, Ana Cecilia; Safaeian, Mahboobeh; Schiffman, Mark; Schiller, John T; Schussler, John; Sherman, Mark E; Bosch, F Xavier; Castellsague, Xavier; Chatterjee, Archana; Chow, Song-Nan; Descamps, Dominique; Diaz-Mitoma, Francisco; Dubin, Gary; Germar, Maria Julieta; Harper, Diane M; Lewis, David J M; Limson, Genara; Naud, Paulo; Peters, Klaus; Poppe, Willy A J; Ramjattan, Brian; Romanowski, Barbara; Salmeron, Jorge; Schwarz, Tino F; Teixeira, Julio C; Tjalma, Wiebren A A

    2015-07-01

    There is some evidence to suggest that one or two doses of the HPV vaccine provides similar protection to the three-dose regimen. The main aim of the study was to ascertain HPV-16/18 vaccine efficacy in both full and naive cohorts and to explore protection conferred against non-vaccine HPV types, by number of doses received. Summary data from the Costa Rica Vaccine Trial (CVT; NCT00128661) and ~the PATRICIA trial (NCT001226810), two phase 3, double-blind, randomised controlled clinical trials of the HPV-16/18 AS04-adjuvanted vaccine in young women, were combined in a post-hoc analysis (GlaxoSmithKline [GSK] e-track number 202142) to investigate the efficacy of fewer than three doses of the HPV-16/18 vaccine after 4 years of follow-up. Women were randomly assigned to receive three doses of the HPV-16/18 vaccine or to a control vaccine; yet, some received fewer doses. After exclusion of women with less than 12 months of follow-up or those who were HPV-16/18 DNA-positive at enrolment (for the HPV-16/18 endpoint), we calculated vaccine efficacy against one-time detection of incident HPV infections after three, two, and one dose(s). The primary study endpoint was one-time detection of first incident HPV-16/18 infections accumulated during the follow-up phase. We assessed vaccine efficacy against incident HPV-16/18 infection in the modified total vaccinated cohort (22 327 received three doses, 1185 two doses, 543 one dose). Vaccine efficacy against incident HPV-16/18 infections for three doses was 77·0% (95% CI 74·7-79·1), two doses was 76·0% (62·0-85·3), and one dose was 85·7% (70·7-93·7). Vaccine efficacy against incident HPV-31/33/45 infections for three doses was 59·7% (56·0-63·0), two doses was 37·7% (12·4-55·9), and one dose was 36·6% (-5·4 to 62·2). Vaccine efficacy against incident HPV-16/18 infection for two-dose women who received their second dose at 1 month was 75·3% (54·2-87·5) and 82·6% (42·3-96·1) for those who received the second

  17. NREL'S Morgan-Smith Honored by Martin Luther King Commission

    Science.gov Websites

    Morgan-Smith Honored by Martin Luther King Commission For more information contact: Sarah Holmes Barba, 303-275-3023 email: Sarah Barba Golden, Colo., Jan. 9, 2001 - Syl Morgan-Smith, Colorado . 10 at 6 p.m. The event will honor the life and work of King and the eight 2001 awardees. Morgan-Smith

  18. Homer W. Smith's contribution to renal physiology.

    PubMed

    Giebisch, Gerhard

    2004-01-01

    Homer Smith was, for three decades, from the 1930s until his death in 1962, one of the leaders in the field of renal physiology. His contributions were many: he played a major role in introducing and popularizing renal clearance methods, introduced non-invasive methods for the measurement of glomerular filtration rate, of renal blood flow and tubular transport capacity, and provided novel insights into the mechanisms of excretion of water and electrolytes. Homer Smith's contributions went far beyond his personal investigations. He was a superb writer of several inspiring textbooks of renal physiology that exerted great and lasting influence on the development of renal physiology. Smith's intellectual insights and ability for critical analysis of data allowed him to create broad concepts that defined the functional properties of glomeruli, tubules and the renal circulation. A distinguishing feature of Homer Smith's career was his close contact and collaboration, over many years, with several clinicians of his alma mater, New York University. For initiating these pathophysiological investigations, he is justly credited to have advanced, in a major way, our understanding of altered renal function in disease. Smith's lasting scientific impact is also reflected by a whole school of investigators that trained with him and who applied his methods, analyses and concepts to the study of renal function all over the world. So great was his influence and preeminence that Robert Pitts, in his excellent tribute to Homer Smith in the Memoirs of the National Academy of Science states that his death brought an end to what might be aptly called the Smithian Era of renal physiology.

  19. 78 FR 23845 - Drawbridge Operation Regulations; Narrow Bay, Smith Point, NY

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-23

    ... Operation Regulations; Narrow Bay, Smith Point, NY AGENCY: Coast Guard, DHS. ACTION: Notice of temporary... deviation from the regulation governing the operation of the Smith Point Bridge, mile 6.1, across Narrow Bay, between Smith Point and Fire Island, New York. The deviation is necessary to facilitate the Smith Point...

  20. Guide to the Logan Pearsall Smith Collection.

    ERIC Educational Resources Information Center

    Pettit, Katherine Denshaw

    A guide to the Logan Pearsall Smith Collection at Trinity University Elizabeth Coates Maddux Library in San Antonio, Texas provides a descriptive overview of the collected works of this renowned epigrammatist, critic, essayist, biographer, and authority on the English language. The guide includes a brief biography of Smith (1865-1946), detailed…

  1. Adam Smith and the Rhetoric of Style.

    ERIC Educational Resources Information Center

    Moran, Michael G.

    Historians of rhetoric have generally accepted the view that Adam Smith rejected the principles of classical rhetoric. However, while there can be no doubt that Smith greatly truncated the five classical arts of rhetoric (invention, arrangement, style, memory, and delivery) by reducing his concerns largely to style and arrangement, he did not…

  2. Drs. Smith Brothers: dental surgeons of Calcutta.

    PubMed

    Sanjeev, Kumar

    2014-01-01

    During the British raj, India attracted dental practitioners from all over the world who set up practices in the Presidency towns of Calcutta, Bombay, Madras and Bangalore. Lured by the abundant opportunity to make good money, these mercenary but courageous dentists counted Viceroys, Indian royalty and political leaders amongst their clients. Some, like the famous American Smith Brothers of Calcutta, were sought after even by the rulers of neighboring countries. Dr. Mark Smith's hazardous visit to the Amir of Afghanistan made worldwide headlines more than 100 years ago for the fabulous fee he was paid for the dental treatment. This paper briefly describes the exploits and experiences of the Smith brothers while in India.

  3. Sunrayce 97 Continues Day 6 - Manhattan to Smith Center

    Science.gov Websites

    6 - Manhattan to Smith Center For more information contact: Patrick Booher, Sunrayce Program Manager (202) 586-0713 Smith Center, Kan.- --Racing across the heartland of Kansas at 46.11 mph

  4. Financial impact to providers using pediatric combination vaccines.

    PubMed

    Shen, Angela K; Sobczyk, Elizabeth; Simonsen, Lone; Khan, Farid; Esber, Allahna; Andreae, Margie C

    2011-12-01

    To understand the financial impact to providers for using a combination vaccine (Pediarix [GlaxoSmithKline Biologicals, King of Prussia, PA]) versus its equivalent component vaccines for children aged 1 year or younger. Using a subscription remittance billing service offered to private-practice office-based physicians, we analyzed charge and payment information submitted by providers to insurance payers from June 2007 through July 2009. We analyzed provider and payer characteristics, payer comments, and the ratio of vaccine product to immunization administration (IA) codes and computed total charges and payments to providers for both arms of the study. Most providers in our data set were pediatricians (74%), and most payers were commercial (75%), primarily managed care. The ratio of the number of vaccine products to the number of IAs was 1:1 in the majority of the claims. Twenty percent of claims were paid with no adjustment by the payer, whereas 76% of the claims were adjusted for charges that exceeded the contract arrangement or the fee schedule. Providers received $23 less from commercial payers and $13 less from Medicaid for the use of Pediarix compared with the equivalent component vaccines. The mean commercial payment was greater for age-specific Current Procedural Terminology IA codes 90465 and 90466 than for non-age-specific codes 90471 and 90472, whereas the reverse was true for Medicaid. Providers who administer vaccines to children face a reduction in payment when choosing to provide combination vaccines. The new IA codes should be monitored for correction of financial barriers to the use of combination vaccines.

  5. [Historical aspects and new formulations of levothyroxine sodium for hypothyroidism treatment].

    PubMed

    Shacham, Elena Chertok; Ishay, Avraham; Luboshitsky, Rafael

    2013-09-01

    At the end of the 19th century symptoms and signs of hypothyroidism were described in the medical literature. At that time myxedema was a main clinical presentation of the hypothyroid patient. Today, the diagnosis of hypothyroidism is determined mainly by laboratory evaluation with most patients exhibiting only a few clinical signs of thyroid dysfunction. The treatment of hypothyroidism has progressed from partially purified extracts of bovine thyroid gland to an oral administration of synthetic hormone. Since 1981 the only thyroid hormone replacement drug approved by the Israeli Ministry of Health was the Eltroxin brand, made by GlaxoSmithKline. Levothyroxine has a narrow therapeutic range, thus a potential variance exists in the therapeutic efficacy among different levothyroxine preparations. In 2007 the Food and Drugs Administration (FDA) announced that the difference in potency of various levothyroxine brands should not exceed ten percent. In 2007 the GSK Company moved the manufacturing of Eltroxin from Canada to Germany. This resulted in a change of the inert ingredients of the drug. It is of interest to know that since the arrival of the new thyroxine formulation in the Israeli pharmaceutical market there has been a dramatic increase in reports of adverse reactions. The media coverage of adverse effects associated with Eltroxin became widespread in television, newspapers and internet sites. This led to a burden on the healthcare system, manifesting itself by an increase in thyroid blood tests, physician follow-up visits, as well as the importing and distribution of a new brand of thyroxine.

  6. A randomized controlled trial of calcium plus vitamin D supplementation and risk of benign proliferative breast disease

    PubMed Central

    Rohan, Thomas E.; Negassa, Abdissa; Chlebowski, Rowan T.; Ceria-Ulep, Clementina D.; Cochrane, Barbara B.; Lane, Dorothy S.; Ginsberg, Mindy; Wassertheil-Smoller, Sylvia; Page, David L.

    2014-01-01

    Experimental evidence provides strong support for anti-carcinogenic effects of calcium and vitamin D with respect to breast cancer. Observational epidemiologic data also provide some support for inverse associations with risk. We tested the effect of calcium plus vitamin D supplementation on risk of benign proliferative breast disease, a condition which is associated with increased risk of breast cancer. We used the Women’s Health Initiative randomized controlled trial. The 36,282 participants were randomized either to 500 mg of elemental calcium as calcium carbonate plus 200 IU of vitamin D3 (GlaxoSmithKline) twice daily (n = 18,176) or to placebo (n = 18,106). Regular mammograms and clinical breast exams were performed. We identified women who had had a biopsy for benign breast disease and subjected histologic sections from the biopsies to standardized review. After an average follow-up period of 6.8 years, 915 incident cases of benign proliferative breast disease had been ascertained, with 450 in the intervention group and 465 in the placebo group. Calcium plus vitamin D supplementation was not associated with altered risk of benign proliferative breast disease overall (hazard ratio = 0.99, 95% confidence interval = 0.86–1.13), or by histologic subtype. Risk varied significantly by levels of age at baseline, but not by levels of other variables. Daily use of 1,000 mg of elemental calcium as calcium carbonate plus 400 IU of vitamin D3 for almost 7 years by postmenopausal women did not alter the overall risk of benign proliferative breast disease. PMID:18853250

  7. The contribution of different information sources for adverse effects data.

    PubMed

    Golder, Su; Loke, Yoon K

    2012-04-01

    The aim of this study is to determine the relative value and contribution of searching different sources to identify adverse effects data. The process of updating a systematic review and meta-analysis of thiazolidinedione-related fractures in patients with type 2 diabetes mellitus was used as a case study. For each source searched, a record was made for each relevant reference included in the review noting whether it was retrieved with the search strategy used and whether it was available but not retrieved. The sensitivity, precision, and number needed to read from searching each source and from different combinations of sources were also calculated. There were 58 relevant references which presented sufficient numerical data to be included in a meta-analysis of fractures and bone mineral density. The highest number of relevant references were retrieved from Science Citation Index (SCI) (35), followed by BIOSIS Previews (27) and EMBASE (24). The precision of the searches varied from 0.88% (Scirus) to 41.67% (CENTRAL). With the search strategies used, the minimum combination of sources required to retrieve all the relevant references was; the GlaxoSmithKline (GSK) website, Science Citation Index (SCI), EMBASE, BIOSIS Previews, British Library Direct, Medscape DrugInfo, handsearching and reference checking, AHFS First, and Thomson Reuters Integrity or Conference Papers Index (CPI). In order to identify all the relevant references for this case study a number of different sources needed to be searched. The minimum combination of sources required to identify all the relevant references did not include MEDLINE.

  8. Switched memory B cells maintain specific memory independently of serum antibodies: the hepatitis B example.

    PubMed

    Rosado, M Manuela; Scarsella, Marco; Pandolfi, Elisabetta; Cascioli, Simona; Giorda, Ezio; Chionne, Paola; Madonne, Elisabetta; Gesualdo, Francesco; Romano, Mariateresa; Ausiello, Clara M; Rapicetta, Maria; Zanetti, Alessandro R; Tozzi, Alberto; Carsetti, Rita

    2011-06-01

    The immunogenicity of a vaccine is conventionally measured through the level of serum Abs early after immunization, but to ensure protection specific Abs should be maintained long after primary vaccination. For hepatitis B, protective levels often decline over time, but breakthrough infections do not seem to occur. The aim of this study was to demonstrate whether, after hepatitis B vaccination, B-cell memory persists even when serum Abs decline. We compared the frequency of anti-hepatitis-specific memory B cells that remain in the blood of 99 children five years after priming with Infanrix -hexa (GlaxoSmithKline) (n=34) or with Hexavac (Sanofi Pasteur MSD) (n=65). These two vaccines differ in their ability to generate protective levels of IgG. Children with serum Abs under the protective level, <10 mIU/mL, received a booster dose of hepatitis B vaccine, and memory B cells and serum Abs were measured 2 wk later. We found that specific memory B cells had a similar frequency in all children independently of primary vaccine. Booster injection resulted in the increase of memory B cell frequencies (from 11.3 in 10(6) cells to 28.2 in 10(6) cells, p<0.01) and serum Abs (geometric mean concentration, GMC from 2.9 to 284 mIU/mL), demonstrating that circulating memory B cells effectively respond to Ag challenge even when specific Abs fall under the protective threshold. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Evaluating the acute effects of oral, non-combustible potential reduced exposure products marketed to smokers

    PubMed Central

    Cobb, CO; Weaver, MF; Eissenberg, T

    2011-01-01

    Background Non-combustible potential reduced exposure products (PREPs; eg, Star Scientific’s Ariva; a variety of other smokeless tobacco products) are marketed to reduce the harm associated with smoking. This marketing occurs despite an absence of objective data concerning the toxicant exposure and effects of these PREPs. Methods used to examine combustible PREPs were adapted to assess the acute effects of non-combustible PREPs for smokers. Methods 28 overnight abstinent cigarette smokers (17 men, 14 non-white) each completed seven, Latin-squared ordered, approximately 2.5 h laboratory sessions that differed by product administered: Ariva, Marlboro Snus (Philip Morris, USA), Camel Snus (RJ Reynolds, Winston-Salem, North Carolina, USA), Commit nicotine lozenge (GlaxoSmithKline; 2 mg), own brand cigarettes, Quest cigarettes (Vector Tobacco; delivers very low levels of nicotine) and sham smoking (ie, puffing on an unlit cigarette). In each session, the product was administered twice (separated by 60 min), and plasma nicotine levels, expired air CO and subjective effects were assessed regularly. Results Non-combustible products delivered less nicotine than own brand cigarettes, did not expose smokers to CO and failed to suppress tobacco abstinence symptoms as effectively as combustible products. Conclusions While decreased toxicant exposure is a potential indicator of harm reduction potential, a failure to suppress abstinence symptoms suggests that currently marketed non-combustible PREPs may not be a viable harm reduction strategy for US smokers. This study demonstrates how clinical laboratory methods can be used to evaluate the short-term effects of non-combustible PREPs for smokers. PMID:19346218

  10. A clinical study to evaluate denture adhesive use in well-fitting dentures.

    PubMed

    Munoz, Carlos A; Gendreau, Linda; Shanga, Gilbert; Magnuszewski, Tabetha; Fernandez, Patricia; Durocher, John

    2012-02-01

    The objective of this study was the assessment of retention and stability and functional benefits of denture adhesive applied to well-fitting and well-made dentures. This was a randomized, crossover study to compare two marketed denture adhesives (test cream, Super Poligrip® Free, and test strip, Super Poligrip® Comfort Seal Strips) and an unmarketed cream adhesive (GlaxoSmith Kline Consumer Healthcare) with no adhesive as the negative control. Thirty-six subjects completed the study. One hour after the application of denture adhesive, retention and stability were measured using the Kapur Index and maxillary incisal bite force. Two hours after application, functional tests were used to assess denture movement and peanut particle migration under the denture. Subjects also rated confidence, comfort, satisfaction with dentures, and denture wobble in conjunction with the functional tests. Denture adhesives significantly (p < 0.05) improved retention and stability of well-fitting dentures. Subjects experienced significantly (p < 0.05) fewer dislodgements while eating an apple after adhesive was applied to dentures. Significant (p < 0.05) increases in subjective ratings of confidence and comfort as well as decreases in denture wobble were associated with the use of adhesive. There was significant (p < 0.05) improvement in satisfaction ratings for cream adhesives. A single application of each denture adhesive was well tolerated. The results of this study provide evidence that use of Super Poligrip® denture adhesives can enhance aspects of performance of complete well-fitting dentures as well as provide increased comfort, confidence, and satisfaction with dentures. © 2011 by the American College of Prosthodontists.

  11. Comparative bioavailability study of cefuroxime axetil (equivalent to 500 mg cefuroxime/tablet) tablets (Zednad® versus Zinnat®) in healthy male volunteers.

    PubMed

    Asiri, Y A; Al-Hadiya, B M; Kadi, A A; Al-Khamis, K I; Mowafy, H A; El-Sayed, Y M

    2011-09-01

    This study was performed to investigate the bioequivalence of cefuroxime axetil tablets between a generic test product (A) Zednad® Tablet (500 mg cefuroxime/ tablet, Diamond Pharma, Syria), and the Reference Product (B) Zinnat® Tablet (500 mg cefuroxime/tablet, GlaxoSmithKline, Saudi Arabia). The bioavailability study was carried out for 24 healthy male volunteers. The subjects received 1 Zednad® Tablet (500 mg/ tablet) and 1 Zinnat® Tablet (500 mg/tablet) in a randomized, two-way crossover design fashion on 2 treatment days, after an overnight fast of at least 10 h, with a washout period of 7 days. 24 volunteers plus 2 alternatives completed the crossover. The bioanalysis of clinical plasma samples was accomplished by HPLC method, which was developed and validated in accordance with international guidelines. Pharmacokinetic parameters, determined by standard non-compartmental methods, and ANOVA statistics were calculated using SAS Statistical Software. The significance of a sequence effect was tested using the subjects nested in sequence as the error term. The 90% confidence intervals for the ratio between the test and reference product pharmacokinetic parameters of AUC0→t, AUC0→∞, and Cmax were calculated and found to be within the confidence limits of 80.00 - 125.00% for AUC0→t, AUC0→∞ and Cmax. The study demonstrated that the test product (A) was found bioequivalent to the reference product (B) following an oral dose of 500 mg tablet. Therefore, the two formulations were considered to be bioequivalent.

  12. A Phenotypic Based Target Screening Approach Delivers New Antitubercular CTP Synthetase Inhibitors.

    PubMed

    Esposito, Marta; Szadocka, Sára; Degiacomi, Giulia; Orena, Beatrice S; Mori, Giorgia; Piano, Valentina; Boldrin, Francesca; Zemanová, Júlia; Huszár, Stanislav; Barros, David; Ekins, Sean; Lelièvre, Joel; Manganelli, Riccardo; Mattevi, Andrea; Pasca, Maria Rosalia; Riccardi, Giovanna; Ballell, Lluis; Mikušová, Katarína; Chiarelli, Laurent R

    2017-06-09

    Despite its great potential, the target-based approach has been mostly unsuccessful in tuberculosis drug discovery, while whole cell phenotypic screening has delivered several active compounds. However, for many of these hits, the cellular target has not yet been identified, thus preventing further target-based optimization of the compounds. In this context, the newly validated drug target CTP synthetase PyrG was exploited to assess a target-based approach of already known, but untargeted, antimycobacterial compounds. To this purpose the publically available GlaxoSmithKline antimycobacterial compound set was assayed, uncovering a series of 4-(pyridin-2-yl)thiazole derivatives which efficiently inhibit the Mycobacterium tuberculosis PyrG enzyme activity, one of them showing low activity against the human CTP synthetase. The three best compounds were ATP binding site competitive inhibitors, with K i values ranging from 3 to 20 μM, but did not show any activity against a small panel of different prokaryotic and eukaryotic kinases, thus demonstrating specificity for the CTP synthetases. Metabolic labeling experiments demonstrated that the compounds directly interfere not only with CTP biosynthesis, but also with other CTP dependent biochemical pathways, such as lipid biosynthesis. Moreover, using a M. tuberculosis pyrG conditional knock-down strain, it was shown that the activity of two compounds is dependent on the intracellular concentration of the CTP synthetase. All these results strongly suggest a role of PyrG as a target of these compounds, thus strengthening the value of this kind of approach for the identification of new scaffolds for drug development.

  13. Impact of high coverage of monovalent human rotavirus vaccine on Emergency Department presentations for rotavirus gastroenteritis.

    PubMed

    Davey, Heather M; Muscatello, David J; Wood, James G; Snelling, Thomas L; Ferson, Mark J; Macartney, Kristine K

    2015-03-30

    Australia was one of the first countries to introduce nationally funded rotavirus vaccination. The program has had a substantial impact on both rotavirus and all-cause acute gastroenteritis (AGE) hospitalisations and rotavirus laboratory tests. Evidence for an impact on Emergency Department (ED) presentations is limited. This study assessed changes in ED presentations for rotavirus in children aged <5 years in New South Wales, Australia, following introduction of monovalent human rotavirus vaccine (RV1, Rotarix(®), GlaxoSmithKline Australia Pty Ltd., Victoria, Australia). A time series analysis to examine trends in total non-admitted ED presentations for all-cause AGE and in the rotavirus-attributable fraction using data on rotavirus positive laboratory tests. A decline in the rate of non-admitted ED presentations for all-cause AGE was observed for all ages, being most notable in 1 year old children. Compared with the pre-vaccination period, we estimated the average weekly rate was lower across the first 4.5 years of the program for both all-cause AGE (18.3%; 70.5 versus 57.5 per 100,000 population) and rotavirus attributable (55.4%; 17.3 versus 7.7 per 100,000 population) presentations. In the fourth year of the program, estimated annual rotavirus attributable presentations were 77% lower than the pre-vaccination annual mean (996 versus 4300 per year). The program was associated with a substantial decline in rotavirus attributable non-admitted AGE presentations to ED among children aged <5 years. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

  14. [Career preferences among medical students].

    PubMed

    Soethout, Marc B M; ten Cate, Olle Th J

    2014-01-01

    Research on the preference of medical specialty among medical students in the Netherlands and the attractiveness of aspects of the medical profession during the period 2009-2013. Retrospective, descriptive research. Data from medical students in the Netherlands who participated in the computer programme Inventory Medical Professionals Choice (IMBK) were analyzed with respect to their preference of medical specialty and the attractiveness of various aspects of the medical profession. The IMBK programme was available free of charge through the Royal Dutch Medical Association (KNMG) website 'Arts in Spe' (Future Physician) during the period 2009-2013. The content of the IMBK programme was based on the questionnaire from the medical profile book developed by the pharmaceutical company GlaxoSmithKline (GSK). General practice was the most popular specialty, particularly among female medical students, with interest increasing during the undergraduate medical curriculum. Hardly any students were interested in insurance medicine, occupational medicine and elderly medicine. Direct patient care was the most attractive professional aspect for medical students. Female students were more attracted to direct and prolonged patient contact than their male counterparts. The number of hours students wished to work in future declined during the course of the undergraduate curriculum, and women were more inclined to prefer regular working hours with adequate leisure time than men. During the course of the undergraduate medical curriculum, medical students changed their preference for medical specialty. Major differences exist between male and female students in terms of preference of medical specialty and attractiveness of aspects of the medical profession.

  15. 76 FR 60733 - Drawbridge Operation Regulations; Narrow Bay, Smith Point, NY

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-30

    ... Operation Regulations; Narrow Bay, Smith Point, NY AGENCY: Coast Guard, DHS. ACTION: Notice of temporary... deviation from the regulation governing the operation of the Smith Point Bridge, 6.1, across Narrow Bay, between Smith Point and Fire Island, New York. The deviation is necessary to facilitate bridge...

  16. Oscar F. Smith Middle School: One Extra Degree

    ERIC Educational Resources Information Center

    Principal Leadership, 2012

    2012-01-01

    This article features Oscar F. Smith Middle School, a challenging school in Chesapeake, Virginia. When Principal Linda Scott exclaims, "Oscar F. Smith Middle School is "hot"!" to visitors, she is not referring to the inside temperature of the bustling school of grades 6-8 located in the historic South Norfolk borough of…

  17. STS-82 Mission Specialist Steven L. Smith Suit Up

    NASA Technical Reports Server (NTRS)

    1997-01-01

    STS-82 Mission Specialist Steven L. Smith gives a ''';thumbs up'''; while donning his launch and entry suit in the Operations and Checkout Building. A suit technician stands ready to assist with final adjustments. This is Smith''';s second space flight. He and the six other crew members will depart shortly for Launch Pad 39A, where the Space Shuttle Discovery awaits liftoff on a 10-day mission to service the orbiting Hubble Space Telescope (HST). This will be the second HST servicing mission. Four back-to-back spacewalks are planned.

  18. Waldo E. Smith receives first award of his namesake medal

    NASA Astrophysics Data System (ADS)

    Smith, Waldo E.

    This evening marks the first presentation of the American Geophysical Union's Waldo E. Smith Award. While all other AGU awards and honors are given for excellence in scientific research in one or another of the geophysical disciplines, this award is different. The Waldo E. Smith Award is given for dedicated and extraordinary service to geophysics and AGU. It is the principal purpose of this citation to show why it is particularly appropriate that an award for service to American geophysics should be called the Waldo E. Smith Award. A secondary objective, aimed at those present tonight, is to introduce the first recipient of this award, Waldo E. Smith, Executive Director Emeritus of AGU.

  19. 78 FR 32250 - CDM Smith and Dynamac Corp; Transfer of Data

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-29

    ... ENVIRONMENTAL PROTECTION AGENCY [EPA-HQ-OPP-2013-0036; FRL-9387-5] CDM Smith and Dynamac Corp... the submitter, will be transferred to CDM Smith and its subcontractor, Dynamac Corp, in accordance with 40 CFR 2.307(h)(3) and 2.308(i)(2). CDM Smith and its subcontractor, Dynamac Corp, have been...

  20. Alternative Fuels Data Center: Smith Dairy Deploys Natural Gas Vehicles and

    Science.gov Websites

    Fueling Infrastructure in the Midwest Smith Dairy Deploys Natural Gas Vehicles and Fueling Infrastructure in the Midwest to someone by E-mail Share Alternative Fuels Data Center: Smith Dairy Deploys Data Center: Smith Dairy Deploys Natural Gas Vehicles and Fueling Infrastructure in the Midwest on

  1. MAGNETIZED GAS IN THE SMITH HIGH VELOCITY CLOUD

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

    Hill, Alex S.; McClure-Griffiths, Naomi M.; Mao, S. A.

    2013-11-01

    We report the first detection of magnetic fields associated with the Smith High Velocity Cloud. We use a catalog of Faraday rotation measures toward extragalactic radio sources behind the Smith Cloud, new H I observations from the Robert C. Byrd Green Bank Telescope, and a spectroscopic map of Hα from the Wisconsin H-Alpha Mapper Northern Sky Survey. There are enhancements in rotation measure (RM) of ≈100 rad m{sup –2} which are generally well correlated with decelerated Hα emission. We estimate a lower limit on the line-of-sight component of the field of ≈8 μG along a decelerated filament; this is amore » lower limit due to our assumptions about the geometry. No RM excess is evident in sightlines dominated by H I or Hα at the velocity of the Smith Cloud. The smooth Hα morphology of the emission at the Smith Cloud velocity suggests photoionization by the Galactic ionizing radiation field as the dominant ionization mechanism, while the filamentary morphology and high (≈1 Rayleigh) Hα intensity of the lower-velocity magnetized ionized gas suggests an ionization process associated with shocks due to interaction with the Galactic interstellar medium. The presence of the magnetic field may contribute to the survival of high velocity clouds like the Smith Cloud as they move from the Galactic halo to the disk. We expect these data to provide a test for magnetohydrodynamic simulations of infalling gas.« less

  2. 77 FR 13593 - PowerSmith Cogeneration Project, LP; Notice of Request for Waiver

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-07

    ...] PowerSmith Cogeneration Project, LP; Notice of Request for Waiver Take notice that on February 27, 2012... CFR 292.205(c), PowerSmith Cogeneration Project, LP (PowerSmith) filed a Request for Waiver, for... Regulations for the topping- cycle cogeneration facility owned and operated by PowerSmith located in Oklahoma...

  3. Fukushima to receive Smith Medal

    NASA Astrophysics Data System (ADS)

    The 1990 Waldo E. Smith Medal for extraordinary service to geophysics will be given to Naoshi Fukushima, who earned an international reputation for his pioneering work in geomagnetic disturbance and ionospheric electric currents. Now retired from the University of Tokyo, Japan, Fukushima is being cited for his public service to international geophysics, and, in particular, his contributions to the International Association of Geomagnetism and Aeronomy, of which he was Secretary General from September 1975 to August 1983.The Smith Medal will be presented as part of the AGU Fall Meeting Honors Night festivities, Wednesday, December 5, in San Francisco, Calif. Three James B. Macelwane Medals, the John Adam Fleming Medal, and the Maurice Ewing Medal will also be presented (see Eos, February 20, 1990, p. 294).

  4. Illustrated & Dissected: Professor Richard Sawdon Smith.

    PubMed

    2015-06-01

    This Alternative Gallery feature introduces the photographic artist Professor Richard Sawdon Smith. Professor Sawdon Smith's work stems around a fascination with representations of anatomy that have been fuelled by his experience as a hospital patient. The work has allowed him to explore ideas through the use of medical illustrations which include early anatomical drawings, personal medical photography and facial modelling. The work highlights how such imagery can be used in the context of a patient seeking understanding and acceptance of ill health and disease using the body as a canvas on which to translate the experience.

  5. STS-103 Crew Interviews: Steven Smith

    NASA Technical Reports Server (NTRS)

    1999-01-01

    Live footage of a preflight interview with Mission Specialist Steven L. Smith is seen. The interview addresses many different questions including why Brown became an astronaut, the events that led to his interest, any role models that he had, and his inspiration. Other interesting information that this one-on-one interview discusses is an explanation of the why this required mission to service the Hubble Space Telescope must take place at such an early date, replacement of the gyroscopes, transistors, and computers. Also discussed is Smith's responsibility during any of the planned space walks scheduled for this mission.

  6. The Smith-Lemli-Opitz syndrome

    PubMed Central

    Kelley, R.; Hennekam, R.

    2000-01-01

    The Smith-Lemli-Opitz syndrome (SLOS) is one of the archetypical multiple congenital malformation syndromes. The recent discovery of the biochemical cause of SLOS and the subsequent redefinition of SLOS as an inborn error of cholesterol metabolism have led to important new treatment possibilities for affected patients. Moreover, the recent recognition of the important role of cholesterol in vertebrate embryogenesis, especially with regard to the hedgehog embryonic signalling pathway and its effects on the expression of homeobox genes, has provided an explanation for the abnormal morphogenesis in the syndrome. The well known role of cholesterol in the formation of steroid hormones has also provided a possible explanation for the abnormal behavioural characteristics of SLOS.


Keywords: Smith-Lemli-Opitz syndrome; cholesterol metabolism; 7-dehydrocholesterol reductase; clinical history; management PMID:10807690

  7. [Drug clinics. Drug of the month. A new measles-rubella-mumps vaccine (Priorix)].

    PubMed

    Senterre, J

    1999-02-01

    A novel measles-mumps-rubella vaccine (Priorix) has been marketed by SmithKline Beecham. It contains live attenuated virus with measles and mumps strains slightly different from those present in MMR VAX (Pasteur Merieux MSD). The indications and contraindications are similar for both vaccines. Immunogenicity is also equivalent as well as general reactogenicity. By contrast local symptoms were reported significantly less frequently after Priorix.

  8. Solar Cycle Fine Structure and Surface Rotation from Ca II K-Line Time Series Data

    NASA Technical Reports Server (NTRS)

    Scargle, Jeff; Keil, Steve; Worden, Pete

    2011-01-01

    Analysis of three and a half decades of data from the NSO/AFRL/Sac Peak K-line monitoring program yields evidence for four components to the variation: (a) the solar cycle, with considerable fine structure and a quasi-periodicity of 122.4 days; (b) a stochastic process, faster than (a) and largely independent of it, (c) a quasi-periodic signal due to rotational modulation, and of course (d) observational errors (shown to be quite small). Correlation and power spectrum analyses elucidate periodic and aperiodic variation of these chromospheric parameters. Time-frequency analysis is especially useful for extracting information about differential rotation, and in particular elucidates the connection between its behavior and fine structure of the solar cycle on approximately one-year time scales. These results further suggest that similar analyses will be useful at detecting and characterizing differential rotation in stars from stellar light-curves such as those being produced at NASA's Kepler observatory.

  9. 40 CFR 81.63 - Metropolitan Fort Smith Interstate Air Quality Control Region.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 17 2010-07-01 2010-07-01 false Metropolitan Fort Smith Interstate Air... Air Quality Control Regions § 81.63 Metropolitan Fort Smith Interstate Air Quality Control Region. The Metropolitan Fort Smith Interstate Air Quality Control Region (Arkansas-Oklahoma) has been revised to consist...

  10. SMITH FARM FROM EBEY ROAD, LOOKING NORTH. (At the right, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    SMITH FARM FROM EBEY ROAD, LOOKING NORTH. (At the right, this image shows the addition added to the granary in 1998 in order to adapt it to a family home.) - Smith Farm, 399 Ebey Road, Coupeville, Island County, WA

  11. Author! Author! The Gallant Children's Author: Dick King-Smith

    ERIC Educational Resources Information Center

    Brodie, Carolyn S.

    2005-01-01

    This column presents a brief biography of Dick King-Smith. Born on March 27, 1922 and raised in Gloucestershire, England, he grew up with animals of all kinds. King-Smith was a farmer for twenty years and then became a school teacher. He was also a soldier during wartime, a traveling salesman, shoe factory worker, and television presenter. He…

  12. Manipulating Smith-Purcell Emission with Babinet Metasurfaces

    NASA Astrophysics Data System (ADS)

    Wang, Zuojia; Yao, Kan; Chen, Min; Chen, Hongsheng; Liu, Yongmin

    2016-10-01

    Swift electrons moving closely parallel to a periodic grating produce far-field radiation of light, which is known as the Smith-Purcell effect. In this letter, we demonstrate that designer Babinet metasurfaces composed of C -aperture resonators offer a powerful control over the polarization state of the Smith-Purcell emission, which can hardly be achieved via traditional gratings. By coupling the intrinsically nonradiative energy bound at the source current sheet to the out-of-plane electric dipole and in-plane magnetic dipole of the C -aperture resonator, we are able to excite cross-polarized light thanks to the bianisotropic nature of the metasurface. The polarization direction of the emitted light is aligned with the orientation of the C -aperture resonator. Furthermore, the efficiency of the Smith-Purcell emission from Babinet metasurfaces is significantly increased by 84%, in comparison with the case of conventional gratings. These findings not only open up a new way to manipulate the electron-beam-induced emission in the near-field region but also promise compact, tunable, and efficient light sources and particle detectors.

  13. Manipulating Smith-Purcell Emission with Babinet Metasurfaces.

    PubMed

    Wang, Zuojia; Yao, Kan; Chen, Min; Chen, Hongsheng; Liu, Yongmin

    2016-10-07

    Swift electrons moving closely parallel to a periodic grating produce far-field radiation of light, which is known as the Smith-Purcell effect. In this letter, we demonstrate that designer Babinet metasurfaces composed of C-aperture resonators offer a powerful control over the polarization state of the Smith-Purcell emission, which can hardly be achieved via traditional gratings. By coupling the intrinsically nonradiative energy bound at the source current sheet to the out-of-plane electric dipole and in-plane magnetic dipole of the C-aperture resonator, we are able to excite cross-polarized light thanks to the bianisotropic nature of the metasurface. The polarization direction of the emitted light is aligned with the orientation of the C-aperture resonator. Furthermore, the efficiency of the Smith-Purcell emission from Babinet metasurfaces is significantly increased by 84%, in comparison with the case of conventional gratings. These findings not only open up a new way to manipulate the electron-beam-induced emission in the near-field region but also promise compact, tunable, and efficient light sources and particle detectors.

  14. The legendary Smiths and their Paris hospital.

    PubMed

    Prewitt, Taylor; Smith, John C; Bell, J P

    2015-01-01

    The Paris Hospital in Paris, Arkansas, provided high quality care during its existence from 1910 to 1971, offering a prepaid health care plan from 1920 to 1971. Three generations of Smith doctors were its nucleus, subsidizing the annual losses of the hospital and providing care to all, regardless of ability to pay. The hospital was a community unto itself for the nurses who lived, trained, and worked there. A unique family in the history of medicine in Arkansas, the Smith physicians were well trained, altruistic, compassionate, and conscientious, exemplifying the traditional values of twentieth century medical practice.

  15. New developments in Smith-Magenis syndrome (del 17p11.2).

    PubMed

    Gropman, Andrea L; Elsea, Sarah; Duncan, Wallace C; Smith, Ann C M

    2007-04-01

    Recent clinical, neuroimaging, sleep, and molecular cytogenetic studies have provided new insights into the mechanisms leading to the Smith-Magenis phenotype and are summarized in this review. Cross sectional studies of patients with Smith-Magenis syndrome have found evidence for central and peripheral nervous system abnormalities, neurobehavioral disturbances, and an inverted pattern of melatonin secretion leading to circadian rhythm disturbance. A common chromosome 17p11.2 deletion interval spanning approximately 3.5 Mb is identified in about 70% of individuals with chromosome deletion. Recently heterozygous point mutations in the RAI1 gene within the Smith-Magenis syndrome critical region have been reported in Smith-Magenis syndrome patients without detectable deletion by fluorescent in-situ hybridization. Patients with intragenic mutations in RAI1 as well as those with deletions share most but not all aspects of the phenotype. Findings from molecular cytogenetic analysis suggest that other genes or genetic background may play a role in altering the functional availability of RAI1 for downstream effects. Further research into additional genes in the Smith-Magenis syndrome critical region will help define the role they play in modifying features or severity of the Smith-Magenis syndrome phenotype. More research is needed to translate advances in clinical research into new treatment options to address the sleep and neurobehavioral problems in this disorder.

  16. 77 FR 58181 - Power Resources, Inc., Smith Ranch Highland Uranium Project; License Renewal Request, Opportunity...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-19

    ... NUCLEAR REGULATORY COMMISSION [Docket No. 04008964, NRC-2012-0214] Power Resources, Inc., Smith... available in ADAMS) is provided the first time that a document is referenced. The Smith Ranch Highland... (Smith Ranch Technical Report); Accession No. ML12234A539 (Smith Ranch Environmental Report). In addition...

  17. Rationalizing fragment based drug discovery for BACE1: insights from FB-QSAR, FB-QSSR, multi objective (MO-QSPR) and MIF studies

    NASA Astrophysics Data System (ADS)

    Manoharan, Prabu; Vijayan, R. S. K.; Ghoshal, Nanda

    2010-10-01

    The ability to identify fragments that interact with a biological target is a key step in FBDD. To date, the concept of fragment based drug design (FBDD) is increasingly driven by bio-physical methods. To expand the boundaries of QSAR paradigm, and to rationalize FBDD using In silico approach, we propose a fragment based QSAR methodology referred here in as FB-QSAR. The FB-QSAR methodology was validated on a dataset consisting of 52 Hydroxy ethylamine (HEA) inhibitors, disclosed by GlaxoSmithKline Pharmaceuticals as potential anti-Alzheimer agents. To address the issue of target selectivity, a major confounding factor in the development of selective BACE1 inhibitors, FB-QSSR models were developed using the reported off target activity values. A heat map constructed, based on the activity and selectivity profile of the individual R-group fragments, and was in turn used to identify superior R-group fragments. Further, simultaneous optimization of multiple properties, an issue encountered in real-world drug discovery scenario, and often overlooked in QSAR approaches, was addressed using a Multi Objective (MO-QSPR) method that balances properties, based on the defined objectives. MO-QSPR was implemented using Derringer and Suich desirability algorithm to identify the optimal level of independent variables ( X) that could confer a trade-off between selectivity and activity. The results obtained from FB-QSAR were further substantiated using MIF (Molecular Interaction Fields) studies. To exemplify the potentials of FB-QSAR and MO-QSPR in a pragmatic fashion, the insights gleaned from the MO-QSPR study was reverse engineered using Inverse-QSAR in a combinatorial fashion to enumerate some prospective novel, potent and selective BACE1 inhibitors.

  18. Influence of compulsivity of drug abuse on dopaminergic modulation of attentional bias in stimulant dependence.

    PubMed

    Ersche, Karen D; Bullmore, Edward T; Craig, Kevin J; Shabbir, Shaila S; Abbott, Sanja; Müller, Ulrich; Ooi, Cinly; Suckling, John; Barnes, Anna; Sahakian, Barbara J; Merlo-Pich, Emilio V; Robbins, Trevor W

    2010-06-01

    There are no effective pharmacotherapies for stimulant dependence but there are many plausible targets for development of novel therapeutics. We hypothesized that dopamine-related targets are relevant for treatment of stimulant dependence, and there will likely be individual differences in response to dopaminergic challenges. To measure behavioral and brain functional markers of drug-related attentional bias in stimulant-dependent individuals studied repeatedly after short-term dosing with dopamine D(2)/D(3) receptor antagonist and agonist challenges. Randomized, double-blind, placebo-controlled, parallel-groups, crossover design using pharmacological functional magnetic resonance imaging. Clinical research unit (GlaxoSmithKline) and local community in Cambridge, England. Stimulant-dependent individuals (n = 18) and healthy volunteers (n = 18). Amisulpride (400 mg), pramipexole dihydrochloride (0.5 mg), or placebo were administered in counterbalanced order at each of 3 repeated testing sessions. Attentional bias for stimulant-related words was measured during functional magnetic resonance imaging by a drug-word Stroop paradigm; trait impulsivity and compulsivity of dependence were assessed at baseline by questionnaire. Drug users demonstrated significant attentional bias for drug-related words, which was correlated with greater activation of the left prefrontal and right cerebellar cortex. Attentional bias was greater in people with highly compulsive patterns of stimulant abuse; the effects of dopaminergic challenges on attentional interference and related frontocerebellar activation were different between high- and low-compulsivity subgroups. Greater attentional bias for and greater prefrontal activation by stimulant-related words constitute a candidate neurocognitive marker for dependence. Individual differences in compulsivity of stimulant dependence had significant effects on attentional bias, its brain functional representation, and its short-term modulation

  19. Chronic obstructive pulmonary disease, bronchial asthma and allergic rhinitis in the adult population within the commonwealth of independent states: rationale and design of the CORE study.

    PubMed

    Feshchenko, Yuriy; Iashyna, Liudmyla; Nugmanova, Damilya; Gyrina, Olga; Polianska, Maryna; Markov, Alexander; Moibenko, Maryna; Makarova, Janina; Tariq, Luqman; Pereira, Marcelo Horacio S; Mammadbayov, Eljan; Akhundova, Irada; Vasylyev, Averyan

    2017-10-10

    Main treatable Chronic Respiratory Diseases (CRDs) like Chronic Obstructive Pulmonary Disease (COPD), Bronchial Asthma (BA) and Allergic Rhinitis (AR) are underdiagnosed and undertreated worldwide. CORE study was aimed to assess the point prevalence of COPD, BA and AR in the adult population of major cities of Commonwealth of Independent States (CIS) countries - Azerbaijan, Kazakhstan, and Ukraine based on study questionnaires and/or spirometry, and to document risk factors, characterize the COPD, BA and AR population to provide a clearer "epidemiological data". A descriptive, cross-sectional, population-based epidemiological study conducted from 2013 to 2015 with two-stage cluster geographical randomization. Interviewers conducted face-to-face visits at respondent's household after informed consent and eligibility assessment including interviews, anthropometry, spirometry (with bronchodilator test) and completion of disease-specific questionnaires. Two thousand eight hundred forty-two respondents (Ukraine: 964 from Ukraine; 945 from Kazakhstan; 933 Azerbaijan) were enrolled. Mean age was 40-42 years and males were 37%-42% across three countries. In Kazakhstan 62.8% were Asians, but in Ukraine and in Azerbaijan 99.7% and 100.0%, respectively, were Caucasians. Manual labourers constituted 40.5% in Ukraine, 22.8% in Kazakhstan and 22.0% in Azerbaijan, while office workers were 16.1%, 31.6% and 36.8% respectively. 51.3% respondents in Ukraine, 64.9% in Kazakhstan and 69.7% in Azerbaijan were married. CORE study collected information that can be supportive for health policy decision makers in allocating healthcare resources in order to improve diagnosis and management of CRDs. The detailed findings will be described in future publications. Study Protocol Summary is disclosed at GlaxoSmithKline Clinical Study Register on Jun 06, 2013, study ID 116757 .

  20. The Potential Public Health Impact of Herpes Zoster Vaccination of People Aged ≥ 50 Years in Japan: Results of a Markov Model Analysis.

    PubMed

    Watanabe, Daisuke; Mizukami, Akiko; Holl, Katsiaryna; Curran, Desmond; Van Oorschot, Desirée; Varghese, Lijoy; Shiragami, Makoto

    2018-06-01

    The aim of this study was to compare the public health impact of introducing two herpes zoster (HZ) vaccines into the vaccination programs for the Japanese population aged ≥ 50 years: a single-dose Varicella Vaccine Live (VVL) or a two-dose adjuvanted Recombinant Zoster Vaccine (RZV). A multi-cohort static Markov model was developed to follow age cohorts (50-59, 60-69, 70-79 and ≥ 80 years) over their remaining lifetime. Japan-specific data inputs for the model were obtained from Japanese data sources. Age-stratified vaccine efficacy and waning rates were based on published clinical trial data. In the base-case analysis, vaccine coverage was assumed to be 40% for both vaccines, and compliance with second-dose of the RZV vaccine was set to 95%. Vaccination with RZV was projected to prevent approximately 3.3 million HZ cases, 692,000 cases of postherpetic neuralgia (PHN), and 281,000 cases of other complications, compared with the prevention of 0.8 million HZ cases, 216,000 PHN cases, and 57,000 other complications with vaccination with VVL. The number of individuals needed to vaccinate in order to prevent one HZ case ranged from 6 to 14 using RZV (depending on age and assumed second-dose compliance) and from 21 to 138 depending on age using VVL. By preventing a higher number of HZ cases and its complications, RZV vaccination led to fewer outpatient visits and hospitalizations than vaccination with VVL. Both vaccines had a positive public health impact compared to no vaccination, but due to its higher vaccine efficacy, RZV demonstrated a superior public health impact compared with VVL. GlaxoSmithKline Biologicals SA.

  1. Rationalizing fragment based drug discovery for BACE1: insights from FB-QSAR, FB-QSSR, multi objective (MO-QSPR) and MIF studies.

    PubMed

    Manoharan, Prabu; Vijayan, R S K; Ghoshal, Nanda

    2010-10-01

    The ability to identify fragments that interact with a biological target is a key step in FBDD. To date, the concept of fragment based drug design (FBDD) is increasingly driven by bio-physical methods. To expand the boundaries of QSAR paradigm, and to rationalize FBDD using In silico approach, we propose a fragment based QSAR methodology referred here in as FB-QSAR. The FB-QSAR methodology was validated on a dataset consisting of 52 Hydroxy ethylamine (HEA) inhibitors, disclosed by GlaxoSmithKline Pharmaceuticals as potential anti-Alzheimer agents. To address the issue of target selectivity, a major confounding factor in the development of selective BACE1 inhibitors, FB-QSSR models were developed using the reported off target activity values. A heat map constructed, based on the activity and selectivity profile of the individual R-group fragments, and was in turn used to identify superior R-group fragments. Further, simultaneous optimization of multiple properties, an issue encountered in real-world drug discovery scenario, and often overlooked in QSAR approaches, was addressed using a Multi Objective (MO-QSPR) method that balances properties, based on the defined objectives. MO-QSPR was implemented using Derringer and Suich desirability algorithm to identify the optimal level of independent variables (X) that could confer a trade-off between selectivity and activity. The results obtained from FB-QSAR were further substantiated using MIF (Molecular Interaction Fields) studies. To exemplify the potentials of FB-QSAR and MO-QSPR in a pragmatic fashion, the insights gleaned from the MO-QSPR study was reverse engineered using Inverse-QSAR in a combinatorial fashion to enumerate some prospective novel, potent and selective BACE1 inhibitors.

  2. Iodine-131 tositumomab (Bexxar) in a radiation oncology environment

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

    Macklis, Roger M.

    2006-10-01

    Iodine-131 (I-131) tositumomab (Bexxar; GlaxoSmithKline, Research Triangle Park, NC) is one of two recently approved radiolabeled antibodies directed against the CD20 surface antigen found on normal B cells and in more than 95% of B cell non-Hodgkin's lymphoma. The compound itself is formulated as an IgG2a immunoglobulin radiolabeled with the mixed beta/gamma emitter I-131. Multicenter clinical trials have repeatedly shown impressive clinical responses (20-40% complete response rates and 60-80% overall response rates) in the patient groups for whom this treatment is indicated. Treatment-related toxicity is generally extremely mild and typically involves only reversible hematopoietic suppression and (in some cases) amore » risk of treatment-induced hypothyroidism. Owing to Radiation safety concerns necessitated by the clinical use of this targeted radiopharmaceutical, it is important for radiation oncology departments wishing to participate in the care of these patients to establish methodologies and standard operating procedures for safe and efficient departmental use. This summary reviews the pertinent background information related to the current clinical experience with I-131 tositumomab and highlights some of the major opportunities for the participation of radiation oncology in the patient evaluation and treatment process. I-131 tositumomab provides an excellent example of the way in which the increasingly important new field of 'targeted therapy' intersects with the practice of clinical radiotherapy. The author contends that it will be worth the time and effort involved in establishing a firm basis for the development of a comprehensive program for systemic targeted radiopharmaceutical therapies (STaRT) within Radiation medicine domain.« less

  3. Role of human papillomavirus and its detection in potentially malignant and malignant head and neck lesions: updated review.

    PubMed

    Chaudhary, Ajay Kumar; Singh, Mamta; Sundaram, Shanthy; Mehrotra, Ravi

    2009-06-25

    Head and neck malignancies are characterized by a multiphasic and multifactorial etiopathogenesis. Tobacco and alcohol consumption are the most common risk factors for head and neck malignancy. Other factors, including DNA viruses, especially human papilloma virus (HPV), may also play a role in the initiation or development of these lesions. The pathways of HPV transmission in the head and neck mucosal lesions include oral-genital contact, more than one sexual partner and perinatal transmission of HPV to the neonatal child. The increase in prevalence of HPV infection in these lesions may be due to wider acceptance of oral sex among teenagers and adults as this is perceived to be a form of safe sex. The prevalence of HPV in benign lesions as well as malignancies has been assessed by many techniques. Among these, the polymerase chain reaction is the most sensitive method. Review of literature reveals that HPV may be a risk factor for malignancies, but not in all cases. For confirmation of the role of HPV in head and neck squamous cell carcinoma, large population studies are necessary in an assortment of clinical settings. Prophylactic vaccination against high-risk HPV types eventually may prevent a significant number of cervical carcinomas. Of the two vaccines currently available, Gardasil (Merck & Co., Inc.) protects against HPV types 6, 11, 16 and 18, while the other vaccine, Cervarix (GlaxoSmithKline, Rixensart, Belgium) protects against HPV types 16 and 18 only. However, the HPV vaccine has, to the best of our knowledge, not been tried in head and neck carcinoma. The role of HPV in etiopathogenesis, prevalence in benign and malignant lesions of this area and vaccination strategies are briefly reviewed here.

  4. One year environmental surveillance of rotavirus specie A (RVA) genotypes in circulation after the introduction of the Rotarix® vaccine in Rio de Janeiro, Brazil.

    PubMed

    Fumian, Tulio Machado; Leite, José Paulo Gagliardi; Rose, Tatiana Lundgreen; Prado, Tatiana; Miagostovich, Marize Pereira

    2011-11-01

    Rotavirus specie A (RVA) infection is the leading cause of severe acute diarrhea among young children worldwide. To reduce this major RVA health impact, the Rotarix® vaccine (GlaxoSmithKline, Rixensart, Belgium) was introduced in the Brazilian Expanded Immunization Program in March 2006 and became available to the entire birth cohort. The aim of this study was to evaluate the spread of RVA in the environment after the introduction of Rotarix® in Brazil. For this purpose, a Wastewater Treatment Plant (WTP) in Rio de Janeiro was monitored for one year to detect, characterize and discriminate RVA genotypes and identify possible circulation of vaccine strains. Using TaqMan® quantitative PCR (qPCR), RVA was detected in 100% (mean viral loads from 2.40×10(5) to 1.16×10(7) genome copies (GC)/L) of sewage influent samples and 71% (mean viral loads from 1.35×10(3) to 1.64×10(5)GC/L) of sewage effluent samples. The most prevalent RVA genotypes were P[4], P[6] and G2, based on VP4 and VP7 classification. Direct nucleotide sequencing (NSP4 fragment) and restriction enzyme digestion (NSP3) analysis did not detect RVA vaccine-like strains from the sewage samples. These data on RVA detection, quantification and molecular characterization highlight the importance of environmental monitoring as a tool to study RVA epidemiology in the surrounding human population and may be useful on ongoing vaccine monitoring programs, since sewage may be a good screening option for a rapid and economical overview of the circulating genotypes. Copyright © 2011 Elsevier Ltd. All rights reserved.

  5. Reactogenicity and safety of a liquid human rotavirus vaccine (RIX4414) in healthy adults, children and infants in China

    PubMed Central

    Li, Rong-Cheng; Li, Yan-Ping; Mo, Zhao-Jun; Luo, Dong; Huang, Teng; Kong, Ji-Lian; Wang, Lao-Hong; Song, Ning-Sheng; Liu, Aixue; Zhang, Helen; Liao, Xueyan; Karkada, Naveen; Han, Htay Htay

    2013-01-01

    We report the findings of three randomized, double-blind, placebo-controlled Phase I studies undertaken to support licensure of the liquid formulation of the human G1P[8] rotavirus (RV) vaccine (RIX4414; GlaxoSmithKline Biologicals SA) in China. Healthy adults aged 18–45 y (n = 48) and children aged 2–6 y (n = 50) received a single dose of the human RV vaccine or placebo. Healthy infants (n = 50) aged 6–16 weeks at the time of first vaccination received two oral doses of the human RV vaccine or placebo according to a 0, 1 mo schedule. In infants, blood samples were collected prior to vaccination and one month post-dose 2 to assess anti-RV IgA antibody concentrations using ELISA. Stool samples were collected from all infants on the day of each vaccination, at 7 and 15 d after each vaccination and one month post-dose 2. Stool samples were analyzed by ELISA for detection of RV antigen to assess RV antigen excretion. The reactogenicity profile of the human RV vaccine was found to be comparable to that of placebo in all age groups studied. The anti-RV IgA antibody seroconversion rate in infants after two vaccine doses was 86.7% (95% CI: 59.5–98.3). Vaccine take in infants who received the liquid human RV vaccine was 86.7% (95% CI: 59.5–98.3). A Phase III efficacy study of the human RV vaccine in the infant population in China has now been completed (ROTA-075/NCT01171963). PMID:23807360

  6. Investigation of a regulatory agency enquiry into potential porcine circovirus type 1 contamination of the human rotavirus vaccine, Rotarix: approach and outcome.

    PubMed

    Dubin, Gary; Toussaint, Jean-François; Cassart, Jean-Pol; Howe, Barbara; Boyce, Donna; Friedland, Leonard; Abu-Elyazeed, Remon; Poncelet, Sylviane; Han, Htay Htay; Debrus, Serge

    2013-11-01

    In January 2010, porcine circovirus type 1 (PCV1) DNA was unexpectedly detected in the oral live-attenuated human rotavirus vaccine, Rotarix (GlaxoSmithKline [GSK] Vaccines) by an academic research team investigating a novel, highly sensitive analysis not routinely used for adventitious agent screening. GSK rapidly initiated an investigation to confirm the source, nature and amount of PCV1 in the vaccine manufacturing process and to assess potential clinical implications of this finding. The investigation also considered the manufacturer's inactivated poliovirus (IPV)-containing vaccines, since poliovirus vaccine strains are propagated using the same cell line as the rotavirus vaccine strain. Results confirmed the presence of PCV1 DNA and low levels of PCV1 viral particles at all stages of the Rotarix manufacturing process. PCV type 2 DNA was not detected at any stage. When tested in human cell lines, productive PCV1 infection was not observed. There was no immunological or clinical evidence of PCV1 infection in infants who had received Rotarix in clinical trials. PCV1 DNA was not detected in the IPV-containing vaccine manufacturing process beyond the purification stage. Retrospective testing confirmed the presence of PCV1 DNA in Rotarix since the initial stages of its development and in vaccine lots used in clinical studies conducted pre- and post-licensure. The acceptable safety profile observed in clinical trials of Rotarix therefore reflects exposure to PCV1 DNA. The investigation into the presence of PCV1 in Rotarix could serve as a model for risk assessment in the event of new technologies identifying adventitious agents in the manufacturing of other vaccines and biological products.

  7. Investigation of a regulatory agency enquiry into potential porcine circovirus type 1 contamination of the human rotavirus vaccine, Rotarix™

    PubMed Central

    Dubin, Gary; Toussaint, Jean-François; Cassart, Jean-Pol; Howe, Barbara; Boyce, Donna; Friedland, Leonard; Abu-Elyazeed, Remon; Poncelet, Sylviane; Han, Htay Htay; Debrus, Serge

    2013-01-01

    In January 2010, porcine circovirus type 1 (PCV1) DNA was unexpectedly detected in the oral live-attenuated human rotavirus vaccine, Rotarix™ (GlaxoSmithKline [GSK] Vaccines) by an academic research team investigating a novel, highly sensitive analysis not routinely used for adventitious agent screening. GSK rapidly initiated an investigation to confirm the source, nature and amount of PCV1 in the vaccine manufacturing process and to assess potential clinical implications of this finding. The investigation also considered the manufacturer’s inactivated poliovirus (IPV)-containing vaccines, since poliovirus vaccine strains are propagated using the same cell line as the rotavirus vaccine strain. Results confirmed the presence of PCV1 DNA and low levels of PCV1 viral particles at all stages of the Rotarix™ manufacturing process. PCV type 2 DNA was not detected at any stage. When tested in human cell lines, productive PCV1 infection was not observed. There was no immunological or clinical evidence of PCV1 infection in infants who had received Rotarix™ in clinical trials. PCV1 DNA was not detected in the IPV-containing vaccine manufacturing process beyond the purification stage. Retrospective testing confirmed the presence of PCV1 DNA in Rotarix™ since the initial stages of its development and in vaccine lots used in clinical studies conducted pre- and post-licensure. The acceptable safety profile observed in clinical trials of Rotarix™ therefore reflects exposure to PCV1 DNA. The investigation into the presence of PCV1 in Rotarix™ could serve as a model for risk assessment in the event of new technologies identifying adventitious agents in the manufacturing of other vaccines and biological products. PMID:24056737

  8. Functional dysconnectivity of corticostriatal circuitry as a risk phenotype for psychosis.

    PubMed

    Fornito, Alex; Harrison, Ben J; Goodby, Emmeline; Dean, Anna; Ooi, Cinly; Nathan, Pradeep J; Lennox, Belinda R; Jones, Peter B; Suckling, John; Bullmore, Edward T

    2013-11-01

    Dysregulation of corticostriatal circuitry has long been thought to be critical in the etiology of psychotic disorders, although the differential roles played by dorsal and ventral systems in mediating risk for psychosis have been contentious. To use resting-state functional magnetic resonance imaging to characterize disease-related, risk-related, and symptom-related changes of corticostriatal functional circuitry in patients with first-episode psychosis and their unaffected first-degree relatives. This case-control cross-sectional study was conducted at a specialist early psychosis clinic, GlaxoSmithKline Clinical Unit, and magnetic resonance imaging facility. Nineteen patients with first-episode psychosis, 25 of their unaffected first-degree relatives, and 26 healthy control subjects were included in this study. Voxelwise statistical parametric maps testing differences in the strength of functional connectivity between 6 striatal seed regions of interest (3 caudate and 3 putamen) per hemisphere and all other brain regions. Disease-related changes, reflecting differences between patients and control subjects, involved widespread dysregulation of corticostriatal systems characterized most prominently by a dorsal-to-ventral gradient of hypoconnectivity to hyperconnectivity between striatal and prefrontal regions. A similar gradient was evident in comparisons between relatives and control subjects, identifying it as a genetically inherited risk phenotype. In patients, functional connectivity in risk-affected and disease-affected dorsal frontostriatal circuitry correlated with the severity of both positive and negative symptoms. First-episode psychosis is associated with pronounced dysregulation of corticostriatal systems, characterized most prominently by hypoconnectivity of dorsal and hyperconnectivity of ventral frontostriatal circuits. These changes correlate with symptom severity and are also apparent in unaffected first-degree relatives, suggesting that they

  9. Antibody persistence and booster responses 24-36 months after different 4CMenB vaccination schedules in infants and children: A randomised trial.

    PubMed

    Martinón-Torres, Federico; Carmona Martinez, Alfonso; Simkó, Róbert; Infante Marquez, Pilar; Arimany, Josep-Lluis; Gimenez-Sanchez, Francisco; Couceiro Gianzo, José Antonio; Kovács, Éva; Rojo, Pablo; Wang, Huajun; Bhusal, Chiranjiwi; Toneatto, Daniela

    2018-03-01

    This phase IIIb, open-label, multicentre, extension study (NCT01894919) evaluated long-term antibody persistence and booster responses in participants who received a reduced 2 + 1 or licensed 3 + 1 meningococcal serogroup B vaccine (4CMenB)-schedule (infants), or 2-dose catch-up schedule (2-10-year-olds) in parent study NCT01339923. Children aged 35 months to 12 years (N = 851) were enrolled. Follow-on participants (N = 646) were randomised 2:1 to vaccination and non-vaccination subsets; vaccination subsets received an additional 4CMenB dose. Newly enrolled vaccine-naïve participants (N = 205) received 2 catch-up doses, 1 month apart (accelerated schedule). Antibody levels were determined using human serum bactericidal assay (hSBA) against MenB indicator strains for fHbp, NadA, PorA and NHBA. Safety was also evaluated. Antibody levels declined across follow-on groups at 24-36 months versus 1 month post-vaccination. Antibody persistence and booster responses were similar between infants receiving the reduced or licensed 4CMenB-schedule. An additional dose in follow-on participants induced higher hSBA titres than a first dose in vaccine-naïve children. Two catch-up doses in vaccine-naïve participants induced robust antibody responses. No safety concerns were identified. Antibody persistence, booster responses, and safety profiles were similar with either 2 + 1 or 3 + 1 vaccination schedules. The accelerated schedule in vaccine-naïve children induced robust antibody responses. Copyright © 2017 GlaxoSmithKline SA. Published by Elsevier Ltd.. All rights reserved.

  10. Post-licensure safety surveillance for human papillomavirus-16/18-AS04-adjuvanted vaccine: more than 4 years of experience

    PubMed Central

    Angelo, Maria-Genalin; Zima, Julia; Tavares Da Silva, Fernanda; Baril, Laurence; Arellano, Felix

    2014-01-01

    Purpose To summarise post-licensure safety surveillance over more than 4 years of routine use of the human papillomavirus-16/18-AS04-adjuvanted vaccine (HPV-16/18 vaccine: Cervarix®, GlaxoSmithKline, Belgium). Methods We describe global post-licensure passive surveillance data based on routine pharmacovigilance from 18 May 2007 until 17 November 2011 and enhanced surveillance implemented during the 2-year national immunisation programme in the UK (school years 2008–2010). Results Spontaneous reports from countries worldwide showed a similar pattern for the most frequently reported adverse events after HPV-16/18 vaccination. No patterns or trends were observed for potential immune-mediated diseases after vaccination. Observed incidences of Bell's palsy and confirmed Guillain–Barré syndrome were within the expected range in the general population. Outcomes of pregnancy in women who were inadvertently exposed to HPV-16/18 vaccine during pregnancy, were in line with published reports for similar populations. Enhanced surveillance of adverse events in the UK triggered a review of cases of anaphylaxis, angioedema and syncope reports, leading to an update to the prescribing information. Conclusion Collaborative partnerships between industry and national regulatory agencies facilitated rapid notification and transfer of safety information, allowing for rapid responses in the event of a safety signal of adverse event of concern. More than 4 years of post-licensure experience may provide confidence to providers and the public about the safety profile of HPV-16/18 vaccine in routine use. The safety profile appears to be consistent with pre-licensure data reporting that HPV-16/18 vaccine has an acceptable benefit–risk profile in adolescent girls and women. PMID:24644078

  11. Comparison of the immunogenicity of Cervarix® and Gardasil® human papillomavirus vaccines for oncogenic non-vaccine serotypes HPV-31, HPV-33, and HPV-45 in HIV-infected adults.

    PubMed

    Toft, Lars; Tolstrup, Martin; Müller, Martin; Sehr, Peter; Bonde, Jesper; Storgaard, Merete; Østergaard, Lars; Søgaard, Ole S

    2014-01-01

    Individuals infected with human immunodeficiency virus (HIV) have excess risk of developing human papillomavirus (HPV)-related disease. A substantial fraction of HPV-associated cancers is caused by HPV serotypes not included in the currently available vaccines. Among healthy women, both Cervarix(®) (HPV-16/18, GlaxoSmithKline Biologicals, GSK) and Gardasil(®) (HPV-6/11/16/18, Merck) have demonstrated partial cross-protection against certain oncogenic non-vaccine HPV-types. Currently, there are no available data on vaccine-induced cross-protection in men and little is known about cross-reactive immunity after HPV-vaccination of HIV-infected individuals. In an investigator-initiated trial, we randomized 91 HIV-positive men and women to receive vaccination with Cervarix(®) or Gardasil(®). The HPV-DNA status of the participants was determined with pcr before and after immunization. Cross-reactive antibody responses against HPV-31, HPV-33, and HPV-45 were evaluated for up to 12 months using a pseudovirion-based neutralization assay (PBNA). Geometric mean antibody titers (GMTs) were compared among vaccine groups and genders at 7 and 12 months.: Both vaccines induced anti-HPV-31, -33, and -45 neutralizing antibodies in participants who were seronegative and HPV-DNA negative for those types at study entry. Geometric mean antibody titers were comparable between vaccine groups. Interestingly, anti-HPV-31 and -33 antibody titers were higher among women compared with men at 7 and 12 months.: In conclusion, both licensed HPV-vaccines induced cross-neutralizing antibodies against frequent oncogenic non-vaccine serotypes HPV-31, HPV-33, and HPV-45 in HIV-infected adults, and women had greater serological responses against HPV-31 and -33 compared with men.

  12. Humoral and B-cell memory responses in children five years after pertussis acellular vaccine priming.

    PubMed

    Carollo, Maria; Pandolfi, Elisabetta; Tozzi, Alberto Eugenio; Buisman, Anne-Marie; Mascart, Françoise; Ausiello, Clara Maria

    2014-04-11

    The resurgence of pertussis suggests the need for greater efforts in understanding the long-lasting protective responses induced by vaccination. In this paper we dissect the persistence of humoral and B-cell memory responses induced by primary vaccination with two different acellular pertussis (aP) vaccines, hexavalent Hexavac(®) vaccine (Hexavac) (Sanofi Pasteur MSD) and Infanrix hexa(®) (Infanrix) (GlaxoSmithKline Biologicals). We evaluated the specific immune responses in the two groups of children, 5 years after primary vaccination by measuring the persistence of IgG and antibody secreting cells (ASC) specific for vaccine antigens. Part of the enrolled children received only primary vaccination, while others had the pre-school boost dose. A similar level of antigen-specific IgG and ASC was found in Infanrix and Hexavac vaccinated children. The mean IgG levels were significantly higher in children that received the pre-school boost as compared with children that did not receive the boost dose. A longer persistence after the pre-school boost of IgG-Pertussis Toxin (PT) and IgG-pertactin levels was observed in Infanrix primed children, but it was not statistically significant. More than 80% of children presented a positive ASC B memory response. Around 50% of children still presented protective IgG-PT levels which are reduced to 36% in no-boosted children. The pre-school booster dose restores the percentage of protected children above 50%. In conclusion our data underline the importance of giving a booster dose 5 years after primary vaccination and suggest the need for a new vaccine able to induce a long lasting protective response. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Safety and immunogenicity of the M72/AS01E candidate tuberculosis vaccine in adults with tuberculosis: A phase II randomised study.

    PubMed

    Gillard, Paul; Yang, Pan-Chyr; Danilovits, Manfred; Su, Wei-Juin; Cheng, Shih-Lung; Pehme, Lea; Bollaerts, Anne; Jongert, Erik; Moris, Philippe; Ofori-Anyinam, Opokua; Demoitié, Marie-Ange; Castro, Marcela

    2016-09-01

    Previous studies have shown that the M72/AS01E candidate tuberculosis vaccine is immunogenic with a clinically acceptable safety profile in healthy and Mycobacterium tuberculosis-infected adults. This phase II, observer-blind, randomised study compared the safety, reactogenicity, and immunogenicity of M72/AS01E in 3 cohorts: tuberculosis-naïve adults (n = 80), adults previously treated for tuberculosis (n = 49), and adults who have completed the intensive phase of tuberculosis treatment (n = 13). In each cohort, 18-59-year-old adults were randomised (1:1) to receive two doses of M72/AS01E (n = 71) or placebo (n = 71) and followed-up until six months post-dose 2. Safety and reactogenicity were assessed as primary objective. Recruitment in the study ended prematurely because of a high incidence of large injection site redness/swelling reactions in M72/AS01E-vaccinated adults undergoing tuberculosis treatment. No additional clinically relevant adverse events were observed, except one possibly vaccine-related serious adverse event (hypersensitivity in a tuberculosis-treated-M72/AS01E participant). Robust and persistent M72-specific humoral and polyfunctional CD4(+) T-cell-mediated immune responses were observed post-M72/AS01E vaccination in each cohort. In conclusion, the M72/AS01E vaccine was immunogenic in adults previously or currently treated for tuberculosis, but further analyses are needed to explain the high local reactogenicity in adults undergoing tuberculosis treatment. ClinicalTrials.gov: NCT01424501. Copyright © 2016 GlaxoSmithKline Biologicals SA. Published by Elsevier Ltd.. All rights reserved.

  14. EPITOME-2: An open-label study assessing the transition to a new formulation of intravenous epoprostenol in patients with pulmonary arterial hypertension.

    PubMed

    Sitbon, Olivier; Delcroix, Marion; Bergot, Emmanuel; Boonstra, Anco B; Granton, John; Langleben, David; Subías, Pilar Escribano; Galiè, Nazzareno; Pfister, Thomas; Lemarié, Jean-Christophe; Simonneau, Gérald

    2014-02-01

    Continuous infusion of epoprostenol is the treatment of choice in patients with pulmonary arterial hypertension in functional classes III to IV. However, this treatment's limitations include instability at room temperature. A new epoprostenol formulation offers improved storage conditions and patient convenience. The EPITOME-2 trial was an open-label, prospective, multicenter, single-arm, phase IIIb study. Patients with pulmonary arterial hypertension on long-term, stable epoprostenol therapy were transitioned from epoprostenol with glycine and mannitol excipients (Flolan; GlaxoSmithKline, Durham, NC) to epoprostenol with arginine and sucrose excipients (Veletri; Actelion Pharmaceuticals Ltd, Allschwil, Switzerland). Patients were followed up for 3 months, and dose adjustments were recorded. Efficacy measures included the 6-minute walk distance, hemodynamics assessed by right heart catheterization, and New York Heart Association functional class. Safety and tolerability of the transition were also evaluated. Quality of life was assessed using the Treatment Satisfaction Questionnaire for Medication. Forty-two patients enrolled in the study, and 1 patient withdrew consent before treatment; thus, 41 patients received treatment and completed the study. Six patients required dose adjustments. There were no clinically relevant changes from baseline to month 3 in any of the efficacy end points. Adverse events were those previously described with intravenous prostacyclin therapy. Treatment Satisfaction Questionnaire for Medication scores showed an improvement from baseline to month 3 in the domain of treatment convenience. Transition from epoprostenol with glycine and mannitol excipients to epoprostenol with arginine and sucrose excipients did not affect treatment efficacy, raised no new safety or tolerability concerns, and provided patients with an increased sense of treatment convenience. © 2014.

  15. Seasonal affective disorder and non-seasonal affective disorders: results from the NESDA study

    PubMed Central

    Roest, Annelieke M.; Bos, Elisabeth H.; Meesters, Ybe; Penninx, Brenda W.J.H.; Nolen, Willem A.; de Jonge, Peter

    2017-01-01

    Background Seasonal affective disorder (SAD) is considered to be a subtype of depression. Aims To compare the clinical picture of SAD to non-seasonal affective disorders (non-SADs). Method Diagnoses according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) were established in 2185 participants of the Netherlands Study of Depression and Anxiety. The Seasonal Pattern Assessment Questionnaire was administered to diagnose SAD. Symptoms of depression and anxiety were measured with the Inventory of Depressive Symptoms, the Beck Anxiety Inventory and the Fear Questionnaire. Results Participants with SAD, participants with a lifetime bipolar disorder and participants with a lifetime comorbid anxiety and depressive disorder scored highest in terms of psychopathology in the past year. The seasonal distribution of major depressive episodes was not different for participants with or without SAD. Conclusions SAD may be a measure of severity of depression with a subjectively perceived worsening of symptoms in the winter months. Declaration of interest Y.M. has received research funding and served as a consultant for Royal Philips Electronics NV and The Litebook Company Ltd. W.A.N. has received grants from the Netherlands Organization for Health Research and Development, the European Union, the Stanley Medical Research Institute, Astra Zeneca, Eli Lilly, GlaxoSmithKline and Wyeth; has received honoraria/speaker’s fees from Astra Zeneca, Pfizer, Servier and Wyeth; and has served in advisory boards for Astra Zeneca, Pfizer and Servier. Copyright and usage © The Royal College of Psychiatrists 2017. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license. PMID:28904813

  16. Oxytocin and Vasopressin Agonists and Antagonists as Research Tools and Potential Therapeutics

    PubMed Central

    Manning, M; Misicka, A; Olma, A; Bankowski, K; Stoev, S; Chini, B; Durroux, T; Mouillac, B; Corbani, M; Guillon, G

    2012-01-01

    We recently reviewed the status of peptide and nonpeptide agonists and antagonists for the V1a, V1b and V2 receptors for arginine vasopressin (AVP) and the oxytocin receptor for oxytocin (OT). In the present review, we update the status of peptides and nonpeptides as: (i) research tools and (ii) therapeutic agents. We also present our recent findings on the design of fluorescent ligands for V1b receptor localisation and for OT receptor dimerisation. We note the exciting discoveries regarding two novel naturally occurring analogues of OT. Recent reports of a selective VP V1a agonist and a selective OT agonist point to the continued therapeutic potential of peptides in this field. To date, only two nonpeptides, the V2/V1a antagonist, conivaptan and the V2 antagonist tolvaptan have received Food and Drug Administration approval for clinical use. The development of nonpeptide AVP V1a, V1b and V2 antagonists and OT agonists and antagonists has recently been abandoned by Merck, Sanofi and Pfizer. A promising OT antagonist, Retosiban, developed at Glaxo SmithKline is currently in a Phase II clinical trial for the prevention of premature labour. A number of the nonpeptide ligands that were not successful in clinical trials are proving to be valuable as research tools. Peptide agonists and antagonists continue to be very widely used as research tools in this field. In this regard, we present receptor data on some of the most widely used peptide and nonpeptide ligands, as a guide for their use, especially with regard to receptor selectivity and species differences. PMID:22375852

  17. Defining Health Research for Development: The perspective of stakeholders from an international health research partnership in Ghana and Tanzania.

    PubMed

    Ward, Claire Leonie; Shaw, David; Anane-Sarpong, Evelyn; Sankoh, Osman; Tanner, Marcel; Elger, Bernice

    2017-05-03

    The study uses a qualitative empirical method to define Health Research for Development. This project explores the perspectives of stakeholders in an international health research partnership operating in Ghana and Tanzania. We conducted 52 key informant interviews with major stakeholders in an international multicenter partnership between GlaxoSmithKline (GSK, Vaccine Developer) and the global health nonprofit organisation PATH and its Malaria Vaccine Initiative program (PATH/MVI, Funder-Development Partner), (RTS, S) (NCT00866619). The respondents included teams from four clinical research centres (two centres in Ghana and two in Tanzania) and various collaborating partners. This paper analyses responses to the question: What is Health Research for Development? Based on the stakeholders' experience the respondents offered many ways of defining Health Research for Development. The responses fell into four broad themes: i) Equitable Partnerships; ii) System Sustainability; iii) Addressing Local Health Targets, and iv) Regional Commitment to Benefit Sharing. Through defining Health Research for Development six key learning points were generated from the four result themes: 1) Ensure there is local research leadership working with the collaborative partnership, and local healthcare system, to align the project agenda and activities with local research and health priorities; 2) Know the country-specific context - map the social, health, legislative and political setting; 3) Define an explicit development component and plan of action in a research project; 4) Address the barriers and opportunities to sustain system capacity. 5) Support decentralised health system decision-making to facilitate the translation pathway; 6) Govern, monitor and evaluate the development components of health research partnerships. Overall, equity and unity between partners are required to deliver health research for development. © 2017 John Wiley & Sons Ltd.

  18. Cost-effectiveness of rotavirus vaccination in peru.

    PubMed

    Clark, Andrew D; Walker, Damian G; Mosqueira, N Rocio; Penny, Mary E; Lanata, Claudio F; Fox-Rushby, Julia; Sanderson, Colin F B

    2009-11-01

    There are plans to introduce the oral rotavirus vaccine Rotarix (GlaxoSmithKline), 1 of 2 recently developed vaccines against rotavirus, in Peru. We modeled the cost-effectiveness of adding a rotavirus vaccine to the Peruvian immunization program under 3 scenarios for the timing of vaccination: (1) strictly according to schedule, at 2 and 4 months of age (on time); (2) distributed around the target ages in the same way as the actual timings in the program (flexible); and (3) flexible but assuming vaccination is not initiated for infants >12 weeks of age (restricted). We assumed an introductory price of US $7.50 per dose, and varied the annual rate of price decrease in sensitivity analyses. The discounted cost per disability-adjusted life-year averted for restricted, flexible, and on-time schedules was $621, $615, and $581, respectively. For each of the 3 scenarios, the percentage reduction in deaths due to rotavirus infection was 53%, 66%, and 69%, respectively. The cost per disability-adjusted life-year averted for alternative "what-if" scenarios ranged from $229 (assuming a 1-dose schedule, administered on time) to $1491 (assuming a 2-dose schedule, with half the baseline vaccine efficacy rates and a restricted timing policy). On the basis of current World Health Organization guidelines, rotavirus vaccination represents a highly cost-effective intervention in Peru. Withholding the vaccine from children who present for their first dose after 12 weeks of age would reduce the number of deaths averted by approximately 20%. A single dose may be more cost-effective than 2 doses, but more evidence on the protection conferred by a single dose is required.

  19. STS-82 Mission Specialist Steven L. Smith during TCDT

    NASA Technical Reports Server (NTRS)

    1997-01-01

    STS-82 Mission Specialist Steven L. Smith adjusts the glove of his launch and entry space suit during a practice countdown at KSC. Smith and the other six STS-82 crew members are at KSC to participate in the Terminal Countdown Demonstration Test (TCDT), a dress rehearsal for launch. STS-82 will be the second Hubble Space Telescope servicing mission. Liftoff is targeted for February 11.

  20. Return to Baseline: Some Comments on Smith's Reinterpretation of Seclusionary Timeout.

    ERIC Educational Resources Information Center

    Polsgrove, Lewis

    1982-01-01

    The author replies to an earlier contention of D. Smith (EC 133 830) that seclusionary timeout for behavior disordered children actually constitutes extinction rather than aversive control. The author cites methodological flaws in Smith's studies. (CL)

  1. Dialogues with Marilyn Cochran-Smith

    ERIC Educational Resources Information Center

    Fiorentini, Dario; Crecci, Vanessa Moreira

    2015-01-01

    For more than 30 years, Dr. Marilyn Cochran-Smith has developed and directed research and contributed to publications about education and "practitioner research," especially about teachers' research and learning in inquiry communities. Her primary topics are inquiry communities, teacher research, teacher education for social…

  2. Adam Smith on population.

    PubMed

    Spengler, J J

    1970-11-01

    Abstract Adam Smith dealt with questions of population mainly in his Wealth of Nations. His discussion falls roughly under five heads and reflects in considerable measure his image of the English economy. (1) A country's population capacity, given the average level of consumption, was conditioned by the stock of land, the skill with which it was cultivated, and the degree to which division of labour could be increased and thereby augment output for domestic use and sale in external markets. (2) Growth of population was essentially in response to growth of the demand for labour and served to increase division of labour. (3) The social mechanisms underlying elevation of the scale of living are touched upon, and in an optimistic spirit. (4) The distribution of a country's population responded to its progress in opulence, with the rate of this progress conditioned by the degree to which inappropriate (e.g. mercantilist) policies were avoided. (5) Smith dealt briefly with such matters as colonies, education, size of economy, environmental influences, and public policy, all of which he recognized as significant for the quantity and quality of a country's numbers.

  3. Searching for Dark Matter Annihilation in the Smith High-Velocity Cloud

    NASA Technical Reports Server (NTRS)

    Drlica-Wagner, Alex; Gomez-Vargas, German A.; Hewitt, John W.; Linden, Tim; Tibaldo, Luigi

    2014-01-01

    Recent observations suggest that some high-velocity clouds may be confined by massive dark matter halos. In particular, the proximity and proposed dark matter content of the Smith Cloud make it a tempting target for the indirect detection of dark matter annihilation. We argue that the Smith Cloud may be a better target than some Milky Way dwarf spheroidal satellite galaxies and use gamma-ray observations from the Fermi Large Area Telescope to search for a dark matter annihilation signal. No significant gamma-ray excess is found coincident with the Smith Cloud, and we set strong limits on the dark matter annihilation cross section assuming a spatially extended dark matter profile consistent with dynamical modeling of the Smith Cloud. Notably, these limits exclude the canonical thermal relic cross section (approximately 3 x 10 (sup -26) cubic centimeters per second) for dark matter masses less than or approximately 30 gigaelectronvolts annihilating via the B/B- bar oscillation or tau/antitau channels for certain assumptions of the dark matter density profile; however, uncertainties in the dark matter content of the Smith Cloud may significantly weaken these constraints.

  4. Searching For Dark Matter Annihilation In The Smith High-Velocity Cloud

    DOE PAGES

    Drlica-Wagner, Alex; Gómez-Vargas, Germán A.; Hewitt, John W.; ...

    2014-06-27

    Recent observations suggest that some high-velocity clouds may be confined by massive dark matter halos. In particular, the proximity and proposed dark matter content of the Smith Cloud make it a tempting target for the indirect detection of dark matter annihilation. We argue that the Smith Cloud may be a better target than some Milky Way dwarf spheroidal satellite galaxies and use γ-ray observations from the Fermi Large Area Telescope to search for a dark matter annihilation signal. No significant γ-ray excess is found coincident with the Smith Cloud, and we set strong limits on the dark matter annihilation crossmore » section assuming a spatially extended dark matter profile consistent with dynamical modeling of the Smith Cloud. Notably, these limits exclude the canonical thermal relic cross section (~3 × 10 -26 cm3 s -1) for dark matter masses . 30 GeV annihilating via the b¯b or τ⁺τ⁻ channels for certain assumptions of the dark matter density profile; however, uncertainties in the dark matter content of the Smith Cloud may significantly weaken these constraints.« less

  5. EVA 1 - Grunsfeld and Smith during RSU changeout

    NASA Image and Video Library

    1999-12-22

    STS-103 mission specialist John M. Grunsfeld (attached to a workstation on the RMS arm) and payload commander Steven L. Smith (free-floating) perform a changeout of the Rate Sensor Units (RSU) in one of the bays of -V3 plane of the Hubble Space Telescope (HST). This repair was performed during the first of three extravehicular activities (EVAs) of the mission. Grunsfeld is distinguished by having no marks on his EMU and Smith is distinguished by the red strip on the pants of his EMU.

  6. Genetics Home Reference: Smith-Magenis syndrome

    MedlinePlus

    ... segment most often includes approximately 3.7 million DNA building blocks (base pairs), also written as 3. ... AM, Lupski JR, Potocki L. Cognitive and adaptive behavior profiles in Smith-Magenis syndrome. J Dev Behav ...

  7. A comparison of free weight squat to Smith machine squat using electromyography.

    PubMed

    Schwanbeck, Shane; Chilibeck, Philip D; Binsted, Gordon

    2009-12-01

    The purpose of this experiment was to determine whether free weight or Smith machine squats were optimal for activating the prime movers of the legs and the stabilizers of the legs and the trunk. Six healthy participants performed 1 set of 8 repetitions (using a weight they could lift 8 times, i.e., 8RM, or 8 repetition maximum) for each of the free weight squat and Smith machine squat in a randomized order with a minimum of 3 days between sessions, while electromyographic (EMG) activity of the tibialis anterior, gastrocnemius, vastus medialis, vastus lateralis, biceps femoris, lumbar erector spinae, and rectus abdominus were simultaneously measured. Electromyographic activity was significantly higher by 34, 26, and 49 in the gastrocnemius, biceps femoris, and vastus medialis, respectively, during the free weight squat compared to the Smith machine squat (p < 0.05). There were no significant differences between free weight and Smith machine squat for any of the other muscles; however, the EMG averaged over all muscles during the free weight squat was 43% higher when compared to the Smith machine squat (p < 0.05). The free weight squat may be more beneficial than the Smith machine squat for individuals who are looking to strengthen plantar flexors, knee flexors, and knee extensors.

  8. Pulmonary vein stenosis in patients with Smith-Lemli-Opitz syndrome.

    PubMed

    Prosnitz, Aaron R; Leopold, Jane; Irons, Mira; Jenkins, Kathy; Roberts, Amy E

    2017-07-01

    To describe a group of children with co-incident pulmonary vein stenosis and Smith-Lemli-Opitz syndrome and to generate hypotheses as to the shared pathogenesis of these disorders. Retrospective case series. Five subjects in a pulmonary vein stenosis cohort of 170 subjects were diagnosed with Smith-Lemli-Opitz syndrome soon after birth. All five cases were diagnosed with Smith-Lemli-Opitz syndrome within 6 weeks of life, with no family history of either disorder. All cases had pathologically elevated 7-dehydrocholesterol levels and two of the five cases had previously reported pathogenic 7-dehydrocholesterol reductase mutations. Smith-Lemli-Opitz syndrome severity scores ranged from mild to classical (2-7). Gestational age at birth ranged from 35 to 39 weeks. Four of the cases were male by karyotype. Pulmonary vein stenosis was diagnosed in all cases within 2 months of life, earlier than most published cohorts. All cases progressed to bilateral disease and three cases developed atresia of at least one vein. Despite catheter and surgical interventions, all subjects' pulmonary vein stenosis rapidly recurred and progressed. Three of the subjects died, at 2 months, 3 months, and 11 months. Survival at 16 months after diagnosis was 43%. Patients with pulmonary vein stenosis who have a suggestive syndromic presentation should be screened for Smith-Lemli-Opitz syndrome with easily obtainable serum sterol tests. Echocardiograms should be obtained in all newly diagnosed patients with Smith-Lemli-Opitz syndrome, with a low threshold for repeating the study if new respiratory symptoms of uncertain etiology arise. Further studies into the pathophysiology of pulmonary vein stenosis should consider the role of cholesterol-based signaling pathways in the promotion of intimal proliferation. © 2017 Wiley Periodicals, Inc.

  9. Last Interview with W. Eugene Smith on the Photo Essay.

    ERIC Educational Resources Information Center

    Kobre, Ken

    An interview with W. Eugene Smith, well-known photographer and photographic essayist, is presented in this paper. The introductory section of the paper contains a biographical sketch of Smith and a discussion of his photographic essays on a number of topics, including World War II scenes, life in a Spanish village, the work of a black midwife in…

  10. A Helping Hand in the Frederick Community—Ross Smith | Poster

    Cancer.gov

    By day, Ross Smith is the compliance and security officer for Data Management Services, Inc., assigned to the National Cancer Institute (NCI) at Frederick. His role is to ensure the secure operation of in-house computer systems, servers, and network connections. But in his spare time, Smith is also a volunteer firefighter and emergency medical technician (EMT).

  11. Father Knows Best: Using Adam Smith to Teach Transactions Costs

    ERIC Educational Resources Information Center

    Dupont, Brandon

    2014-01-01

    Adam Smith's moral philosophy can be used to introduce economics students to the important idea of transactions costs. The author provides a brief background in this article to Smith's moral philosophy and connects it to the costs of transacting in a way that fits easily into the standard principles of microeconomics classroom. By doing…

  12. Two Rival Conceptions of Vocational Education: Adam Smith and Friedrich List.

    ERIC Educational Resources Information Center

    Winch, Christopher

    1998-01-01

    Examines and discusses two views of political economy: (1) the classical model of Adam Smith; and (2) the social capitalist model associated with Friedrich List. Explores two varieties of vocational education and training that emerge from a comparison of Smith's and List's ideas. (CMK)

  13. Rediscovering Major N. Clark Smith.

    ERIC Educational Resources Information Center

    Buckner, Reginald T.

    1985-01-01

    Historians of American music education have yet to recognize a Black music educator as important and worthy of observation. This article discusses a candidate--Major Nathaniel Clark Smith, a little-known Black music educator, composer of more than a hundred works, businessman, humanitarian, and teacher of numerous big-name jazz musicians. (RM)

  14. A Cabinet of Mathematical Curiosities at Teachers College: David Eugene Smith's Collection

    ERIC Educational Resources Information Center

    Murray, Diane R.

    2012-01-01

    This dissertation is a history of David Eugene Smith's collection of historical books, manuscripts, portraits, and instruments related to mathematics. The study analyzes surviving documents, images, objects, college announcements and catalogs, and secondary sources related to Smith's collection. David Eugene Smith (1860-1944) travelled…

  15. SMITH: a LIMS for handling next-generation sequencing workflows.

    PubMed

    Venco, Francesco; Vaskin, Yuriy; Ceol, Arnaud; Muller, Heiko

    2014-01-01

    Life-science laboratories make increasing use of Next Generation Sequencing (NGS) for studying bio-macromolecules and their interactions. Array-based methods for measuring gene expression or protein-DNA interactions are being replaced by RNA-Seq and ChIP-Seq. Sequencing is generally performed by specialized facilities that have to keep track of sequencing requests, trace samples, ensure quality and make data available according to predefined privileges. An integrated tool helps to troubleshoot problems, to maintain a high quality standard, to reduce time and costs. Commercial and non-commercial tools called LIMS (Laboratory Information Management Systems) are available for this purpose. However, they often come at prohibitive cost and/or lack the flexibility and scalability needed to adjust seamlessly to the frequently changing protocols employed. In order to manage the flow of sequencing data produced at the Genomic Unit of the Italian Institute of Technology (IIT), we developed SMITH (Sequencing Machine Information Tracking and Handling). SMITH is a web application with a MySQL server at the backend. Wet-lab scientists of the Centre for Genomic Science and database experts from the Politecnico of Milan in the context of a Genomic Data Model Project developed SMITH. The data base schema stores all the information of an NGS experiment, including the descriptions of all protocols and algorithms used in the process. Notably, an attribute-value table allows associating an unconstrained textual description to each sample and all the data produced afterwards. This method permits the creation of metadata that can be used to search the database for specific files as well as for statistical analyses. SMITH runs automatically and limits direct human interaction mainly to administrative tasks. SMITH data-delivery procedures were standardized making it easier for biologists and analysts to navigate the data. Automation also helps saving time. The workflows are available

  16. SMITH: a LIMS for handling next-generation sequencing workflows

    PubMed Central

    2014-01-01

    Background Life-science laboratories make increasing use of Next Generation Sequencing (NGS) for studying bio-macromolecules and their interactions. Array-based methods for measuring gene expression or protein-DNA interactions are being replaced by RNA-Seq and ChIP-Seq. Sequencing is generally performed by specialized facilities that have to keep track of sequencing requests, trace samples, ensure quality and make data available according to predefined privileges. An integrated tool helps to troubleshoot problems, to maintain a high quality standard, to reduce time and costs. Commercial and non-commercial tools called LIMS (Laboratory Information Management Systems) are available for this purpose. However, they often come at prohibitive cost and/or lack the flexibility and scalability needed to adjust seamlessly to the frequently changing protocols employed. In order to manage the flow of sequencing data produced at the Genomic Unit of the Italian Institute of Technology (IIT), we developed SMITH (Sequencing Machine Information Tracking and Handling). Methods SMITH is a web application with a MySQL server at the backend. Wet-lab scientists of the Centre for Genomic Science and database experts from the Politecnico of Milan in the context of a Genomic Data Model Project developed SMITH. The data base schema stores all the information of an NGS experiment, including the descriptions of all protocols and algorithms used in the process. Notably, an attribute-value table allows associating an unconstrained textual description to each sample and all the data produced afterwards. This method permits the creation of metadata that can be used to search the database for specific files as well as for statistical analyses. Results SMITH runs automatically and limits direct human interaction mainly to administrative tasks. SMITH data-delivery procedures were standardized making it easier for biologists and analysts to navigate the data. Automation also helps saving time. The

  17. Immunogenicity and safety of a quadrivalent meningococcal serogroups A, C, W-135 and Y tetanus toxoid conjugate vaccine (MenACWY-TT) administered to adults aged 56 Years and older: results of an open-label, randomized, controlled trial.

    PubMed

    Dbaibo, Ghassan; El-Ayoubi, Nabil; Ghanem, Soha; Hajar, Farah; Bianco, Veronique; Miller, Jacqueline M; Mesaros, Narcisa

    2013-05-01

    The burden of invasive meningococcal disease is substantial in older adults in whom the case fatality rate is high. Travelers to regions with high rates of meningococcal disease, such as Hajj pilgrims, are at increased risk of meningococcal infection, and disease transmission from travelers to their close contacts has been documented. In younger individuals, meningococcal conjugate vaccines offer advantages over polysaccharide vaccines in terms of duration of protection and boostability, and induction of herd immune effects through reductions in nasopharyngeal carriage of meningococci. To date, few data are available evaluating meningococcal conjugate vaccine use in adults >55 years of age. To evaluate the immunogenicity and safety of quadrivalent meningococcal serogroups A, C, W-135 and Y vaccine with all serogroups conjugated to tetanus toxoid (MenACWY-TT, Nimenrix™, GlaxoSmithKline, Belgium) and a licensed quadrivalent polysaccharide vaccine (MenPS, Mencevax™ GlaxoSmithKline, Belgium) in adults >55 years of age. This was a phase IIIb, open-label, randomized (3:1), controlled study conducted at one study center in Lebanon. A total of 400 healthy adults between 56 and 103 years of age without previous MenPS or tetanus toxoid vaccination within the previous 5 years or meningococcal conjugate vaccination at any time previously were included. They received a single-dose vaccination with MenACWY-TT or MenPS with blood sampling before and 1 month after vaccination. The main outcome measures were serum bactericidal activity (rabbit complement source: rSBA) vaccine response (VR) rate [rSBA titer of ≥1:32 in initially seronegative subjects (rSBA titer <1:8); ≥4-fold increase in subjects with pre-vaccination rSBA titers between 1:8 and 1:128, and ≥2-fold increase in subjects with pre-vaccination rSBA titers ≥1:128]. The percentages of subjects with rSBA titers ≥1:8 and ≥1:128 and rSBA geometric mean titers (GMTs) were assessed. Solicited adverse events

  18. 77 FR 64411 - Safety Zone; Cooper T. Smith Fireworks Event; Mobile River; Mobile, AL

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-22

    ... 1625-AA00 Safety Zone; Cooper T. Smith Fireworks Event; Mobile River; Mobile, AL AGENCY: Coast Guard.... Smith Fireworks Event. Entry into, transiting or anchoring in this zone is prohibited to all vessels... safety hazards associated with a fireworks display. B. Basis and Purpose Cooper T. Smith Corp. has hired...

  19. Green Bank Telescope OH Observations of Smith's Cloud: Evidence Of A Lack Of Chemistry

    NASA Astrophysics Data System (ADS)

    Minter, Anthony

    2017-03-01

    Smith's Cloud is a large few × 106 Solar Mass cloud which will impact the Milk Way disk in about 35 Million Years (Lockman et al., 2008). Green Bank Telescope OH observations indicate that there are no molecules present in Smith's Cloud, and thus there is no active ongoing chemistry in Smith's Cloud.

  20. Arthur Smith, Local Baptist Pastor.

    ERIC Educational Resources Information Center

    Heaton, Moss, Ed.

    1985-01-01

    Written and published by the students at Gary High School this volume has three articles dealing with East Texas life. The first "Arthur Smith" (David Hancock and others) is an account of growing up in Marian County, Texas is described by the local Baptist minister. The pastor begins with the year of his birth and gives detailed…

  1. Portrait of Waldo Smith

    NASA Astrophysics Data System (ADS)

    Spilhaus, Fred

    2009-01-01

    In 1944, Waldo Smith was looking for a place where he could make a difference. He had taught in universities in the United States and Turkey, and he had worked as an engineer in the field of hydrology in the United States. Somehow, a chance meeting with John Adam Fleming, AGU's long-time General Secretary, led to Waldo's becoming the first executive officer employed by the Union. That, in turn, brought him the opportunity to make a difference.

  2. Measuring short electron bunch lengths using coherent smith-purcell radiation

    DOEpatents

    Nguyen, Dinh C.

    1999-01-01

    A method is provided for directly determining the length of sub-picosecond electron bunches. A metallic grating is formed with a groove spacing greater than a length expected for the electron bunches. The electron bunches are passed over the metallic grating to generate coherent and incoherent Smith-Purcell radiation. The angular distribution of the coherent Smith-Purcell radiation is then mapped to directly deduce the length of the electron bunches.

  3. Meet EPA Scientist Betsy Smith, Ph.D.

    EPA Pesticide Factsheets

    Dr. Betsy Smith is Associate National Program Director for Systems Analysis within the Sustainable and Healthy Communities Research Program. Her work has focused on new methods to analyze spatial data on multiple problems.

  4. 75 FR 41922 - Notice of Intent To Rule on Request To Release Airport Property at Fort Smith Regional Airport...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-19

    ... To Release Airport Property at Fort Smith Regional Airport, Fort Smith, AR AGENCY: Federal Aviation... rule and invites public comment on the release of land at Fort Smith Regional Airport under the.... John Parker, Airport Director, Fort Smith Regional Airport, at the following address: Fort Smith...

  5. Measuring short electron bunch lengths using coherent Smith-Purcell radiation

    DOEpatents

    Nguyen, D.C.

    1999-03-30

    A method is provided for directly determining the length of sub-picosecond electron bunches. A metallic grating is formed with a groove spacing greater than a length expected for the electron bunches. The electron bunches are passed over the metallic grating to generate coherent and incoherent Smith-Purcell radiation. The angular distribution of the coherent Smith-Purcell radiation is then mapped to directly deduce the length of the electron bunches. 8 figs.

  6. Lisa Smith in MSFC's Laboratory Training Complex

    NASA Image and Video Library

    2015-02-11

    LISA SMITH, THE TRAINING TEAM LEAD IN MARSHALL'S MISSION OPERATIONS LAB, EXAMINES THE DRAWERS IN THE GLACIER MOCK-UP, A TRAINING VERSION OF A FREEZER ON THE INTERNATIONAL SPACE STATION INSTALLED IN THE MARSHALL CENTER'S LABORATORY TRAINING COMPLEX

  7. A Disciplinary Immigrant. Alexander Smith at the University of Chicago, 1894-1911

    ERIC Educational Resources Information Center

    Cotter, Donald

    2008-01-01

    The publication in 1906 of Alexander Smith's "Introduction to general inorganic chemistry" inaugurated a decisive change in chemical pedagogy in the US, the effects of which are still evident. The nature and extent of Smith's innovations are described through a comparison of his text to its source material and contemporaries. His…

  8. Understanding patient and physician perceptions of male androgenetic alopecia treatments in Asia-Pacific and Latin America.

    PubMed

    Lulic, Zrinka; Inui, Shigeki; Sim, Woo-Young; Kang, Hoon; Choi, Gwang Seong; Hong, Woosung; Hatanaka, Toshiki; Wilson, Timothy; Manyak, Michael

    2017-08-01

    This survey aimed to explore patient and physician attitudes towards male androgenetic alopecia (AGA), satisfaction with currently available male AGA treatments and investigate the factors affecting treatment choice. The survey was carried out in five countries (Japan, South Korea, Taiwan, Mexico and Brazil) between November and December 2015 using a standard market research methodology. Questionnaires were completed by patients with male AGA or hair loss/thinning and practicing physicians who were responsible for prescribing AGA treatment. In total, 835 patients and 338 physicians completed the questionnaire. Overall, 37.6% of patients reported satisfaction with the treatments they had used. The highest patient satisfaction was reported for 5-alpha-reductase inhibitors (53.9% of patients satisfied). In all countries, physicians were more likely than patients to think that male AGA has a major impact on patient confidence (89.3% vs 70.4%, respectively). There was agreement by physicians and patients that male AGA patients who are involved in their treatment decisions have better outcomes. Patients who were satisfied with AGA treatments were more likely to have the level of involvement they desired in treatment decisions (69.1% of satisfied patients) than dissatisfied patients (56.4% of dissatisfied patients). This survey provides valuable insights into the attitudes of patients and physicians in Asia and Latin America about male AGA and its treatments. The survey identified areas of disconnect between physicians and patients regarding the impact of male AGA, treatment consultations and the importance of treatment attributes. It also highlights the need for physicians to spend sufficient time with patients discussing AGA treatment approaches. © 2017 GlaxoSmithKline. The Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Dermatological Association.

  9. Safety and immunogenicity of a CRM or TT conjugated meningococcal vaccine in healthy toddlers.

    PubMed

    Bona, Gianni; Castiglia, Paolo; Zoppi, Giorgio; de Martino, Maurizio; Tasciotti, Annaelisa; D'Agostino, Diego; Han, Linda; Smolenov, Igor

    2016-06-17

    MenACWY-CRM (Menveo(®); GlaxoSmithKline) and MenACWY-TT (Nimenrix(®); Pfizer) are two meningococcal vaccines licensed in the European Union for use in both children and adults. While both vaccines target meningococcal serogroups A, C, W and Y, immunogenicity and reactogenicity of these quadrivalent meningococcal conjugate vaccines may differ due to differences in formulation processes and chemical structure. Yet data on the comparability of these two vaccines are limited. The reactogenicity and immunogenicity of one dose of either MenACWY-CRM or MenACWY-TT were evaluated in healthy toddlers aged 12-15 months. Immunogenicity was assessed using serum bactericidal antibody assays (SBA) with human (hSBA) and rabbit (rSBA) complement. A total of 202 children aged 12-15 months were enrolled to receive one dose of MenACWY-CRM or MenACWY-TT. Similar numbers of subjects reported solicited reactions within 7 days following either vaccination. Tenderness at the injection site was the most common local reaction. Systemic reactions reported were similar for both vaccines and mostly mild to moderate in severity: irritability, sleepiness and change in eating habits were most commonly reported. Immunogenicity at 1 month post-vaccination was generally comparable for both vaccines across serogroups. At 6 months post-vaccination antibody persistence against serogroups C, W, and Y was substantial for both vaccines, as measured by both assay methodologies. For serogroup A, hSBA titers declined in both groups, while rSBA titers remained high. Despite differences in composition, the MenACWY-CRM and MenACWY-TT vaccines have comparable reactogenicity and immunogenicity profiles. Immediate immune responses and short-term antibody persistence were largely similar between groups. Both vaccines were well-tolerated and no safety concerns were identified. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  10. The upper bound to the Relative Reporting Ratio—a measure of the impact of the violation of hidden assumptions underlying some disproportionality methods used in signal detection

    PubMed Central

    Van Holle, Lionel; Bauchau, Vincent

    2014-01-01

    Purpose For disproportionality measures based on the Relative Reporting Ratio (RRR) such as the Information Component (IC) and the Empirical Bayesian Geometrical Mean (EBGM), each product and event is assumed to represent a negligible fraction of the spontaneous report database (SRD). Here, we provide the tools for allowing signal detection experts to assess the consequence of the violation of this assumption on their specific SRD. Methods For each product–event pair (P–E), a worst-case scenario associated all the reported events-of-interest with the product of interest. The values of the RRR under this scenario were measured for different sets of stratification factors using the GlaxoSmithKline vaccines SRD. These values represent the RRR upper bound that RRR cannot exceed whatever the true strength of association. Results Depending on the choice of stratification factors, the RRR could not exceed an upper bound of 2 for up to 2.4% of the P–Es. For Engerix™, 23.4% of all reports in the SDR, the RRR could not exceed an upper bound of 2 for up to 13.8% of pairs. For the P–E Rotarix™-Intussusception, the choice of stratification factors impacted the upper bound to RRR: from 52.5 for an unstratified RRR to 2.0 for a fully stratified RRR. Conclusions The quantification of the upper bound can indicate whether measures such as EBGM, IC, or RRR can be used for SRD for which products or events represent a non-negligible fraction of the entire SRD. In addition, at the level of the product or P–E, it can also highlight detrimental impact of overstratification. © 2014 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons, Ltd. PMID:24395594

  11. Primary and booster vaccination in Latin American children with a DTPw-HBV/Hib combination: a randomized controlled trial.

    PubMed

    Espinoza, Felix; Tregnaghi, Miguel; Gentile, Angela; Abarca, Katia; Casellas, Javier; Collard, Alix; Lefevre, Inge; Jacquet, Jeanne-Marie

    2010-10-15

    Diphtheria-tetanus-whole-cell pertussis (DTPw)-based combination vaccines are an attractive option to rapidly achieve high coverage and protection against other important pathogens, such as hepatitis B virus (HBV) and Haemophilus influenzae type B (Hib). To ensure adequate antigen supply, GlaxoSmithKline Biologicals has introduced a new DTPw antigen source and developed a new DTPw-HBV/Hib combination vaccine containing a reduced amount of Hib polyribosylribitol phosphate (PRP). This study was undertaken to compare the immunogenicity and reactogenicity of this new DTPw-HBV/Hib vaccine with a licensed DTPw-HBV/Hib vaccine (Tritanrix™-HBV/Hib). This was a randomized, partially-blind, multicenter study in three countries in Latin America (Argentina, Chile and Nicaragua). Healthy children received either the new DTPw-HBV/Hib vaccine (1 of 3 lots; n = 439; double-blind) or Tritanrix™-HBV/Hib (n = 146; single-blind) co-administered with oral poliovirus vaccine (OPV) at 2, 4 and 6 months, with a booster dose at 18-24 months. One month after the end of the 3-dose primary vaccination course, the new DTPw-HBV/Hib vaccine was non-inferior to Tritanrix™-HBV/Hib in terms of seroprotection/vaccine response rates for all component antigens; ≥97.3% and ≥93.9% of subjects in the two groups, respectively, had seroprotective levels of antibodies against diphtheria, tetanus, hepatitis B and Hib and a vaccine response to the pertussis component. Persistence of antibodies against all vaccine antigens was comparable between groups, with marked increases in all antibody concentrations after booster administration in both groups. Both vaccines were generally well-tolerated as primary and booster doses. Results confirm the suitability of this new DTPw-HBV/Hib vaccine comprising antigens from a new source and a reduced PRP content for inclusion into routine childhood vaccination programs. http://www.clinicaltrials.gov NCT00332566.

  12. The effects of combined versus selective adrenergic blockade on left ventricular and systemic hemodynamics, myocardial substrate preference, and regional perfusion in conscious dogs with dilated cardiomyopathy.

    PubMed

    Nikolaidis, Lazaros A; Poornima, Indu; Parikh, Pratik; Magovern, Megan; Shen, You-Tang; Shannon, Richard P

    2006-05-02

    Given that adverse effects of chronic sympathetic activation are mediated by all three adrenergic receptor subtypes (beta1, beta2, alpha1), we examined the effects of standard doses of carvedilol and metoprolol succinate (metoprolol controlled release/extended release [CR/XL]) on hemodynamics, myocardial metabolism, and regional organ perfusion. Both beta1 selective and combined adrenergic blockade reduce morbidity and mortality in heart failure. Whether there are advantages of one class over the other remains controversial, even in the wake of the Carvedilol Or Metoprolol European Trial (COMET). Similarly, the mechanistic basis for the relative differences is incompletely understood. Thirty-three conscious, chronically instrumented dogs with pacing-induced (240 min(-1) for 4 weeks) dilated cardiomyopathy (DCM) were randomized to carvedilol (25 mg twice daily, Coreg, Glaxo Smith Kline, Research Triangle, North Carolina) or metoprolol succinate (100 mg qd, Toprol XL, Astra Zeneca, Wilmington, Delaware). Left ventricular and systemic hemodynamics, myocardial substrate uptake, and norepinephrine spillover were measured before and after three days of treatment. Regional (renal, hepatic, skeletal muscle) blood flows were measured using neutron-activated microspheres. Both agents had comparable heart rate effects. However, carvedilol-treated dogs showed significantly greater increases in stroke volume and cardiac output and decreases in left ventricular end-diastolic pressure and systemic vascular resistance. Carvedilol increased renal, hepatic, and skeletal muscle blood flow. Carvedilol increased myocardial glucose uptake and suppressed norepinephrine and glucagon. Carvedilol antagonized the response to exogenous norepinephrine to a greater extent than metoprolol CR/XL. At doses inducing comparable heart rate reductions, short-term treatment with carvedilol had superior hemodynamic and metabolic effects compared with metoprolol CR/XL. These data suggest important

  13. Post-marketing monitoring of intussusception after rotavirus vaccination in Japan.

    PubMed

    Bauchau, Vincent; Van Holle, Lionel; Mahaux, Olivia; Holl, Katsiaryna; Sugiyama, Keiji; Buyse, Hubert

    2015-07-01

    Rotarix(TM) was launched in November 2011 in Japan to prevent rotavirus gastroenteritis. Some studies suggest that Rotarix(TM) may have a temporal association with a risk of intussusception (IS). We assessed a possible association between IS and Rotarix(TM) vaccination in Japan. All IS cases spontaneously reported post-vaccination (Brighton collaboration levels 1, 2, and 3) were extracted from the GlaxoSmithKline spontaneous report database on the 11th of January 2013. Expected numbers of IS cases were estimated using the number of vaccine doses distributed and the Japanese incidence rate of IS stratified by month of age. The observed versus expected analysis considered the IS cases for each risk period (7 and 30 days post-vaccination) and for each vaccine dose (two doses). Before January 2013, approximately 601 000 Rotarix(TM) doses were distributed in Japan. For a risk period of 7 days post-dose 1 and post-dose 2, 10 and five IS cases were observed, whereas 3.4 and 7.6 were expected, providing an observed-to-expected ratio of 2.96 (95% confidence interval [CI]: 1.42; 5.45) and 0.66 (95% CI: 0.21; 1.53), respectively. For a risk period of 30 days post-dose 1 and post-dose 2, 14 and eight cases were observed, whereas 14.5 and 32.7 were expected, providing an observed-to-expected ratio of 0.97 (95% CI: 0.53; 1.62) and 0.24 (95% CI: 0.11; 0.48), respectively. A statistically significant excess of IS cases was observed within 7 days post-dose 1, but not post-dose 2. These results are consistent with previous observations in large post-marketing safety studies in other world regions. © 2015 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons, Ltd.

  14. Rotavirus vaccine effectiveness in Hong Kong children.

    PubMed

    Yeung, Karene Hoi Ting; Tate, Jacqueline E; Chan, Ching Ching; Chan, Martin C W; Chan, Paul K S; Poon, Kin Hung; Siu, Sylvia Luen Yee; Fung, Genevieve Po Gee; Ng, Kwok Leung; Chan, Iris Mei Ching; Yu, Pui Tak; Ng, Chi Hang; Lau, Yu Lung; Nelson, E Anthony S

    2016-09-22

    Rotavirus is a common infectious cause of childhood hospitalisation in Hong Kong. Rotavirus vaccines have been used in the private sector since licensure in 2006 but have not been incorporated in the government's universal Childhood Immunisation Programme. This study aimed to evaluate rotavirus vaccine effectiveness against hospitalisation. This case-control study was conducted in the 2014/2015 rotavirus season in six public hospitals. Hospitalised acute gastroenteritis patients meeting inclusion criteria were recruited and copies of their immunisation records were collected. Case-patients were defined as enrolled subjects with stool specimens obtained in the first 48h of hospitalisation that tested positive for rotavirus, whereas control-patients were those with stool specimens obtained in the first 48h of hospitalisation testing negative for rotavirus. Vaccine effectiveness for administration of at least one dose of either Rotarix(®) (GlaxoSmithKline Biologicals) or RotaTeq(®) (Merck Research Laboratories) was calculated as 1 minus the odds ratio for rotavirus vaccination history for case-patients versus control-patients. Among the 525 eligible subjects recruited, immunisation records were seen in 404 (77%) subjects. 31% (162/525 and 126/404) tested positive for rotavirus. In the 404 subjects assessed for vaccine effectiveness, 2.4% and 24% received at least 1 dose of either rotavirus vaccine in case- and control-patients respectively. The unmatched vaccine effectiveness against hospitalisation for administration of at least one dose of either rotavirus vaccines was 92% (95% confidence interval [CI]: 75%, 98%). The matched analyses by age only and both age and admission date showed 96% (95% CI: 72%, 100%) and 89% (95% CI: 51%, 97%) protection against rotavirus hospitalisation respectively. Rotavirus vaccine is highly effective in preventing hospitalisation from rotavirus disease in young Hong Kong children. Copyright © 2016 The Authors. Published by Elsevier

  15. Post‐marketing monitoring of intussusception after rotavirus vaccination in Japan†

    PubMed Central

    Bauchau, Vincent; Van Holle, Lionel; Mahaux, Olivia; Holl, Katsiaryna; Sugiyama, Keiji

    2015-01-01

    Abstract Purpose Rotarix TM was launched in November 2011 in Japan to prevent rotavirus gastroenteritis. Some studies suggest that Rotarix TM may have a temporal association with a risk of intussusception (IS). We assessed a possible association between IS and Rotarix TM vaccination in Japan. Methods All IS cases spontaneously reported post‐vaccination (Brighton collaboration levels 1, 2, and 3) were extracted from the GlaxoSmithKline spontaneous report database on the 11th of January 2013. Expected numbers of IS cases were estimated using the number of vaccine doses distributed and the Japanese incidence rate of IS stratified by month of age. The observed versus expected analysis considered the IS cases for each risk period (7 and 30 days post‐vaccination) and for each vaccine dose (two doses). Results Before January 2013, approximately 601 000 Rotarix TM doses were distributed in Japan. For a risk period of 7 days post‐dose 1 and post‐dose 2, 10 and five IS cases were observed, whereas 3.4 and 7.6 were expected, providing an observed‐to‐expected ratio of 2.96 (95% confidence interval [CI]: 1.42; 5.45) and 0.66 (95% CI: 0.21; 1.53), respectively. For a risk period of 30 days post‐dose 1 and post‐dose 2, 14 and eight cases were observed, whereas 14.5 and 32.7 were expected, providing an observed‐to‐expected ratio of 0.97 (95% CI: 0.53; 1.62) and 0.24 (95% CI: 0.11; 0.48), respectively. Conclusion A statistically significant excess of IS cases was observed within 7 days post‐dose 1, but not post‐dose 2. These results are consistent with previous observations in large post‐marketing safety studies in other world regions. © 2015 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons, Ltd. PMID:26013569

  16. Post-marketing safety evaluation of a tetanus toxoid, reduced diphtheria toxoid and 3-component acellular pertussis vaccine administered to a cohort of adolescents in a United States health maintenance organization.

    PubMed

    Klein, Nicola P; Hansen, John; Lewis, Edwin; Lyon, Liisa; Nguyen, Bessie; Black, Steven; Weston, Wayde M; Wu, Sterling; Li, Ping; Howe, Barbara; Friedland, Leonard R

    2010-07-01

    Prelicensure clinical studies may not include sufficient numbers of subjects to assess the potential for rare postvaccination adverse events. The aim of this postlicensure study (NCT00297856) was to evaluate uncommon outcomes following vaccination with a tetanus, reduced-antigen-content diphtheria, and acellular pertussis vaccine (Tdap, Boostrix GlaxoSmithKline) in a large adolescent cohort. We monitored safety outcomes among 13,427 10 to 18-year-old adolescents enrolled in the Northern California Kaiser Permanente Health Care Plan who received Tdap vaccination as part of their normal health care. Subjects were evaluated using self-control analysis comparing days 0 to 29 to days 30 to 59 postvaccination for neurologic events, hematologic events and allergic reactions. We evaluated new onset chronic illnesses within 6 months of Tdap vaccination by comparing with historical Td controls matched for age at vaccination, season, sex, and geographic area. We also compared the incidence of events of interest between the Tdap and historical cohorts as exploratory analyses. No increased risk for medically attended neurologic (odds ratio [OR], 0.962; 95% confidence interval [CI], 0.533-1.733) or allergic reactions (OR, 1.091; 95% CI, 0.441-2.729) was observed following Tdap vaccination when comparing the first 30 postvaccination days to the second 30 postvaccination days. There was one hematologic event within 30 days of Tdap, compared with 0 events within days 30 to 59 (P = 1.0). When compared with matched historical Td recipients, no increase in new onset chronic illnesses (OR, 0.634; 95% CI, 0.475-0.840) was seen after Tdap. No deaths occurred in the Tdap cohort during the study. This study provides no evidence for an increased risk for neurologic, hematologic, allergic events, or new onset of chronic illnesses among adolescents vaccinated with Tdap.

  17. Influence of Compulsivity of Drug Abuse on Dopaminergic Modulation of Attentional Bias in Stimulant Dependence

    PubMed Central

    Ersche, Karen D.; Bullmore, Edward T.; Craig, Kevin J.; Shabbir, Shaila S.; Abbott, Sanja; Müller, Ulrich; Ooi, Cinly; Suckling, John; Barnes, Anna; Sahakian, Barbara J.; Merlo-Pich, Emilio V.; Robbins, Trevor W.

    2013-01-01

    Context There are no effective pharmacotherapies for stimulant dependence but there are many plausible targets for development of novel therapeutics. We hypothesized that dopamine-related targets are relevant for treatment of stimulant dependence, and there will likely be individual differences in response to dopaminergic challenges. Objective To measure behavioral and brain functional markers of drug-related attentional bias in stimulant-dependent individuals studied repeatedly after short-term dosing with dopamine D2/D3 receptor antagonist and agonist challenges. Design Randomized, double-blind, placebo-controlled, parallel-groups, crossover design using pharmacological functional magnetic resonance imaging. Setting Clinical research unit (GlaxoSmithKline) and local community in Cambridge, England. Participants Stimulant-dependent individuals (n=18) and healthy volunteers (n=18). Interventions Amisulpride (400 mg), pramipexole dihydrochloride (0.5 mg), or placebo were administered in counterbalanced order at each of 3 repeated testing sessions. Main Outcome Measures Attentional bias for stimulant-related words was measured during functional magnetic resonance imaging by a drug-word Stroop paradigm; trait impulsivity and compulsivity of dependence were assessed at baseline by questionnaire. Results Drug users demonstrated significant attentional bias for drug-related words, which was correlated with greater activation of the left prefrontal and right cerebellar cortex. Attentional bias was greater in people with highly compulsive patterns of stimulant abuse; the effects of dopaminergic challenges on attentional interference and related frontocerebellar activation were different between high- and low-compulsivity subgroups. Conclusions Greater attentional bias for and greater prefrontal activation by stimulant-related words constitute a candidate neurocognitive marker for dependence. Individual differences in compulsivity of stimulant dependence had significant

  18. Progression of HPV infection to detectable cervical lesions or clearance in adult women: Analysis of the control arm of the VIVIANE study.

    PubMed

    Skinner, S Rachel; Wheeler, Cosette M; Romanowski, Barbara; Castellsagué, Xavier; Lazcano-Ponce, Eduardo; Del Rosario-Raymundo, M Rowena; Vallejos, Carlos; Minkina, Galina; Pereira Da Silva, Daniel; McNeil, Shelly; Prilepskaya, Vera; Gogotadze, Irina; Money, Deborah; Garland, Suzanne M; Romanenko, Viktor; Harper, Diane M; Levin, Myron J; Chatterjee, Archana; Geeraerts, Brecht; Struyf, Frank; Dubin, Gary; Bozonnat, Marie-Cécile; Rosillon, Dominique; Baril, Laurence

    2016-05-15

    The control arm of the phase III VIVIANE (Human PapillomaVIrus: Vaccine Immunogenicity ANd Efficacy; NCT00294047) study in women >25 years was studied to assess risk of progression from cervical HPV infection to detectable cervical intraepithelial neoplasia (CIN). The risk of detecting CIN associated with the same HPV type as the reference infection was analysed using Kaplan-Meier and multivariable Cox models. Infections were categorised depending upon persistence as 6-month persistent infection (6MPI) or infection of any duration. The 4-year interim analysis included 2,838 women, of whom 1,073 (37.8%) experienced 2,615 infections of any duration and 708 (24.9%) experienced 1,130 6MPIs. Infection with oncogenic HPV types significantly increased the risk of detecting CIN grade 2 or greater (CIN2+) versus non-oncogenic types. For 6MPI, the highest risk was associated with HPV-33 (hazard ratio [HR]: 31.9 [8.3-122.2, p < 0.0001]). The next highest risk was with HPV-16 (21.1 [6.3-70.0], p < 0.0001). Similar findings were seen for infections of any duration. Significant risk was also observed for HPV-18, HPV-31, and HPV-45. Concomitant HPV infection or CIN grade 1 or greater associated with a different oncogenic HPV type increased risk. Most women (79.3%) with an HPV infection at baseline cleared detectable infections of any duration, and 69.9% cleared a 6MPI. The risk of progression of HPV infection to CIN2+ in women >25 years in this study was similar to that in women 15-25 years in PATRICIA. © 2015 The Authors and GlaxoSmithKline. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.

  19. Post-licensure safety surveillance for human papillomavirus-16/18-AS04-adjuvanted vaccine: more than 4 years of experience.

    PubMed

    Angelo, Maria-Genalin; Zima, Julia; Tavares Da Silva, Fernanda; Baril, Laurence; Arellano, Felix

    2014-05-01

    To summarise post-licensure safety surveillance over more than 4 years of routine use of the human papillomavirus-16/18-AS04-adjuvanted vaccine (HPV-16/18 vaccine: Cervarix®, GlaxoSmithKline, Belgium). We describe global post-licensure passive surveillance data based on routine pharmacovigilance from 18 May 2007 until 17 November 2011 and enhanced surveillance implemented during the 2-year national immunisation programme in the UK (school years 2008-2010). Spontaneous reports from countries worldwide showed a similar pattern for the most frequently reported adverse events after HPV-16/18 vaccination. No patterns or trends were observed for potential immune-mediated diseases after vaccination. Observed incidences of Bell's palsy and confirmed Guillain-Barré syndrome were within the expected range in the general population. Outcomes of pregnancy in women who were inadvertently exposed to HPV-16/18 vaccine during pregnancy, were in line with published reports for similar populations. Enhanced surveillance of adverse events in the UK triggered a review of cases of anaphylaxis, angioedema and syncope reports, leading to an update to the prescribing information. Collaborative partnerships between industry and national regulatory agencies facilitated rapid notification and transfer of safety information, allowing for rapid responses in the event of a safety signal of adverse event of concern. More than 4 years of post-licensure experience may provide confidence to providers and the public about the safety profile of HPV-16/18 vaccine in routine use. The safety profile appears to be consistent with pre-licensure data reporting that HPV-16/18 vaccine has an acceptable benefit-risk profile in adolescent girls and women. © 2014 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons, Ltd.

  20. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes.

    PubMed

    Nissen, Steven E; Wolski, Kathy

    2007-06-14

    Rosiglitazone is widely used to treat patients with type 2 diabetes mellitus, but its effect on cardiovascular morbidity and mortality has not been determined. We conducted searches of the published literature, the Web site of the Food and Drug Administration, and a clinical-trials registry maintained by the drug manufacturer (GlaxoSmithKline). Criteria for inclusion in our meta-analysis included a study duration of more than 24 weeks, the use of a randomized control group not receiving rosiglitazone, and the availability of outcome data for myocardial infarction and death from cardiovascular causes. Of 116 potentially relevant studies, 42 trials met the inclusion criteria. We tabulated all occurrences of myocardial infarction and death from cardiovascular causes. Data were combined by means of a fixed-effects model. In the 42 trials, the mean age of the subjects was approximately 56 years, and the mean baseline glycated hemoglobin level was approximately 8.2%. In the rosiglitazone group, as compared with the control group, the odds ratio for myocardial infarction was 1.43 (95% confidence interval [CI], 1.03 to 1.98; P=0.03), and the odds ratio for death from cardiovascular causes was 1.64 (95% CI, 0.98 to 2.74; P=0.06). Rosiglitazone was associated with a significant increase in the risk of myocardial infarction and with an increase in the risk of death from cardiovascular causes that had borderline significance. Our study was limited by a lack of access to original source data, which would have enabled time-to-event analysis. Despite these limitations, patients and providers should consider the potential for serious adverse cardiovascular effects of treatment with rosiglitazone for type 2 diabetes. Copyright 2007 Massachusetts Medical Society.

  1. Synthesis of 5-(ethylsulfonyl)-2-methoxyaniline: An important pharmacological fragment of VEGFR2 and other inhibitors

    PubMed Central

    Murár, Miroslav; Addová, Gabriela

    2013-01-01

    Summary Background: 5-(Ethylsulfonyl)-2-methoxyaniline (5) is part of the structure in 131 compounds possessing different biological activities. In most cases, they have antitumor properties (112 compounds). Other compounds are described as cardiovascular agents, ion-channel blockers, nervous-system blockers, anti-inflammatory agents, or antidiabetic, antiosteoporotic and hypolipemic species. Compound 5 is a precursor of different protein-kinase inhibitors or enzyme modulators (EGFR, PDGFR, ckit, CDK 2 and 4, MMPs 2, 3, 9 and 13, etc.). The structure of 5 represents a fragment for several powerful inhibitors of VEGFR2, a key angiogenic receptor. Antiangiogenic inhibitors slow down or stop new blood-vessel formation from pre-existing vasculature. Some antiangiogenic drugs inhibiting the VEGFR2 receptor are successfully used in clinics for the treatment of several types of tumours in synergy with chemotherapy (e.g., Nexavar® from Bayer, Sutent® from Pfizer and Votrient® from GlaxoSmithKline, approved by the FDA in 2005, 2006 and 2009, respectively). The structure of 5 is an important pharmacophoric fragment of potent VEGFR2 inhibitors (e.g., AAZ from PDB complex 1Y6A, enzymatic IC50 = 22 nM). Up to now, 25 VEGFR2 inhibitors possessing a fragment of 5 can be found in the literature. Despite the high significance of 5-(ethylsulfonyl)-2-methoxyaniline (5) its preparation has not yet been described. Results: Here we have developed a convenient synthesis of important polyheterosubstituted aniline 5 starting from commercially available 4-methoxybenzene-1-sulfonyl chloride (1) in four steps and 59% overall yield. The target 5-(ethylsulfonyl)-2-methoxyaniline (5) and its synthetic intermediates 2–4 together with a new compound 5-(ethylsulfonyl)-2-methoxy-1,3-dinitrobenzene (4a) have been precisely physicochemically characterised. PMID:23399884

  2. Human rights responsibilities of pharmaceutical companies in relation to access to medicines.

    PubMed

    Lee, Joo-Young; Hunt, Paul

    2012-01-01

    Although access to medicines is a vital feature of the right to the highest attainable standard of health ("right to health"), almost two billion people lack access to essential medicines, leading to immense avoidable suffering. While the human rights responsibility to provide access to medicines lies mainly with States, pharmaceutical companies also have human rights responsibilities in relation to access to medicines. This article provides an introduction to these responsibilities. It briefly outlines the new UN Guiding Principles on Business and Human Rights and places the human rights responsibilities of pharmaceutical companies in this context. The authors draw from the work of the first UN Special Rapporteur on the right to the highest attainable standard of health, in particular the Human Rights Guidelines for Pharmaceutical Companies in Relation to Access to Medicines that he presented to the UN General Assembly in 2008, and his UN report on GlaxoSmithKline (GSK). While the Guiding Principles on Business and Human Rights are general human rights standards applicable to all business entities, the Human Rights Guidelines for Pharmaceutical Companies consider the specific human rights responsibilities of one sector (pharmaceutical companies) in relation to one area of activity (access to medicines). The article signals the human rights responsibilities of all pharmaceutical companies, with particular attention to patent-holding pharmaceutical companies. Adopting a right-to-health "lens," the article discusses GSK and accountability. The authors argue that human rights should shape pharmaceutical companies' policies, and provide standards in relation to which pharmaceutical companies could, and should, be held accountable. They conclude that it is now crucial to devise independent, accessible, transparent, and effective mechanisms to monitor pharmaceutical companies and hold them publicly accountable for their human rights responsibilities. © 2012 American

  3. Burden of rotavirus in India--is rotavirus vaccine an answer to it?

    PubMed

    Taneja, Davendra K; Malik, Akash

    2012-01-01

    Rotavirus is currently by far the most common cause of severe diarrhea in infants and young children worldwide and of diarrheal deaths in developing countries. Worldwide Rotavirus is responsible for 611,000 childhood deaths out of which more than 80% occur in low-income countries. The resistance of rotavirus to commonly used disinfectants and ineffectiveness of oral rehydration therapy due to severe vomiting indicates that if an effective vaccine is the preferred option. WHO has recommended inclusion of rotavirus vaccine in the National Schedules where under 5 mortality due to diarrheal diseases is ≥ 10%. Currently two vaccines are available against rotavirus. Rotarix (GlaxoSmithKline) is a monovalent vaccine recommended to be orally administered in two doses at 6-12 weeks. Rota Teq (Merck) is a pentavalent vaccine recommended to be orally administered in three doses starting at 6-12 weeks of age. Serodiversity of rotavirus in India and its regional variation favor either a monovalent vaccine that can induce heterotypic immunity or a polyvalent vaccine incorporating majority of serotypes prevalent in the country. However, the efficacy of available rotavirus vaccines is less in low-income countries. Both the candidate vaccines when coadministered with OPV, immune response to first dose of these vaccines is reduced. However, immune responses to subsequent rotavirus vaccine doses are not affected. In view of this, WHO recommends three doses of either vaccine to be given to children in developing countries to produce the optimum response. Indigenous vaccine, 116E (Bharat Biotech) based on human rotavirus of serotype G9P [11] is still under Phase 2 trials. Another multivalent vaccine is being developed by Shantha Biotechnics in India. The cost effectiveness of the three dose schedule of the available and the rsults of the field trials of the indigenous vaccines should be assessed before inclusion of rotavirus vaccine in the National Immunization Schedule.

  4. The economic consequences of generic substitution for antiepileptic drugs in a public payer setting: the case of lamotrigine.

    PubMed

    Duh, Mei Sheng; Andermann, Frederick; Paradis, Pierre Emmanuel; Weiner, Jennifer; Manjunath, Ranjani; Crémieux, Pierre-Yves

    2007-08-01

    Generic substitution of antiepileptic drugs (AEDs) may increase pharmacy utilization, thus counterbalancing per-pill savings. The purpose of our study was to analyze the economic impact of government-mandated switching from branded to generic lamotrigine. Patients in a Canadian public pharmacy claims database using branded lamotrigine (Lamictal GlaxoSmithKline, UK) in 2002 converted to generic lamotrigine in 2003 and were observed from July 2002 to March 2006. Patients used branded lamotrigine for >or=90 days pre-generic entry and had >or=1 claim for generic lamotrigine post-generic entry. For the generic period, observed per-patient monthly drug costs were calculated as the sum of costs for lamotrigine, other AEDs, and non-AEDs. Expected per-patient drug costs were estimated assuming lamotrigine dose and other prescription drug utilization in the generic period were identical to those observed during the brand period. Differences between observed and expected costs were compared. Among 1,142 branded lamotrigine users, overall average monthly drug costs per person were expected to decrease by $30.55 due to lower pill costs. Instead, they fell by $11.98 from the brand to the generic periods (p < 0.001). Because of dosage changes, lamotrigine costs decreased by $29.92 instead of the anticipated $33.87 (p < 0.001). Increased pharmacy utilization caused other AED costs to rise by $6.29 versus the expected $0.36 (p < 0.001), while non-AED drug cost increased by $11.64 rather than by $2.95 (p < 0.001). We concluded that conversion to generic lamotrigine resulted in lower than expected cost savings. Further research is necessary to determine whether this is due to reduced effectiveness and/or tolerability. Payers may weigh smaller-than-expected cost reductions against a possible decrease in effectiveness to assess the relevance of mandatory generic switching of lamotrigine.

  5. Identification of ADAMTS7 as a novel locus for coronary atherosclerosis and association of ABO with myocardial infarction in the presence of coronary atherosclerosis: two genome-wide association studies.

    PubMed

    Reilly, Muredach P; Li, Mingyao; He, Jing; Ferguson, Jane F; Stylianou, Ioannis M; Mehta, Nehal N; Burnett, Mary Susan; Devaney, Joseph M; Knouff, Christopher W; Thompson, John R; Horne, Benjamin D; Stewart, Alexandre F R; Assimes, Themistocles L; Wild, Philipp S; Allayee, Hooman; Nitschke, Patrick Linsel; Patel, Riyaz S; Martinelli, Nicola; Girelli, Domenico; Quyyumi, Arshed A; Anderson, Jeffrey L; Erdmann, Jeanette; Hall, Alistair S; Schunkert, Heribert; Quertermous, Thomas; Blankenberg, Stefan; Hazen, Stanley L; Roberts, Robert; Kathiresan, Sekar; Samani, Nilesh J; Epstein, Stephen E; Rader, Daniel J

    2011-01-29

    We tested whether genetic factors distinctly contribute to either development of coronary atherosclerosis or, specifically, to myocardial infarction in existing coronary atherosclerosis. We did two genome-wide association studies (GWAS) with coronary angiographic phenotyping in participants of European ancestry. To identify loci that predispose to angiographic coronary artery disease (CAD), we compared individuals who had this disorder (n=12,393) with those who did not (controls, n=7383). To identify loci that predispose to myocardial infarction, we compared patients who had angiographic CAD and myocardial infarction (n=5783) with those who had angiographic CAD but no myocardial infarction (n=3644). In the comparison of patients with angiographic CAD versus controls, we identified a novel locus, ADAMTS7 (p=4·98×10(-13)). In the comparison of patients with angiographic CAD who had myocardial infarction versus those with angiographic CAD but no myocardial infarction, we identified a novel association at the ABO locus (p=7·62×10(-9)). The ABO association was attributable to the glycotransferase-deficient enzyme that encodes the ABO blood group O phenotype previously proposed to protect against myocardial infarction. Our findings indicate that specific genetic predispositions promote the development of coronary atherosclerosis whereas others lead to myocardial infarction in the presence of coronary atherosclerosis. The relation to specific CAD phenotypes might modify how novel loci are applied in personalised risk assessment and used in the development of novel therapies for CAD. The PennCath and MedStar studies were supported by the Cardiovascular Institute of the University of Pennsylvania, by the MedStar Health Research Institute at Washington Hospital Center and by a research grant from GlaxoSmithKline. The funding and support for the other cohorts contributing to the paper are described in the webappendix. Copyright © 2011 Elsevier Ltd. All rights reserved.

  6. Assessment of preparation time with fully-liquid versus non-fully liquid paediatric hexavalent vaccines. A time and motion study.

    PubMed

    De Coster, Ilse; Fournie, Xavier; Faure, Céline; Ziani, Eddy; Nicolas, Laurence; Soubeyrand, Benoit; Van Damme, Pierre

    2015-07-31

    Simplified vaccine preparation steps would save time and reduce potential immunisation errors. The aim of the study was to assess vaccine preparation time with fully-liquid hexavalent vaccine (DTaP-IPV-HB-PRP-T, Sanofi Pasteur MSD) versus non-fully liquid hexavalent vaccine that needs reconstitution (DTPa-HBV-IPV/Hib, GlaxoSmithKline Biologicals). Ninety-six Health Care Professionals (HCPs) participated in a randomised, cross-over, open-label, time and motion study in Belgium (2014). HCPs prepared each vaccine in a cross-over manner with a wash-out period of 3-5min. An independent nurse assessed preparation time and immunisation errors by systematic review of the videos. HCPs satisfaction and preference were evaluated by a self-administered questionnaire. Average preparation time was 36s for the fully-liquid vaccine and 70.5s for the non-fully liquid vaccine. The time saved using the fully-liquid vaccine was 34.5s (p≤0.001). On 192 preparations, 57 immunisation errors occurred: 47 in the non-fully liquid vaccine group (including one missing reconstitution of Hib component), 10 in the fully-liquid vaccine group. 71.9% of HCPs were very or somewhat satisfied with the ease of handling of both vaccines; 66.7% and 67.7% were very or somewhat satisfied with speed of preparation in the fully-liquid vaccine and the non-fully liquid vaccine groups, respectively. Almost all HCPs (97.6%) stated they would prefer the use of the fully-liquid vaccine in their daily practice. Preparation of a fully-liquid hexavalent vaccine can be completed in half the time necessary to prepare a non-fully liquid vaccine. The simplicity of the fully-liquid hexavalent vaccine preparation helps optimise reduction of immunisation errors. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  7. The role of vaccines and vaccine decision-making to achieve the goals of the Grand Convergence in public health.

    PubMed

    Kaslow, David C; Kalil, Jorge; Bloom, David; Breghi, Gianluca; Colucci, Anna Maria; De Gregorio, Ennio; Madhavan, Guru; Meier, Genevieve; Seabrook, Richard; Xu, Xiaoning

    2017-01-20

    On 17 and 18 July 2015, a meeting in Siena jointly sponsored by ADITEC and GlaxoSmithKline (GSK) was held to review the goals of the Global Health 2035 Grand Convergence, to discuss current vaccine evaluation methods, and to determine the feasibility of reaching consensus on an assessment framework for comprehensively and accurately capturing the full benefits of vaccines. Through lectures and workshops, participants reached a consensus that Multi-Criteria-Decision-Analysis is a method suited to systematically account for the many variables needed to evaluate the broad benefits of vaccination, which include not only health system savings, but also societal benefits, including benefits to the family and increased productivity. Participants also agreed on a set of "core values" to be used in future assessments of vaccines for development and introduction. These values include measures of vaccine efficacy and safety, incident cases prevented per year, the results of cost-benefit analyses, preventable mortality, and the severity of the target disease. Agreement on this set of core assessment parameters has the potential to increase alignment between manufacturers, public health agencies, non-governmental organizations (NGOs), and policy makers (see Global Health 2035 Mission Grand Convergence [1]). The following sections capture the deliberations of a workshop (Working Group 4) chartered to: (1) review the list of 24 parameters selected from SMART vaccines (see the companion papers by Timmis et al. and Madhavan et al., respectively) to determine which represent factors (see Table 1) that should be taken into account when evaluating the role of vaccines in maximizing the success of the Global Health 2035 Grand Convergence; (2) develop 3-5 "core values" that should be taken into account when evaluating vaccines at various stages of development; and (3) determine how vaccines can best contribute to the Global Health 2035 Grand Convergence effort. Copyright © 2016.

  8. Darapladib for preventing ischemic events in stable coronary heart disease.

    PubMed

    White, Harvey D; Held, Claes; Stewart, Ralph; Tarka, Elizabeth; Brown, Rebekkah; Davies, Richard Y; Budaj, Andrzej; Harrington, Robert A; Steg, P Gabriel; Ardissino, Diego; Armstrong, Paul W; Avezum, Alvaro; Aylward, Philip E; Bryce, Alfonso; Chen, Hong; Chen, Ming-Fong; Corbalan, Ramon; Dalby, Anthony J; Danchin, Nicolas; De Winter, Robbert J; Denchev, Stefan; Diaz, Rafael; Elisaf, Moses; Flather, Marcus D; Goudev, Assen R; Granger, Christopher B; Grinfeld, Liliana; Hochman, Judith S; Husted, Steen; Kim, Hyo-Soo; Koenig, Wolfgang; Linhart, Ales; Lonn, Eva; López-Sendón, José; Manolis, Athanasios J; Mohler, Emile R; Nicolau, José C; Pais, Prem; Parkhomenko, Alexander; Pedersen, Terje R; Pella, Daniel; Ramos-Corrales, Marco A; Ruda, Mikhail; Sereg, Mátyás; Siddique, Saulat; Sinnaeve, Peter; Smith, Peter; Sritara, Piyamitr; Swart, Henk P; Sy, Rody G; Teramoto, Tamio; Tse, Hung-Fat; Watson, David; Weaver, W Douglas; Weiss, Robert; Viigimaa, Margus; Vinereanu, Dragos; Zhu, Junren; Cannon, Christopher P; Wallentin, Lars

    2014-05-01

    Elevated lipoprotein-associated phospholipase A2 activity promotes the development of vulnerable atherosclerotic plaques, and elevated plasma levels of this enzyme are associated with an increased risk of coronary events. Darapladib is a selective oral inhibitor of lipoprotein-associated phospholipase A2. In a double-blind trial, we randomly assigned 15,828 patients with stable coronary heart disease to receive either once-daily darapladib (at a dose of 160 mg) or placebo. The primary end point was a composite of cardiovascular death, myocardial infarction, or stroke. Secondary end points included the components of the primary end point as well as major coronary events (death from coronary heart disease, myocardial infarction, or urgent coronary revascularization for myocardial ischemia) and total coronary events (death from coronary heart disease, myocardial infarction, hospitalization for unstable angina, or any coronary revascularization). During a median follow-up period of 3.7 years, the primary end point occurred in 769 of 7924 patients (9.7%) in the darapladib group and 819 of 7904 patients (10.4%) in the placebo group (hazard ratio in the darapladib group, 0.94; 95% confidence interval [CI], 0.85 to 1.03; P=0.20). There were also no significant between-group differences in the rates of the individual components of the primary end point or in all-cause mortality. Darapladib, as compared with placebo, reduced the rate of major coronary events (9.3% vs. 10.3%; hazard ratio, 0.90; 95% CI, 0.82 to 1.00; P=0.045) and total coronary events (14.6% vs. 16.1%; hazard ratio, 0.91; 95% CI, 0.84 to 0.98; P=0.02). In patients with stable coronary heart disease, darapladib did not significantly reduce the risk of the primary composite end point of cardiovascular death, myocardial infarction, or stroke. (Funded by GlaxoSmithKline; STABILITY ClinicalTrials.gov number, NCT00799903.).

  9. Vaccine purchasing groups in the United States: An overview of their policies and practices.

    PubMed

    Cowan, Anne E; Clark, Sarah J; Gordon, Jennifer L; Bok, Karin; Shen, Angela K

    2016-09-30

    Vaccine purchasing groups (VPGs) may help reduce the upfront cost of vaccines. The objective of this study was to describe key business practices of VPGs in the United States. Semi-structured, qualitative telephone interviews were conducted with representatives from 11 VPGs, based on a sampling frame of 53 VPGs. Interviews were transcribed and summarized by topic. Characteristics of the 11 VPGs interviewed reflect the broader VPG population: 64% national vs 36% regional; 8% charge a membership fee; membership ranging from 40 to over 300,000 sites. VPGs establish agreements with vaccine manufacturers, typically with either GlaxoSmithKline or Merck and Sanofi Pasteur; 1 VPG reported a single-product (Trumenba) agreement with Pfizer. VPG agreements specify "product loyalty" benchmarks (proportion of that manufacturer's product line) that the VPG and its members must meet to receive discounted vaccine pricing. The amount of discount is considered proprietary. Practices may actively participate with only one VPG; the member discount is automatically applied by the manufacturer at the time of ordering. Vaccine manufacturers monitor sales data to ensure compliance with product loyalty terms; practices that do not meet benchmarks may be removed from the VPG. VPGs are paid administration fees by the manufacturers. VPGs use these fees to cover their operating expenses and often rebate a portion of these fees back to their members. All 11 VPGs offer additional services to members, ranging from immunization-focused education and technical assistance to discounts on a broad range of medical and business supplies. VPGs can facilitate access to reduced purchase prices for most vaccines routinely recommended in the United States. Data on the magnitude of the price reductions were not publicly available. VPG members must balance loyalty-based price reductions against considerations of having a wider choice of vaccine products. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. [Vaccines against varicella-zoster virus (VZV)].

    PubMed

    Salleras, Luis; Salleras, Montserrat; Soldevila, Nuria; Prat, Andreu; Garrido, Patricio; Domínguez, Ángela

    2015-01-01

    In Western countries, two attenuated varicella vaccines derived from the OKA strain are licensed: Varilrix® GlaxoSmithKline (OKA/RIT strain) and Varivax® Merck Sharp and Dohme (OKA/Merck strain). Currently, in Spain, varicella vaccination is only included in the Ministry of Health, Social Services and Equality official vaccination calendar for administration in adolescents who have not had the disease. Given the good results obtained in Navarra and Madrid with universal administration of the vaccine in children, it would be desirable to include the vaccine in the routine immunization schedule, with the administration of two doses at 15-18 months of age in the future. The protective efficacy of the attenuated herpes zoster vaccine was evaluated in the Shingles Prevention Study, which showed that in the short term (0-4 years) the vaccine reduced the incidence of herpes zoster by 53%, post-herpetic neuralgia by 66%, and the disease burden in immunocompetent persons aged ≥60 years by 61%. Another study demonstrated protective efficacy in persons aged 50-59 years. Over time, the protective efficacy decreases, but remains at acceptable levels, especially for post-herpetic neuralgia and the disease burden. Recently, the results of a controlled clinical trial (phase III) conducted in 18 countries to assess the protective efficacy of the inactivated subunit vaccine (glycoprotein E) adjuvanted with the adjuvant AS01B were published. The study inferred that the vaccine significantly reduced the incidence of herpes zoster in the short term (3.2 years) in people aged ≥50 years. Vaccine protection did not decrease with age at vaccination, ranging between 96.8% and 97.9% in all age groups. Copyright © 2015. Published by Elsevier España, S.L.U.

  11. Pharmacy executive leadership issues and associated skills, knowledge, and abilities.

    PubMed

    Meadows, Andrew B; Maine, Lucinda L; Keyes, Elizabeth K; Pearson, Kathy; Finstuen, Kenn

    2005-01-01

    To identify challenges that current and future pharmacy executives are facing or will face in the future and to define what skills, knowledge, and abilities (SKAs) are required to successfully negotiate these challenges. Delphi method for executive decision making. Civilian pharmacy profession. 110 pharmacists who graduated from the GlaxoSmithKline Executive Management Program for Pharmacy Leaders. Two iterations of the Delphi method for executive decision making separated by an expert panel content analysis. Round 1--participants were asked to identify five major issues they believed to be of greatest importance to pharmacy leaders in the next 5-10 years and name specific SKAs that might be needed by future leaders to successfully deal with those issues. An expert panel reviewed the issues, classified issues into specific domains, and titled each domain. Round 2-participants rated the SKAs on a 7-point scale according to their individual assessment of importance in each domain. For Delphi rounds 1 and 2, response rates were 21.8% and 18.2%, respectively. More than 100 total issue statements were identified. The expert panel sorted the issues into five domains: management and development of the pharmacy workforce, pharmacy finance, total quality management of work-flow systems, influences on the practice of pharmacy, and professional pharmacy leadership. Five of the top 15 SKAs-and all four highest ranked items--came from the professional pharmacy leadership domain, including ability to see the big picture, ability to demonstrate the value of pharmacy services, ability to lead and manage in an ethical manner, and skills for influencing an organization's senior leadership. Through successful integration of communication skills, critical thinking, and problem solving techniques, future public-sector pharmacy executives will be better equipped to effectively position their organizations and the profession for the challenges that lie ahead.

  12. MenACWY-TT is immunogenic when co-administered with Tdap and AS04-HPV16/18 in girls and young women: Results from a phase III randomized trial.

    PubMed

    Rivera, Luis; Chanthavanich, Pornthep; Põder, Airi; Suryakiran, P V; Jastorff, Archana; Van der Wielen, Marie

    2018-06-22

    Co-administration of vaccines in adolescents may improve coverage. We assessed co-administration of quadrivalent meningococcal serogroups A, C, W and Y tetanus toxoid-conjugate vaccine (MenACWY-TT), human papillomavirus 16/18 AS04-adjuvanted vaccine (AS04-HPV16/18) and tetanus-diphtheria-acellular pertussis vaccine (Tdap) in girls and young women. In this phase IIIb study (NCT01755689), 1300 healthy 9-25-year-old females were randomized (1:1:1:1:1) to receive: MenACWY-TT at month (M) 0 and AS04-HPV16/18 at M1, M2, M7; MenACWY-TT and AS04-HPV16/18 at M0 and AS04-HPV16/18 at M1, M6; AS04-HPV16/18 at M0, M1, M6; MenACWY-TT, Tdap and AS04-HPV16/18 at M0 and AS04-HPV16/18 at M1, M6; Tdap and AS04-HPV16/18 at M0 and AS04-HPV16/18 at M1, M6. Immunogenicity, safety and reactogenicity were evaluated. Immunogenicity of MenACWY-TT and AS04-HPV16/18 when co-administered was non-inferior to that of the 2 vaccines given separately. Co-administration of MenACWY-TT, AS04-HPV16/18 and Tdap was non-inferior to MenACWY-TT administered alone or to Tdap co-administered with AS04-HPV16/18 in terms of immunogenicity for all vaccine components, except pertussis antigens. Post-vaccination, ≥89.5% of participants reached antibody levels above the pre-specified threshold for all antigens. No safety concerns were identified. Our data support co-administration of MenACWY-TT with Tdap and AS04-HPV16/18 vaccines in adolescents. Copyright © 2018 GlaxoSmithKline Biologicals SA. Published by Elsevier Ltd.. All rights reserved.

  13. Effects of topical acne treatment on the ocular surface in patients with acne vulgaris.

    PubMed

    Aslan Bayhan, Seray; Bayhan, Hasan Ali; Çölgeçen, Emine; Gürdal, Canan

    2016-12-01

    To assess the ocular side effects during topical retinoid-antibiotic combination treatment in patients with facial acne vulgaris. Forty-three patients applying topical isotretinoin+erythromycin combination (isotrexin gel, GlaxoSmithKline) once daily for the treatment of acne vulgaris were enrolled. Full ophthalmologic examination, Schirmer test (with topical anesthesia), fluorescein break-up time (BUT), corneal fluorescein staining and tear osmolarity measurement with the TearLab system (TearLab Corporation) were carried out before and at the end of the first month of the treatment. For evaluation of symptoms participants completed the ocular surface disease index (OSDI) questionnaire at each visit. The mean age of the patients was 23.16±3.03 (18-30) years. Mean tear osmolarity increased significantly from 282.09±8.95 mOsm/L at baseline to 300.39±16.65 mOsm/L after the treatment (p<0.001). BUT decreased from an average of 11.93±1.12s at baseline to 6.65±3.03s at the end of the first month (p<0.001). The OSDI score worsened significantly (5.41±3.65 vs 21.53±12.95, p<0.001) and punctate epitheliopathy was seen in 51% of eyes after the treatment. The average Schirmer values were 13.09±1.90 and 12.41±2.44mm/5min before and at the end of the first month of the treatment, respectively (p=0.117). The findings of this study indicate that topical retinoid-antibiotic combination treatment causes significant signs and symptoms of dry eye. Patients receiving topical treatment for acne should be evaluated regularly to ensure the timely detection and treatment of pathologic signs on the ocular surface. Copyright © 2016 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.

  14. Characterisation of a novel, high affinity and selective αvβ6 integrin RGD-mimetic radioligand.

    PubMed

    Hall, Eleanor R; Bibby, Lloyd I; Slack, Robert J

    2016-10-01

    The alpha-v beta-6 (αvβ6) integrin has been identified as playing a key role in the activation of transforming growth factor-β (TGFβ) that is hypothesised to be pivotal in the development of cancer and fibrotic diseases. Therefore, the αvβ6 integrin is an attractive therapeutic target for these debilitating diseases and a drug discovery programme to identify small molecule αvβ6 selective arginyl-glycinyl-aspartic acid (RGD)-mimetics was initiated within GlaxoSmithKline. The primary aim of this study was to pharmacologically characterise the binding to αvβ6 of a novel clinical candidate, compound 1, using a radiolabelled form. Radioligand binding studies were completed with [(3)H]compound 1 against the human and mouse soluble protein forms of αvβ6 to determine accurate affinity estimates and binding kinetics. The selectivity of compound 1 for the RGD integrin family was also determined using saturation binding studies (αvβ1, αvβ3, αvβ5, αvβ8, α5β1 and α8β1 integrins) and fibrinogen-induced platelet aggregation (αIIbβ3 integrin). In addition, the relationship between divalent metal cation type and concentration and αvβ6 RGD site binding was also investigated. Compound 1 has been demonstrated to bind with extremely high affinity and selectivity for the αvβ6 integrin and has the potential as a clinical tool and therapeutic for investigating the role of αvβ6 in a range of disease states both pre-clinically and clinically. In addition, this is the first study that has successfully applied radioligand binding to the RGD integrin field to accurately determine the affinity and selectivity profile of a small molecule RGD-mimetic. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Significantly Reduced Genoprevalence of Vaccine-Type HPV-16/18 Infections among Vaccinated Compared to Non-Vaccinated Young Women 5.5 Years after a Bivalent HPV-16/18 Vaccine (Cervarix®) Pilot Project in Uganda

    PubMed Central

    Berggren, Vanja; Wabinga, Henry; Lillsunde-Larsson, Gabriella; Helenius, Gisela; Kaliff, Malin; Karlsson, Mats; Kirimunda, Samuel; Musubika, Caroline; Andersson, Sören

    2016-01-01

    The objective of this study was to determine the prevalence and some predictors for vaccine and non-vaccine types of HPV infections among bivalent HPV vaccinated and non-vaccinated young women in Uganda. This was a comparative cross sectional study 5.5 years after a bivalent HPV 16/18 vaccination (Cervarix®, GlaxoSmithKline, Belgium) pilot project in western Uganda. Cervical swabs were collected between July 2014-August 2014 and analyzed with a HPV genotyping test, CLART® HPV2 assay (Genomica, Madrid Spain) which is based on PCR followed by microarray for determination of genotype. Blood samples were also tested for HIV and syphilis infections as well as CD4 and CD8 lymphocyte levels. The age range of the participants was 15–24 years and mean age was 18.6(SD 1.4). Vaccine-type HPV-16/18 strains were significantly less prevalent among vaccinated women compared to non-vaccinated women (0.5% vs 5.6%, p 0.006, OR 95% CI 0.08(0.01–0.64). At type-specific level, significant difference was observed for HPV16 only. Other STIs (HIV/syphilis) were important risk factors for HPV infections including both vaccine types and non-vaccine types. In addition, for non-vaccine HPV types, living in an urban area, having a low BMI, low CD4 count and having had a high number of life time sexual partners were also significant risk factors. Our data concurs with the existing literature from other parts of the world regarding the effectiveness of bivalent HPV-16/18 vaccine in reducing the prevalence of HPV infections particularly vaccine HPV- 16/18 strains among vaccinated women. This study reinforces the recommendation to vaccinate young girls before sexual debut and integrate other STI particularly HIV and syphilis interventions into HPV vaccination packages. PMID:27482705

  16. Toothbrush abrasivity in a long-term simulation on human dentin depends on brushing mode and bristle arrangement.

    PubMed

    Bizhang, Mozhgan; Schmidt, Ilka; Chun, Yong-Hee Patricia; Arnold, Wolfgang H; Zimmer, Stefan

    2017-01-01

    The aim of this study was to evaluate the susceptibility of dentin to brushing abrasion using four different toothbrushes (rotating-oscillating, sonic and two types of manual toothbrushes) with the same brushing forces. Dentin samples (n = 72) were selected from 72 impacted third molars. Half of the surface of dentin samples was covered with an adhesive tape, creating a protected and a freely exposed area in the same specimen. Brushing was performed with either a: sonic (Sonicare PowerUp, Philips GmbH, Hamburg, Germany), b: oscillating-rotating (Oral B Vitality Precisions Clean, Procter & Gamble, Schwalbach am Taunus, Germany) or two different manual toothbrushes c: flat trim brush head toothbrush (Dr. Best: Original, Glaxo-Smith-Kline, Bühl, Germany) and d: rippled-shaped brush head toothbrush (Blend-a-Dent, Complete V-Interdental, Blend-a-med, Schwalbach, Germany) in a custom made automatic brushing machine. The brushing force was set to 2 N and a whitening toothpaste (RDA = 150) was used. The simulation period was performed over a calculated period to mimic a brushing behavior of two times a day brushing for eight years and six months. Dentin loss was quantitatively determined by profilometry and statistically analyzed by Wilcoxon and Mann-Whitney-U Test (p < 0.05). The mean (standard deviation) surface loss was 21.03 (±1.26) μm for the sonic toothbrush, 15.71 (±0.85) μm for the oscillating-rotating toothbrush, 6.13 (±1.24) μm for the manual toothbrush with flat trim brush head and 2.50 (±0.43) μm for the manual toothbrush with rippled-shaped brush head. Differences between all groups were statistically significant at p<0.05. Using the same brushing force and a highly abrasive toothpaste, manual toothbrushes are significantly less abrasive compared to power toothbrushes for an 8.5-year simulation.

  17. Case Report of Bullous Pemphigoid following Fundus Fluorescein Angiography

    PubMed Central

    Demirci, Goktug; Demirci, Gulsen Tukenmez; Gulkilik, Gokhan

    2010-01-01

    Purpose To report a first case of bullous pemphigoid (BP) following intravenous fluorescein for fundus angiography. Clinical Features: A 70-year-old male patient was admitted to the intensive care unit with BP and sepsis. He reported a history of fundus fluorescein angiography with a pre-diagnosis of senile macular degeneration 2 months prior to presentation. At that time, fluorescein extravasated at the antecubital region. Following the procedure, pruritus and erythema began at the wrists bilaterally, and quickly spread to the entire body. The patient also reported a history of allergy to human albumin solution (Plamasteril®; Abbott) 15 years before, during bypass surgery. On dermatologic examination, erythematous patches were present on the scalp, chest and anogenital region. Vesicles and bullous lesions were present on upper and lower extremities. On day 2 of hospitalization, tense bullae appeared on the upper and lower extremities. The patient was treated with oral methylprednisolone 48 mg (Prednol®; Mustafa Nevzat), topical clobetasol dipropionate 0.05% cream (Dermovate®; Glaxo SmithKline), and topical 4% urea lotion (Excipial Lipo®; Orva) for presumptive bullous pemphigoid. Skin punch biopsy provided tissue for histopathology, direct immunofluorescence examination, and salt extraction, which were all consistent with BP. After 1 month, the patient was transferred to the intensive care unit with sepsis secondary to urinary tract infection; he died 2 weeks later from sepsis and cardiac failure. Conclusions To our knowledge, this is the first reported case of BP following fundus fluorescein angiography in a patient with known human albumin solution allergy. Consideration should be made to avoid fluorescein angiography, change administration route, or premedicate with antihistamines in patients with known human albumin solution allergy. The association between fundus fluorescein angiography and BP should be further investigated. PMID:20737052

  18. Auditory Phenotype of Smith-Magenis Syndrome

    ERIC Educational Resources Information Center

    Brendal, Megan A.; King, Kelly A.; Zalewski, Christopher K.; Finucane, Brenda M.; Introne, Wendy; Brewer, Carmen C.; Smith, Ann C. M.

    2017-01-01

    Purpose: The purpose of this study was to describe the auditory phenotype of a large cohort with Smith-Magenis syndrome (SMS), a rare disorder including physical anomalies, cognitive deficits, sleep disturbances, and a distinct behavioral phenotype. Method: Hearing-related data were collected for 133 individuals with SMS aged 1-49 years. Audiogram…

  19. Uric acid and allopurinol aggravate absence epileptic activity in Wistar Albino Glaxo Rijswijk rats.

    PubMed

    Lakatos, Renáta Krisztina; Dobolyi, Árpád; Kovács, Zsolt

    2018-05-01

    Uric acid has a role in several physiological and pathophysiological processes. For example, uric acid may facilitate seizure generalization while reducing uric acid level may evoke anticonvulsant/antiepileptic effects. Allopurinol blocks the activity of xanthine oxidase, by which allopurinol inhibits catabolism of hypoxanthine to xanthine and uric acid and, as a consequence, decreases the level of uric acid. Although the modulation of serum uric acid level is a widely used strategy in the treatment of certain diseases, our knowledge regarding the effects of uric acid on epileptic activity is far from complete. Thus, the main aim of this study was the investigation of the effect of uric acid on absence epileptic seizures (spike-wave discharges: SWDs) in a model of human absence epilepsy, the Wistar Albino Glaxo/Rijswijk (WAG/Rij) rat. We investigated the influence of intraperitoneally (i.p.) injected uric acid (100 mg/kg and 200 mg/kg), allopurinol (50 mg/kg and 100 mg/kg), a cyclooxygenase 1 and 2 (COX-1 and COX-2) inhibitor indomethacin (10 mg/kg) and inosine (500 mg/kg) alone and the combined application of allopurinol (50 mg/kg) with uric acid (100 mg/kg) or inosine (500 mg/kg) as well as indomethacin (10 mg/kg) with uric acid (100 mg/kg) and inosine (500 mg/kg) with uric acid (100 mg/kg) on absence epileptic activity. We demonstrated that both uric acid and allopurinol alone significantly increased the number of SWDs whereas indomethacin abolished the uric acid-evoked increase in SWD number. Our results suggest that uric acid and allopurinol have proepileptic effects in WAG/Rij rats. Copyright © 2018 Elsevier B.V. All rights reserved.

  20. 'Nothing is so soon forgot as pain': Reading Agony in Adam Smith's The Theory of Moral Sentiments.

    PubMed

    Franson, Craig

    2014-01-01

    Giving a rigorous philosophical explanation to the imagination's role in sympathy, Adam Smith's The Theory of Moral Sentiments became a central text in Romantic aesthetics. It not only justified the age's vogue for making suffering an object of artistic pleasure, it treated suffering's affectivity as the very foundation of society. Depicting agony as a spectacle to be read by others, Smith transformed morality into rhetoric, making human subjects into readers of a sentimentalised, textual world. Yet Smith's work restricted the bonds of sympathy, too, following established distinctions between mind and body that helped him to exclude physical pain from sympathetic response. This essay looks to Smith's context in the overlapping philosophical and medical discourses of the Scottish Enlightenment, exploring his moral theory's resonance with the nerve theories of Robert Whytt and William Cullen, then the leading figures in Scotland's rising medical community. Deepening our understanding of Smith's probable sources, it reframes Smith's intellectual and ideological legacy, foregrounding some of the ambivalent cultural and political implications of Smith's troubling censure of physical pain.

  1. Smith-Purcell radiation from concave dotted gratings

    NASA Astrophysics Data System (ADS)

    Sergeeva, D. Yu.; Tishchenko, A. A.; Aryshev, A. S.; Strikhanov, M. N.

    2018-02-01

    We present the first-principles theory of Smith-Purcell effect from the concave dotted grating consisting of bent chains of separated micro- or nanoparticles. The numerical analysis demonstrates that the obtained spectral-angular distributions change significantly depending on the structure of the grating.

  2. The Importance of What You Leave Behind: A Conversation with Carl Smith

    ERIC Educational Resources Information Center

    Teagarden, Jim; Zabel, Robert; Kaff, Marilyn

    2017-01-01

    Dr. Carl Smith shares his reflections on a varied career that included many different roles and responsibilities but shared a focus on children with behavior disorders. Dr. Smith also provides insight into where he believes the field is heading and offers his advice to those just entering the field. Perhaps the lasting advice to all is to focus on…

  3. Rhetorical Studies: A Reassessment of Adam Smith's Lectures on Rhetoric and Belles Lettres.

    ERIC Educational Resources Information Center

    Purcell, William M.

    1986-01-01

    Offers a dissenting interpretation of Adam Smith's Lectures on Rhetoric and Belles Lettres and a more conservative perspective on Smith's significance to the history of rhetorical theory. Views the lectures as an historical commentary on literature and rhetoric from the perspective of an eighteenth-century lecturer. (JD)

  4. 78 FR 2295 - Charlissa C. Smith; Establishment of Atomic Safety and Licensing Board

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-10

    ... NUCLEAR REGULATORY COMMISSION [Docket No. 55-23694-SP; ASLBP No. 13-925-01-SP-BD01] Charlissa C... (Board) is being established to preside over the following proceeding: Charlissa C. Smith, (Denial of Senior Reactor Operator License). This proceeding concerns a hearing request from Charlissa C. Smith...

  5. Starry Campus: Reducing Light Pollution at Smith College

    NASA Astrophysics Data System (ADS)

    Brenon, Alexandria

    2017-01-01

    This is the start of a program to teach Smith College students about the dangers posed by light pollution and inspire them to help make Smith a better dark sky area. This will focus both on general astronomy education to catch their interest and speciic light pollution information as well. My advisor is creating an initiative for dark skies education and preservation on college campuses, with this as the pilot program. College students can help both on campus and off when they will be able to take what they learn to inform their decisions about lighting when they move out on their own. The ultimate goal is to convince Smith College to make the changes it needs to reduce its light pollution as well as to motivate its students to learn more about astronomy and light pollution. I am developing an education and outreach program using venues such as house teas, lectures, and meetings to teach other students, the staff, and faculty about the issue. I am also working with existing clubs and organizations on campus such as the Green Team, the landscape studies department, and the Center for the Environment, Ecological Design, and Sustainability. This will help to develop campus lighting standards. These lighting standards will be proposed to the college, as there are no current standards in place for lighting around campus.

  6. The Behavioural Phenotype of Smith-Magenis Syndrome: Evidence for a Gene-Environment Interaction

    ERIC Educational Resources Information Center

    Taylor, L.; Oliver, C.

    2008-01-01

    Background: Behaviour problems and a preference for adult contact are reported to be prominent in the phenotype of Smith-Magenis syndrome. In this study we examined the relationship between social interactions and self-injurious and aggressive/disruptive behaviour in Smith-Magenis syndrome to explore potential operant reinforcement of problem…

  7. Processing Semblances Induced through Inter-Postsynaptic Functional LINKs, Presumed Biological Parallels of K-Lines Proposed for Building Artificial Intelligence

    PubMed Central

    Vadakkan, Kunjumon I.

    2011-01-01

    The internal sensation of memory, which is available only to the owner of an individual nervous system, is difficult to analyze for its basic elements of operation. We hypothesize that associative learning induces the formation of functional LINK between the postsynapses. During memory retrieval, the activation of either postsynapse re-activates the functional LINK evoking a semblance of sensory activity arriving at its opposite postsynapse, nature of which defines the basic unit of internal sensation – namely, the semblion. In neuronal networks that undergo continuous oscillatory activity at certain levels of their organization re-activation of functional LINKs is expected to induce semblions, enabling the system to continuously learn, self-organize, and demonstrate instantiation, features that can be utilized for developing artificial intelligence (AI). This paper also explains suitability of the inter-postsynaptic functional LINKs to meet the expectations of Minsky’s K-lines, basic elements of a memory theory generated to develop AI and methods to replicate semblances outside the nervous system. PMID:21845180

  8. 75 FR 11919 - Smith and Nephew, Inc., Wound Management-Largo Division, Including On-Site Leased Workers From...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-12

    ... DEPARTMENT OF LABOR Employment and Training Administration [TA-W-70,151] Smith and Nephew, Inc... November 5, 2009, applicable to workers of Smith and Nephew, Inc., Wound Management-Largo Division, Largo... workers leased from Adecco were employed on-site at the Largo, Florida location of Smith and Nephew, Inc...

  9. STS-82 training in WETF facility with Steve Smith and Mark Lee

    NASA Image and Video Library

    1996-06-10

    S96-11807 (10 June 1996) --- Astronaut Steven L. Smith (right), STS-82 mission specialist assigned to extravehicular activity (EVA) involved with the servicing of the Hubble Space Telescope (HST), gets help with the final touches of suit donning from crewmate Joseph R. Tanner. Minutes later, Smith was underwater in a nearby tank and neutrally buoyant, rehearsing some of the HST servicing chores with a crewmate.

  10. Henry Hollingsworth Smith and His Bibliographical Index and Historical Record: The Beginning of American Surgical Historiography.

    PubMed

    Rutkow, Ira

    2016-04-01

    To explore the details of Henry Hollingsworth Smith's (1815-1890) achievement as the first physician to organize in a systematic and chronologic manner the details of the history of surgery in America and prepare a register of men who performed surgical operations. The life of Smith, the earliest of the nation's surgeons to elucidate the history of American surgery, is little known. His boosting the image of the scalpel wielder helped shape the future of the craft, in particular, surgery's rise as a specialty and profession. An analysis of the published medical literature and unpublished documents relating to Smith and his work to document the history of American surgery. During the 1850 s, a time when surgery was not considered a separate branch of medicine but a mere technical mode of treatment, Smith's efforts in surgical history provided much needed encouragement to surgeons in their pursuit of professional recognition. Although Smith's accomplishment as the nation's first compiler of the history of American surgery has long been forgotten, his effort afforded the men who performed surgical operations their earliest measure of self-respect. As such, Smith belongs in America's pantheon of surgical heroes.

  11. Smith predictor based-sliding mode controller for integrating processes with elevated deadtime.

    PubMed

    Camacho, Oscar; De la Cruz, Francisco

    2004-04-01

    An approach to control integrating processes with elevated deadtime using a Smith predictor sliding mode controller is presented. A PID sliding surface and an integrating first-order plus deadtime model have been used to synthesize the controller. Since the performance of existing controllers with a Smith predictor decrease in the presence of modeling errors, this paper presents a simple approach to combining the Smith predictor with the sliding mode concept, which is a proven, simple, and robust procedure. The proposed scheme has a set of tuning equations as a function of the characteristic parameters of the model. For implementation of our proposed approach, computer based industrial controllers that execute PID algorithms can be used. The performance and robustness of the proposed controller are compared with the Matausek-Micić scheme for linear systems using simulations.

  12. 76 FR 59115 - Notice of Availability of Patent Fee Changes Under the Leahy-Smith America Invents Act

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-23

    ... new programs provided for in the Leahy-Smith America Invents Act (e.g., post-grant review, inter... Availability of Patent Fee Changes Under the Leahy- Smith America Invents Act AGENCY: United States Patent and... of the Leahy-Smith America Invents Act (i.e., September 26, 2011) by operation of the fifteen percent...

  13. RadNet Air Data From Fort Smith, AR

    EPA Pesticide Factsheets

    This page presents radiation air monitoring and air filter analysis data for Fort Smith, AR from EPA's RadNet system. RadNet is a nationwide network of monitoring stations that measure radiation in air, drinking water and precipitation.

  14. Breeding habitat associations and predicted distribution of an obligate tundra-breeding bird, Smith's Longspur

    USGS Publications Warehouse

    Wild, Teri C.; Kendall, Steven J.; Guldager, Nikki; Powell, Abby N.

    2015-01-01

    Smith's Longspur (Calcarius pictus) is a species of conservation concern which breeds in Arctic habitats that are expected to be especially vulnerable to climate change. We used bird presence and habitat data from point-transect surveys conducted at 12 sites across the Brooks Range, Alaska, 2003–2009, to identify breeding areas, describe local habitat associations, and identify suitable habitat using a predictive model of Smith's Longspur distribution. Smith's Longspurs were observed at seven sites, where they were associated with a variety of sedge–shrub habitats composed primarily of mosses, sedges, tussocks, and dwarf shrubs; erect shrubs were common but sparse. Nonmetric multidimensional scaling ordination of ground cover revealed positive associations of Smith's Longspur presence with sedges and mosses and a negative association with high cover of shrubs. To model predicted distribution, we used boosted regression trees to relate landscape variables to occurrence. Our model predicted that Smith's Longspurs may occur in valleys and foothills of the northeastern and southeastern mountains and in upland plateaus of the western mountains, and farther west than currently documented, over a predicted area no larger than 15% of the Brooks Range. With climate change, shrubs are expected to grow larger and denser, while soil moisture and moss cover are predicted to decrease. These changes may reduce Smith's Longspur habitat quality and limit distribution in the Brooks Range to poorly drained lowlands and alpine plateaus where sedge–shrub tundra is likely to persist. Conversely, northward advance of shrubs into sedge tundra may create suitable habitat, thus supporting a northward longspur distribution shift.

  15. Adam Smith, Religion, and Tuition Tax Credits.

    ERIC Educational Resources Information Center

    Alexander, Kern

    1983-01-01

    Examines tuition tax credit programs in framework of Adam Smith's ideas on the economic impact of established churches. Finds that tuition tax credits would amount to state expenditures to relieve the financial burden of parochial school parents and would allow churches to invest commercially to maintain their charitable functions. (JW)

  16. Spectral and spatial shaping of Smith-Purcell radiation

    NASA Astrophysics Data System (ADS)

    Remez, Roei; Shapira, Niv; Roques-Carmes, Charles; Tirole, Romain; Yang, Yi; Lereah, Yossi; Soljačić, Marin; Kaminer, Ido; Arie, Ady

    2017-12-01

    The Smith-Purcell effect, observed when an electron beam passes in the vicinity of a periodic structure, is a promising platform for the generation of electromagnetic radiation in previously unreachable spectral ranges. However, most of the studies of this radiation were performed on simple periodic gratings, whose radiation spectrum exhibits a single peak and its higher harmonics predicted by a well-established dispersion relation. Here, we propose a method to shape the spatial and spectral far-field distribution of the radiation using complex periodic and aperiodic gratings. We show, theoretically and experimentally, that engineering multiple peak spectra with controlled widths located at desired wavelengths is achievable using Smith-Purcell radiation. Our method opens the way to free-electron-driven sources with tailored angular and spectral responses, and gives rise to focusing functionality for spectral ranges where lenses are unavailable or inefficient.

  17. Groundwater and surface-water interaction within the upper Smith River Watershed, Montana 2006-2010

    USGS Publications Warehouse

    Caldwell, Rodney R.; Eddy-Miller, Cheryl A.

    2013-01-01

    The 125-mile long Smith River, a tributary of the Missouri River, is highly valued as an agricultural resource and for its many recreational uses. During a drought starting in about 1999, streamflow was insufficient to meet all of the irrigation demands, much less maintain streamflow needed for boating and viable fish habitat. In 2006, the U.S. Geological Survey, in cooperation with the Meagher County Conservation District, initiated a multi-year hydrologic investigation of the Smith River watershed. This investigation was designed to increase understanding of the water resources of the upper Smith River watershed and develop a detailed description of groundwater and surface-water interactions. A combination of methods, including miscellaneous and continuous groundwater-level, stream-stage, water-temperature, and streamflow monitoring was used to assess the hydrologic system and the spatial and temporal variability of groundwater and surface-water interactions. Collectively, data are in agreement and show: (1) the hydraulic connectedness of groundwater and surface water, (2) the presence of both losing and gaining stream reaches, (3) dynamic changes in direction and magnitude of water flow between the stream and groundwater with time, (4) the effects of local flood irrigation on groundwater levels and gradients in the watershed, and (5) evidence and timing of irrigation return flows to area streams. Groundwater flow within the alluvium and older (Tertiary) basin-fill sediments generally followed land-surface topography from the uplands to the axis of alluvial valleys of the Smith River and its tributaries. Groundwater levels were typically highest in the monitoring wells located within and adjacent to streams in late spring or early summer, likely affected by recharge from snowmelt and local precipitation, leakage from losing streams and canals, and recharge from local flood irrigation. The effects of flood irrigation resulted in increased hydraulic gradients

  18. Solar Cycle Fine Structure and Surface Rotation from Ca II K-Line Time Series Data

    NASA Astrophysics Data System (ADS)

    Scargle, Jeff; Keil, Steve; Worden, Pete

    2011-10-01

    Analysis of three and a half decades of data from the NSO/AFRL/Sac Peak K-line monitoring program yields evidence for four components to the variation: (a) the solar cycle, with considerable fine structure and a quasi-periodicity of 122.4 days; (b) a stochastic process, faster than (a) and largely independent of it, (c) a quasi-periodic signal due to rotational modulation, and of course (d) observational errors (shown to be quite small). Correlation and power spectrum analyses elucidate periodic and aperiodic variation of these chromospheric parameters. Time-frequency analysis is especially useful for extracting information about differential rotation, and in particular elucidates the connection between its behavior and fine structure of the solar cycle on approximately one-year time scales. These results further suggest that similar analyses will be useful at detecting and characterizing differential rotation in stars from stellar light-curves such as those being produced by NASA's Kepler observatory. Component (b) consists of variations over a range of timescales, in the manner of a "1/f" random process. A time-dependent Wilson-Bappu effect appears to be present in the solar cycle variations (a), but not in the stochastic process (b). The data can be found at the National Solar Observatory web site http://nsosp.nso.edu/data/cak_mon.html, or by file transfer protocol at ftp://ftp.nso.edu/idl/cak.parameters.

  19. Smiths Medical Medfusion 3010a syringe pump may overinfuse if software is outdated.

    PubMed

    2010-04-01

    Smiths Medical Medfusion 3010a syringe pumps that aren't equipped with the latest software version (2.0.6) could overinfuse if the "recall last settings" function is used following an infusion in volume/time mode. If your facility has pumps equipped with software versions older than 2.0.6, contact Smiths Medical to obtain an upgrade.

  20. Speech/Language Pathologists Reflect on Sally Smith and the Lab School of Washington

    ERIC Educational Resources Information Center

    Learning Disabilities: A Multidisciplinary Journal, 2010

    2010-01-01

    Sally L. Smith had a clear vision of how she thought speech and language services should be integrated into her school, The Lab School of Washington. It was Smith's idea that language therapists should work individually with students to help them make gains in their particular areas of need, as well as to work collaboratively with the teachers,…

  1. Neurologic and developmental features of the Smith-Magenis syndrome (del 17p11.2).

    PubMed

    Gropman, Andrea L; Duncan, Wallace C; Smith, Ann C M

    2006-05-01

    The Smith-Magenis syndrome is a rare, complex multisystemic disorder featuring, mental retardation and multiple congenital anomalies caused by a heterozygous interstitial deletion of chromosome 17p11.2. The phenotype of Smith-Magenis syndrome is characterized by a distinct pattern of features including infantile hypotonia, generalized complacency and lethargy in infancy, minor skeletal (brachycephaly, brachydactyly) and craniofacial features, ocular abnormalities, middle ear and laryngeal abnormalities including hoarse voice, as well as marked early expressive speech and language delays, psychomotor and growth retardation, and a 24-hour sleep disturbance. A striking neurobehavioral pattern of stereotypies, hyperactivity, polyembolokoilamania, onychotillomania, maladaptive and self-injurious and aggressive behavior is observed with increasing age. The diagnosis of Smith-Magenis syndrome is based upon the clinical recognition of a constellation of physical, developmental, and behavioral features in combination with a sleep disorder characterized by inverted circadian rhythm of melatonin secretion. Many of the features of Smith-Magenis syndrome are subtle in infancy and early childhood, and become more recognizable with advancing age. Infants are described as looking "cherubic" with a Down syndrome-like appearance, whereas with age the facial appearance is that of relative prognathism. Early diagnosis requires awareness of the often subtle clinical and neurobehavioral phenotype of the infant period. Speech delay with or without hearing loss is common. Most children are diagnosed in mid-childhood when the features of the disorder are most recognizable and striking. While improvements in cytogenetic analysis help to bring cases to clinical recognition at an earlier age, this review seeks to increase clinical awareness about Smith-Magenis syndrome by presenting the salient features observed at different ages including descriptions of the neurologic and behavioral

  2. C-smithing of Voyager 2 non-imaging instrument pointing information at Uranus

    NASA Technical Reports Server (NTRS)

    Wang, Tseng-Chan; Acton, Charles H.; Underwood, Ian M.; Synnott, Stephen P.

    1988-01-01

    The development of a family of techniques, collectively called C-smithing, for improving spacecraft nonimaging instrument pointing knowledge is discussed. C-smithing studies using data from the Voyager 2 Uranus Encounter show that significant improvements in pointing knowledge for nonimaging instruments can be achieved with these techniques. This improved pointing information can be used to regenerate instrument viewing geometry parameters for the encounter, which can then be made available to science investigators.

  3. Smith and Valley-Gray to Lead NASP

    ERIC Educational Resources Information Center

    Deupree, Charles

    2011-01-01

    The 2011 elections are complete and Amy Smith has been elected to lead NASP in 2012. Amy has a long history of serving her state and national professional organizations, most recently as NASP program manager for advocacy and before that as the Pennsylvania delegate and Northeast Region delegate representative. She served the Association of School…

  4. Theory of the special Smith-Purcell radiation from a rectangular grating

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

    Liu, Weihao, E-mail: liuwhao@ustc.edu.cn; He, Zhigang, E-mail: hezhg@ustc.edu.cn; Jia, Qika

    2015-12-15

    The recently uncovered special Smith-Purcell radiation (S-SPR) from the rectangular grating has significantly higher intensity than the ordinary Smith-Purcell radiation (SPR). Its monochromaticity and directivity are also much better. Here we explored the mechanism of the S-SPR by applying the fundamental electromagnetic theory and simulations. We have confirmed that the S-SPR is exactly from the radiating eigen modes of the grating. Its frequency and direction are well correlated with the beam velocity and structure parameters, which indicates its promising applications in tunable wave generation and beam diagnostic.

  5. British medicine in the Peruvian Andes: the travels of Archibald Smith M.D. (1820-1870).

    PubMed

    Lossio, Jorge

    2006-01-01

    This article traces the travels of the Scottish physician Archibald Smith through the Peruvian Andes between the 1820s and 1860s. Despite his prominent role in the nineteenth-century Peruvian medical scene, almost nothing has been written on Archibald Smith. By exploring Smith's medical activities, publications, and debates, this article intends to uncover unexplored areas of Peruvian medical history, such as the animosity between local and foreign physicians during the post-Independence war era and the important role played by medical geography as a scientific discipline for redefining ethnical and regional issues.

  6. How To Survive in Postindustrial Environments: Adam Smith's Advice for Today's Colleges and Universities.

    ERIC Educational Resources Information Center

    Ortmann, Andreas

    1997-01-01

    Adam Smith's discussion of the payment modes of teachers and resulting consequences for the quality of teaching and process of curricular innovation are reviewed through the conceptual lens of modern agency theory. Smith's analysis of higher education in his day (eighteenth century) sheds light on faculty incentive and assessment problems that…

  7. 77 FR 30047 - Notice of Opportunity for Public Comment on Surplus Property Release at Michael J Smith Field...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-21

    ... Comment on Surplus Property Release at Michael J Smith Field, Beaufort, NC AGENCY: Federal Aviation... J Smith Field, be used for aeronautical purposes. DATES: Comments must be received on or before June... property at the Michael J Smith Field. The property consists of one parcel located on the north side of...

  8. 75 FR 9441 - Lucas-Smith Automotive, Inc.: Potosi, MO; Notice of Negative Determination Regarding Application...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-02

    ... DEPARTMENT OF LABOR Employment and Training Administration [TA-W-71,388] Lucas-Smith Automotive, Inc.: Potosi, MO; Notice of Negative Determination Regarding Application for Reconsideration By...), applicable to workers and former workers of Lucas- Smith Automotive, Inc., Potosi, Missouri (subject firm...

  9. A comparison of muscle activation between a Smith machine and free weight bench press.

    PubMed

    Schick, Evan E; Coburn, Jared W; Brown, Lee E; Judelson, Daniel A; Khamoui, Andy V; Tran, Tai T; Uribe, Brandon P

    2010-03-01

    The bench press exercise exists in multiple forms including the machine and free weight bench press. It is not clear though how each mode differs in its effect on muscle activation. The purpose of this study was to compare muscle activation of the anterior deltoid, medial deltoid, and pectoralis major during a Smith machine and free weight bench press at lower (70% 1 repetition maximum [1RM]) and higher (90% 1RM) intensities. Normalized electromyography amplitude values were used during the concentric phase of the bench press to compare muscle activity between a free weight and Smith machine bench press. Participants were classified as either experienced or inexperienced bench pressers. Two testing sessions were used, each of which entailed either all free weight or all Smith machine testing. In each testing session, each participant's 1RM was established followed by 2 repetitions at 70% of 1RM and 2 repetitions at 90% of 1RM. Results indicated greater activation of the medial deltoid on the free weight bench press than on the Smith machine bench press. Also, there was greater muscle activation at the 90% 1RM load than at the 70% 1RM load. The results of this study suggest that strength coaches should consider choosing the free weight bench press over the Smith machine bench press because of its potential for greater upper-body muscular development.

  10. An Alternative View of the Instructional Design Process: A Response to Smith and Boling

    ERIC Educational Resources Information Center

    Gibbons, Andrew S.; Yanchar, Stephen C.

    2010-01-01

    A recent literature review by Smith and Boling (2009) critically examines the received view of instructional design in educational technology. Smith and Boling conclude that the foundational literature characterizes design in a way that leads to a constrained understanding of design, especially by novices. They suggest that as a field we move…

  11. The Adventures of Captain John Smith, Pocahontas and a Sundial: Cosmology, Mathematics, and Power at the Time of Jamestown

    NASA Astrophysics Data System (ADS)

    Schechner, Sara J.

    2007-12-01

    While exploring the Chickahominy River in Virginia by canoe in December 1607, Captain John Smith was ambushed by 200 Powhatan Indians and chased into the swamp. Wounded by arrows and mired in the cold mud, Smith surrendered and was led to their chieftain, Opechancanough. Smith played for time. He pulled out his pocket sundial and proceeded to deliver a lecture on astronomy. The Indians marveled at the dancing needle of the magnetic compass, which they could plainly see but not touch because of the glass cover. They apparently thought less of his discourse in a foreign language on the sun, moon, and planets, as within the hour, Smith's captors had him tied to a tree and were ready to shoot him. But then, Opechancanough held the sundial aloft and spared Smith's life. For the next month, Smith was paraded around various Indian villages before being condemned to have his head bashed in. Pocahontas, however, threw herself across Smith's body in order to save his life. This legendary episode reveals more than Smith's ingenuity. His compass sundial, shaped and marked like a celestial globe, was a microcosm of his universe. It embodied the belief that the smallest things mirrored the large, that number was the key to God's creation, and that by means of mathematical instruments, men could dominate that world (or at least extricate themselves from tight spots!). This paper will examine the astronomical ideas and instruments on which these beliefs were based, and show how ultimately, Smith's sundial also represented the clash of two cosmologies-that of the Indians and European settlers.

  12. Recent insights into the Smith-Lemli-Opitz syndrome.

    PubMed

    Yu, H; Patel, S B

    2005-11-01

    Recent insights into the Smith-Lemli-Opitz syndrome. The Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive multiple congenital anomaly/mental retardation disorder caused by an inborn error of post-squalene cholesterol biosynthesis. Deficient cholesterol synthesis in SLOS is caused by inherited mutations of 3beta-hydroxysterol-Delta7 reductase gene (DHCR7). DHCR7 deficiency impairs both cholesterol and desmosterol production, resulting in elevated 7DHC/8DHC levels, typically decreased cholesterol levels and, importantly, developmental dysmorphology. The discovery of SLOS has led to new questions regarding the role of the cholesterol biosynthesis pathway in human development. To date, a total of 121 different mutations have been identified in over 250 patients with SLOS who represent a continuum of clinical severity. Two genetic mouse models have been generated which recapitulate some of the developmental abnormalities of SLOS and have been useful in elucidating the pathogenesis. This mini review summarizes the recent insights into SLOS genetics, pathophysiology and potential therapeutic approaches for the treatment of SLOS.

  13. Taxonomic notes and description of the male of Xenochlora nigrofemorata (Smith, 1879) (Hymenoptera: Apidae: Halictinae).

    PubMed

    Santos, Leandro M; Melo, Gabriel A R

    2013-01-01

    The present work describes for the first time the male of the bee genus Xenochlora Engel, Brooks & Yanega, 1997. The male of X. nigrofemorata (Smith, 1879) is described and illustrated. Additionally, Megalopta opacicollis Friese, 1926 is placed as a junior synonym of X. nigrofemorata (Smith, 1879).

  14. Smith-Magenis Syndrome: Genetic Basis and Clinical Implications

    ERIC Educational Resources Information Center

    Finucane, Brenda; Haas-Givler, Barbara

    2009-01-01

    Smith-Magenis syndrome (SMS) is a neurobehavioral disorder associated with deletions and mutations of the "RAI1" gene on chromosome 17p11.2. Clinical features of the syndrome include intellectual disability, sleep disturbance, craniofacial differences, and a distinctive profile of stereotypic and self-injurious behaviors. Although the functional…

  15. 18. Photocopy of print (Original in Smith's History of Delaware ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    18. Photocopy of print (Original in Smith's History of Delaware County, Pennsylvania) MAIN AND EAST ELEVATIONS - Caleb Pusey House, 15 Race Street (Landingford Plantation), Upland, Delaware County, PA

  16. Durham Smith Vest-Over-Pant Technique: Simple Procedure for a Complex Problem (Post-Hypospadias Repair Fistula).

    PubMed

    Gite, Venkat A; Patil, Saurabh R; Bote, Sachin M; Siddiqui, Mohd Ayub Karam Nabi; Nikose, Jayant V; Kandi, Anitha J

    2017-01-01

    Urethrocutaneous fistula, which occurs after hypospadias surgery, is often a baffling problem and its treatment is challenging. The study aimed to evaluate the results of the simple procedure (Durham Smith vest-over-pant technique) for this complex problem (post-hypospadias repair fistula). During the period from 2011 to 2015, 20 patients with post-hypospadias repair fistulas underwent Durham Smith repair. Common age group was between 5 and 12 years. Site wise distribution of fistula was coronal 2 (10%), distal penile 7 (35%), mid-penile 7 (35%), and proximal-penile 4 (20%). Out of 20 patients, 15 had fistula of size <5 mm (75%) and 5 patients had fistula of size >5 mm (25%). All cases were repaired with Durham Smith vest-over-pant technique by a single surgeon. In case of multiple fistulas adjacent to each other, all fistulas were joined to form single fistula and repaired. We have successfully repaired all post-hypospadias surgery urethrocutaneous fistulas using the technique described by Durham Smith with 100% success rate. Durham Smith vest-over-pant technique is a simple solution for a complex problem (post hypospadias surgery penile fistulas) in properly selected patients. © 2017 S. Karger AG, Basel.

  17. Adam Smith and the Teaching of English Literature.

    ERIC Educational Resources Information Center

    Court, Franklin E.

    1985-01-01

    Adam Smith used selections from English literature in his classroom during the eighteenth century because he believed that vernacular literature could provide a ready context for the teaching of ideological, social, and moral lessons. He believed that higher education should prepare students for the real business of the real world. (RM)

  18. The Garrett Lee Smith Memorial Suicide Prevention Program

    ERIC Educational Resources Information Center

    Goldston, David B.; Walrath, Christine M.; McKeon, Richard; Puddy, Richard W.; Lubell, Keri M.; Potter, Lloyd B.; Rodi, Michael S.

    2010-01-01

    In response to calls for greater efforts to reduce youth suicide, the Garrett Lee Smith (GLS) Memorial Act has provided funding for 68 state, territory, and tribal community grants, and 74 college campus grants for suicide prevention efforts. Suicide prevention activities supported by GLS grantees have included education, training programs…

  19. STS-82 M.S. Steven Smith in White Room

    NASA Technical Reports Server (NTRS)

    1997-01-01

    STS-82 Mission Specialist Steven L. Smith prepares to enter the Space Shuttle Discovery at Launch Pad 39A, with the assistance of white room closeout crew members Dave Law, in front; Carlous Gillis, at left; and James Davis.

  20. The education and medical practice of Dr. James McCune Smith (1813-1865), first black American to hold a medical degree.

    PubMed Central

    Morgan, Thomas M.

    2003-01-01

    James McCune Smith (1813-1865)--first black American to obtain a medical degree, prominent abolitionist and suffragist, compassionate physician, prolific writer, and public intellectual--has been relatively neglected by historians of medicine. No biography of Smith exists to this day, though he has been the subject of several essays. Born, in his own words, "the son of a self-emancipated bond-woman," and denied admission to colleges in the United States, his native land, Smith earned medical, master's, and baccalaureate degrees at Glasgow University in Scotland. On his return to New York City in 1837, Smith became the first black physician to publish articles in US medical journals. Smith was broadly involved in the anti-slavery and suffrage movements, contributing to and editing abolitionist newspapers and serving as an officer of many organizations for the improvement of social conditions in the black community. In his scientific writings Smith debunked the racial theories in Thomas Jefferson's Notes on the State of Virginia, refuted phrenology and homeopathy, and responded with a forceful statistical critique to the racially biased US Census of 1840. Frederick Douglass, Gerrit Smith, and John Brown personally collaborated with James McCune Smith in the fight for black freedom. As the learned physician-scholar of the abolition movement, Smith was instrumental in making the overthrow of slavery credible and successful. Images Figure 1 PMID:12911258

  1. 75 FR 16099 - Mr. Jerry McMillan and Ms. Christine Smith; Notice of Termination of License by Implied Surrender...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-31

    ... McMillan and Ms. Christine Smith; Notice of Termination of License by Implied Surrender and Soliciting... surrender b. Project No.: P-9907-018 c. Licensees: Mr. Jerry McMillan and Ms. Christine Smith d. Name of... ] 62,282). The project was transferred to Mr. Jerry McMillan and Ms. Christine Smith by order on...

  2. 78 FR 16182 - Changes To Implement the First Inventor To File Provisions of the Leahy-Smith America Invents Act...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-14

    ...-2012-0015] RIN 0651-AC77 Changes To Implement the First Inventor To File Provisions of the Leahy-Smith... inventor to file provisions of the Leahy-Smith America Invents Act (AIA) (First Inventor to File Final Rule... provisions of the AIA. See Changes To Implement the First Inventor To File Provisions of the Leahy-Smith...

  3. Breeding productivity of Smith Island black ducks

    USGS Publications Warehouse

    Haramis, G.M.; Jorde, Dennis G.; Olsen, Glenn H.; Stotts, D.B.; Harrison, M.K.; Perry, M.C.

    2002-01-01

    We investigated the breeding performance of American black ducks (Anas rubripes) on Smith Island, Chesapeake Bay, to improve our understanding of island black duck breeding ecology and to make management recommendations to enhance productivity. During 1995-96, we implanted 56 female black ducks with 20-g radio transmitters and tracked 35 of the individuals through the breeding season to locate nests, determine nest fate, and identify brood habitat. We also increased preseason banding efforts and compared capture characteristics over 12 years with those from the Deal Island Wildlife Management Area, a banding site on the mainland of Tangier Sound. A low rate of nesting (37%), lack of renesting, and poor hatching success (31%) indicated that island salt marsh habitats present a harsh environment for breeding black ducks. Black ducks located 11 of 13 nests (85%) in black needlerush (Juncus roemerianus) marsh where they were vulnerable to flooding from extreme tides and to egg predators. No nests were found on forested tree hammocks, a feature that distinguishes Smith Island from nearby South Marsh and Bloodsworth Islands. Nest predators included red foxes (Vulpes vulpes), herring gulls (Larus argentams), fish crows (Corvus ossifragus), and, potentially, Norway rats (Rattus norvegicus). Unlike mainland red foxes, foxes radio tracked on Smith Island were found to be capable swimmers and effective low marsh predators. We found shoreline meadows of widgeon grass (Ruppia maritima) to be important foraging sites for black ducks and suspected that the virtual absence of fresh water in this high salinity environment (1217+ ppt) to incur some cost in terms of growth and survival of ducklings. Preseason bandings revealed a high proportion of banded adults and a strong positive correlation in age ratios with the Deal Island banding site. This latter finding strongly suggests a negative universal effect of storm tides on nest success for Tangier Sound black ducks. Management to

  4. Denial and Defensiveness in the Place of Fact and Reason: Rejoinder to Smith and Lovass.

    ERIC Educational Resources Information Center

    Gresham, Frank M.; MacMillan, Donald L.

    1997-01-01

    Responds to "The UCLA Young Autism Project: A Reply to Gresham and MacMillan" (Smith and Lovaas), which criticized a review questioning the effectiveness of an intervention for children with autism. The Smith and Lovass article is described as defensive, factually inaccurate, and as not adequately addressing the question of external validity.…

  5. Unconscious Odour Conditioning 25 Years Later: Revisiting and Extending "Kirk-Smith, Van Toller and Dodd"

    ERIC Educational Resources Information Center

    Zucco, Gesualdo M.; Paolini, Michela; Schaal, Benoist

    2009-01-01

    The pioneering work by Kirk-Smith, Van Toller, and Dodd [Kirk-Smith, M. D., Van Toller, C., & Dodd, G. H. (1983). "Unconscious odour conditioning in human subjects." "Biological Psychology," 17, 221-231], established that an unnoticed odorant paired with an emotionally meaningful task can influence mood and attitudes when the odorant alone is…

  6. Class Size Revisited: Glass and Smith in Perspective.

    ERIC Educational Resources Information Center

    Hess, Fritz

    Gene V. Glass and Mary Lee Smith claim in their report, "Meta-Analysis of Research on the Relationship of Class-Size and Achievement" (ED 168 129), that their integration of data from 80 previous studies through complex regression analysis techniques revealed a "clear and strong relationship" between decreases in class size and increases in…

  7. Smith Assists in Superstorm Sandy Relief Efforts | Poster

    Cancer.gov

    By Cathy McClintock, Guest Writer It should have been routine by now for a 30-year volunteer firefighter/ emergency medical technician from Thurmont, Md., but it wasn’t. That first night, as Ross Smith, IT security, looked across the Hudson River from Jersey City, N.J., he saw an unusually dark New York skyline.

  8. 5. Historic American Buildings Survey Frances Rand Smith Collection California ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    5. Historic American Buildings Survey Frances Rand Smith Collection California Historical Society Original: After 1860's Re-photo: January 1940 FIRST FRAME CHURCH (LEFT) - Mission San Rafael Archangel, San Rafael, Marin County, CA

  9. 5. Historic American Buildings Survey, From J. Smith Futhey and ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    5. Historic American Buildings Survey, From J. Smith Futhey and Gilbert Cope, History of Chester County, Pennsylvania, 1881, page 234, EXTERIOR SKETCH, 1881. - Birmingham Friends Meetinghouse, Birmingham & Meetinghouse Roads, Birmingham, Chester County, PA

  10. 10. Historic American Buildings Survey Frances Rand Smith Collection California ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    10. Historic American Buildings Survey Frances Rand Smith Collection California Historical Society Original: About 1890 Re-photo: January 1940 SECOND FRAME CHURCH REPLACING MISSION (1890) - Mission San Rafael Archangel, San Rafael, Marin County, CA

  11. Cecil Green receives Smith Medal

    NASA Astrophysics Data System (ADS)

    Press, Frank; Green, Cecil

    The Waldo E. Smith Medal, which is awarded for extraordinary service to geophysics, was presented to Cecil H. Green at the 1994 AGU Fall Meeting Honors Ceremony on December 7, 1994 in San Francisco. The award citation and Green's response are given here.“It would take a book to do justice to Cecil Green's extraordinary contributions to the geophysics and electronics industries, to the training of scientists, physicians, and engineers, and to strengthening education and research institutions. In fact, such a book has been written about Cecil's multiple lives as engineer, geophysicist, cofounder of Texas Instruments, and partner with his wife, Ida, in international philanthropy.

  12. 37. BRIDGE 115, SMITH RIVER MIDDLE FORK OREGON STATE HIGHWAY ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    37. BRIDGE 1-15, SMITH RIVER MIDDLE FORK OREGON STATE HIGHWAY 199. JOSEPHINE COUNTY, OREGON. LOOKING SSW. - Redwood National & State Parks Roads, California coast from Crescent City to Trinidad, Crescent City, Del Norte County, CA

  13. The Early Childhood Song Books of Eleanor Smith: Their Affinity with the Philosophy of Friedrich Froebel.

    ERIC Educational Resources Information Center

    Alper, Clifford D.

    1980-01-01

    Eleanor Smith (1858-1942), an outstanding composer of children's songs, was perhaps the most significant musician to embrace the philosophy of Friedrich Froebel (1782-1852), who founded the kindergarten in 1837 and consistently acknowledged and dignified children's natural capabilities and interests. Smith's songs still appear in published song…

  14. What's in a Surname? Physique, Aptitude, and Sports Type Comparisons between Tailors and Smiths.

    PubMed

    Voracek, Martin; Rieder, Stephan; Stieger, Stefan; Swami, Viren

    2015-01-01

    Combined heredity of surnames and physique, coupled with past marriage patterns and trade-specific physical aptitude and selection factors, may have led to differential assortment of bodily characteristics among present-day men with specific trade-reflecting surnames (Tailor vs. Smith). Two studies reported here were partially consistent with this genetic-social hypothesis, first proposed by Bäumler (1980). Study 1 (N = 224) indicated significantly higher self-rated physical aptitude for prototypically strength-related activities (professions, sports, hobbies) in a random sample of Smiths. The counterpart effect (higher aptitude for dexterity-related activities among Tailors) was directionally correct, but not significant, and Tailor-Smith differences in basic physique variables were nil. Study 2 examined two large total-population-of-interest datasets (Austria/Germany combined, and UK: N = 7001 and 20,532) of men's national high-score lists for track-and-field events requiring different physiques. In both datasets, proportions of Smiths significantly increased from light-stature over medium-stature to heavy-stature sports categories. The predicted counterpart effect (decreasing prevalences of Tailors along these categories) was not supported. Related prior findings, the viability of possible alternative interpretations of the evidence (differential positive selection for trades and occupations, differential endogamy and assortative mating patterns, implicit egotism effects), and directions for further inquiry are discussed in conclusion.

  15. Vascular Plant Species of the Forest Ecology Research and Demonstration Area, Paul Smith's, New York

    Treesearch

    Gary L. Wade; Jonathan A. Myers; Cecilia R. Martin; Kathie Detmar; William, III Mator; Mark J. Twery; Mike Rechlin

    2003-01-01

    Five forest harvest methods (single-tree selection, group selection, two-age cut, shelterwood cut, and clearcut) are being demonstrated on 5-acre tracts near the Adirondack Park Agency?s Visitor Interpretation Center (VIC) at Paul Smith?s, New York. The tracts are part of the agency?s Forest Ecology Research and Demonstration Area. A primary goal is to show visitors...

  16. STS-103 Mission Specialist Smith suits up before launch

    NASA Technical Reports Server (NTRS)

    1999-01-01

    After donning his launch and entry suit, sts-103 Mission Specialist Steven L. Smith shows a positive attitude over the second launch attempt for Space Shuttle Discovery. The previous launch attempt on Dec. 17 was scrubbed about 8:52 p.m. due to numerous violations of weather launch commit criteria at KSC. Smith and other crew members Commander Curtis L. Brown Jr., Pilot Scott J. Kelly and Mission Specialists C. Michael Foale (Ph.D.), John M. Grunsfeld (Ph.D.), Claude Nicollier of Switzerland and Jean-Francois Clervoy of France are scheduled to lift off at 7:50 p.m. EST Dec. 19 on mission STS-103, servicing the Hubble Space Telescope. Objectives for the nearly eight-day mission include replacing gyroscopes and an old computer, installing another solid state recorder, and replacing damaged insulation in the telescope. Discovery is expected to land at KSC Monday, Dec. 27, at about 5:24 p.m. EST.

  17. Pharmacological Cognitive Enhancers: Comment on Smith and Farah (2011)

    ERIC Educational Resources Information Center

    Elliott, Glen R.; Elliott, Mark D.

    2011-01-01

    Smith and Farah (2011) provided a thought-provoking and perhaps deliberately provocative literature review of the use of stimulants to improve cognitive functioning in humans. They addressed the apparently increasing willingness of individuals mostly in the United States to use stimulants for this purpose and then summarized published literature…

  18. Back to the Future with Patty Smith Hill

    ERIC Educational Resources Information Center

    Crawford, Patricia A.

    2017-01-01

    Generations after her passing, Patty Smith Hill (1868-1946) remains a towering figure in the world of early childhood education. Her words continue to offer insight, not only for those who work with young children, but also for those who help to prepare the teachers of young children for the important work they do--for those who both engage in and…

  19. 8. Historic American Buildings Survey Frances Rand Smith Collection California ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    8. Historic American Buildings Survey Frances Rand Smith Collection California Historical Society Original: 1870's Re-photo: January, 1940 FIRST FRAME CHURCH (LEFT), OLD MARIN COUNTY COURT HOUSE (CENTER) - Mission San Rafael Archangel, San Rafael, Marin County, CA

  20. BATH. VIEW FACING NORTH Camp H.M. Smith and Navy ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    BATH. VIEW FACING NORTH - Camp H.M. Smith and Navy Public Works Center Manana Title VII (Capehart) Housing, Four-Bedroom, Single-Family Type 10, Birch Circle, Elm Drive, Elm Circle, and Date Drive, Pearl City, Honolulu County, HI

  1. Defenses and morality: Adam Smith, Sigmund Freud, and contemporary psychoanalysis.

    PubMed

    Gabrinetti, Paul A; Özler, Sule

    2014-10-01

    In this paper we follow the development and transmission of moral learning from Adam Smith's impartial spectator to Sigmund Freud's superego and then to contemporary psychoanalysis. We argue that defenses are an integral component in the acquisition of any moral system. Elaborating on this argument, we assert that there is a progression from defensive systems that are "closed" to defensive systems that are "open," as defined in a recent work by Novick and Novick. The former system is "static, avoids reality, and is characterized by power dynamics, sadomasochism, and omnipotent defense." The latter, on the other hand, is a system that allows for "joy, creativity, spontaneity, love and it is attuned to reality." Furthermore, while Smith and Freud's systems are more one-person systems of defense, contemporary psychoanalysis has moved to more of a two-person system.

  2. DETAIL OF WESTINGHOUSE AND B. MORGAN SMITH NAMEPLATES ON ELECTRIC ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    DETAIL OF WESTINGHOUSE AND B. MORGAN SMITH NAMEPLATES ON ELECTRIC GENERATOR IN UPPER LEVEL OF HYDROELECTRIC POWER HOUSE - St. Lucie Canal, Lock No. 1, Hydroelectric Power House, St. Lucie, Cross State Canal, Okeechobee Intracoastal Waterway, Stuart, Martin County, FL

  3. BEDROOM 2. VIEW FACING EAST Camp H.M. Smith and ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    BEDROOM 2. VIEW FACING EAST - Camp H.M. Smith and Navy Public Works Center Manana Title VII (Capehart) Housing, Three-Bedroom Single-Family Type 7, Birch Circle, Elm Drive, Elm Circle, and Date Drive, Pearl City, Honolulu County, HI

  4. BEDROOM 3. VIEW FACING EAST Camp H.M. Smith and ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    BEDROOM 3. VIEW FACING EAST - Camp H.M. Smith and Navy Public Works Center Manana Title VII (Capehart) Housing, Four-Bedroom, Single-Family Type 10, Birch Circle, Elm Drive, Elm Circle, and Date Drive, Pearl City, Honolulu County, HI

  5. MASTER BEDROOM. VIEW FACING NORTH Camp H.M. Smith and ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    MASTER BEDROOM. VIEW FACING NORTH - Camp H.M. Smith and Navy Public Works Center Manana Title VII (Capehart) Housing, Four-Bedroom, Single-Family Type 10, Birch Circle, Elm Drive, Elm Circle, and Date Drive, Pearl City, Honolulu County, HI

  6. BEDROOM 3. VIEW FACING EAST Camp H.M. Smith and ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    BEDROOM 3. VIEW FACING EAST - Camp H.M. Smith and Navy Public Works Center Manana Title VII (Capehart) Housing, Three-Bedroom Single-Family Type 7, Birch Circle, Elm Drive, Elm Circle, and Date Drive, Pearl City, Honolulu County, HI

  7. UTILITY ROOM. VIEW FACING WEST Camp H.M. Smith and ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    UTILITY ROOM. VIEW FACING WEST - Camp H.M. Smith and Navy Public Works Center Manana Title VII (Capehart) Housing, Three-Bedroom Single-Family Type 7, Birch Circle, Elm Drive, Elm Circle, and Date Drive, Pearl City, Honolulu County, HI

  8. OBLIQUE VIEW FROM THE SOUTH Camp H.M. Smith and ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    OBLIQUE VIEW FROM THE SOUTH - Camp H.M. Smith and Navy Public Works Center Manana Title VII (Capehart) Housing, Three-Bedroom Single-Family Type 7, Birch Circle, Elm Drive, Elm Circle, and Date Drive, Pearl City, Honolulu County, HI

  9. Smith predictor-based multiple periodic disturbance compensation for long dead-time processes

    NASA Astrophysics Data System (ADS)

    Tan, Fang; Li, Han-Xiong; Shen, Ping

    2018-05-01

    Many disturbance rejection methods have been proposed for processes with dead-time, while these existing methods may not work well under multiple periodic disturbances. In this paper, a multiple periodic disturbance rejection is proposed under the Smith predictor configuration for processes with long dead-time. One feedback loop is added to compensate periodic disturbance while retaining the advantage of the Smith predictor. With information of the disturbance spectrum, the added feedback loop can remove multiple periodic disturbances effectively. The robust stability can be easily maintained through the rigorous analysis. Finally, simulation examples demonstrate the effectiveness and robustness of the proposed method for processes with long dead-time.

  10. Memorial to Robert Leland Smith 1920-2016

    USGS Publications Warehouse

    Bacon, Charles R.

    2016-01-01

    Robert L. Smith, renowned volcanologist and distinguished scientist with the U.S. Geological Survey (USGS), was a world authority on ash-flow tuffs, silicic volcanism, and caldera structures. Bob died peacefully in Sacramento, California, June 17, 2016, a few days short of his ninety-sixth birthday. His publications on ash flows and their deposits brought about an international revolution in understanding of explosive silicic volcanism and, in his fifty-year career, he profoundly influenced USGS programs and countless scientists.

  11. Installation summary report : GRS instrumentation I-70 over Smith Road.

    DOT National Transportation Integrated Search

    2016-07-04

    This report presents a summary of the I-70 over Smith Road GRS Instrumentation Project (the project) in Aurora, Colorado. The report summarizes the instruments used, installation means and methods, and a discussion on the web-based data interface. CD...

  12. DINING ROOM. VIEW FACING NORTHWEST Camp H.M. Smith and ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    DINING ROOM. VIEW FACING NORTHWEST - Camp H.M. Smith and Navy Public Works Center Manana Title VII (Capehart) Housing, Three-Bedroom Single-Family Types 8 and 11, Birch Circle, Elm Drive, Elm Circle, and Date Drive, Pearl City, Honolulu County, HI

  13. BATH. VIEW FACING NORTH Camp H.M. Smith and Navy ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    BATH. VIEW FACING NORTH - Camp H.M. Smith and Navy Public Works Center Manana Title VII (Capehart) Housing, U-Shaped Two-Bedroom Single-Family Type 6, Birch Circle, Elm Drive, Elm Circle, and Date Drive, Pearl City, Honolulu County, HI

  14. BEDROOM 2. VIEW FACING EAST Camp H.M. Smith and ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    BEDROOM 2. VIEW FACING EAST - Camp H.M. Smith and Navy Public Works Center Manana Title VII (Capehart) Housing, U-Shaped Two-Bedroom Single-Family Type 6, Birch Circle, Elm Drive, Elm Circle, and Date Drive, Pearl City, Honolulu County, HI

  15. Dyadic Power Theory, Touch, and Counseling Psychology: A Response to Smith, Vogel, Madon, and Edwards (2011)

    ERIC Educational Resources Information Center

    Dunbar, Norah E.; Abra, Gordon

    2012-01-01

    Smith, Vogel, Madon, and Edwards' (2011) recent article tested dyadic power theory (DPT) by examining the use of touch as a compliance-gaining tactic in the conflicts of married couples. In this response, we raise a methodological issue about the touch behaviors examined by Smith et al. and also pose a theoretical critique that their test of DPT…

  16. User experience network. Erroneous downstream occlusion alarms may disable Smiths Medical CADD-Solis infusion pumps.

    PubMed

    2010-10-01

    Due to an issue in manufacturing, downstream occlusion (DSO) sensors in some Smiths Medical CADD-Solis infusion pumps may drift out of calibration, potentially resulting in erroneous alarms that disable the units. Hospitals experiencing the problem should return affected units to Smiths Medical for recalibration (free of charge) and should consider testing all their CADD-Solis pumps during routine maintenance to ensure that they alarm appropriately for downstream occlusions.

  17. Efficacy of an adjuvanted herpes zoster subunit vaccine in older adults.

    PubMed

    Lal, Himal; Cunningham, Anthony L; Godeaux, Olivier; Chlibek, Roman; Diez-Domingo, Javier; Hwang, Shinn-Jang; Levin, Myron J; McElhaney, Janet E; Poder, Airi; Puig-Barberà, Joan; Vesikari, Timo; Watanabe, Daisuke; Weckx, Lily; Zahaf, Toufik; Heineman, Thomas C

    2015-05-28

    In previous phase 1-2 clinical trials involving older adults, a subunit vaccine containing varicella-zoster virus glycoprotein E and the AS01B adjuvant system (called HZ/su) had a clinically acceptable safety profile and elicited a robust immune response. We conducted a randomized, placebo-controlled, phase 3 study in 18 countries to evaluate the efficacy and safety of HZ/su in older adults (≥50 years of age), stratified according to age group (50 to 59, 60 to 69, and ≥70 years). Participants received two intramuscular doses of the vaccine or placebo 2 months apart. The primary objective was to assess the efficacy of the vaccine, as compared with placebo, in reducing the risk of herpes zoster in older adults. A total of 15,411 participants who could be evaluated received either the vaccine (7698 participants) or placebo (7713 participants). During a mean follow-up of 3.2 years, herpes zoster was confirmed in 6 participants in the vaccine group and in 210 participants in the placebo group (incidence rate, 0.3 vs. 9.1 per 1000 person-years) in the modified vaccinated cohort. Overall vaccine efficacy against herpes zoster was 97.2% (95% confidence interval [CI], 93.7 to 99.0; P<0.001). Vaccine efficacy was between 96.6% and 97.9% for all age groups. Solicited reports of injection-site and systemic reactions within 7 days after vaccination were more frequent in the vaccine group. There were solicited or unsolicited reports of grade 3 symptoms in 17.0% of vaccine recipients and 3.2% of placebo recipients. The proportions of participants who had serious adverse events or potential immune-mediated diseases or who died were similar in the two groups. The HZ/su vaccine significantly reduced the risk of herpes zoster in adults who were 50 years of age or older. Vaccine efficacy in adults who were 70 years of age or older was similar to that in the other two age groups. (Funded by GlaxoSmithKline Biologicals; ZOE-50 ClinicalTrials.gov number, NCT01165177.).

  18. Comparison of the immunogenicity of the human papillomavirus (HPV)-16/18 vaccine and the HPV-6/11/16/18 vaccine for oncogenic non-vaccine types HPV-31 and HPV-45 in healthy women aged 18-45 years.

    PubMed

    Einstein, Mark H; Baron, Mira; Levin, Myron J; Chatterjee, Archana; Fox, Bradley; Scholar, Sofia; Rosen, Jeffrey; Chakhtoura, Nahida; Lebacq, Marie; van der Most, Robbert; Moris, Philippe; Giannini, Sandra L; Schuind, Anne; Datta, Sanjoy K; Descamps, Dominique

    2011-12-01

    Protection against oncogenic non-vaccine types (cross-protection) offered by human papillomavirus (HPV) vaccines may provide a significant medical benefit. Available clinical efficacy data suggest the two licensed vaccines (HPV-16/18 vaccine, GlaxoSmithKline Biologicals (GSK), and HPV-6/11/16/18 vaccine, Merck & Co., Inc.) differ in terms of protection against oncogenic non-vaccine HPV types -31/45. The immune responses induced by the two vaccines against these two non-vaccine HPV types (cross-reactivity) was compared in an observer-blind study up to Month 24 (18 mo post-vaccination), in women HPV DNA-negative and seronegative prior to vaccination for the HPV type analyzed (HPV-010 [NCT00423046]). Geometric mean antibody titers (GMTs) measured by pseudovirion-based neutralization assay (PBNA) and enzyme-linked immunosorbent assay (ELISA) were similar between vaccines for HPV-31/45. Seropositivity rates for HPV-31 were also similar between vaccines; however, there was a trend for higher seropositivity with the HPV-16/18 vaccine (13.0-16.7%) versus the HPV-6/11/16/18 vaccine (0.0-5.0%) for HPV-45 with PBNA, but not ELISA. HPV-31/45 cross-reactive memory B-cell responses were comparable between vaccines. Circulating antigen-specific CD4+ T-cell frequencies were higher for the HPV-16/18 vaccine than the HPV-6/11/16/18 vaccine (HPV-31 [geometric mean ratio [GMR] =2.0; p=0.0002] and HPV-45 [GMR=2.6; p=0.0092]), as were the proportion of T-cell responders (HPV-31, p=0.0009; HPV-45, p=0.0793). In conclusion, immune response to oncogenic non-vaccine HPV types -31/45 was generally similar for both vaccines with the exception of T-cell response which was higher with the HPV-16/18 vaccine. Considering the differences in cross-protective efficacy between the two vaccines, the results might provide insights into the underlying mechanism(s) of protection.

  19. Comparative immunogenicity and safety of human papillomavirus (HPV)-16/18 vaccine and HPV-6/11/16/18 vaccine: follow-up from months 12-24 in a Phase III randomized study of healthy women aged 18-45 years.

    PubMed

    Einstein, Mark H; Baron, Mira; Levin, Myron J; Chatterjee, Archana; Fox, Bradley; Scholar, Sofia; Rosen, Jeffrey; Chakhtoura, Nahida; Meric, Dorothée; Dessy, Francis J; Datta, Sanjoy K; Descamps, Dominique; Dubin, Gary

    2011-12-01

    In this observer-blind study (NCT00423046), women (N=1,106), stratified by age (18-26, 27-35, 36-45 y), were randomized (1:1) to receive the HPV-16/18 vaccine (Cervarix®, GlaxoSmithKline Biologicals, Months 0, 1, 6) or the HPV-6/11/16/18 vaccine (Gardasil® Merck & Co., Inc., Months 0, 2, 6). Month 7 results were previously reported; we now report Month 24 results. In the according-to-protocol cohort for immunogenicity (seronegative and DNA-negative at baseline for HPV type analyzed), seropositivity rates of neutralizing antibodies (nAbs) [pseudovirion-based neutralization assay] were, across all age strata, 100% (HPV-16/18 vaccine) and 97.5-100% (HPV-6/11/16/18 vaccine) for HPV-16, and 99.0-100% (HPV-16/18 vaccine) and 72.3-84.4% (HPV-6/11/16/18 vaccine) for HPV-18. Corresponding geometric mean titers (GMTs) were 2.4-5.8-fold higher for HPV-16 and 7.7-9.4-fold higher for HPV-18 with the HPV-16/18 vaccine versus the HPV-6/11/16/18 vaccine; HPV-16 and HPV-18 GMTs were significantly higher with the HPV-16/18 vaccine than the HPV-6/11/16/18 vaccine (p< 0.0001) in the total vaccinated cohort (received ≥1 vaccine dose, irrespective of baseline sero/DNA-status). Similar results were obtained using enzyme-linked immunosorbent assay (ELISA). Positivity rates and GMTs of antigen-specific IgG antibodies in cervicovaginal secretions (ELISA) were not significantly different between vaccines. At Month 24, CD4⁺ T-cell responses for HPV-16 and HPV-18 were higher with the HPV-16/18 vaccine; memory B-cell response was higher for HPV-18 with the HPV-16/18 vaccine and similar between vaccines for HPV-16. Both vaccines were generally well tolerated. Although an immunological correlate of protection has not been defined, differences in the magnitude of immune response between vaccines may represent determinants of duration of protection.

  20. Comparison of the immunogenicity and safety of Cervarix and Gardasil human papillomavirus (HPV) cervical cancer vaccines in healthy women aged 18-45 years.

    PubMed

    Einstein, Mark H; Baron, Mira; Levin, Myron J; Chatterjee, Archana; Edwards, Robert P; Zepp, Fred; Carletti, Isabelle; Dessy, Francis J; Trofa, Andrew F; Schuind, Anne; Dubin, Gary

    2009-10-01

    This observer-blind study compared the prophylactic human papillomavirus (HPV) vaccines, Cervarix (GlaxoSmithKline) and Gardasil (Merck), by assessing immunogenicity and safety through one month after completion of the three-dose vaccination course. Women (n = 1106) were stratified by age (18-26, 27-35, 36-45 years) and randomized (1:1) to receive Cervarix (Months 0, 1, 6) or Gardasil (Months 0, 2, 6). At Month 7 after first vaccination, all women in the according-to-protocol cohort who were seronegative/DNA negative before vaccination for the HPV type analyzed had seroconverted for HPV-16 and HPV-18 serum neutralizing antibodies, as measured by pseudovirion-based neutralization assay (PBNA), except for two women aged 27-35 years in the Gardasil group who did not seroconvert for HPV-18 (98%). Geometric mean titers of serum neutralizing antibodies ranged from 2.3-4.8-fold higher for HPV-16 and 6.8-9.1-fold higher for HPV-18 after vaccination with Cervarix compared with Gardasil, across all age strata. In the total vaccinated cohort (all women who received at least one vaccine dose, regardless of their serological and DNA status prior to vaccination), Cervarix induced significantly higher serum neutralizing antibody titers in all age strata (p < 0.0001). Positivity rates for anti-HPV-16 and -18 neutralizing antibodies in cervicovaginal secretions and circulating HPV-16 and -18 specific memory B-cell frequencies were also higher after vaccination with Cervarix compared with Gardasil. Both vaccines were generally well tolerated. The incidence of unsolicited adverse events was comparable between vaccinated groups. The incidence of solicited symptoms was generally higher after Cervarix, injection site reactions being most common. However, compliance rates with the three-dose schedules were similarly high (>or= 84%) for both vaccines. Although the importance of differences in magnitude of immune response between these vaccines is unknown, they may represent determinants

  1. Integrating in Silico and in Vitro Approaches To Predict Drug Accessibility to the Central Nervous System.

    PubMed

    Zhang, Yan-Yan; Liu, Houfu; Summerfield, Scott G; Luscombe, Christopher N; Sahi, Jasminder

    2016-05-02

    Estimation of uptake across the blood-brain barrier (BBB) is key to designing central nervous system (CNS) therapeutics. In silico approaches ranging from physicochemical rules to quantitative structure-activity relationship (QSAR) models are utilized to predict potential for CNS penetration of new chemical entities. However, there are still gaps in our knowledge of (1) the relationship between marketed human drug derived CNS-accessible chemical space and preclinical neuropharmacokinetic (neuroPK) data, (2) interpretability of the selected physicochemical descriptors, and (3) correlation of the in vitro human P-glycoprotein (P-gp) efflux ratio (ER) and in vivo rodent unbound brain-to-blood ratio (Kp,uu), as these are assays routinely used to predict clinical CNS exposure, during drug discovery. To close these gaps, we explored the CNS druglike property boundaries of 920 market oral drugs (315 CNS and 605 non-CNS) and 846 compounds (54 CNS drugs and 792 proprietary GlaxoSmithKline compounds) with available rat Kp,uu data. The exact permeability coefficient (Pexact) and P-gp ER were determined for 176 compounds from the rat Kp,uu data set. Receiver operating characteristic curves were performed to evaluate the predictive power of human P-gp ER for rat Kp,uu. Our data demonstrates that simple physicochemical rules (most acidic pKa ≥ 9.5 and TPSA < 100) in combination with P-gp ER < 1.5 provide mechanistic insights for filtering BBB permeable compounds. For comparison, six classification modeling methods were investigated using multiple sets of in silico molecular descriptors. We present a random forest model with excellent predictive power (∼0.75 overall accuracy) using the rat neuroPK data set. We also observed good concordance between the structural interpretation results and physicochemical descriptor importance from the Kp,uu classification QSAR model. In summary, we propose a novel, hybrid in silico/in vitro approach and an in silico screening model for the

  2. Comparison of four recombinant hepatitis B vaccines applied on an accelerated schedule in healthy adults.

    PubMed

    Hernández-Bernal, Francisco; Aguilar-Betancourt, Arístides; Aljovin, Virginia; Arias, Gloria; Valenzuela, Carmen; de Alejo, Karen Pérez; Hernández, Karina; Oquendo, Orcilia; Figueredo, Niurka; Figueroa, Nelvis; Musacchio, Alexis; Véliz, Gloria; García, Elizeth; Mollineda, Alina D; Juvier, Ana Isabel; Trujillo, Janette; Delahanty, Aurora; Ortega, D; Cinza, Z; González, Verena L Muzio

    2011-10-01

    A post-marketing, double blind, randomised, controlled clinical trial to assess the immunogenicity and safety profiles of four commercially available recombinant hepatitis B vaccines was performed. The vaccines included in this study were Heberbiovac-HB (®) (Heber Biotec S.A., Havana, Cuba), Euvax-B (®) (LG Chemical Ltd., Seoul, Korea), Hepavax-Gene (®)   (Greencross Vaccine Corp., Seoul, Korea), and Engerix-B (®) (GlaxoSmithKline Biologicals, Rixensart, Belgium). Vaccines were administered intramuscularly to healthy adults in three 20mg doses at monthly intervals (0 - 1 -  2 months). Four hundred volunteers aged 18 to 45 years (average age, 35 years) non-reactive for serological markers of hepatitis B virus infection were vaccinated. Volunteers were randomly assigned (ratio 1:1:1:1) to one of the four treatment groups. The antibody response (anti-HBs) was assessed at days 60, 90 and 365 post-vaccination using a commercial kit. The four vaccines showed to be safe and highly immunogenic. Similar seroprotection rates (anti-HBs ≥10 IU/L) about one month after application of the second and third dose were obtained for Engerix-B (®) , Hepavax-Gene (®) , Euvax-B (®) , and Heberbiovac-HB (®) vaccines 96.7%, 96.6%, 100%, 100% and 98.8%, 89.5%, 100%, 100%, respectively.. Heberbiovac-HB (®) vaccine achieved significantly higher geometric mean antibody titers (GMT) and rate of good and  hyper-responders at all time-points post-vaccination. The GMT on day 365 after full vaccination was significantly reduced in all groups compared to day 90, although Heberbiovac-HB (®) showed the highest anti-HBs GMT and good-responders rate. The four vaccines were well tolerated and poorly reactogenic. No serious adverse events were observed. This study confirms an overall good immune response and rapid priming for the  four vaccines in the course of an accelerated schedule, with higher anti-HBs geometric mean concentrations and better responses for Heberbiovac-HB (®) . [WHO

  3. Health related quality of life of women in TEACH, a randomised placebo controlled adjuvant trial of lapatinib in early stage Human Epidermal Growth Factor Receptor (HER2) overexpressing breast cancer.

    PubMed

    Boyle, Frances M; Smith, Ian E; O'Shaughnessy, Joyce; Ejlertsen, Bent; Buzdar, Aman U; Fumoleau, Pierre; Gradishar, William; Martin, Miguel; Moy, Beverly; Piccart-Gebhart, Martine; Pritchard, Kathleen I; Lindquist, Deborah; Amonkar, Mayur; Huang, Yingjie; Rappold, Erica; Williams, Lisa S; Wang-Silvanto, Jing; Kaneko, Tomomi; Finkelstein, Dianne M; Goss, Paul E

    2015-04-01

    metastatic HER2 positive breast cancer. GlaxoSmithKline. The AVON Foundation NY supported PEG, DF and BM and The Friends of the Mater Foundation supported FB. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Rotarix in Japan: Expectations and Concerns.

    PubMed

    Nakagomi, Osamu; Nakagomi, Toyoko

    2011-01-01

    A live-attenuated, orally-administered, monovalent, human rotavirus vaccine, Rotarix® (GlaxoSmithKline Biologicals, Rixensart, Belgium), was licensed and launched in 2011 as the first rotavirus vaccine in Japan. The rotavirus causes a substantial disease burden with an estimated 790,000 outpatient visits, 27,000-78,000 hospitalizations, and approximately 10 deaths each year in Japan. Since a recent clinical trial showed that Rotarix was as efficacious in Japan as in other industrialized countries, it is expected that the annual number of rotavirus hospitalizations will be reduced to between 1000-3000, and that outpatient visits will be reduced to 200,000. The universal rotavirus immunization program with Rotarix was calculated to be at the threshold of being cost-effective, even from the healthcare perspective, and it was highly cost-effective from the societal perspective, assuming that Rotarix is co-administered with other childhood vaccines. While Rotarix contains only a single G1P[8] human rotavirus, the postlicensure studies in Brazil showed that Rotarix provided a 75%-85% protective efficacy against severe dehydrating diarrhea or hospitalizations due to fully-heterotypic G2P[4] strains. While postlicensure studies detected a small and finite risk of intussusception associated with the administration of Rotarix, the authors conclude that Rotarix is safe to administer to infants between 6-12 weeks of age for the first dose and by 24 weeks of age for the second dose. However, the authors strongly discourage the delayed administration of the first dose between 13-20 weeks of age, which is allowed without any warning. Given the high incidence of naturally-occurring intussusception in Japan (185 cases per 100,000 children/year among children less than 1 year of age), this should prevent pediatricians and parents from having ill-perceptions of Rotarix being associated with an increased number of temporally-associated intussusception, and fully appreciate the

  5. Cost effectiveness evaluation of a rotavirus vaccination program in Argentina.

    PubMed

    Martí, Sebastián García; Alcaraz, Andrea; Valanzasca, Pilar; McMullen, Mercedes; Standaert, Baudouin; Garay, Ulises; Lepetic, Alejandro; Gomez, Jorge

    2015-10-13

    Rotavirus diarrhea is one of the most important vaccine-preventable causes of severe diarrhea in children worldwide. There are two live-attenuated virus vaccines licensed, Rotarix (RV1) a monovalent vaccine by GlaxoSmithKline and a pentavalent vaccine, RotaTeq(RV5), by Merck & Co., with similar results. This study aim was to evaluate the cost-effectiveness of the utilization of RV1 compared with RV5 in Argentina. A deterministic Markov model based on the lifetime follow up of a static cohort was used. Quality Adjusted Life Years (QALYs) as a measure of results, the perspective of the health care system and a 5% discount rate for health benefits and costs has been used. A review of the literature to obtain epidemiologic and resources utilization of rotavirus diarrhea was performed. The sources used to estimate epidemiologic parameters were the National Health Surveillance System, the national mortality statistics and national database of hospital discharges records. Costs were obtained from different health subsectors and are expressed in local currency. Both vaccination alternatives were less costly and more effective than the strategy without vaccination (total costs $ 69,700,645 and 2575 total QALYs lost). When comparing RV1 vs. RV5, RV1 was less expensive ($ 60,174,508 vs. $ 67,545,991 total costs) and more effective (1105 vs. 1213 total QALYs lost) than RV5, RV1 being therefore a dominating strategy. Probabilistic sensitivity analysis showed results to be robust with a 100% probability of being cost-effective at a WTP threshold of 1 GDP per capita when comparing the RV1 vs. no vaccination. Both RV1 and RV5 schedules dominate the no vaccination strategy and RV5 was dominated by RV1. This information is a valuable input regarding the incorporation of this kind of vaccines into the national vaccination programs. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Meterology-driven Prediction of RSV/RHV Incidence in Rural Nepal

    PubMed Central

    Scott, Anna; Englund, Janet; Chu, Helen; Tielsch, James; Tielsch, James; Khatry, Subarna; Leclerq, Steven C; Shrestha, Laxman; Kuypers, Jane; Steinhoff, Mark C; Katz, Joanne

    2017-01-01

    , Research support Novavax: Investigator, Research support MedImmune: Investigator, Research support GlaxoSmithKline: Investigator, Research support

  7. Does industry-sponsored education foster overdiagnosis and overtreatment of depression, osteoporosis and over­active bladder syndrome? An Australian cohort study

    PubMed Central

    Mintzes, Barbara; Swandari, Swestika; Fabbri, Alice; Grundy, Quinn; Moynihan, Ray; Bero, Lisa

    2018-01-01

    Objectives To investigate patterns of industry-sponsored educational events that focus on specific health conditions for which there are concerns about overdiagnosis and overtreatment. Design and setting This retrospective cohort study examines publicly reported industry-sponsored events in Australia from October 2011 to September 2015 for three conditions potentially subject to overdiagnosis and overtreatment: depression, osteoporosis and overactive bladder. We used a database of transparency reports to identify events with a focus on depression, osteoporosis and overactive bladder and compared these with other sponsored events. We hypothesised that companies marketing treatments for each condition would sponsor related events and that target audiences would mainly work in primary care, reflecting a broad patient population. Main outcome measures Event and attendee characteristics, sponsoring companies, related marketed treatments, cost-effectiveness ratings and dispensing rates. Results Over the study period, we identified 1567 events focusing on depression, 1375 on osteoporosis and 190 on overactive bladder (total n=3132, with 96 660 attendees). These events were attended by primary care doctors more often than sponsored events without a focus on these three conditions: relative risk (RR)=3.06 (95% CI 2.81 to 3.32) for depression, RR=1.48 (95% CI 1.41 to 1.55) for osteoporosis and RR=2.59 (95% CI 2.09 to 3.21) for overactive bladder. Servier, which markets agomelatine and AstraZeneca (quetiapine) sponsored 51.2% and 23.0% of depression events, respectively. Amgen and GlaxoSmithKline, which co-market denosumab, sponsored 49.5% of osteoporosis events and Astellas and Commonwealth Serum Laboratories (CSL) (mirabegron and solifenacin) sponsored 80.5% of overactive bladder events. Conclusions This 4-year overview of industry-sponsored events on three overdiagnosed and overtreated conditions found that primary care clinicians were often targeted, dinner was often

  8. Invasive pneumococcal disease in children aged younger than 5 years in India: a surveillance study.

    PubMed

    Manoharan, Anand; Manchanda, Vikas; Balasubramanian, Sundaram; Lalwani, Sanjay; Modak, Meera; Bai, Sushama; Vijayan, Ajith; Shet, Anita; Nagaraj, Savitha; Karande, Sunil; Nataraj, Gita; Yewale, Vijay N; Joshi, Shrikrishna A; Iyer, Ranganathan N; Santosham, Mathuram; Kahn, Geoffrey D; Knoll, Maria Deloria

    2017-03-01

    , and data generated over the 4·5 years of the study are representative of data for most of India. Continued surveillance is warranted as the decision to introduce protein conjugated vaccine in India is made. GlaxoSmithKline India. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Comparison of the immunogenicity of the human papillomavirus (HPV)-16/18 vaccine and the HPV-6/11/16/18 vaccine for oncogenic non-vaccine types HPV-31 and HPV-45 in healthy women aged 18–45 years

    PubMed Central

    Baron, Mira; Levin, Myron J; Chatterjee, Archana; Fox, Bradley; Scholar, Sofia; Rosen, Jeffrey; Chakhtoura, Nahida; Lebacq, Marie; van der Most, Robbert; Moris, Philippe; Giannini, Sandra L; Schuind, Anne; Datta, Sanjoy K; Descamps, Dominique

    2011-01-01

    Protection against oncogenic non-vaccine types (cross-protection) offered by human papillomavirus (HPV) vaccines may provide a significant medical benefit. Available clinical efficacy data suggest the two licensed vaccines [HPV-16/18 vaccine, GlaxoSmithKline Biologicals (GSK), and HPV-6/11/16/18 vaccine, Merck and Co., Inc.,] differ in terms of protection against oncogenic non-vaccine HPV types -31/45. The immune responses induced by the two vaccines against these two non-vaccine HPV types (cross-reactivity) was compared in an observer-blind study up to Month 24 (18 mo postvaccination), in women HPV DNA-negative and seronegative prior to vaccination for the HPV type analyzed [HPV-010 (NCT00423046)]. Geometric mean antibody titers (GMTs) measured by pseudovirion-based neutralization assay (PBNA) and enzyme-linked immunosorbent assay (ELISA ) were similar between vaccines for HPV-31/45. Seropositivity rates for HPV-31 were also similar between vaccines; however, there was a trend for higher seropositivity with the HPV-16/18 vaccine (13.0–16.7%) vs. the HPV-6/11/16/18 vaccine (0.0–5.0%) for HPV-45 with PBNA, but not ELISA . HPV-31/45 cross-reactive memory B-cell responses were comparable between vaccines. Circulating antigen-specific CD4+ T-cell frequencies were higher for the HPV-16/18 vaccine than the HPV-6/11/16/18 vaccine {HPV-31 [geometric mean ratio (GMR) = 2.0; p = 0.0002] and HPV-45 [GMR = 2.6; p = 0.0092]}, as were the proportion of T-cell responders (HPV-31, p = 0.0009; HPV-45, p = 0.0793). In conclusion, immune response to oncogenic non-vaccine HPV types -31/45 was generally similar for both vaccines with the exception of T-cell response which was higher with the HPV-16/18 vaccine. Considering the differences in cross-protective efficacy between the two vaccines, the results might provide insights into the underlying mechanism(s) of protection. PMID:22048172

  10. Comparative immunogenicity and safety of human papillomavirus (HPV)-16/18 vaccine and HPV-6/11/16/18 vaccine

    PubMed Central

    Baron, Mira; Levin, Myron J; Chatterjee, Archana; Fox, Bradley; Scholar, Sofia; Rosen, Jeffrey; Chakhtoura, Nahida; Meric, Dorothée; Dessy, Francis J; Datta, Sanjoy K; Descamps, Dominique; Dubin, Gary

    2011-01-01

    In this observer-blind study (NCT00423046), women (N = 1,106), stratified by age (18–26, 27–35, 36–45 y), were randomized (1:1) to receive the HPV-16/18 vaccine (Cervarix®, GlaxoSmithKline Biologicals, Months 0, 1, 6) or the HPV-6/11/16/18 vaccine (Gardasil® Merck and Co., Inc., Months 0, 2, 6). Month 7 results were previously reported; we now report Month 24 results. In the according-to-protocol cohort for immunogenicity (seronegative and DNA-negative at baseline for HPV type analyzed), seropositivity rates of neutralizing antibodies (nAbs) [pseudovirion-based neutralization assay] were, across all age strata, 100% (HPV-16/18 vaccine) and 97.5–100% (HPV-6/11/16/18 vaccine) for HPV-16, and 99.0–100% (HPV-16/18 vaccine) and 72.3–84.4% (HPV-6/11/16/18 vaccine) for HPV-18. Corresponding geometric mean titers (GMTs) were 2.4–5.8-fold higher for HPV-16 and 7.7–9.4-fold higher for HPV-18 with the HPV-16/18 vaccine vs. the HPV-6/11/16/18 vaccine; HPV-16 and HPV-18 GMTs were significantly higher with the HPV-16/18 vaccine than the HPV-6/11/16/18 vaccine (p < 0.0001) in the total vaccinated cohort (received ≥1 vaccine dose, irrespective of baseline sero/DNA-status). Similar results were obtained using enzyme-linked immunosorbent assay (ELISA ). Positivity rates and GMTs of antigen-specific IgG antibodies in cervicovaginal secretions (ELISA) were not significantly different between vaccines. At Month 24, CD4+ T-cell responses for HPV-16 and HPV-18 were higher with the HPV-16/18 vaccine; memory B-cell response was higher for HPV-18 with the HPV-16/18 vaccine and similar between vaccines for HPV-16. Both vaccines were generally well tolerated. Although an immunological correlate of protection has not been defined, differences in the magnitude of immune response between vaccines may represent determinants of duration of protection. PMID:22048173

  11. Efficacy and safety of once-weekly GLP-1 receptor agonist albiglutide (HARMONY 2): 52 week primary endpoint results from a randomised, placebo-controlled trial in patients with type 2 diabetes mellitus inadequately controlled with diet and exercise.

    PubMed

    Nauck, Michael A; Stewart, Murray W; Perkins, Christopher; Jones-Leone, Angela; Yang, Fred; Perry, Caroline; Reinhardt, Rickey R; Rendell, Marc

    2016-02-01

    Additional safe and effective therapies for type 2 diabetes are needed, especially ones that do not cause weight gain and have a low risk of hypoglycaemia. The present study evaluated albiglutide as monotherapy. In this placebo-controlled study, 309 patients (aged ≥ 18 years) with type 2 diabetes inadequately controlled by diet and exercise and who were not using a glucose-lowering agent (HbA1c 7.0-10.0% [53.00-85.79 mmol/mol], body mass index 20-45 kg/m(2), and fasting C-peptide ≥ 0.26 nmol/l) were randomised (1:1:1 on a fixed randomisation schedule using an interactive voice response system) to receive once-weekly albiglutide 30 mg (n = 102) or 50 mg (n = 102) or matching placebo (n = 105). The study treatments were blinded to both patients and study personnel. All study data were collected at individual patient clinic visits. The primary efficacy endpoint was change in HbA1c from baseline to week 52. The primary analysis was applied to the intent-to-treat population. Additional efficacy and safety endpoints were assessed. At week 52, both albiglutide 30 mg and 50 mg were superior to placebo in reducing HbA1c. The least-squares means treatment difference from placebo was -0.84% (95% CI -1.11%, -0.58%; p < 0.0001) with albiglutide 30 mg and -1.04% (-1.31%, -0.77%; p < 0.0001) with albiglutide 50 mg. Injection-site reactions were reported more frequently with albiglutide (30 mg: 17.8%; 50 mg: 22.2%) than with placebo (9.9%). Other commonly reported adverse events included nausea, diarrhoea, vomiting and hypoglycaemia; the incidences of these were generally similar across treatment groups. Albiglutide is safe and effective as monotherapy and significantly lowered HbA1c levels over 52 weeks, did not cause weight gain, and had good gastrointestinal tolerability and a low rate of hypoglycaemia compared with placebo. Trial registration ClinicalTrials.gov NCT00849017 Funding This study was sponsored by GlaxoSmithKline.

  12. Pooled analysis of large and long-term safety data from the human papillomavirus-16/18-AS04-adjuvanted vaccine clinical trial programme

    PubMed Central

    Angelo, Maria-Genalin; David, Marie-Pierre; Zima, Julia; Baril, Laurence; Dubin, Gary; Arellano, Felix; Struyf, Frank

    2014-01-01

    Purpose The purpose of this study is to further evaluate the safety of the human papillomavirus (HPV)-16/18-AS04-adjuvanted vaccine (HPV-16/18-vaccine Cervarix®, GlaxoSmithKline, Belgium) through a pooled analysis of data from 42 completed/ongoing clinical studies. Methods Unsolicited adverse events (AEs) were reported for 30 days after each dose. Medically significant conditions, serious AEs (SAEs), potential immune-mediated diseases (pIMDs) and pregnancy outcomes were captured until study completion. Events leading to subject withdrawal were reviewed. Relative risks compared incidences of spontaneous abortion and pIMDs in controlled studies. Results Thirty one thousand one hundred seventy-three adolescent girls/women received HPV-16/18-vaccine alone (HPV group), 2166 received HPV-16/18-vaccine coadministered with another vaccine and 24 241 were controls. Mean follow-up was 39 months (range 0–113.3). Incidences of unsolicited AEs reported within 30 days after any dose were similar between HPV and Control groups (30.8%/29.7%). During the entire study period, reports of medically significant conditions (25.0%/28.3%) and SAEs (7.9%/9.3%) were also similarly distributed between groups. Deaths were rare: HPV (alone/coadministered) n = 25, controls n = 20 (n = 18 in blinded groups). pIMDs within 1 year were reported by 0.2% of HPV-16/18 vaccinees and controls. For each pIMD event category, no increased relative risks were reported for HPV-16/18 vaccinees versus controls. Coadministration did not change the overall safety profile. Pregnancy outcomes and withdrawal rates were similar between groups. Conclusions Analysis of safety data arising from 57 580 subjects and 96 704 HPV-16/18-vaccine doses shows that the incidences and distribution of AEs were similar among HPV-16/18-vaccine recipients and controls. No new safety signals were identified. The data confirm previous findings that HPV-16/18-vaccine has an acceptable benefit-risk profile in adolescent girls and

  13. Validation studies of the site-directed docking program LibDock.

    PubMed

    Rao, Shashidhar N; Head, Martha S; Kulkarni, Amit; LaLonde, Judith M

    2007-01-01

    The performance of the site-features docking algorithm LibDock has been evaluated across eight GlaxoSmithKline targets as a follow-up to a broad validation study of docking and scoring software (Warren, G. L.; Andrews, W. C.; Capelli, A.; Clarke, B.; Lalonde, J.; Lambert, M. H.; Lindvall, M.; Nevins, N.; Semus, S. F.; Senger, S.; Tedesco, G.; Walls, I. D.; Woolven, J. M.; Peishoff, C. E.; Head, M. S. J. Med. Chem. 2006, 49, 5912-5931). Docking experiments were performed to assess both the accuracy in reproducing the binding mode of the ligand and the retrieval of active compounds in a virtual screening protocol using both the DJD (Diller, D. J.; Merz, K. M., Jr. Proteins 2001, 43, 113-124) and LigScore2 (Krammer, A. K.; Kirchoff, P. D.; Jiang, X.; Venkatachalam, C. M.; Waldman, M. J. Mol. Graphics Modell. 2005, 23, 395-407) scoring functions. This study was conducted using DJD scoring, and poses were rescored using all available scoring functions in the Accelrys LigandFit module, including LigScore2. For six out of eight targets at least 30% of the ligands were docked within a root-mean-square difference (RMSD) of 2.0 A for the crystallographic poses when the LigScore2 scoring function was used. LibDock retrieved at least 20% of active compounds in the top 10% of screened ligands for four of the eight targets in the virtual screening protocol. In both studies the LigScore2 scoring function enhanced the retrieval of crystallographic poses or active compounds in comparison with the results obtained using the DJD scoring function. The results for LibDock accuracy and ligand retrieval in virtual screening are compared to 10 other docking and scoring programs. These studies demonstrate the utility of the LigScore2 scoring function and that LibDock as a feature directed docking method performs as well as docking programs that use genetic/growing and Monte Carlo driven algorithms.

  14. Reduced schedules of 4CMenB vaccine in infants and catch-up series in children: Immunogenicity and safety results from a randomised open-label phase 3b trial.

    PubMed

    Martinón-Torres, Federico; Safadi, Marco Aurelio P; Martinez, Alfonso Carmona; Marquez, Pilar Infante; Torres, Juan Carlos Tejedor; Weckx, Lily Yin; Moreira, Edson Duarte; Mensi, Ilhem; Calabresi, Marco; Toneatto, Daniela

    2017-06-16

    This study evaluated the immunogenicity and safety of a licensed meningococcal serogroup B vaccine (4CMenB) administered alone according to reduced schedules in infants or catch-up series in children. In this open-label, multicentre, phase 3b study (NCT01339923), infants randomised 1:1:1 received 4CMenB: 2+1 doses at 3½-5-11months or 6-8-11months of age, 3+1 doses at ages 2½-3½-5-11months. Children aged 2-10years received 2 catch-up doses administered 2months apart. Immune responses were measured by hSBA assays against 4 strains specific for vaccine components fHbp, NadA, PorA and NHBA. Sufficiency of immune responses was defined in groups with 2+1 doses schedules as a lower limit ≥70% for the 97.5% confidence interval of the percentage of infants with hSBA titres ≥4, 1month post-dose 2 for fHbp, NadA, PorA. Adverse events were collected for 7days post-vaccination; serious adverse events (SAEs) throughout the study. 754 infants and 404 children were enrolled. Post-primary vaccination, 98-100% of infants across all groups developed hSBA titres ≥4 for fHbp, NadA, PorA, and 48-77% for NHBA. Sufficiency of immune responses in infants receiving 2+1 schedules was demonstrated for fHbp, NadA, PorA after 2 doses of 4CMenB, as pre-specified criteria were met. Following receipt of 2 catch-up doses, 95-99% of children developed hSBA titres ≥4 for 4CMenB components. Similar safety profiles were observed across groups. A total of 45 SAEs were reported, 3 of which were related to vaccination. Reduced infant schedules and catch-up series in children were immunogenic and safe, having the potential to widen 4CMenB vaccine coverage. GlaxoSmithKline Biologicals SA. Copyright © 2017. Published by Elsevier Ltd.

  15. Promotion by the British pharmaceutical industry, 1983-8: a critical analysis of self regulation.

    PubMed Central

    Herxheimer, A; Collier, J

    1990-01-01

    Since 1958 the Association of the British Pharmaceutical Industry (ABPI) has attempted to regulate the promotion of prescription medicines through its code of practice. This regulation is described and analysed for the six years 1983-8 using the reports on 302 complaints considered by its code of practice committee and annual reports. The complaints came mainly from doctors (143, 48%) and competing companies (103, 33%). The committee found a total of 379 breaches of the code in 192 (63%) of the complaints. Additional breaches were detected by informational scrutiny of advertisements by the ABPI secretariat. Analysis showed that 270 (71%) of these breaches involved possible breaches of the Medicines Act. The rules that forbid misleading or unsubstantiated information and misleading claims or comparisons were broken most often. The committee found the most frequent offenders to be Organon (32 breaches), Smith Kline and French (23), Glaxo (21), A H Robins (18), Bayer (17), Merck Sharp and Dohme (17), and Lederle (16). Often the promotion of one product led to several breaches. The promotional wars over histamine H2 receptor antagonists accounted for 33 breaches. It is estimated that in 1983-8 about 100 breaches of the code were detected a year. In the 18 years 1972-88 the Medicines Act was breached probably over 1200 times. Health ministers, by not enforcing the regulations controlling promotion, have abrogated their responsibility to the ABPI, but the evidence suggests that the code has failed to deter promotional excesses. The ABPI's wish to secure compliance with the code seems weaker than its wish to pre-empt outside criticism and action: its self regulation seems to be a service to itself rather than to the public. It is suggested that the code of practice committee should become publicly accountable, that the majority of its members should represent the health professions and the public, and that effective sanctions are needed. PMID:2106963

  16. Preclinical immunogenicity and functional activity studies of an A+W meningococcal outer membrane vesicle (OMV) vaccine and comparisons with existing meningococcal conjugate- and polysaccharide vaccines.

    PubMed

    Tunheim, G; Arnemo, M; Næss, L M; Fjeldheim, Å K; Nome, L; Bolstad, K; Aase, A; Mandiarote, A; González, H; González, D; García, L; Cardoso, D; Norheim, G; Rosenqvist, E

    2013-12-09

    Meningococci of serogroups A and W (MenA and MenW) are the main causes of epidemic bacterial meningitis outbreaks in sub-Saharan Africa. In this study we prepared a detergent extracted outer membrane vesicle (dOMV) vaccine from representative African MenA and MenW strains, and compared the immunogenicity of this vaccine with existing meningococcal conjugate and polysaccharide (PS) vaccines in mice. NMRI mice were immunized with preclinical batches of the A+W dOMV vaccine, or with commercially available vaccines; a MenA conjugate vaccine (MenAfriVac(®), Serum Institute of India), ACYW conjugate vaccine (Menveo(®), Novartis) or ACYW PS vaccine (Mencevax(®), GlaxoSmithKline). The mice received 2 doses of 1/10 or 1/50 of a human dose with a three week interval. Immune responses were tested in ELISA, serum bactericidal activity (SBA) and opsonophagocytic activity (OPA) assays. High levels of IgG antibodies against both A and W dOMV were detected in mice receiving the A+W dOMV vaccine. High SBA titers against both MenA and MenW vaccine strains were detected after only one dose of the A+W dOMV vaccine, and the titers were further increased after the second dose. The SBA and OPA titers in mice immunized with dOMV vaccine were significantly higher than in mice immunized with the ACYW-conjugate vaccine or the PS vaccine. Furthermore, the A+W dOMV vaccine was shown to induce SBA and OPA titers against MenA of the same magnitude as the titers induced by the A-conjugate vaccine. In conclusion, the A+W dOMV vaccine induced high levels of functional antibodies to both MenA and MenW strains, levels that were shown to be higher or equal to the levels induced by licensed meningococcal vaccines. Thus, an A+W dOMV vaccine could potentially serve as an alternative or a supplement to existing conjugate and PS vaccines in the African meningitis belt. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. CYP2C19*17 increases clopidogrel-mediated platelet inhibition but does not alter the pharmacokinetics of the active metabolite of clopidogrel.

    PubMed

    Pedersen, Rasmus Steen; Nielsen, Flemming; Stage, Tore Bjerregaard; Vinholt, Pernille Just; el Achwah, Alaa Bilal; Damkier, Per; Brosen, Kim

    2014-11-01

    The aim of the present study was to determine the impact of CYP2C19*17 on the pharmacokinetics and pharmacodynamics of the active metabolite of clopidogrel and the pharmacokinetics of proguanil. Thus, we conducted an open-label two-phase cross-over study in 31 healthy male volunteers (11 CYP2C19*1/*1, 11 CYP2C19*1/*17 and nine CYP2C19*17/*17). In Phase A, the pharmacokinetics of the derivatized active metabolite of clopidogrel (CAMD) and platelet function were determined after administration of a single oral dose of 600 mg clopidogrel (Plavix; Sanofi-Avensis, Horsholm, Denmark). In Phase B, the pharmacokinetics of proguanil and its metabolites cycloguanil and 4-chlorphenylbiguanide (4-CPB) were determined in 29 of 31 subjects after a single oral dose of 200 mg proguanil given as the combination drug Malarone (GlaxoSmithKline Pharma, Brondby, Denmark). Significant correlations were found between the area under the time-concentration curve (AUC0-∞ ) of CAMD and both the absolute ADP-induced P2Y12 receptor-activated platelet aggregation (r = -0.60, P = 0.0007) and the percentage inhibition of aggregation (r = 0.59, P = 0.0009). In addition, the CYP2C19*17/*17 and CYP2C19*1/*17 genotype groups had significantly higher percentage inhibition of platelet aggregation compared with the CYP2C19*1/*1 subjects (geometric mean percentage inhibition of 84%, 73% and 63%, respectively; P = 0.014). Neither the absolute ADP-induced P2Y12 receptor-activated platelet aggregation, exposure to CAMD nor the pharmacokinetic parameters of proguanil, cycloguanil and 4-CPB exhibited any significant differences among the genotype groups. In conclusion, carriers of CYP2C19*17 exhibit higher percentage inhibition of platelet aggregation, but do not have significantly lower absolute P2Y12 receptor-activated platelet aggregation or higher exposure to the active metabolite after a single oral administration of 600 mg clopidogrel. © 2014 Wiley Publishing Asia Pty Ltd.

  18. A Review of Clinical Trials of Human Papillomavirus Prophylactic Vaccines

    PubMed Central

    Schiller, John T.; Castellsagué, Xavier; Garland, Suzanne M.

    2015-01-01

    End of study analyses of the phase III trials of prophylactic human papillomavirus (HPV) virus-like particle (VLP) vaccines in young women are now largely completed. Two distinct vaccines were evaluated, Gardasil® (Merck & Co., Whitehouse Station, NJ USA) a quadrivalent vaccine containing VLPs of types 6, 11, 16 and 18 and Cervarix® (GlaxoSmithKline Biologicals, Rixensart, Belgium), a bivalent vaccine containing VLPs of types 16 and 18. Both vaccines exhibited excellent safety and immunogenicity profiles. The vaccines also demonstrated remarkably high and similar efficacy against the vaccine-targeted types for a range of cervical endpoints from persistent infection to cervical intraepithelial neoplasia grade 3 (CIN3) in women naïve to the corresponding type at the time of vaccination. However, protection from incident infection or disease from non-vaccine types was restricted, and the vaccines had no effect on prevalent infection or disease. Gardasil® also demonstrated strong protection against genital warts and vulvar/vaginal neoplasia associated with the vaccine types. In other trials, Gardasil® protected mid-adult women from incident infection and CIN caused by the vaccine types and protected men for incident infection, genital warts and anal intraepithelial neoplasia by the vaccine types. Cervarix® protected against vaccine-targeted anal infections in women in an end of study evaluation. For practical reasons, efficacy studies have not been conducted in the primary target populations of current vaccination programs, adolescent girls and boys. However, immunogenicity bridging studies demonstrating excellent safety and strong immune responses in adolescence, coupled with the documentation of durable antibody responses and protection in young adults, leads to an optimistic projection of the effectiveness of the vaccines in adolescent vaccination programs. Taken together, the excellent clinical trial results strongly support the potential of the vaccines as

  19. Safety and immunogenicity of the HPV-16/18 AS04-adjuvanted vaccine in HIV-positive women in South Africa: a partially-blind randomised placebo-controlled study.

    PubMed

    Denny, Lynette; Hendricks, Bronwyn; Gordon, Chivaugn; Thomas, Florence; Hezareh, Marjan; Dobbelaere, Kurt; Durand, Christelle; Hervé, Caroline; Descamps, Dominique

    2013-11-19

    In developing countries, risk of human papillomavirus (HPV) infection may be increased by the high prevalence of human immunodeficiency virus (HIV) infection. We evaluated the safety and immunogenicity of the HPV-16/18 AS04-adjuvanted vaccine in HIV-infected women in South Africa. Asymptomatic HIV-positive women aged 18-25 years (N=120) were stratified by CD4⁺ T-cell count and randomised (1:1) to receive HPV-16/18 vaccine (Cervarix®; GlaxoSmithKline Vaccines) or placebo (Al[OH]3) at 0, 1 and 6 months (double-blind). HIV-negative women (N=30) received HPV-16/18 vaccine (open label). Anti-HPV-16/18 antibody and CD4⁺ T-cell responses, CD4⁺ T-cell count, HIV viral load, HIV clinical stage and safety were evaluated for 12 months. The safety and reactogenicity profile of the HPV-16/18 vaccine was comparable in HIV-positive and HIV-negative women. Irrespective of baseline HPV status, all HIV-positive and HIV-negative women who received the HPV-16/18 vaccine were seropositive for both HPV-16 and HPV-18 after the second vaccine dose (month 2) and remained seropositive for both antigens at month 12. Anti-HPV-16/18 antibody titres at month 12 remained substantially above levels associated with natural infection. The HPV-16/18 vaccine induced sustained anti-HPV-16/18 CD4⁺ T-cell responses in both HIV-positive and HIV-negative women. No impact of baseline CD4⁺ T-cell count or HIV viral load was observed on the magnitude of the immune response in HIV-positive women. In HIV-positive women, CD4⁺ T-cell count, HIV viral load and HIV clinical stage were unaffected by HPV-16/18 vaccine administration. In conclusion, the HPV-16/18 AS04-adjuvanted vaccine appears immunogenic and well-tolerated in women with HIV infection. Study ID: 107863/NCT00586339. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

  20. Treatment and Prevention of Pandemic H1N1 Influenza.

    PubMed

    Rewar, Suresh; Mirdha, Dashrath; Rewar, Prahlad

    2015-01-01

    Swine influenza is a respiratory infection common to pigs worldwide caused by type A influenza viruses, principally subtypes H1N1, H1N2, H2N1, H3N1, H3N2, and H2N3. Swine influenza viruses also can cause moderate to severe illness in humans and affect persons of all age groups. People in close contact with swine are at especially high risk. Until recently, epidemiological study of influenza was limited to resource-rich countries. The World Health Organization declared an H1N1 pandemic on June 11, 2009, after more than 70 countries reported 30,000 cases of H1N1 infection. In 2015, incidence of swine influenza increased substantially to reach a 5-year high. In India in 2015, 10,000 cases of swine influenza were reported with 774 deaths. The Centers for Disease Control and Prevention recommend real-time polymerase chain reaction as the method of choice for diagnosing H1N1. Antiviral drugs are the mainstay of clinical treatment of swine influenza and can make the illness milder and enable the patient to feel better faster. Antiviral drugs are most effective when they are started within the first 48 hours after the clinical signs begin, although they also may be used in severe or high-risk cases first seen after this time. The Centers for Disease Control and Prevention recommends use of oseltamivir (Tamiflu, Genentech) or zanamivir (Relenza, GlaxoSmithKline). Prevention of swine influenza has 3 components: prevention in swine, prevention of transmission to humans, and prevention of its spread among humans. Because of limited treatment options, high risk for secondary infection, and frequent need for intensive care of individuals with H1N1 pneumonia, environmental control, including vaccination of high-risk populations and public education are critical to control of swine influenza out breaks. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  1. Antibody persistence for 3 years following two doses of tetravalent measles-mumps-rubella-varicella vaccine in healthy children.

    PubMed

    Knuf, Markus; Zepp, Fred; Helm, Klaus; Maurer, Hartwig; Prieler, Albrecht; Kieninger-Baum, Dorothee; Douha, Martine; Willems, Paul

    2012-03-01

    Two doses of a varicella-containing vaccine in healthy children <12 years are suggested to induce better protection than a single dose. Persistence of immunity against measles, mumps, rubella, and varicella as well as varicella breakthrough cases were assessed 3 years after two-dose measles, mumps, rubella, and varicella (MMRV) vaccination or concomitant MMR (Priorix™) and varicella (Varilrix™) vaccination. Four hundred ninety-four healthy children, 12-18 months old at the time of the first dose, received either two doses of MMRV vaccine (GlaxoSmithKline Biologicals) 42-56 days apart (MMRV, N = 371) or one dose of MMR and varicella vaccines administered simultaneously at separate sites, followed by another MMR vaccination 42-56 days later (MMR + V, N = 123). Three hundred-four subjects participated in 3-year follow-up for persistence of immunity and occurrence of breakthrough varicella (MMRV, N = 225; MMR + V, N = 79). Antibodies were measured by ELISA (measles, mumps, rubella) and immunofluorescence (varicella). Contacts with individuals with varicella or zoster and cases of breakthrough varicella disease were recorded. Three years post-vaccination seropositivity rates in subjects seronegative before vaccination were: MMRV-measles, 98.5% (geometric mean titer [GMT] = 3,599.6); mumps, 97.4% (GMT = 1,754.5); rubella, 100% (GMT = 51.9); varicella, 99.4% (GMT = 225.5); MMR + V-measles, 97.0% (GMT = 1,818.8); mumps, 93.8% (GMT = 1,454.6); rubella, 100% (GMT = 53.8); and varicella, 96.8% (GMT = 105.8). Of the subjects, 15-20% reported contact with individuals with varicella/zoster each year. After 3 years, the cumulative varicella breakthrough disease rate was 0.7% (two cases) in the MMRV group and 5.4% (five cases) in the MMR + V group. Immunogenicity of the combined MMRV vaccine was sustained 3 years post-vaccination. (208136/041/NCT00406211).

  2. Immunogenicity and Safety of Three Doses of a Bivalent (B:4:P1.19,15 and B:4:P1.7-2,4) Meningococcal Outer Membrane Vesicle Vaccine in Healthy Adolescents▿

    PubMed Central

    Boutriau, Dominique; Poolman, Jan; Borrow, Ray; Findlow, Jamie; Domingo, Javier Diez; Puig-Barbera, Joan; Baldó, José María; Planelles, Victoria; Jubert, Angels; Colomer, Julia; Gil, Angel; Levie, Karin; Kervyn, Anne-Diane; Weynants, Vincent; Dominguez, Francisco; Barberá, Ramon; Sotolongo, Franklin

    2007-01-01

    An experimental bivalent meningococcal outer membrane vesicle (OMV) vaccine (B:4:P1.19,15 and B:4:P1.7-2,4) has been developed to provide wide vaccine coverage particularly of the circulating strains in Europe. A randomized, controlled phase II study (study identification number, 710158/002; ClinicalTrials.gov identifier number, NCT00137917) to evaluate the immunogenicity and safety of three doses of the OMV vaccine when given to healthy 12- to 18-year-olds on a 0-2-4 month (n = 162) or 0-1-6 month schedule (n = 159). A control group received two doses of hepatitis A and one of conjugated meningococcal serogroup C vaccine on a 0-1-6 month schedule (n = 157). Immune response, defined as a fourfold increase in serum bactericidal titer using a range of vaccine-homologous or PorA-related and heterologous strains, was determined for samples taken before and 1 month after vaccination; assays were performed at two laboratories. As measured at the GlaxoSmithKline (GSK) laboratory, the OMV vaccine induced an immune response against homologous or PorA-related strains (in at least 51% of subjects against strains of serosubtype P1.19,15 and at least 66% against strains of serosubtype P1.7-2,4) and against a set of three heterologous strains (in 28% to 46% of subjects). Both laboratories showed consistent results for immune response rates. The OMV vaccine had a similar reactogenicity profile for each schedule. Pain preventing normal activities occurred in approximately one-fifth of the subjects; this was significantly higher than in the control group. The immune responses induced by the bivalent OMV vaccine demonstrated the induction of bactericidal antibodies against the vaccine-homologous/PorA-related strains but also against heterologous strains, indicating the presence of protective antigens in OMVs and confirming the potential of clinical cross-protection. PMID:17065257

  3. Safety of Adding Salmeterol to Fluticasone Propionate in Children with Asthma.

    PubMed

    Stempel, David A; Szefler, Stanley J; Pedersen, Søren; Zeiger, Robert S; Yeakey, Anne M; Lee, Laurie A; Liu, Andrew H; Mitchell, Herman; Kral, Kenneth M; Raphiou, Ibrahim H; Prillaman, Barbara A; Buaron, Kathleen S; Yun Kirby, Suyong; Pascoe, Steven J

    2016-09-01

    Long-acting beta-agonists (LABAs) have been shown to increase the risk of asthma-related death among adults and the risk of asthma-related hospitalization among children. It is unknown whether the concomitant use of inhaled glucocorticoids with LABAs mitigates those risks. This trial prospectively evaluated the safety of the LABA salmeterol, added to fluticasone propionate, in a fixed-dose combination in children. We randomly assigned, in a 1:1 ratio, children 4 to 11 years of age who required daily asthma medications and had a history of asthma exacerbations in the previous year to receive fluticasone propionate plus salmeterol or fluticasone alone for 26 weeks. The primary safety end point was the first serious asthma-related event (death, endotracheal intubation, or hospitalization), as assessed in a time-to-event analysis. The statistical design specified that noninferiority would be shown if the upper boundary of the 95% confidence interval of the hazard ratio for the primary safety end point was less than 2.675. The main efficacy end point was the first severe asthma exacerbation that led to treatment with systemic glucocorticoids, as assessed in a time-to-event analysis. Among the 6208 patients, 27 patients in the fluticasone-salmeterol group and 21 in the fluticasone-alone group had a serious asthma-related event (all were hospitalizations); the hazard ratio with fluticasone-salmeterol versus fluticasone alone was 1.28 (95% confidence interval [CI], 0.73 to 2.27), which showed the noninferiority of fluticasone-salmeterol (P=0.006). A total of 265 patients (8.5%) in the fluticasone-salmeterol group and 309 (10.0%) in the fluticasone-alone group had a severe asthma exacerbation (hazard ratio, 0.86; 95% CI, 0.73 to 1.01). In this trial involving children with asthma, salmeterol in a fixed-dose combination with fluticasone was associated with the risk of a serious asthma-related event that was similar to the risk with fluticasone alone. (Funded by GlaxoSmithKline

  4. Real-life effectiveness and safety of salbutamol Steri-Neb™ vs. Ventolin Nebules® for exacerbations in patients with COPD: Historical cohort study

    PubMed Central

    Gefen, Eran; Gopalan, Gokul; McDonald, Rosie; Thomas, Vicky; Ming, Simon Wan Yau; Davis, Emily

    2018-01-01

    Introduction Ventolin Nebules® (reference product; GlaxoSmithKline) was the first licensed nebulizer solution containing the rapid-onset, short-acting β2-agonist salbutamol. Salbutamol Steri-Neb™ (comparator; Teva Pharmaceuticals, Inc.) has the same chemical composition as the reference product. This study evaluated whether the effectiveness of the comparator is non-inferior to the reference product alongside concomitant medications during real-life clinical management of COPD exacerbations. Safety in terms of adverse events (AEs) was also examined. Methods This matched (1:1) historical cohort study evaluated data from 2 UK primary care databases on patients prescribed the salbutamol comparator or reference. The study included a 1-year baseline period, starting 1 year before the index prescription date, and 1-year outcome period. Cohorts were matched for baseline COPD respiratory medications. The primary outcome was analysis of non-inferiority for the comparator versus reference product for the rate of moderate and severe COPD exacerbations. Non-inferiority was satisfied if the 95% confidence interval (CI) upper limit for mean differences in proportions between treatments was <15%. Secondary outcomes were examined through rate ratios (RR) of severe exacerbations and AEs. Results After matching, 1191 patients were included in each cohort. Adjusted upper 95% CI for the difference in proportion of patients experiencing moderate or severe exacerbations between comparator and reference groups was 0.032 (3.2%), demonstrating non-inferiority. No significant differences were observed in rates of moderate and severe exacerbations (RR: 1.00; 95% CI: 0.91, 1.10), severe exacerbations (RR: 0.76; 95% CI: 0.49, 1.17), or AEs (RR: 0.98; 95% CI: 0.78, 1.22) after adjusting for baseline confounders. No significant differences across cohorts were observed for rates of any AE or death. Conclusion This matched cohort study of real-life management of COPD patients supports the

  5. Toothbrush abrasivity in a long-term simulation on human dentin depends on brushing mode and bristle arrangement

    PubMed Central

    2017-01-01

    Objective The aim of this study was to evaluate the susceptibility of dentin to brushing abrasion using four different toothbrushes (rotating-oscillating, sonic and two types of manual toothbrushes) with the same brushing forces. Methods Dentin samples (n = 72) were selected from 72 impacted third molars. Half of the surface of dentin samples was covered with an adhesive tape, creating a protected and a freely exposed area in the same specimen. Brushing was performed with either a: sonic (Sonicare PowerUp, Philips GmbH, Hamburg, Germany), b: oscillating-rotating (Oral B Vitality Precisions Clean, Procter & Gamble, Schwalbach am Taunus, Germany) or two different manual toothbrushes c: flat trim brush head toothbrush (Dr. Best: Original, Glaxo-Smith-Kline, Bühl, Germany) and d: rippled-shaped brush head toothbrush (Blend-a-Dent, Complete V-Interdental, Blend-a-med, Schwalbach, Germany) in a custom made automatic brushing machine. The brushing force was set to 2 N and a whitening toothpaste (RDA = 150) was used. The simulation period was performed over a calculated period to mimic a brushing behavior of two times a day brushing for eight years and six months. Dentin loss was quantitatively determined by profilometry and statistically analyzed by Wilcoxon and Mann-Whitney-U Test (p < 0.05). Results The mean (standard deviation) surface loss was 21.03 (±1.26) μm for the sonic toothbrush, 15.71 (±0.85) μm for the oscillating-rotating toothbrush, 6.13 (±1.24) μm for the manual toothbrush with flat trim brush head and 2.50 (±0.43) μm for the manual toothbrush with rippled-shaped brush head. Differences between all groups were statistically significant at p<0.05. Conclusion Using the same brushing force and a highly abrasive toothpaste, manual toothbrushes are significantly less abrasive compared to power toothbrushes for an 8.5—year simulation. PMID:28222156

  6. 76 FR 72675 - Voluntary Termination of Foreign-Trade Subzone 90A Smith Corona Corporation, Cortland County, New...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-25

    ... DEPARTMENT OF COMMERCE Foreign-Trade Zones Board [Order No. 1799] Voluntary Termination of Foreign-Trade Subzone 90A Smith Corona Corporation, Cortland County, New York Pursuant to the authority granted... Smith Corona Corporation plant in Cortland County, New York (Board Order 300, 50 FR 15469, 04/18/85...

  7. Exogenous Ketone Supplements Reduce Anxiety-Related Behavior in Sprague-Dawley and Wistar Albino Glaxo/Rijswijk Rats

    PubMed Central

    Ari, Csilla; Kovács, Zsolt; Juhasz, Gabor; Murdun, Cem; Goldhagen, Craig R.; Koutnik, Andrew P.; Poff, Angela M.; Kesl, Shannon L.; D’Agostino, Dominic P.

    2016-01-01

    Nutritional ketosis has been proven effective for seizure disorders and other neurological disorders. The focus of this study was to determine the effects of ketone supplementation on anxiety-related behavior in Sprague-Dawley (SPD) and Wistar Albino Glaxo/Rijswijk (WAG/Rij) rats. We tested exogenous ketone supplements added to food and fed chronically for 83 days in SPD rats and administered sub-chronically for 7 days in both rat models by daily intragastric gavage bolus followed by assessment of anxiety measures on elevated plus maze (EPM). The groups included standard diet (SD) or SD + ketone supplementation. Low-dose ketone ester (LKE; 1,3-butanediol-acetoacetate diester, ~10 g/kg/day, LKE), high dose ketone ester (HKE; ~25 g/kg/day, HKE), beta-hydroxybutyrate-mineral salt (βHB-S; ~25 g/kg/day, KS) and βHB-S + medium chain triglyceride (MCT; ~25 g/kg/day, KSMCT) were used as ketone supplementation for chronic administration. To extend our results, exogenous ketone supplements were also tested sub-chronically on SPD rats (KE, KS and KSMCT; 5 g/kg/day) and on WAG/Rij rats (KE, KS and KSMCT; 2.5 g/kg/day). At the end of treatments behavioral data collection was conducted manually by a blinded observer and with a video-tracking system, after which blood βHB and glucose levels were measured. Ketone supplementation reduced anxiety on EPM as measured by less entries to closed arms (sub-chronic KE and KS: SPD rats and KSMCT: WAG/Rij rats), more time spent in open arms (sub-chronic KE: SPD and KSMCT: WAG/Rij rats; chronic KSMCT: SPD rats), more distance traveled in open arms (chronic KS and KSMCT: SPD rats) and by delayed latency to entrance to closed arms (chronic KSMCT: SPD rats), when compared to control. Our data indicates that chronic and sub-chronic ketone supplementation not only elevated blood βHB levels in both animal models, but reduced anxiety-related behavior. We conclude that ketone supplementation may represent a promising anxiolytic strategy through a

  8. Harry Smith — recipient of the 2008 Molecular Ecology Prize

    USDA-ARS?s Scientific Manuscript database

    Harry Smith is a scholar, mentor, internationally renowned researcher, eloquent speaker and author, pioneering journal editor and highly valued colleague who has contributed greatly in multiple ways to plant science and the community. He richly deserves the honour of the Molecular Ecology Prize....

  9. OBLIQUE VIEW FROM THE SOUTH CORNER Camp H.M. Smith ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    OBLIQUE VIEW FROM THE SOUTH CORNER - Camp H.M. Smith and Navy Public Works Center Manana Title VII (Capehart) Housing, U-Shaped Two-Bedroom Single-Family Type 6, Birch Circle, Elm Drive, Elm Circle, and Date Drive, Pearl City, Honolulu County, HI

  10. Empathy's purity, sympathy's complexities; De Waal, Darwin and Adam Smith.

    PubMed

    van der Weele, Cor

    2011-07-01

    Frans de Waal's view that empathy is at the basis of morality directly seems to build on Darwin, who considered sympathy as the crucial instinct. Yet when we look closer, their understanding of the central social instinct differs considerably. De Waal sees our deeply ingrained tendency to sympathize (or rather: empathize) with others as the good side of our morally dualistic nature. For Darwin, sympathizing was not the whole story of the "workings of sympathy"; the (selfish) need to receive sympathy played just as central a role in the complex roads from sympathy to morality. Darwin's understanding of sympathy stems from Adam Smith, who argued that the presence of morally impure motives should not be a reason for cynicism about morality. I suggest that De Waal's approach could benefit from a more thorough alignment with the analysis of the workings of sympathy in the work of Darwin and Adam Smith.

  11. Computational study of packing a collagen-like molecule: quasi-hexagonal vs "Smith" collagen microfibril model.

    PubMed

    Lee, J; Scheraga, H A; Rackovsky, S

    1996-01-01

    The lateral packing of a collagen-like molecule, CH3CO-(Gly-L-Pro-L-Pro)4-NHCH3, has been examined by energy minimization with the ECEPP/3 force field. Two current packing models, the Smith collagen microfibril twisted equilateral pentagonal model and the quasi-hexagonal packing model, have been extensively investigated. In treating the Smith microfibril model, energy minimization was carried out on various conformations including those with the symmetry of equivalent packing, i.e., in which the triple helices were arranged equivalently with respect to each other. Both models are based on the experimental observation of the characteristic axial periodicity, D = 67 nm, of light and dark bands, indicating that, if any superstructure exists, it should consist of five triple helices. The quasi-hexagonal packing structure is found to be energetically more favorable than the Smith microfibril model by as much as 31.2 kcal/mol of five triple helices. This is because the quasi-hexagonal packing geometry provides more nonbonded interaction possibilities between triple helices than does the Smith microfibril geometry. Our results are consistent with recent x-ray studies with synthetic collagen-like molecules and rat tail tendon, in which the data were interpreted as being consistent with either a quasi-hexagonal or a square-triangular structure.

  12. The Smith Cloud: surviving a high-speed transit of the Galactic disc

    NASA Astrophysics Data System (ADS)

    Tepper-García, Thor; Bland-Hawthorn, Joss

    2018-02-01

    The origin and survival of the Smith high-velocity H I cloud has so far defied explanation. This object has several remarkable properties: (i) its prograde orbit is ≈100 km s-1 faster than the underlying Galactic rotation; (ii) its total gas mass (≳ 4 × 106 M⊙) exceeds the mass of all other high-velocity clouds (HVCs) outside of the Magellanic Stream; (iii) its head-tail morphology extends to the Galactic H I disc, indicating some sort of interaction. The Smith Cloud's kinetic energy rules out models based on ejection from the disc. We construct a dynamically self-consistent, multi-phase model of the Galaxy with a view to exploring whether the Smith Cloud can be understood in terms of an infalling, compact HVC that has transited the Galactic disc. We show that while a dark-matter (DM) free HVC of sufficient mass and density can reach the disc, it does not survive the transit. The most important ingredient to survival during a transit is a confining DM subhalo around the cloud; radiative gas cooling and high spatial resolution (≲ 10pc) are also essential. In our model, the cloud develops a head-tail morphology within ∼10 Myr before and after its first disc crossing; after the event, the tail is left behind and accretes on to the disc within ∼400 Myr. In our interpretation, the Smith Cloud corresponds to a gas 'streamer' that detaches, falls back and fades after the DM subhalo, distorted by the disc passage, has moved on. We conclude that subhaloes with MDM ≲ 109 M⊙ have accreted ∼109 M⊙ of gas into the Galaxy over cosmic time - a small fraction of the total baryon budget.

  13. Faster Smith-Waterman database searches with inter-sequence SIMD parallelisation.

    PubMed

    Rognes, Torbjørn

    2011-06-01

    The Smith-Waterman algorithm for local sequence alignment is more sensitive than heuristic methods for database searching, but also more time-consuming. The fastest approach to parallelisation with SIMD technology has previously been described by Farrar in 2007. The aim of this study was to explore whether further speed could be gained by other approaches to parallelisation. A faster approach and implementation is described and benchmarked. In the new tool SWIPE, residues from sixteen different database sequences are compared in parallel to one query residue. Using a 375 residue query sequence a speed of 106 billion cell updates per second (GCUPS) was achieved on a dual Intel Xeon X5650 six-core processor system, which is over six times more rapid than software based on Farrar's 'striped' approach. SWIPE was about 2.5 times faster when the programs used only a single thread. For shorter queries, the increase in speed was larger. SWIPE was about twice as fast as BLAST when using the BLOSUM50 score matrix, while BLAST was about twice as fast as SWIPE for the BLOSUM62 matrix. The software is designed for 64 bit Linux on processors with SSSE3. Source code is available from http://dna.uio.no/swipe/ under the GNU Affero General Public License. Efficient parallelisation using SIMD on standard hardware makes it possible to run Smith-Waterman database searches more than six times faster than before. The approach described here could significantly widen the potential application of Smith-Waterman searches. Other applications that require optimal local alignment scores could also benefit from improved performance.

  14. Camp H.M. Smith and Navy Public Works Center Manana Title ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Camp H.M. Smith and Navy Public Works Center Manana Title VII (Capehart) Housing, Four-Bedroom, Single-Family Type 10, Birch Circle, Elm Drive, Elm Circle, and Date Drive, Pearl City, Honolulu County, HI

  15. Camp H.M. Smith and Navy Public Works Center Manana Title ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Camp H.M. Smith and Navy Public Works Center Manana Title VII (Capehart) Housing, Three-Bedroom Single-Family Type 7, Birch Circle, Elm Drive, Elm Circle, and Date Drive, Pearl City, Honolulu County, HI

  16. Camp H.M. Smith and Navy Public Works Center Manana Title ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Camp H.M. Smith and Navy Public Works Center Manana Title VII (Capehart) Housing, Three-Bedroom Single-Family Type 9, Birch Circle, Elm Drive, Elm Circle, and Date Drive, Pearl City, Honolulu County, HI

  17. 1st EVA - MS Smith and Grunsfeld during RSU changeout

    NASA Image and Video Library

    2000-01-26

    STS103-331-013 (19-27 December 1999) --- Astronauts John M. Grunsfeld (right) and Steven L. Smith share space on the end of the remote manipulator system (RMS) as they change out gyroscopes, contained in rate sensor units (RSU) inside the Hubble Space Telescope (HST).

  18. Camp H.M. Smith and Navy Public Works Center Manana Title ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Camp H.M. Smith and Navy Public Works Center Manana Title VII (Capehart) Housing, U-Shaped Three-Bedroom Duplex Type 4, Acacia Road, Birch Circle, Cedar Drive and Elm Drive, Pearl City, Honolulu County, HI

  19. Does the Watson-Jones or Modified Smith-Petersen Approach Provide Superior Exposure for Femoral Neck Fracture Fixation?

    PubMed

    Lichstein, Paul M; Kleimeyer, John P; Githens, Michael; Vorhies, John S; Gardner, Michael J; Bellino, Michael; Bishop, Julius

    2018-07-01

    A well-reduced femoral neck fracture is more likely to heal than a poorly reduced one, and increasing the quality of the surgical exposure makes it easier to achieve anatomic fracture reduction. Two open approaches are in common use for femoral neck fractures, the modified Smith-Petersen and Watson-Jones; however, to our knowledge, the quality of exposure of the femoral neck exposure provided by each approach has not been investigated. (1) What is the respective area of exposed femoral neck afforded by the Watson-Jones and modified Smith-Petersen approaches? (2) Is there a difference in the ability to visualize and/or palpate important anatomic landmarks provided by the Watson-Jones and modified Smith-Petersen approaches? Ten fresh-frozen human pelvi underwent both modified Smith-Petersen (utilizing the caudal extent of the standard Smith-Petersen interval distal to the anterosuperior iliac spine and parallel to the palpable interval between the tensor fascia lata and the sartorius) and Watson-Jones approaches. Dissections were performed by three fellowship-trained orthopaedic traumatologists with extensive experience in both approaches. Exposure (in cm) was quantified with calibrated digital photographs and specialized software. Modified Smith-Petersen approaches were analyzed before and after rectus femoris tenotomy. The ability to visualize and palpate seven clinically relevant anatomic structures (the labrum, femoral head, subcapital femoral neck, basicervical femoral neck, greater trochanter, lesser trochanter, and medial femoral neck) was also recorded. The quantified area of the exposed proximal femur was utilized to compare which approach afforded the largest field of view of the femoral neck and articular surface for assessment of femoral neck fracture and associated femoral head injury. The ability to visualize and palpate surrounding structures was assessed so that we could better understand which approach afforded the ability to assess structures that

  20. Acceleration of the Smith-Waterman algorithm using single and multiple graphics processors

    NASA Astrophysics Data System (ADS)

    Khajeh-Saeed, Ali; Poole, Stephen; Blair Perot, J.

    2010-06-01

    Finding regions of similarity between two very long data streams is a computationally intensive problem referred to as sequence alignment. Alignment algorithms must allow for imperfect sequence matching with different starting locations and some gaps and errors between the two data sequences. Perhaps the most well known application of sequence matching is the testing of DNA or protein sequences against genome databases. The Smith-Waterman algorithm is a method for precisely characterizing how well two sequences can be aligned and for determining the optimal alignment of those two sequences. Like many applications in computational science, the Smith-Waterman algorithm is constrained by the memory access speed and can be accelerated significantly by using graphics processors (GPUs) as the compute engine. In this work we show that effective use of the GPU requires a novel reformulation of the Smith-Waterman algorithm. The performance of this new version of the algorithm is demonstrated using the SSCA#1 (Bioinformatics) benchmark running on one GPU and on up to four GPUs executing in parallel. The results indicate that for large problems a single GPU is up to 45 times faster than a CPU for this application, and the parallel implementation shows linear speed up on up to 4 GPUs.

  1. Camp H.M. Smith and Navy Public Works Center Manana Title ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Camp H.M. Smith and Navy Public Works Center Manana Title VII (Capehart) Housing, Three-Bedroom Single-Family Types 8 and 11, Birch Circle, Elm Drive, Elm Circle, and Date Drive, Pearl City, Honolulu County, HI

  2. Camp H.M. Smith and Navy Public Works Center Manana Title ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Camp H.M. Smith and Navy Public Works Center Manana Title VII (Capehart) Housing, U-Shaped Two-Bedroom Single-Family Type 6, Birch Circle, Elm Drive, Elm Circle, and Date Drive, Pearl City, Honolulu County, HI

  3. George E. KidderSmith, April 1945, Photograph #1338. VIEW OF BUILDING ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    George E. Kidder-Smith, April 1945, Photograph #133-8. VIEW OF BUILDING 23, FRONT SIDE FROM ACROSS COURTYARD, FACING WEST - Roosevelt Base, Auditorium-Gymnasium, West Virginia Street between Richardson & Reeves Avenues, Long Beach, Los Angeles County, CA

  4. George E. KidderSmith, photographer, April 1945, Photograph #1101. VIEW OF ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    George E. Kidder-Smith, photographer, April 1945, Photograph #110-1. VIEW OF BUILDING 23, SOUTH SIDE WITH ARCADE, FACING NORTHWEST - Roosevelt Base, Auditorium-Gymnasium, West Virginia Street between Richardson & Reeves Avenues, Long Beach, Los Angeles County, CA

  5. Obituary: Harding Eugene (Gene) Smith, Jr., 1947-2007

    NASA Astrophysics Data System (ADS)

    Lonsdale, Carol; Soifer, Tom

    2009-01-01

    Harding Eugene Smith Junior, or Gene, as he was known to family, friends, and colleagues, passed away after an automobile accident in Encinitas, California, on 16 August 2007. He was 60 years old. Gene had recently retired from UCSD after thirty years of service. A memorial service was held at Quail Botanical Gardens in Encinitas, California, on 23 August 2007. A web page is dedicated to his memory at http://harding.smith.muchloved.com, where contributions of memories are invited. Gene was born in San Jose, California in 1947, to Harding Eugene Smith Senior, and Bernice Smith (nee Smith). Harding Smith Senior was an air-force navigator; therefore Gene spent his childhood moving from one air-force base to another. Although an only child, Gene was very close to his cousin Meg, whom he lived nearby to in Gilroy for a time, and the two were like brother and sister. The elder Harding Smith was lost in action over Cambodia in the mid-sixties. Gene was a dedicated student, a boy scout, and a Presidential Scholar. He majored in Physics at Caltech, where he also took a lively interest in the football team and the Glee Club, and was elected a House Officer. To his close friends, he was known at Caltech as Smitty, and the closest of them was Rob Drew, who gave a glimpse into that period of Gene's life at the memorial: "Gene arrived early at campus his first year, in response to an invitation to join the football team. Gene's size and features reminded the head coach of a long-forgotten player named 'Johnson.' After a few days of confusion, Gene simply replaced the name on his helmet. 'Johnson!' coach would yell, 'get in there!' If Johnson was going to get to play, Gene was going to be the best Johnson available!" Gene spent the summer of 1966 working at Kitt Peak, where his lifetime love of observing with ground-based telescopes began, though he learned some things the hard way, such as the fact that trying to squeeze 40,000 numbers onto a computer that stored only 32

  6. Philosophy versus Student Need? A Reply to Smith and Hilton.

    ERIC Educational Resources Information Center

    Rainforth, Beverly

    1994-01-01

    This response to Smith and Hilton (1994) suggests that those authors reject philosophical bases for decision making regarding program design for students with mental retardation while actually proposing their own philosophical base for such decision making. The importance of philosophy in guiding decisions and practice over the last several…

  7. What’s in a Surname? Physique, Aptitude, and Sports Type Comparisons between Tailors and Smiths

    PubMed Central

    Voracek, Martin; Rieder, Stephan; Stieger, Stefan; Swami, Viren

    2015-01-01

    Combined heredity of surnames and physique, coupled with past marriage patterns and trade-specific physical aptitude and selection factors, may have led to differential assortment of bodily characteristics among present-day men with specific trade-reflecting surnames (Tailor vs. Smith). Two studies reported here were partially consistent with this genetic-social hypothesis, first proposed by Bäumler (1980). Study 1 (N = 224) indicated significantly higher self-rated physical aptitude for prototypically strength-related activities (professions, sports, hobbies) in a random sample of Smiths. The counterpart effect (higher aptitude for dexterity-related activities among Tailors) was directionally correct, but not significant, and Tailor-Smith differences in basic physique variables were nil. Study 2 examined two large total-population-of-interest datasets (Austria/Germany combined, and UK: N = 7001 and 20532) of men’s national high-score lists for track-and-field events requiring different physiques. In both datasets, proportions of Smiths significantly increased from light-stature over medium-stature to heavy-stature sports categories. The predicted counterpart effect (decreasing prevalences of Tailors along these categories) was not supported. Related prior findings, the viability of possible alternative interpretations of the evidence (differential positive selection for trades and occupations, differential endogamy and assortative mating patterns, implicit egotism effects), and directions for further inquiry are discussed in conclusion. PMID:26161803

  8. Building Energy Audit Report for Camp Smith, HI

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

    Chvala, William D.; De La Rosa, Marcus I.; Brown, Daryl R.

    2010-09-30

    A detailed energy assessment was performed by a team of engineers from Pacific Northwest National Laboratory (PNNL) under contract to the Department of Energy/Federal Energy Management program (FEMP). The effort used the Facility Energy Decision System (FEDS) model to determine how energy is consumed at Camp Smith, identify the most cost-effective energy retrofit measures, and calculate the potential energy and cost savings. This report documents the results of that assessment.

  9. Faster Smith-Waterman database searches with inter-sequence SIMD parallelisation

    PubMed Central

    2011-01-01

    Background The Smith-Waterman algorithm for local sequence alignment is more sensitive than heuristic methods for database searching, but also more time-consuming. The fastest approach to parallelisation with SIMD technology has previously been described by Farrar in 2007. The aim of this study was to explore whether further speed could be gained by other approaches to parallelisation. Results A faster approach and implementation is described and benchmarked. In the new tool SWIPE, residues from sixteen different database sequences are compared in parallel to one query residue. Using a 375 residue query sequence a speed of 106 billion cell updates per second (GCUPS) was achieved on a dual Intel Xeon X5650 six-core processor system, which is over six times more rapid than software based on Farrar's 'striped' approach. SWIPE was about 2.5 times faster when the programs used only a single thread. For shorter queries, the increase in speed was larger. SWIPE was about twice as fast as BLAST when using the BLOSUM50 score matrix, while BLAST was about twice as fast as SWIPE for the BLOSUM62 matrix. The software is designed for 64 bit Linux on processors with SSSE3. Source code is available from http://dna.uio.no/swipe/ under the GNU Affero General Public License. Conclusions Efficient parallelisation using SIMD on standard hardware makes it possible to run Smith-Waterman database searches more than six times faster than before. The approach described here could significantly widen the potential application of Smith-Waterman searches. Other applications that require optimal local alignment scores could also benefit from improved performance. PMID:21631914

  10. Solar Cycle Variability and Surface Differential Rotation from Ca II K-line Time Series Data

    NASA Astrophysics Data System (ADS)

    Scargle, Jeffrey D.; Keil, Stephen L.; Worden, Simon P.

    2013-07-01

    Analysis of over 36 yr of time series data from the NSO/AFRL/Sac Peak K-line monitoring program elucidates 5 components of the variation of the 7 measured chromospheric parameters: (a) the solar cycle (period ~ 11 yr), (b) quasi-periodic variations (periods ~ 100 days), (c) a broadband stochastic process (wide range of periods), (d) rotational modulation, and (e) random observational errors, independent of (a)-(d). Correlation and power spectrum analyses elucidate periodic and aperiodic variation of these parameters. Time-frequency analysis illuminates periodic and quasi-periodic signals, details of frequency modulation due to differential rotation, and in particular elucidates the rather complex harmonic structure (a) and (b) at timescales in the range ~0.1-10 yr. These results using only full-disk data suggest that similar analyses will be useful for detecting and characterizing differential rotation in stars from stellar light curves such as those being produced by NASA's Kepler observatory. Component (c) consists of variations over a range of timescales, in the manner of a 1/f random process with a power-law slope index that varies in a systematic way. A time-dependent Wilson-Bappu effect appears to be present in the solar cycle variations (a), but not in the more rapid variations of the stochastic process (c). Component (d) characterizes differential rotation of the active regions. Component (e) is of course not characteristic of solar variability, but the fact that the observational errors are quite small greatly facilitates the analysis of the other components. The data analyzed in this paper can be found at the National Solar Observatory Web site http://nsosp.nso.edu/cak_mon/, or by file transfer protocol at ftp://ftp.nso.edu/idl/cak.parameters.

  11. SOLAR CYCLE VARIABILITY AND SURFACE DIFFERENTIAL ROTATION FROM Ca II K-LINE TIME SERIES DATA

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

    Scargle, Jeffrey D.; Worden, Simon P.; Keil, Stephen L.

    Analysis of over 36 yr of time series data from the NSO/AFRL/Sac Peak K-line monitoring program elucidates 5 components of the variation of the 7 measured chromospheric parameters: (a) the solar cycle (period {approx} 11 yr), (b) quasi-periodic variations (periods {approx} 100 days), (c) a broadband stochastic process (wide range of periods), (d) rotational modulation, and (e) random observational errors, independent of (a)-(d). Correlation and power spectrum analyses elucidate periodic and aperiodic variation of these parameters. Time-frequency analysis illuminates periodic and quasi-periodic signals, details of frequency modulation due to differential rotation, and in particular elucidates the rather complex harmonic structuremore » (a) and (b) at timescales in the range {approx}0.1-10 yr. These results using only full-disk data suggest that similar analyses will be useful for detecting and characterizing differential rotation in stars from stellar light curves such as those being produced by NASA's Kepler observatory. Component (c) consists of variations over a range of timescales, in the manner of a 1/f random process with a power-law slope index that varies in a systematic way. A time-dependent Wilson-Bappu effect appears to be present in the solar cycle variations (a), but not in the more rapid variations of the stochastic process (c). Component (d) characterizes differential rotation of the active regions. Component (e) is of course not characteristic of solar variability, but the fact that the observational errors are quite small greatly facilitates the analysis of the other components. The data analyzed in this paper can be found at the National Solar Observatory Web site http://nsosp.nso.edu/cak{sub m}on/, or by file transfer protocol at ftp://ftp.nso.edu/idl/cak.parameters.« less

  12. 37 CFR 1.130 - Affidavit or declaration of attribution or prior public disclosure under the Leahy-Smith America...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2013-07-01 2013-07-01 false Affidavit or declaration of attribution or prior public disclosure under the Leahy-Smith America Invents Act. 1.130 Section 1.130 Patents... or declaration of attribution or prior public disclosure under the Leahy-Smith America Invents Act...

  13. 37 CFR 1.130 - Affidavit or declaration of attribution or prior public disclosure under the Leahy-Smith America...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2014-07-01 2014-07-01 false Affidavit or declaration of attribution or prior public disclosure under the Leahy-Smith America Invents Act. 1.130 Section 1.130 Patents... or declaration of attribution or prior public disclosure under the Leahy-Smith America Invents Act...

  14. ESTIMATION OF SURPLUS BIOMASS OF CLUPEIDS IN SMITH MOUNTAIN LAKE, VIRGINIA

    EPA Science Inventory

    Mean annual estimates of surplus biomass of alewife Alosa pseudoharengus and gizzard shad Dorosoma cepedianum in Smith Mountain Lake, Virginia, were calculated using data on the biomass, growth, and mortality of each clupeid species. Surplus biomass, defined as production over a...

  15. TROPHIC DYNAMICS OF STRIPED BASS IN SMITH MOUNTAIN LAKE, VIRGINIA

    EPA Science Inventory

    We examined the adequacy of the forage base to meet demand of striped bass in Smith Mountain Lake, Virginia. In regards to prey supply, mean alewife biomass from 1993-1998 was 37 kg/ha and mean gizzard shad biomass from 1990-1997 was 112 kg/ha. Mean annual alewife surplus produ...

  16. A Case Study of Early Development in Smith-Magenis Syndrome

    ERIC Educational Resources Information Center

    Fidler, Deborah J.; Philofsky, Amy D.; Hepburn, Susan L.

    2006-01-01

    The aim of this article is to provide an in-depth description of early development in a young child with Smith-Magenis syndrome (SMS). SMS is a multisystem, neurodevelopmental genetic disorder associated with mental retardation that predisposes individuals to a distinct pattern of maladaptive behaviors and other neuropsychological impairments.…

  17. Causality and collateral estoppel: process and content of recent SSRI litigation.

    PubMed

    Whitehead, Paul D

    2003-01-01

    In Tobin v. SmithKline Beecham Pharmaceuticals a jury in the U.S. District Court for the District of Wyoming found that the medication Paxil "can cause some individuals to commit homicide and/or suicide," and that it was a legal cause of the deaths in this case. A motion was recently put before the United States District Court for the District of Utah to adopt the findings of the Tobin case--via the application of collateral estoppel--to a case involving an individual's suicide while prescribed Paxil. This article summarizes these two cases, as reflected in court documents, and comments on limitations of common causality assertions.

  18. 37 CFR 1.109 - Effective filing date of a claimed invention under the Leahy-Smith America Invents Act.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2014-07-01 2014-07-01 false Effective filing date of a claimed invention under the Leahy-Smith America Invents Act. 1.109 Section 1.109 Patents, Trademarks, and... a claimed invention under the Leahy-Smith America Invents Act. (a) The effective filing date for a...

  19. 37 CFR 1.109 - Effective filing date of a claimed invention under the Leahy-Smith America Invents Act.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2013-07-01 2013-07-01 false Effective filing date of a claimed invention under the Leahy-Smith America Invents Act. 1.109 Section 1.109 Patents, Trademarks, and... a claimed invention under the Leahy-Smith America Invents Act. (a) The effective filing date for a...

  20. Modelling the joint torques and loadings during squatting at the Smith machine.

    PubMed

    Biscarini, Andrea; Benvenuti, Paolo; Botti, Fabio; Mastrandrea, Francesco; Zanuso, Silvano

    2011-03-01

    An analytical biomechanical model was developed to establish the relevant properties of the Smith squat exercise, and the main differences from the free barbell squat. The Smith squat may be largely patterned to modulate the distributions of muscle activities and joint loadings. For a given value of the included knee angle (θ(knee)), bending the trunk forward, moving the feet forward in front of the knees, and displacing the weight distribution towards the forefoot emphasizes hip and lumbosacral torques, while also reducing knee torque and compressive tibiofemoral and patellofemoral forces (and vice versa). The tibiofemoral shear force φ(t) displays more complex trends that strongly depend on θ(knee). Notably, for 180° ≥ θ(knee) ≥ 130°, φ(t) and cruciate ligament strain forces can be suppressed by selecting proper pairs of ankle and hip angles. Loading of the posterior cruciate ligament increases (decreases) in the range 180° ≥ θ(knee) ≥ 150° (θ(knee) ≤ 130°) with knee extension, bending the trunk forward, and moving the feet forward in front of the knees. In the range 150° > θ(knee) > 130°, the behaviour changes depending on the foot weight distribution. The conditions for the development of anterior cruciate ligament strain forces are explained. This work enables careful use of the Smith squat in strengthening and rehabilitation programmes.

  1. Jamestown IslandHog IslandCaptain John Smith Chesapeake National Historic Trail District, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Jamestown Island-Hog Island-Captain John Smith Chesapeake National Historic Trail District, James River plus the land 0.5 miles inland, roughly from Swann's Point to Pagan River, Jamestown, James City County, VA

  2. Charles Darwin's Theory of Moral Sentiments: What Darwin's Ethics Really Owes to Adam Smith.

    PubMed

    Priest, Greg

    2017-01-01

    When we read the Origin, we cannot help but hear echoes of the Wealth of Nations. Darwin's "economy of nature" features a "division of labour" that leads to complexity and productivity. We should not, however, analyze Darwin's ethics through this lens. Darwin did not draw his economic ideas from Smith, nor did he base his ethics on an economic foundation. Darwin's ethics rest on Smith's notion from the Theory of Moral Sentiments of an innate human faculty of sympathy. Darwin gave this faculty an evolutionary interpretation and built on this foundation an ethics far removed from what is commonly supposed.

  3. NORTH FORK SMITH RIVER ROADLESS AREA, CALIFORNIA AND OREGON.

    USGS Publications Warehouse

    Gray, Floyd; Hamilton, Michael

    1984-01-01

    Geologic, geochemical, and geophysical investigations and a survey of mines and prospects were conducted to evaluate the mineral-resource potential of the North Fork Smith River Roadless Area, California. The area has probable and sustantiated resource potential for nickel, chromium, copper, and mercury and approximately 2300 mining claims exist in or adjacent to the area. The geologic terrane precludes the occurrence of fossil fuel resources.

  4. Revisiting "No Easy Answers": Application of Sally Smith's Methods in the Lab School of Washington High School Program

    ERIC Educational Resources Information Center

    Reynolds, Meredith

    2010-01-01

    The first edition of "No Easy Answers" (Smith, 1995) was published in 1979, thirty years ago. That seminal work is as relevant today as it was when the book first appeared. This article provides a description of how Sally Smith's Academic Club Method is implemented in the High School program of The Lab School of Washington.

  5. Adam Smith and the Moral Economy of the Classroom System.

    ERIC Educational Resources Information Center

    Hamilton, D.

    1980-01-01

    Traces the development of mass schooling to its origins in 19th-century Glasgow. Its importance as an intellectual and economic center enabled Glasgow to invent a solution to the problem of urban schooling, while the association of scholars like Adam Smith with Glasgow University made Scottish educational theories acceptable around the world. (DB)

  6. Looking east at canal and R. Paul Smith Power Station. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Looking east at canal and R. Paul Smith Power Station. The dark trestle at right center carried the spur track to coal unloading facilities located in the space now occupied by the coal pile. - Potomac Edison Company, Chesapeake & Ohio Canal Bridge, Spanning C & O Canal South of U.S. 11, Williamsport, Washington County, MD

  7. Patty Smith Hill, Gifted Early Childhood Educator of the Progressive Era.

    ERIC Educational Resources Information Center

    Rudnitski, Rose A.

    1995-01-01

    This article chronicles the development of Patty Smith Hill, eminent educator of the Progressive Era. Hill was largely responsible for adding kindergarten to the elementary school curriculum, was the author of the "Happy Birthday" song, and a member of the Woman's Suffrage Movement. (DB)

  8. Decision making regarding Smith-Petersen vs. pedicle subtraction osteotomy vs. vertebral column resection for spinal deformity.

    PubMed

    Bridwell, Keith H

    2006-09-01

    Author experience and literature review. To investigate and discuss decision-making on when to perform a Smith-Petersen osteotomy as opposed to a pedicle subtraction procedure and/or a vertebral column resection. Articles have been published regarding Smith-Petersen osteotomies, pedicle subtraction procedures, and vertebral column resections. Expectations and complications have been reviewed. However, decision-making regarding which of the 3 procedures is most useful for a particular spinal deformity case is not clearly investigated. Discussed in this manuscript is the author's experience and the literature regarding the operative options for a fixed coronal or sagittal deformity. There are roles for Smith-Petersen osteotomy, pedicle subtraction, and vertebral column resection. Each has specific applications and potential complications. As the magnitude of resection increases, the ability to correct deformity improves, but also the risk of complication increases. Therein, an understanding of potential applications and complications is helpful.

  9. The Edwin Smith papyrus: a clinical reappraisal of the oldest known document on spinal injuries

    PubMed Central

    Sanchez, Gonzalo M.; Burridge, Alwyn L.

    2010-01-01

    Dating from the seventeenth century b.c. the Edwin Smith papyrus is a unique treatise containing the oldest known descriptions of signs and symptoms of injuries of the spinal column and spinal cord. Based on a recent “medically based translation” of the Smith papyrus, its enclosed treasures in diagnostic, prognostic and therapeutic reasoning are revisited. Although patient demographics, diagnostic techniques and therapeutic options considerably changed over time, the documented rationale on spinal injuries can still be regarded as the state-of-the-art reasoning for modern clinical practice. PMID:20697750

  10. Smith-Lemli-Opitz syndrome: review and report of two affected siblings.

    PubMed

    Johnson, V P

    1975-01-01

    This paper reports two siblings with the Smith-Lemli-Opitz syndrome and reviews the literature on the subject. SLOS is a syndrome of multiple congenital anomalies with mental and growth retardation, unusual facies, genito-urinary and hand and foot abnormalities inherited as an autosomal recessive trait.

  11. 77 FR 43742 - Changes To Implement the First Inventor To File Provisions of the Leahy-Smith America Invents Act

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-26

    ... 0651-AC77 Changes To Implement the First Inventor To File Provisions of the Leahy-Smith America Invents.... SUMMARY: The Leahy-Smith America Invents Act (AIA) amends the patent laws pertaining to the conditions of patentability to convert the United States patent system from a ``first to invent'' system to a ``first inventor...

  12. Analysis of augmented aircraft flying qualities through application of the Neal-Smith criterion

    NASA Technical Reports Server (NTRS)

    Bailey, R. E.; Smith, R. E.

    1981-01-01

    The Neal-Smith criterion is examined for possible applications in the evaluation of augmented fighter aircraft flying qualities. Longitudinal and lateral flying qualities are addressed. Based on the application of several longitudinal flying qualities data bases, revisions are proposed to the original criterion. Examples are given which show the revised criterion to be a good discriminator of pitch flying qualities. Initial results of lateral flying qualities evaluation through application of the Neal-Smith criterion are poor. Lateral aircraft configurations whose flying qualities are degraded by roll ratcheting effects map into the Level 1 region of the criterion. A third dimension of the criterion for flying qualities specification is evident. Additional criteria are proposed to incorporate this dimension into the criterion structure for flying qualities analysis.

  13. "Comments on Coulter and Smith": Relational Ontological Commitments in Narrative Research

    ERIC Educational Resources Information Center

    Clandinin, D. Jean; Murphy, M. Shaun

    2009-01-01

    In this comment article on Coulter and Smith (2009), the authors raise concerns that focusing exclusively on issues of representation may lead readers to misunderstandings about narrative research. The authors argue that narrative ways of thinking about the phenomena under study are interwoven with narrative research methodologies. Drawing on…

  14. Comparing Adam Smith's Wealth of Nations to James Madison's Federalist #10.

    ERIC Educational Resources Information Center

    Mundell, Jean

    1987-01-01

    Presents a lesson which calls upon students to compare Adam Smith's WEALTH OF NATIONS to James Madison's FEDERALIST #10 to see how the ancient concept of individual rights and liberties was used to describe both economic and governmental systems. Presents questions to provide the basis for comparison. (GEA)

  15. No information or horizon paradoxes for Th. Smiths

    NASA Astrophysics Data System (ADS)

    Maes, Christian

    2015-10-01

    The Statistical mechanician in the street (our Th. Smiths) must be surprised upon hearing popular versions of some of today's most discussed paradoxes in astronomy and cosmology. In fact, rather standard reminders of the meaning of thermal probabilities in statistical mechanics appear to answer the horizon problem (one of the major motivations for inflation theory) and the information paradox (related to black hole physics), at least as they are usually presented. Still the paradoxes point to interesting gaps in our statistical understanding of (quantum) gravitational effects.

  16. Can standard anterior Smith-Robinson supramanubrial approach be utilized for approach down to T2 or T3?

    PubMed

    Singhatanadgige, Weerasak; Zebala, Lukas P; Luksanapruksa, Panya; Daniel Riew, K

    2017-09-01

    The aim of this study was to determine a plain radiographic criterion for determining the feasibility of using the standard anterior Smith-Robinson supramanubrial approach for anterior surgery down to T2 or T3. The surgical database (2002-2014) was searched to identify patients with anterior cervical surgery to T2 or T3. A method to determine whether a standard anterior Smith-Robinson approach can be used to operate on the upper thoracic levels was evaluated. The surgeon chose the surgical approach preoperatively using a lateral radiograph by determining if a line from the intended skin incision to the lower instrumented level (LIV) passed above the top of the manubrium. If so, a standard Smith-Robinson approach was selected. Another spine surgeon then analyzed all patients who had anterior thoracic fusion to T2 or below. The lateral radiographs were retrospectively reviewed. A total of 44 patients who underwent anterior surgery down to T2 or T3 vertebrae were identified. T2 was the LIV in 39 patients. T3 was the LIV in five patients. No surgery was abandoned or converted to a difference approach after making the standard Smith-Robinson approach. To increase visualization, T1 corpectomy was necessary in 4 of 39 patients when T2 was the LIV. T2 corpectomy was necessary in 2 of 5 patients when T3 was the LIV. If a line from the intended skin incision to the LIV passes over the top of the manubrium, a standard Smith-Robinson approach without sternotomy can be successfully used.

  17. Another Look at the Glass and Smith Study on Class Size

    ERIC Educational Resources Information Center

    Phelps, James L.

    2011-01-01

    One of the most influential studies affecting educational policy is Glass and Smith's 1978 study, "Meta-Analysis of Research on the Relationship of Class-Size and Achievement." Since its publication, educational policymakers have referenced it frequently as the justification for reducing class size. While teachers and the public had long believed…

  18. Back to Beginnings: Credentialism, Productivity, and Adam Smith's Division of Labour.

    ERIC Educational Resources Information Center

    Davis, Denis J.

    1981-01-01

    The foundation of factional pressures for upgrading educational credentials in the labor market is examined through a review of human capital and screening theories. The writings of Adam Smith are referenced to show that the claims of the beneficial effects of educational upgrading have been questioned for 200 years. (Author/MLW)

  19. Analysis of the Sensory Profile in Children with Smith-Magenis Syndrome

    ERIC Educational Resources Information Center

    Hildenbrand, Hanna L.; Smith, Ann C. M.

    2012-01-01

    This study systematically assessed sensory processing in 34 children, aged 3-14 years, with Smith-Magenis syndrome (SMS) using the Sensory Profile Caregiver Questionnaire. Scores for the SMS cohort were significantly different from scores of the national sample of children with and without disabilities in all Sensory Profile categories and…

  20. OCLC Looks to an Online Future: An Interview with K. Wayne Smith.

    ERIC Educational Resources Information Center

    Arnold, Stephen

    1993-01-01

    Provides an interview with K. Wayne Smith, chief executive officer of OCLC, that focuses on OCLC's online reference services. Topics include the ratio between technical and online reference services, how OCLC fits into the online industry, telecommunications, electronic publishing, pricing, database tape leases, and CD-ROM. (EAM)

  1. CUDASW++: optimizing Smith-Waterman sequence database searches for CUDA-enabled graphics processing units

    PubMed Central

    Liu, Yongchao; Maskell, Douglas L; Schmidt, Bertil

    2009-01-01

    Background The Smith-Waterman algorithm is one of the most widely used tools for searching biological sequence databases due to its high sensitivity. Unfortunately, the Smith-Waterman algorithm is computationally demanding, which is further compounded by the exponential growth of sequence databases. The recent emergence of many-core architectures, and their associated programming interfaces, provides an opportunity to accelerate sequence database searches using commonly available and inexpensive hardware. Findings Our CUDASW++ implementation (benchmarked on a single-GPU NVIDIA GeForce GTX 280 graphics card and a dual-GPU GeForce GTX 295 graphics card) provides a significant performance improvement compared to other publicly available implementations, such as SWPS3, CBESW, SW-CUDA, and NCBI-BLAST. CUDASW++ supports query sequences of length up to 59K and for query sequences ranging in length from 144 to 5,478 in Swiss-Prot release 56.6, the single-GPU version achieves an average performance of 9.509 GCUPS with a lowest performance of 9.039 GCUPS and a highest performance of 9.660 GCUPS, and the dual-GPU version achieves an average performance of 14.484 GCUPS with a lowest performance of 10.660 GCUPS and a highest performance of 16.087 GCUPS. Conclusion CUDASW++ is publicly available open-source software. It provides a significant performance improvement for Smith-Waterman-based protein sequence database searches by fully exploiting the compute capability of commonly used CUDA-enabled low-cost GPUs. PMID:19416548

  2. Adam Smith and the Educative Critique: A Response to My Commentators

    ERIC Educational Resources Information Center

    Weinstein, Jack Russell

    2015-01-01

    This paper is both a response to the four reviewers in a special symposium on my book Adam Smith's Pluralism and a substantive discussion of philosophy of education. In it, I introduce what I call "the educative critique," a mode of analysis similar to Marxist, feminist, or postcolonial critiques, but focusing on the educative role of a…

  3. Finding revelation in anthropology: Alexander Winchell, William Robertson Smith and the heretical imperative.

    PubMed

    Livingstone, David N

    2015-09-01

    Anthropological inquiry has often been considered an agent of intellectual secularization. Not least is this so in the sphere of religion, where anthropological accounts have often been taken to represent the triumph of naturalism. This metanarrative, however, fails to recognize that naturalistic explanations could sometimes be espoused for religious purposes and in defence of confessional creeds. This essay examines two late nineteenth-century figures--Alexander Winchell in the United States and William Robertson Smith in Britain--who found in anthropological analysis resources to bolster rather than undermine faith. In both cases these individuals found themselves on the receiving end of ecclesiastical censure and were dismissed from their positions at church-governed institutions. But their motivation was to vindicate divine revelation, in Winchell's case from the physical anthropology of human origins and in Smith's from the cultural anthropology of Semitic ritual.

  4. Smith college secondary math and science outreach program

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

    Powell, J.A.; Clark, C.

    1994-12-31

    The Smith College Secondary Math and Science Outreach Program works collaboratively with front-line educators to encourage young women students of all abilities, especially underrepresented and underserved minorities, to continue studying math and science throughout high school. The program includes three main components: (1) Twenty-five to thirty teams of math/science teachers and guidance counselors participate in a year-long program which begins with a three-day Current Students/Future Scientists and Engineering Workshop. This event includes a keynote address, presentations and workshops by successful women in science and engineering, and hands-on laboratory sessions. Each participant receives a stipend and free room and board. Returningmore » to their schools, the teacher-counselor teams implement ongoing plans designed to counteract gender bias in the sciences and to alert female students to the broad range of math, science, and engineering career choices open to them. A follow-up session in the spring allows the teams to present and discuss their year-long activities. (2) TRI-ON, a day of science for 120 ninth- and tenth- grade girls from schools with a large underserved and underrepresented population, is held in early spring. Girls discover the excitement of laboratory investigation and interact with female college science and math majors. (3) Teaching Internships, initiated in 1991, involve ten to fifteen Smith College math and science majors in teaching in public schools. The teaching interns experience the rewards and challenges of classroom teaching, and they also serve as role models for younger students.« less

  5. Calculation of force and power during bench throws using a Smith machine: the importance of considering the effect of counterweights.

    PubMed

    Kobayashi, Y; Narazaki, K; Akagi, R; Nakagaki, K; Kawamori, N; Ohta, K

    2013-09-01

    For achieving accurate and safe measurements of the force and power exerted on a load during resistance exercise, the Smith machine has been used instead of free weights. However, because some Smith machines possess counterweights, the equation for the calculation of force and power in this system should be different from the one used for free weights. The purpose of this investigation was to calculate force and power using an equation derived from a dynamic equation for a Smith machine with counterweights and to determine the differences in force and power calculated using 2 different equations. One equation was established ignoring the effect of the counterweights (Method 1). The other equation was derived from a dynamic equation for a barbell and counterweight system (Method 2). 9 female collegiate judo athletes performed bench throws using a Smith machine with a counterweight at 6 different loading conditions. Barbell displacement was recorded using a linear position transducer. The force and power were subsequently calculated by Methods 1 and 2. The results showed that the mean and peak power and force in Method 1 were significantly lower relative to those of Method 2 under all loading conditions. These results indicate that the mean and peak power and force during bench throwing using a Smith machine with counterweights would be underestimated when the calculations used to determine these parameters do not account for the effect of counterweights. © Georg Thieme Verlag KG Stuttgart · New York.

  6. 76 FR 26767 - Captain John Smith Chesapeake National Historic Trail Advisory Council

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-09

    ... Trail Advisory Council AGENCY: National Park Service, Interior. ACTION: Notice of meeting. SUMMARY: As... that the Advisory Committee on the Captain John Smith Chesapeake National Historic Trail will hold a meeting. Designated through an amendment to the National Trails System Act (16 U.S.C. 1241), the trail...

  7. 76 FR 52691 - Captain John Smith Chesapeake National Historic Trail Advisory Council

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-23

    ... Trail Advisory Council AGENCY: National Park Service, Interior. ACTION: Notice of meeting. SUMMARY: As... that the Advisory Committee on the Captain John Smith Chesapeake National Historic Trail will hold a meeting. Designated through an amendment to the National Trails System Act (16 U.S.C. 1241), the trail...

  8. The Garrett Lee Smith memorial suicide prevention program.

    PubMed

    Goldston, David B; Walrath, Christine M; McKeon, Richard; Puddy, Richard W; Lubell, Keri M; Potter, Lloyd B; Rodi, Michael S

    2010-06-01

    In response to calls for greater efforts to reduce youth suicide, the Garrett Lee Smith (GLS) Memorial Act has provided funding for 68 state, territory, and tribal community grants, and 74 college campus grants for suicide prevention efforts. Suicide prevention activities supported by GLS grantees have included education, training programs (including gatekeeper training), screening activities, infrastructure for improved linkages to services, crisis hotlines, and community partnerships. Through participation in both local- and cross-site evaluations, GLS grantees are generating data regarding the local context, proximal outcomes, and implementation of programs, as well as opportunities for improvement of suicide prevention efforts.

  9. The Garrett Lee Smith Memorial Suicide Prevention Program

    PubMed Central

    Goldston, David B.; Walrath, Christine M.; McKeon, Richard; Puddy, Richard W.; Lubell, Keri M.; Potter, Lloyd B.; Rodi, Michael S.

    2011-01-01

    Responding to calls for greater efforts to reduce youth suicide, the Garrett Lee Smith (GLS) Memorial Act to date has provided funding for 68 state, territory, and tribal community grants, and 74 college campus grants for suicide prevention efforts. Suicide prevention activities supported by GLS grantees have included education, training programs including gatekeeper training, screening activities, infrastructure for improved linkages to services, crisis hotlines, and community partnerships. Through participation in both local- and cross-site evaluations, GLS grantees are generating data regarding the local context, proximal outcomes, and implementation of programs, as well as opportunities for improvement of suicide prevention efforts. PMID:20560746

  10. June 6, 2011 Letter from Shelley Lucas to Stephen Smith and Melissa Waters

    EPA Pesticide Factsheets

    June 6, 2011 Letter from Shelley Lucas to Stephen Smith and Melissa Waters, USEPA, Subject: Response to Information Request Under 92 U.S.C. 9604 to Gannett Co., Inc., Dated March 24, 2011, Regarding Capitol City Plume Site, Montgomery, AL

  11. 26. The StillwellBierce and SmithVaile Company, Dayton, Ohio, 13 April ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    26. The Stillwell-Bierce and Smith-Vaile Company, Dayton, Ohio, 13 April 1904 ELEVATION AND CUTAWAY DRAWINGS OF A TURBINE-GENERATOR UNIT IDENTICAL TO UNITS 4 AND 5 - Washington Water Power Company Monroe Street Plant, Units 4 & 5, South Bank Spokane River, below Monroe Street Bridge, Spokane, Spokane County, WA

  12. Sally L. Smith: A Genius at Seeing the Potential in People

    ERIC Educational Resources Information Center

    Edgerton, Mary Allen

    2010-01-01

    What this author admired most about Sally Smith was the fact that she was a visionary about people and what they could accomplish. She saw more potential in a person--young or old--than anybody or even they themselves, frankly, had ever even considered possible. She was a genius at seeing the potential in people, expecting them to find it in…

  13. CUDA compatible GPU cards as efficient hardware accelerators for Smith-Waterman sequence alignment

    PubMed Central

    Manavski, Svetlin A; Valle, Giorgio

    2008-01-01

    Background Searching for similarities in protein and DNA databases has become a routine procedure in Molecular Biology. The Smith-Waterman algorithm has been available for more than 25 years. It is based on a dynamic programming approach that explores all the possible alignments between two sequences; as a result it returns the optimal local alignment. Unfortunately, the computational cost is very high, requiring a number of operations proportional to the product of the length of two sequences. Furthermore, the exponential growth of protein and DNA databases makes the Smith-Waterman algorithm unrealistic for searching similarities in large sets of sequences. For these reasons heuristic approaches such as those implemented in FASTA and BLAST tend to be preferred, allowing faster execution times at the cost of reduced sensitivity. The main motivation of our work is to exploit the huge computational power of commonly available graphic cards, to develop high performance solutions for sequence alignment. Results In this paper we present what we believe is the fastest solution of the exact Smith-Waterman algorithm running on commodity hardware. It is implemented in the recently released CUDA programming environment by NVidia. CUDA allows direct access to the hardware primitives of the last-generation Graphics Processing Units (GPU) G80. Speeds of more than 3.5 GCUPS (Giga Cell Updates Per Second) are achieved on a workstation running two GeForce 8800 GTX. Exhaustive tests have been done to compare our implementation to SSEARCH and BLAST, running on a 3 GHz Intel Pentium IV processor. Our solution was also compared to a recently published GPU implementation and to a Single Instruction Multiple Data (SIMD) solution. These tests show that our implementation performs from 2 to 30 times faster than any other previous attempt available on commodity hardware. Conclusions The results show that graphic cards are now sufficiently advanced to be used as efficient hardware

  14. Hydrogeochemical and stream sediment reconnaissance basic data for Philip Smith Mountains Quadrangle, Alaska

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

    Not Available

    1981-05-29

    Field and laboratory data are presented for 1128 water samples from the Philip Smith Mountains Quadrangle, Alaska. The samples were collected by Los Alamos Scientific Laboratory; laboratory analysis and data reporting were performed by the Uranium Resource Evaluation Project at Oak Ridge, Tennessee.

  15. Investigation on the special Smith-Purcell radiation from a nano-scale rectangular metallic grating

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

    Li, Weiwei; Liu, Weihao, E-mail: liuwhao@ustc.edu.cn; Jia, Qika

    The special Smith-Purcell radiation (S-SPR), which is from the radiating eigen modes of a grating, has remarkable higher intensity than the ordinary Smith-Purcell radiation. Yet in previous studies, the gratings were treated as perfect conductor without considering the surface plasmon polaritons (SPPs) which are of significance for the nano-scale gratings especially in the optical region. In present paper, the rigorous theoretical investigations on the S-SPR from a nano-grating with SPPs taken into consideration are carried out. The dispersion relations and radiation characteristics are obtained, and the results are verified by simulations. According to the analyses, the tunable light radiation canmore » be achieved by the S-SPR from a nano-grating, which offers a new prospect for developing the nano-scale light sources.« less

  16. Ground Reaction Force and Mechanical Differences Between the Interim Resistive Exercise Device (iRED) and Smith Machine While Performing a Squat

    NASA Technical Reports Server (NTRS)

    Amonette, William E.; Bentley, Jason R.; Lee, Stuart M. C.; Loehr, James A.; Schneider, Suzanne

    2004-01-01

    Musculoskeletal unloading in microgravity has been shown to induce losses in bone mineral density, muscle cross-sectional area, and muscle strength. Currently, an Interim Resistive Exercise Device (iRED) is being flown on board the ISS to help counteract these losses. Free weight training has shown successful positive musculoskeletal adaptations. In biomechanical research, ground reaction forces (GRF) trajectories are used to define differences between exercise devices. The purpose of this evaluation is to quantify the differences in GRF between the iRED and free weight exercise performed on a Smith machine during a squat. Due to the differences in resistance properties, inertial loading and load application to the body between the two devices, we hypothesize that subjects using iRED will produce GRF that are significantly different from the Smith machine. There will be differences in bar/harness range of motion and the time when peak GRF occurred in the ROMbar. Three male subjects performed three sets of ten squats on the iRED and on the Smith Machine on two separate days at a 2-second cadence. Statistically significant differences were found between the two devices in all measured GRF variables. Average Fz and Fx during the Smith machine squat were significantly higher than iRED. Average Fy (16.82 plus or minus.23; p less than .043) was significantly lower during the Smith machine squat. The mean descent/ascent ratio of the magnitude of the resultant force vector of all three axes for the Smith machine and iRED was 0.95 and 0.72, respectively. Also, the point at which maximum Fz occurred in the range of motion (Dzpeak) was at different locations with the two devices.

  17. 78 FR 15747 - Charlissa C. Smith (Denial of Senior Reactor Operator License)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-12

    ... NUCLEAR REGULATORY COMMISSION [Docket No. 55-23694-SP; ASLBP No. 13-925-01-SP-BD01] Charlissa C... Reconstitution Pursuant to 10 CFR 2.313(c) and 2.321(b), the Atomic Safety and Licensing Board (Board) in the above-captioned Charlissa C. Smith case is hereby reconstituted because Administrative Judge Alan S...

  18. Birth of the first ESS: George Price, John Maynard Smith, and the discovery of the lost "Antlers" paper.

    PubMed

    Harman, Oren

    2011-01-15

    The application of game theory to evolutionary problems is so commonplace today, that few stop to consider how it all began. John Maynard Smith and George R. Price's 1973 Nature article, "The Logic of Animal Conflict," is often referred to as the first description in the literature of the concept of an evolutionary stable strategy (ESS), but what was the "behind the scenes" of the writing of that seminal paper? This article tracks the little known story of the curious American polymath, George Price. As will be shown, it was an earlier paper, the lost "Antlers, Intraspecific Combat, and Altruism," sent by Price to Nature in August 1968 (Unpublished), and refereed by Maynard Smith, which instigated the birth of the first ESS. Recently, the "Antlers" paper has been re-discovered by the author, shedding new light, together with letters and journals from the personal papers of George Price and John Maynard Smith, on their historical paper. © 2010 Wiley-Liss, Inc.

  19. Monogenean parasites from fishes of the Vaal Dam, Gauteng Province, South Africa. I. Winter survey versus summer survey comparison from Labeo capensis (Smith, 1841) and Labeo umbratus (Smith, 1841) hosts.

    PubMed

    Crafford, Dionne; Luus-Powell, Wilmien; Avenant-Oldewage, Annemariè

    2014-03-01

    Indigenous South African Labeo spp. show promise with regard to development of semi-intensive aquaculture, yet little research on their monogenean fauna has been conducted. Ecological aspects of monogenean fauna of the moggel Labeo umbratus (Smith 1841) and the Orange River mudfish Labeo capensis (Smith 1841), as recorded during both winter and summer sampling surveys, are reported here. Fish were collected using gill nets, euthanized and gills removed and examined to both quantify parasite numbers and distribution on the gills. Results obtained support the hypothesis that gill site preference is not due to active choice for a particular attachment site, but rather a result of water flow over gills during respiration in conjunction with fish behaviour and habitat use. Interaction between individual elements investigated (temperature effects, parasite population dynamics and host population dynamics) may be largely responsible for seasonal differences in infection statistics of monogenean parasites. Such interactions should be investigated in future large scale ecological studies, in combination with experimental studies, to further elucidate these effects.

  20. STS-110 M.S. Smith suits up for TCDT

    NASA Technical Reports Server (NTRS)

    2002-01-01

    KENNEDY SPACE CENTER, FLA. -- STS-110 Mission Specialist Steven Smith relaxes during suit fit, which is part of Terminal Countdown Demonstration Test activities. The TCDT is held at KSC prior to each Space Shuttle flight to provide flight crews an opportunity to participate in simulated launch countdown activities. Scheduled for launch April 4, the 11-day mission will feature Shuttle Atlantis docking with the International Space Station (ISS) and delivering the S0 truss, the centerpiece-segment of the primary truss structure that will eventually extend over 300 feet.

  1. Coherent Terahertz Smith Purcell radiation from beam bunching

    NASA Astrophysics Data System (ADS)

    Shi, Zongjun; Yang, Ziqiang; Liang, Zheng; Lan, Feng; Liu, Wenxin; Gao, Xi; Li, D.

    2007-08-01

    This paper presents a possible method to produce beam bunching and obtain coherent Terahertz (THz) Smith-Purcell (SP) radiation. A model of two-section rectangular grating is proposed. In the first section with a flat conducting roof, a continuous beam is bunched by using an 88.5 GHz input signal. In the second section without metal roof, the coherent THz SP radiation is stimulated by the bunched beam interacting with the grating. The particle-in-cell (PIC) simulations show that the beam is bunched at the downstream of the first section. The strongest radiation is observed at 120° with the frequency of 266.5 GHz in the second section.

  2. 36th Annual David W. Smith Workshop on Malformations and Morphogenesis: Abstracts of the 2015 annual meeting.

    PubMed

    Gripp, Karen W; Adam, Margaret P; Hudgins, Louanne; Carey, John C

    2016-07-01

    The 36th Annual David W Smith Workshop on Malformations and Morphogenesis was held on August 14-19, 2015 at the Harbourtowne Conference Center in St. Michaels Maryland. The Workshop, which honors the legacy of David W Smith, brought together over 120 clinicians and researchers interested in congenital malformations and their underlying mechanisms of morphogenesis. As is the tradition of the meeting, the Workshop highlighted five themes besides mechanisms of morphogenesis: Rasopathies, Eye Malformations, Therapeutics, Prenatal Diagnosis, and Disorders of Sex Development. This Conference Report includes the abstracts presented at the 2015 Workshop. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  3. The Giant Resin Bee, Megachile sculpturalis Smith: New Distributional Records for the Mid- and Gulf-south USA

    PubMed Central

    Tripodi, Amber D.; Sampson, Blair J.

    2015-01-01

    Abstract Background Megachile (Callomegachile) sculpturalis Smith, the giant resin bee, is an adventive species in the United States. First established in the United States during the early 1990s, records currently exist from most states east of the Mississippi River along with Iowa and Kansas. New information New distributional records are presented for Megachile (Callomegachile) sculpturalis Smith, an introduced bee. Additional records presented here expand the known distribution southwest through Arkansas, Louisiana, Mississippi, Missouri, and Texas. An updated host plant list containing new records is also presented, expanding the number of known floral associations. PMID:26696766

  4. How Smith Cleared the Way for More Transfer Students from a Community College.

    ERIC Educational Resources Information Center

    Geraghty, Mary

    1997-01-01

    Smith College (Massachusetts) has established formal articulation agreements with Santa Monica College (California) and Miami-Dade Community College (Florida) to grant credit to community college students transferring to the private college. Vassar College (New York) is another private liberal arts college seeking more community college transfer…

  5. Differences in Social Motivation in Children with Smith-Magenis Syndrome and Down Syndrome

    ERIC Educational Resources Information Center

    Wilde, Lucy; Mitchell, Anna; Oliver, Chris

    2016-01-01

    Social excesses, characterised by heightened social motivation, are important for describing social functioning. Smith-Magenis syndrome (SMS) is a potential exemplar of a disorder where heightened social motivation is associated with negative behavioural outcomes. In Down syndrome (DS) strong social motivation is described, but less commonly…

  6. Immunogenicity and safety of an inactivated quadrivalent influenza vaccine co-administered with a 23-valent pneumococcal polysaccharide vaccine versus separate administration, in adults ≥50years of age: Results from a phase III, randomized, non-inferiority trial.

    PubMed

    Ofori-Anyinam, Opokua; Leroux-Roels, Geert; Drame, Mamadou; Aerssens, Annelies; Maes, Cathy; Amanullah, Arshad; Schuind, Anne; Li, Ping; Jain, Varsha K; Innis, Bruce L

    2017-11-01

    . Co-administration of PPV23 at the annual influenza vaccination visit may improve uptake. Comorbidities had no impact on IIV4 immunogenicity, supporting its value in older adults with chronic medical conditions. Clinical Trial Registry Number: NCT02218697. Copyright © 2017 GlaxoSmithKline SA. Published by Elsevier Ltd.. All rights reserved.

  7. Mepolizumab treatment in patients with severe eosinophilic asthma.

    PubMed

    Ortega, Hector G; Liu, Mark C; Pavord, Ian D; Brusselle, Guy G; FitzGerald, J Mark; Chetta, Alfredo; Humbert, Marc; Katz, Lynn E; Keene, Oliver N; Yancey, Steven W; Chanez, Pascal

    2014-09-25

    .44 points greater in the two mepolizumab groups, respectively, than in the placebo group (minimal clinically important change, 0.5 points) (P<0.001 for all comparisons). The safety profile of mepolizumab was similar to that of placebo. Mepolizumab administered either intravenously or subcutaneously significantly reduced asthma exacerbations and was associated with improvements in markers of asthma control. (Funded by GlaxoSmithKline; MENSA ClinicalTrials.gov number, NCT01691521.).

  8. Public health impact of Rotarix vaccination among commercially insured children in the United States.

    PubMed

    Krishnarajah, Girishanthy; Kageleiry, Andrew; Korves, Caroline; Lefebvre, Patrick; Duh, Mei S

    2017-09-05

    %CI: $9855-$12,024) and $46,772 (95%CI: $26,268-$66,604) lower, respectively, for completely vaccinated children. RV1 vaccination confers benefits in reduction of RV incidence, RV- and diarrhea-related healthcare resource utilization, and RV- and diarrhea-related healthcare costs. Copyright © 2017 GlaxoSmithKline. Published by Elsevier Ltd.. All rights reserved.

  9. Vaccine-Derived NSP2 Segment in Rotaviruses from Vaccinated Children with Gastroenteritis in Nicaragua

    PubMed Central

    Bucardo, Filemón; Rippinger, Christine M.; Svensson, Lennart; Patton, John T.

    2012-01-01

    Rotavirus (RV) vaccination programs have been established in several countries using the human-attenuated G1P[8] monovalent vaccine Rotarix™ (GlaxoSmithKline) and/or the human-bovine reassortant G1, G2, G3, G4, P[8] pentavalent vaccine RotaTeq™ (Merck). The efficacy of both vaccines is high (~90%) in developed countries, but can be remarkably lower in developing countries. For example, a vaccine efficacy against severe diarrhea of only 58% was observed in a 2007–2009 Nicaraguan study using RotaTeq. To gain insight into the significant level of vaccine failure in this country, we sequenced the genomes of RVs recovered from vaccinated Nicaraguan children with gastroenteritis. The results revealed that all had genotype specificities typical for human RVs (11 G1P[8], 1 G3P[8]) and that the sequences and antigenic epitopes of the outer capsid proteins (VP4 and VP7) of these viruses were similar to those reported for RVs isolated elsewhere in the world. As expected, nine of the G1P[8] viruses and the single G3P[8] virus had genome constellations typical of human G1P[8] and G3P[8] RVs: G1/3-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1. However, two of the G1P[8] viruses had atypical constellations, G1-P[8]-I1-R1-C1-M1-A1-N2-T1-E1-H1, due to the presence of a genotype-2 NSP2 (N2) gene. The sequence of the N2 NSP2 gene was identical to the bovine N2 NSP2 gene of RotaTeq, indicating that the two atypical viruses originated via reassortment of human G1P[8] RVs with RotaTeq viruses. Together, our data suggest that the high level of vaccine failure in Nicaraguan is probably not due to antigenic drift of commonly circulating virus strains nor the emergence of new antigenetically distinct virus strains. Furthermore, our data suggests that the widespread use of the RotaTeq vaccine has led to the introduction of vaccine genes into circulating human RVs. PMID:22487061

  10. Adjuvant Dabrafenib plus Trametinib in Stage III BRAF-Mutated Melanoma.

    PubMed

    Long, Georgina V; Hauschild, Axel; Santinami, Mario; Atkinson, Victoria; Mandalà, Mario; Chiarion-Sileni, Vanna; Larkin, James; Nyakas, Marta; Dutriaux, Caroline; Haydon, Andrew; Robert, Caroline; Mortier, Laurent; Schachter, Jacob; Schadendorf, Dirk; Lesimple, Thierry; Plummer, Ruth; Ji, Ran; Zhang, Pingkuan; Mookerjee, Bijoyesh; Legos, Jeff; Kefford, Richard; Dummer, Reinhard; Kirkwood, John M

    2017-11-09

    Combination therapy with the BRAF inhibitor dabrafenib plus the MEK inhibitor trametinib improved survival in patients with advanced melanoma with BRAF V600 mutations. We sought to determine whether adjuvant dabrafenib plus trametinib would improve outcomes in patients with resected, stage III melanoma with BRAF V600 mutations. In this double-blind, placebo-controlled, phase 3 trial, we randomly assigned 870 patients with completely resected, stage III melanoma with BRAF V600E or V600K mutations to receive oral dabrafenib at a dose of 150 mg twice daily plus trametinib at a dose of 2 mg once daily (combination therapy, 438 patients) or two matched placebo tablets (432 patients) for 12 months. The primary end point was relapse-free survival. Secondary end points included overall survival, distant metastasis-free survival, freedom from relapse, and safety. At a median follow-up of 2.8 years, the estimated 3-year rate of relapse-free survival was 58% in the combination-therapy group and 39% in the placebo group (hazard ratio for relapse or death, 0.47; 95% confidence interval [CI], 0.39 to 0.58; P<0.001). The 3-year overall survival rate was 86% in the combination-therapy group and 77% in the placebo group (hazard ratio for death, 0.57; 95% CI, 0.42 to 0.79; P=0.0006), but this level of improvement did not cross the prespecified interim analysis boundary of P=0.000019. Rates of distant metastasis-free survival and freedom from relapse were also higher in the combination-therapy group than in the placebo group. The safety profile of dabrafenib plus trametinib was consistent with that observed with the combination in patients with metastatic melanoma. Adjuvant use of combination therapy with dabrafenib plus trametinib resulted in a significantly lower risk of recurrence in patients with stage III melanoma with BRAF V600E or V600K mutations than the adjuvant use of placebo and was not associated with new toxic effects. (Funded by GlaxoSmithKline and Novartis; COMBI

  11. Meta-analysis of suicidality in placebo-controlled clinical trials of adults taking bupropion.

    PubMed

    Wightman, Donna S; Foster, Vicki J; Krishen, Alok; Richard, Nathalie E; Modell, Jack G

    2010-01-01

    To assess a possible relationship between treatment with bupropion (vs placebo) and expressed suicidal ideation and behavior. This analysis, based on the US Food and Drug Administration's (FDA's) analysis of antidepressant suicidality data, included 8,953 adult subjects receiving bupropion and 6,520 adult subjects receiving placebo from randomized, placebo-controlled trials with bupropion conducted between 1976 and 2006 across multiple indications, including major depressive disorder (MDD). A text string search of the adverse event database and case report form comments was performed to identify potential suicidal events. FDA search criteria included the following text strings: accident-, injur-, suic-, or overdos-, including all events coded as accidental overdose, attempt, cut, gas, hang, hung, jump, mutilat-, self damag-, self harm, self inflict-, shoot, slash, poison, asphyxiation, suffocation, firearm, burn, drown, gun, immolat-, and monoxide, and the following terms were added by GlaxoSmithKline to the search criteria: accident, lacerat-, MVA, and hospital. The database search included data beginning from the first dose of study medication through 1 day following the last dose. Suicidal event narratives were classified using the Columbia Classification Algorithm for Suicide Assessment. Additionally, changes on rating scale items for depressed mood and suicidality were analyzed. In the MDD population, the incidence of suicidal behavior or ideation was 17/3,179 (0.53%) versus 11/2,310 (0.48%) for the bupropion and placebo groups, respectively (OR = 1.28; 95% CI, 0.59-2.86). For suicidal behavior, the incidence was 8/3,179 (0.25%) versus 2/2,310 (0.09%), respectively (OR = 3.52; 95% CI, 0.81-24.48). No suicidal behavior event was noted in the other indications, and no completed suicides were reported during treatment. No significant worsening was observed for bupropion relative to placebo on the rating scale items. No differential treatment effects were observed

  12. The responses of Aboriginal Canadians to adjuvanted pandemic (H1N1) 2009 influenza vaccine

    PubMed Central

    Rubinstein, Ethan; Predy, Gerald; Sauvé, Laura; Hammond, Greg W.; Aoki, Fred; Sikora, Chris; Li, Yan; Law, Barbara; Halperin, Scott; Scheifele, David

    2011-01-01

    Background: Because many Aboriginal Canadians had severe cases of pandemic (H1N1) 2009 influenza, they were given priority access to vaccine. However, it was not known if the single recommended dose would adequately protect people at high risk, prompting our study to assess responses to the vaccine among Aboriginal Canadians. Methods: We enrolled First Nations and Métis adults aged 20–59 years in our prospective cohort study. Participants were given one 0.5-mL dose of ASO3-adjuvanted pandemic (H1N1) 2009 vaccine (Arepanrix, GlaxoSmithKline Canada). Blood samples were taken at baseline and 21–28 days after vaccination. Paired sera were tested for hemagglutination-inhibiting antibodies at a reference laboratory. To assess vaccine safety, we monitored the injection site symptoms of each participant for seven days. We also monitored patients for general symptoms within 7 days of vaccination and any use of the health care system for 21–28 days after vaccination. Results: We enrolled 138 participants in the study (95 First Nations, 43 Métis), 137 of whom provided all safety data and 136 of whom provided both blood samples. First Nations and Métis participants had similar characteristics, including high rates of chronic health conditions (74.4%–76.8%). Pre-existing antibody to the virus was detected in 34.3% of the participants, all of whom boosted strongly with vaccination (seroprotection rate [titre ≥ 40] 100%, geometric mean titre 531–667). Particpants with no pre-existing antibody also responded well. Fifty-eight of 59 (98.3%) First Nations participants showed seroprotection and a geometric mean titre of 353.6; all 30 Métis participants with no pre-existing antibody showed seroprotection and a geometric mean titre of 376.2. Pain at the injection site and general symptoms frequently occurred but were short-lived and generally not severe, although three participants (2.2%) sought medical attention for general symptoms. Interpretation: First Nations and

  13. Immunogenicity and safety of the quadrivalent meningococcal ACWY-tetanus toxoid conjugate vaccine (MenACWY-TT) in splenectomized or hyposplenic children and adolescents: Results of a phase III, open, non-randomized study.

    PubMed

    Klein, Nicola P; Habanec, Tomas; Kosina, Pavel; Shah, Nirmish R; Kolhe, Devayani; Miller, Jacqueline M; Hezareh, Marjan; Van der Wielen, Marie

    2018-04-19

    acceptable safety profile in children and adolescents with impaired splenic activity and in healthy controls. Copyright © 2018 GlaxoSmithKline Biologicals SA. Published by Elsevier Ltd.. All rights reserved.

  14. Long-Term Safety and Efficacy of Belimumab in Patients With Systemic Lupus Erythematosus: A Continuation of a Seventy-Six-Week Phase III Parent Study in the United States.

    PubMed

    Furie, Richard A; Wallace, Daniel J; Aranow, Cynthia; Fettiplace, James; Wilson, Barbara; Mistry, Prafull; Roth, David A; Gordon, David

    2018-06-01

    We undertook this US multicenter continuation study (GlaxoSmithKline study BEL112233; ClinicalTrials.gov identifier: NCT00724867) to assess long-term safety and efficacy of belimumab in patients with systemic lupus erythematosus (SLE) who completed the Study of Belimumab in Subjects with SLE 76-week trial (ClinicalTrials.gov identifier: NCT00410384). Patients continued to receive the same belimumab dose plus standard therapy; patients previously receiving placebo received 10 mg/kg belimumab. The primary outcome measure was long-term safety of belimumab (frequency of adverse events [AEs] and damage assessed using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index [SDI], evaluated every 48 weeks [1 study year]). Other assessments included the SLE Responder Index (SRI), flare rates (using the modified SLE Flare Index [SFI]), prednisone use, and B cell levels. Of 268 patients, 140 completed the study and 128 withdrew. The mean ± SD score on the Safety of Estrogens in Lupus Erythematosus National Assessment version of the SLE Disease Activity Index (SELENA-SLEDAI) at baseline was 7.8 ± 3.86. The mean ± SD SDI score increased by 0.4 ± 0.68 from its value at baseline (1.2 ± 1.51). The overall incidence of treatment-related and serious AEs remained stable or declined through study year 7. An SRI response was achieved by 41.9% and 75.6% of patients at the study year 1 and study year 7 midpoints, respectively. At the study year 7 midpoint, relative to baseline, 78.2% had achieved a ≥4-point reduction in the SELENA-SLEDAI score, 98.4% had no new British Isles Lupus Assessment Group (BILAG) A organ domain score and no more than 1 new BILAG B organ domain score, 93.7% had no worsening in the physician's global assessment of disease activity, 20.6% had experienced ≥1 severe SFI flare, the mean decrease in prednisone dose was 31.4%, and the median change in CD20+ B cell numbers was -83.2%. These long-term exposure results

  15. Effectiveness of Pandemic and Seasonal Influenza Vaccines in Preventing Laboratory-Confirmed Influenza in Adults: A Clinical Cohort Study during Epidemic Seasons 2009–2010 and 2010–2011 in Finland

    PubMed Central

    Syrjänen, Ritva K.; Jokinen, Jukka; Ziegler, Thedi; Sundman, Jonas; Lahdenkari, Mika; Julkunen, Ilkka; Kilpi, Terhi M.

    2014-01-01

    Background One dose of pandemic influenza vaccine Pandemrix (GlaxoSmithKline) was offered to the entire population of Finland in 2009–10. We conducted a prospective clinical cohort study to determine the vaccine effectiveness in preventing febrile laboratory-confirmed influenza infection during the influenza season 2009–10 and continued the study in 2010–11. Methods In total, 3,518 community dwelling adults aged 18–75 years living in Tampere city were enrolled. The participants were not assigned to any vaccination regimen, but they could participate in the study regardless of their vaccination status or intention to be vaccinated with the pandemic or seasonal influenza vaccine. They were asked to report if they received Pandemrix in 2009–10 and/or trivalent influenza vaccine in 2010–11. Vaccinations were verified from medical records. The participants were instructed to report all acute symptoms of respiratory tract infection with fever (at least 38°C) and pneumonias to the study staff. Nasal and oral swabs were obtained within 5–7 days after symptom onset and influenza-specific RNA was identified by reverse transcription polymerase chain reaction. Results In 2009–10, the estimated vaccine effectiveness was 81% (95%CI 30–97). However, the vaccine effectiveness could not be estimated reliably, because only persons in prioritized groups were vaccinated before/during the first pandemic wave and many participants were enrolled when they already had the symptoms of A(H1N1)pdm09 influenza infection. In 2010–11, 2,276 participants continued the follow-up. The vaccine effectiveness, adjusted for potential confounding factors was 81% (95%CI 41–96) for Pandemrix only and 88% (95%CI 63–97) for either Pandemrix or trivalent influenza vaccine 2010–11 or both, respectively. Conclusion Vaccination with an AS03-adjuvanted pandemic vaccine in 2009–10 was still effective in preventing A(H1N1)pdm09 influenza during the following epidemic season in 2010

  16. A novel omega-3 free fatty acid formulation has dramatically improved bioavailability during a low-fat diet compared with omega-3-acid ethyl esters: the ECLIPSE (Epanova(®) compared to Lovaza(®) in a pharmacokinetic single-dose evaluation) study.

    PubMed

    Davidson, Michael H; Johnson, Judith; Rooney, Michael W; Kyle, Michael L; Kling, Douglas F

    2012-01-01

    Omega-3 (OM-3) fatty acid products are indicated for the treatment of severe hypertriglyceridemia; however, the omega-3-acid ethyl ester (OM-3 EE) formulations require significant pancreatic lipase stimulation with high-fat meals for adequate intestinal absorption of the metabolites eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). A novel omega-3 free fatty acid (OM-3 FFA) formulation (Epanova(®), Omthera Pharmaceuticals Inc., Princeton, NJ) was developed to maximize EPA and DHA bioavailability during a low-fat diet. To compare the relative bioavailability of EPA and DHA from single 4-gram doses of OM-3 FFA and a prescription OM-3 EE (Lovaza(®), GlaxoSmithKline, Research Triangle Park, NC). This was a randomized, open-label, single dose, 4-way crossover, bioavailability study of OM-3 FFA and OM-3 EE administered during periods of low-fat and high-fat consumption to 54 overweight adults. Bioavailability was determined by the ln-transformed area under the plasma concentration versus time curve (AUC(0-t)) during a 24-hour interval for EPA and DHA (baseline-adjusted). The baseline-adjusted AUC(0-t) for total EPA + DHA during the low-fat period was 4.0-fold greater with OM-3 FFA compared with OM-3 EE (2650.2 vs 662.0 nmol·h/mL, respectively; P < .0001). During the high-fat period, AUC(0-t) for OM-3 FFA was approximately 1.3-fold greater than OM-3 EE (P < .0001). During the low-fat period, 30 of 51 (58.8%) subjects dosed with OM-3 FFA maintained an AUC(0-t) that was ≥50% of the respective high-fat AUC(0-t) in contrast to only 3 of 50 (6.0%) subjects dosed with OM-3 EE. During a low-fat consumption period, the OM-3 FFA formulation provided dramatically improved bioavailability over the OM-3 EE formulation in overweight subjects. These findings offer a potential therapeutic advantage of the OM-3 FFA formulation for the treatment of severe hypertriglyceridemia as these patients are expected to adhere to a low-fat diet. Copyright © 2012 National Lipid

  17. Does industry-sponsored education foster overdiagnosis and overtreatment of depression, osteoporosis and over-active bladder syndrome? An Australian cohort study.

    PubMed

    Mintzes, Barbara; Swandari, Swestika; Fabbri, Alice; Grundy, Quinn; Moynihan, Ray; Bero, Lisa

    2018-02-13

    To investigate patterns of industry-sponsored educational events that focus on specific health conditions for which there are concerns about overdiagnosis and overtreatment. This retrospective cohort study examines publicly reported industry-sponsored events in Australia from October 2011 to September 2015 for three conditions potentially subject to overdiagnosis and overtreatment: depression, osteoporosis and overactive bladder. We used a database of transparency reports to identify events with a focus on depression, osteoporosis and overactive bladder and compared these with other sponsored events. We hypothesised that companies marketing treatments for each condition would sponsor related events and that target audiences would mainly work in primary care, reflecting a broad patient population. Event and attendee characteristics, sponsoring companies, related marketed treatments, cost-effectiveness ratings and dispensing rates. Over the study period, we identified 1567 events focusing on depression, 1375 on osteoporosis and 190 on overactive bladder (total n=3132, with 96 660 attendees). These events were attended by primary care doctors more often than sponsored events without a focus on these three conditions: relative risk (RR)=3.06 (95% CI 2.81 to 3.32) for depression, RR=1.48 (95% CI 1.41 to 1.55) for osteoporosis and RR=2.59 (95% CI 2.09 to 3.21) for overactive bladder. Servier, which markets agomelatine and AstraZeneca (quetiapine) sponsored 51.2% and 23.0% of depression events, respectively. Amgen and GlaxoSmithKline, which co-market denosumab, sponsored 49.5% of osteoporosis events and Astellas and Commonwealth Serum Laboratories (CSL) (mirabegron and solifenacin) sponsored 80.5% of overactive bladder events. This 4-year overview of industry-sponsored events on three overdiagnosed and overtreated conditions found that primary care clinicians were often targeted, dinner was often provided and that a few companies sponsored most events. In most cases

  18. C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality: an individual participant meta-analysis.

    PubMed

    Kaptoge, Stephen; Di Angelantonio, Emanuele; Lowe, Gordon; Pepys, Mark B; Thompson, Simon G; Collins, Rory; Danesh, John

    2010-01-09

    Heart Foundation, UK Medical Research Council, BUPA Foundation, and GlaxoSmithKline. Copyright 2010 Elsevier Ltd. All rights reserved.

  19. Immunogenicity and safety of the quadrivalent meningococcal vaccine MenACWY-TT co-administered with a combined diphtheria-tetanus-acellular pertussis vaccine versus their separate administration in adolescents and young adults: A phase III, randomized study.

    PubMed

    Rivera, Luis; Schwarz, Tino F; Kim, Kyung-Hyo; Kim, Yun-Kyung; Behre, Ulrich; Cha, Sung-Ho; Jo, Dae Sun; Lee, Jacob; Lee, Jin-Soo; Cheuvart, Brigitte; Jastorff, Archana; Van der Wielen, Marie

    2018-06-27

    concentrations observed against the pertussis components may be of limited clinical relevance since robust anti-pertussis booster responses were observed. This study supports concurrent administration of the 2 vaccines in adolescents. Copyright © 2018 GlaxoSmithKline Biologicals SA. Published by Elsevier Ltd.. All rights reserved.

  20. Gene therapy in rare diseases: the benefits and challenges of developing a patient-centric registry for Strimvelis in ADA-SCID.

    PubMed

    Stirnadel-Farrant, Heide; Kudari, Mahesh; Garman, Nadia; Imrie, Jessica; Chopra, Bikramjit; Giannelli, Stefania; Gabaldo, Michela; Corti, Ambra; Zancan, Stefano; Aiuti, Alessandro; Cicalese, Maria Pia; Batta, Rohit; Appleby, Jonathan; Davinelli, Mario; Ng, Pauline

    2018-04-06

    Strimvelis (autologous CD34+ cells transduced to express adenosine deaminase [ADA]) is the first ex vivo stem cell gene therapy approved by the European Medicines Agency (EMA), indicated as a single treatment for patients with ADA-severe combined immunodeficiency (ADA-SCID) who lack a suitable matched related bone marrow donor. Existing primary immunodeficiency registries are tailored to transplantation outcomes and do not capture the breadth of safety and efficacy endpoints required by the EMA for the long-term monitoring of gene therapies. Furthermore, for extended monitoring of Strimvelis, the young age of children treated, small patient numbers, and broad geographic distribution of patients all increase the risk of loss to follow-up before sufficient data have been collected. Establishing individual investigator sites would be impractical and uneconomical owing to the small number of patients from each location receiving Strimvelis. An observational registry has been established to monitor the safety and effectiveness of Strimvelis in up to 50 patients over a minimum of 15 years. To address the potential challenges highlighted above, data will be collected by a single investigator site at Ospedale San Raffaele (OSR), Milan, Italy, and entered into the registry via a central electronic platform. Patients/families and the patient's local physician will also be able to submit healthcare information directly to the registry using a uniquely designed electronic platform. Data entry will be monitored by a Gene Therapy Registry Centre (funded by GlaxoSmithKline) who will ensure that necessary information is collected and flows between OSR, the patient/family and the patient's local healthcare provider. The Strimvelis registry sets a precedent for the safety monitoring of future gene therapies. A unique, patient-focused design has been implemented to address the challenges of long-term follow-up of patients treated with gene therapy for a rare disease. Strategies to

  1. Immunogenicity and reactogenicity of a decennial booster dose of a combined reduced-antigen-content diphtheria-tetanus-acellular pertussis and inactivated poliovirus booster vaccine (dTpa-IPV) in healthy adults.

    PubMed

    Kovac, Martina; Rathi, Niraj; Kuriyakose, Sherine; Hardt, Karin; Schwarz, Tino F

    2015-05-21

    Pertussis in adults and adolescents could be reduced by replacing traditional tetanus and diphtheria (Td) boosters with reduced-antigen-content diphtheria-tetanus-acellular pertussis (dTpa) vaccines. This study evaluated the administration of dTpa-IPV (dTpa-inactivated poliovirus) in adults ten years after they received a booster dose of either dTpa-IPV, dTpa+IPV or Td-IPV in trial NCT01277705. Open multicentre, phase IV study (www.clinicaltrials.govNCT01323959) in which healthy adults, who had received a previous dose of dTpa-IPV, dTpa+IPV or Td-IPV ten years earlier, received a single decennial booster dose of dTpa-IPV (Boostrix-polio, GlaxoSmithKline Vaccines). Blood samples were collected before and one month after booster vaccination. Antibody concentrations against all vaccine antigens were measured and reactogenicity and safety were assessed. A total of 211 subjects (mean age 50.3 years) received vaccination of whom 201 were included in the according-to-protocol cohort for immunogenicity. Before the decennial dTpa-IPV booster, ≥71.0% subjects were seroprotected/seropositive against all vaccine antigens. One month after the booster dose, all subjects were seroprotected against tetanus and poliovirus types 2 and 3; ≥95.7% subjects were seroprotected against diphtheria and ≥98.3% against poliovirus type 1. Anti-pertussis booster responses for the various antigens were observed in ≥76.5% (pertussis toxoid; PT), ≥85.1% (filamentous haemagglutinin; FHA) and ≥63.2% (pertactin; PRN) of subjects. During the 4-day follow-up, the overall incidence of local AEs was 71.6%, 75.0% and 72.2% in dTpa-IPV, dTpa+IPV and Td-IPV groups, respectively. Pain was the most frequent solicited local adverse event (AE; ≥62.7% subjects) and fatigue the most frequent solicited general AE (≥18.5%). No serious AEs were reported during the study. A booster dose of dTpa-IPV was immunogenic and well tolerated in adults who had received a booster dose of either dTpa-IPV, d

  2. HER2-positive male breast cancer: an update

    PubMed Central

    Ottini, Laura; Capalbo, Carlo; Rizzolo, Piera; Silvestri, Valentina; Bronte, Giuseppe; Rizzo, Sergio; Russo, Antonio

    2010-01-01

    Although rare, male breast cancer (MBC) remains a substantial cause for morbidity and mortality in men. Based on age frequency distribution, age-specific incidence rate pattern, and prognostic factor profiles, MBC is considered similar to postmenopausal breast cancer (BC). Compared with female BC (FBC), MBC cases are more often hormonal receptor (estrogen receptor/progesterone receptor [ER/PR]) positive and human epidermal growth factor receptor 2 (HER2) negative. Treatment of MBC patients follows the same indications as female postmenopausal with surgery, systemic therapy, and radiotherapy. To date, ER/PR and HER2 status provides baseline predictive information used in selecting optimal adjuvant/neoadjuvant therapy and in the selection of therapy for recurrent or metastatic disease. HER2 represents a very interesting molecular target and a number of compounds (trastuzumab [Herceptin®; F. Hoffmann-La Roche, Basel, Switzerland] and lapatinib [Tykerb®, GlaxoSmithKline, London, UK]) are currently under clinical evaluation. Particularly, trastuzumab, a monoclonal antibody which selectively binds the extracellular domain of HER2, has become an important therapeutic agent for women with HER2-positive (HER2+) BC. Currently, data regarding the use of trastuzumab in MBC patients is limited and only few case reports exist. In all cases, MBC patients received trastuzumab concomitantly with other drugs and no severe toxicity above grade 3 was observed. However, MBC patients that would be candidate for trastuzumab therapy (ie, HER2+/ER+ or HER2+/ER− MBCs) represent only a very small percentage of MBC cases. This is noteworthy, when taking into account that trastuzumab is an important and expensive component of systemic BC therapy. Since there is no data supporting the fact that response to therapy is different for men or women, we concluded that systemic therapy in MBC should be considered on the same basis as for FBC. Particularly in male patients, trastuzumab should be

  3. Prevention and control of meningococcal disease: recommendations of the Advisory Committee on Immunization Practices (ACIP).

    PubMed

    Cohn, Amanda C; MacNeil, Jessica R; Clark, Thomas A; Ortega-Sanchez, Ismael R; Briere, Elizabeth Z; Meissner, H Cody; Baker, Carol J; Messonnier, Nancy E

    2013-03-22

    Meningococcal disease describes the spectrum of infections caused by Neisseria meningiditis, including meningitdis, bacteremia, and bacteremic pneumonia. Two quadrivalent meningococcal polysaccharide-protein conjugate vaccines that provide protection against meningococcal serogroups A, C, W, and Y (MenACWY-D [Menactra, manufactured by Sanofi Pasteur, Inc., Swiftwater, Pennsylvania] and MenACWY-CRM [Menveo, manufactured by Novartis Vaccines, Cambridge, Massachusetts]) are licensed in the United States for use among persons aged 2 through 55 years. MenACWY-D also is licensed for use among infants and toddlers aged 9 through 23 months. Quadrivalent meningococcal polysaccharide vaccine (MPSV4 [Menommune, manufactured by sanofi pasteur, Inc., Swiftwater, Pennsylvania]) is the only vaccine licensed for use among persons aged ≥56 years. A bivalent meningococcal polysaccharide protein conjugate vaccine that provides protection against meningococcal serogroups C and Y along with Haemophilus influenzae type b (Hib) (Hib-MenCY-TT [MenHibrix, manufactured by GlaxoSmithKline Biologicals, Rixensart, Belgium]) is licensed for use in children aged 6 weeks through 18 months. This report compiles and summarizes all recommendations from CDC's Advisory Committee on Immunization Practices (ACIP) regarding prevention and control of meningococcal disease in the United States, specifically the changes in the recommendations published since 2005 (CDC. Prevention and control of meningococcal disease: recommendations of the Advisory Committee on Immunization Practices [ACIP]. MMWR 2005;54 [No. RR-7]). As a comprehensive summary of previously published recommendations, this report does not contain any new recommendations; it is intended for use by clinicians as a resource. ACIP recommends routine vaccination with a quadrivalent meningococcal conjugate vaccine (MenACWY) for adolescents aged 11 or 12 years, with a booster dose at age 16 years. ACIP also recommends routine vaccination for

  4. Safety, reactogenicity and immunogenicity of a novel pneumococcal protein-based vaccine in adults: a phase I/II randomized clinical study.

    PubMed

    Leroux-Roels, Geert; Maes, Cathy; De Boever, Fien; Traskine, Magali; Rüggeberg, Jens U; Borys, Dorota

    2014-11-28

    New vaccines containing highly conserved Streptococcus pneumoniae proteins such as pneumolysin toxoid (dPly) and histidine-triad protein D (PhtD) are being developed to provide broader protection against pneumococcal disease. This study evaluated the safety, reactogenicity and immunogenicity of different pneumococcal protein-containing formulations in adults. In a phase I double-blind study (www.clinicaltrials.gov: NCT00707798), healthy adults (18-40 years) were randomized (1:2:2:2:2:2:2) to receive two doses of one of six investigational vaccine formulations 2 months apart, or a single dose of the control 23-valent pneumococcal polysaccharide vaccine (23PPV; Pneumovax23™, Sanofi Pasteur MSD) followed by placebo. The investigational formulations contained dPly alone (10 or 30 μg), or both dPly and PhtD (10 or 30 μg each) alone or combined with the polysaccharide conjugates of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV; Synflorix™, GlaxoSmithKline Vaccines). Two groups primed with a formulation containing dPly and PhtD (10 or 30 μg each) continued to the follow-up phase II study (NCT00896064), in which they received a booster dose at 5-9 months after primary vaccination. Of 156 enrolled and vaccinated adults, 146 completed the primary immunization and 43 adults received a booster dose. During primary and booster vaccination, for any formulation, ≤ 8.9% of doses were followed by grade 3 solicited local or general adverse events. No fever >39.5°C (oral temperature) was reported. Unsolicited adverse events considered causally related to vaccination were reported following ≤ 33.3% of investigational vaccine doses. No serious adverse events were reported for adults receiving investigational vaccine formulations. Formulations containing dPly with or without PhtD were immunogenic for these antigens; polysaccharide conjugate-containing formulations were also immunogenic for those 10 polysaccharides

  5. Re-evaluation of the definition of remission on the 17-item Hamilton Depression Rating Scale based on recovery in health-related quality of life in an observational post-marketing study.

    PubMed

    Sawamura, Jitsuki; Ishigooka, Jun; Nishimura, Katsuji

    2018-01-16

    Although a score of less than 7 for the 17-item Hamilton Depression Rating Scale (HAM-D17) has been widely adopted to define remission of depression, a full recovery from depression is closely related to the patient's quality of life as well. Accordingly, we re-evaluated this definition of remission using HAM-D17 in comparison with the corresponding score for health-related quality of life (HRQOL) measured by the SF-36. Using the data for depressive patients reported by GlaxoSmithKline K.K. (Study No. BRL29060A/863) in a post-marketing observational study of paroxetine, with a sample size of n = 722, multivariate logistic regression was performed with the HAM-D17 score as a dependent variable and with each of the eight domain scores of HRQOL (from the SF-36) transformed into a binominal form according to the national standard value for Japan. Then, area under curve of receiver operating characteristic analyses were conducted. Based on the obtained results, a multivariate analysis was performed using the HAM-D17 score in a binomial form with HAM-D17 as a dependent variable and with each of the eight HRQOL domain scores (SF-36) as binominalized independent variables. A cutoff value for the HAM-D17 score of 5 provided the maximum ROC-AUC at "0.864." The significantly associated scores of the eight HRQOL domains (SF-36) were identified for the HAM-D17 cutoff values of ≥5 and ≤4. The scores for physical functioning (odds ratio, 0.473), bodily pain (0.557), vitality (0.379), social functioning (0.540), role-emotion (0.265), and mental health (0.467) had a significant negative association with the HAM-D17 score (p < 0.05), and HRQOL domain scores for HAM-D17 ≥ 5 were significantly lower compared with those for HAM-D17 ≤ 4. A cutoff value for HAM-D17 of less than or equal to 4 was the best candidate for indicating remission of depression when the recovery of HRQOL is considered. Restoration of social function and performance should be considered

  6. Effectiveness of Fluticasone Furoate-Vilanterol for COPD in Clinical Practice.

    PubMed

    Vestbo, Jørgen; Leather, David; Diar Bakerly, Nawar; New, John; Gibson, J Martin; McCorkindale, Sheila; Collier, Susan; Crawford, Jodie; Frith, Lucy; Harvey, Catherine; Svedsater, Henrik; Woodcock, Ashley

    2016-09-29

    fluticasone furoate and vilanterol was associated with a lower rate of exacerbations than usual care, without a greater risk of serious adverse events. (Funded by GlaxoSmithKline; Salford Lung Study ClinicalTrials.gov number, NCT01551758 .).

  7. Celebrating the Past, Ensuring the Future--A Profile of President Glenn Smith

    ERIC Educational Resources Information Center

    Blumenthal, Anita

    2013-01-01

    "I had no idea how to convince someone to hire me," recalls APPA President, Glen Smith. His first interview was with Bryn Mawr College, a small, prestigious private college with Quaker roots, located 12 miles west of Philadelphia. That was in 1997, after 24 years in the Naval Civil Engineer Corps, and he still remembers a certain…

  8. Truman Smith's Reports on Nazi Militarism: Domestic Political Priorities and U.S. Foreign Policy-Making in Franklin Roosevelt's First and Second Terms

    ERIC Educational Resources Information Center

    Shearer, Sam

    2015-01-01

    After an accomplished military career leading up to and during World War II, Truman Smith (1893-1970) was seemingly forgotten. His name was seldom mentioned after the war until his memoirs were published posthumously in 1984. History shows Smith to be an astoundingly successful figure in military intelligence. This article provides a biography on…

  9. Changes in abundance of vascular plants under varying silvicultural systems at the Forest Ecosystem Research and Demonstration Area, Paul Smiths, New York

    Treesearch

    Mark J. Twery; Elizabeth Olson; Gary L. Wade; Michael. Rechlin

    2013-01-01

    The Forest Ecosystem Research and Demonstration Area (FERDA) was established in 1998 adjacent to the Visitor Interpretive Center (VIC) for the Adirondack Park in Paul Smiths, NY, to provide visitors with first-hand exposure to forest management activities and to provide research opportunities for scientists and students at Paul Smith's College. This research note...

  10. The Basis of James W. Fowler's Understanding of Faith in the Research of Wilfred Cantwell Smith: An Examination from an Evangelical Perspective

    ERIC Educational Resources Information Center

    Jones, Timothy Paul

    2004-01-01

    This article focuses on the influence of Wilfred Cantwell Smith's presentation of the nature of faith on James W. Fowler's faith-development paradigm. Smith contended that, in the pre-modern era, terms translated by the English words "faith" and "believe" denoted a personal allegiance that did not require assent to any objective assertions. Two…

  11. Hybrid Smith predictor and phase lead based divergence compensation for hardware-in-the-loop contact simulation with measurement delay

    NASA Astrophysics Data System (ADS)

    Qi, Chenkun; Gao, Feng; Zhao, Xianchao; Wang, Qian; Ren, Anye

    2018-06-01

    On the ground the hardware-in-the-loop (HIL) simulation is a good approach to test the contact dynamics of spacecraft docking process in space. Unfortunately, due to the time delay in the system the HIL contact simulation becomes divergent. However, the traditional first-order phase lead compensation approach still result in a small divergence for the pure time delay. The serial Smith predictor and phase lead compensation approach proposed by the authors recently will lead to an over-compensation and an obvious convergence. In this study, a hybrid Smith predictor and phase lead compensation approach is proposed. The hybrid Smith predictor and phase lead compensation can achieve a higher simulation fidelity with a little convergence. The phase angle of the compensator is analyzed and the stability condition of the HIL simulation system is given. The effectiveness of the proposed compensation approach is tested by simulations on an undamped elastic contact process.

  12. A View from the ToP and Beyond: An Interview with Randolph A. Smith.

    ERIC Educational Resources Information Center

    Scoby, Alma

    2002-01-01

    Presents an interview with Randolph A. Smith, the editor of the journal "Teaching of Psychology." Covers topics, such as his background, his thoughts on issues related to the journal, his teaching experiences, and the relationship between his teaching and editorial post. (CMK)

  13. Hidden species complexes within distinctive taxa: the case of Epanthidium bicoloratum (Smith) (Hymenoptera: Megachilidae)

    USDA-ARS?s Scientific Manuscript database

    Epanthidium bicoloratum (Smith) differs from all other Neotropical Anthidiini in the distinctive tegula, which is narrowed posteriorly forming a slender wedge. Examination of material standing under this name revealed that it represents a species complex that includes three new cryptic species, E. ...

  14. Understanding the output of a Smith-Root GPP electrofisher

    USGS Publications Warehouse

    Miranda, L.E.; Spencer, A.B.

    2005-01-01

    There is confusion among biologists about the use of the percent of range control in the GPP series of Smith-Root electrofishers. We evaluated the output of a GPP 7.5 electrofisher to examine how adjustments to the percent of range control affect voltage, pulse width, duty cycle, and waveform. We found that contrary to how most users interpret the labels on the GPP unit, adjustments to the percent of range control are linked only indirectly to changes in peak voltage. Suggestions for dealing with the restrictions of the GPP units are offered. ?? Copyright by the American Fisheries Society 2005.

  15. Smith Newton Vehicle Performance Evaluation - Gen 2 - Cumulative (Brochure)

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

    Not Available

    2014-08-01

    The Fleet Test and Evaluation Team at the U.S. Department of Energy's National Renewable Energy Laboratory is evaluating and documenting the performance of electric and plug-in hybrid electric drive systems in medium-duty trucks across the nation. U.S. companies participating in this evaluation project received funding from the American Recovery and Reinvestment Act to cover part of the cost of purchasing these vehicles. Through this project, Smith Electric Vehicles is building and deploying 500 all-electric medium-duty trucks that will be deployed by a variety of companies in diverse climates across the country.

  16. Characterization of Self-Injurious Behaviors in Children and Adults with Smith-Magenis Syndrome.

    ERIC Educational Resources Information Center

    Finucane, Brenda; Dirrigl, Karen Haines; Simon, Elliot W.

    2001-01-01

    This study examined the prevalence and severity of self-injurious behavior (SIB) in 29 children and adults with Smith-Magenis syndrome, a genetic disorder usually involving moderate mental retardation. Findings confirmed the near universal presence of SIB in this population. The overall prevalence of SIB increased with age. Number of types of SIB…

  17. Guanosine may increase absence epileptic activity by means of A2A adenosine receptors in Wistar Albino Glaxo Rijswijk rats.

    PubMed

    Lakatos, Renáta Krisztina; Dobolyi, Árpád; Todorov, Mihail Ivilinov; Kékesi, Katalin A; Juhász, Gábor; Aleksza, Magdolna; Kovács, Zsolt

    2016-06-01

    The non-adenosine nucleoside guanosine (Guo) was demonstrated to decrease quinolinic acid(QA)-induced seizures, spontaneously emerged absence epileptic seizures and lipopolysaccharide(LPS)-evoked induction of absence epileptic seizures suggesting its antiepileptic potential. It was also described previously that intraperitoneal (i.p.) injection of 20 and 50mg/kg Guo decreased the number of spike-wave discharges (SWDs) in a well investigated model of human absence epilepsy, the Wistar Albino Glaxo Rijswijk (WAG/Rij) rats during 4th (20mg/kg Guo) and 3rd as well as 4th (50mg/kg Guo) measuring hours. Guanosine can potentially decrease SWD number by means of its putative receptors but absence epileptic activity changing effects of Guo by means of increased extracellular adenosine (Ado) cannot be excluded. An increase in the dose of i.p. injected Guo is limited by its low solubility in saline, therefore, we addressed in the present study whether higher doses of Guo, diluted in sodium hydroxide (NaOH) solution, have more potent antiepileptic effect in WAG/Rij rats. We confirmed that i.p. 50mg/kg Guo decreased but, surprisingly, i.p. 100mg/kg Guo enhanced the number of SWDs in WAG/Rij rats. Combined i.p. injection of a non-selective Ado receptor antagonist theophylline (5mg/kg) or a selective Ado A2A receptor (A2AR) antagonist SCH 58261 (7-(2-phenylethyl)-5-amino-2-(2-furyl)-pyrazolo-[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine) (1mg/kg) and a cyclooxygenase 1 and 2/COX-1 and COX-2 inhibitor indomethacin (10mg/kg) with 100mg/kg Guo decreased the SWD number compared to i.p. 100mg/kg Guo alone. The results suggest that i.p. 100mg/kg Guo can increase SWD number by means of the adenosinergic system. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Anxiolytic Effect of Exogenous Ketone Supplementation Is Abolished by Adenosine A1 Receptor Inhibition in Wistar Albino Glaxo/Rijswijk Rats.

    PubMed

    Kovács, Zsolt; D'Agostino, Dominic P; Ari, Csilla

    2018-01-01

    Anxiety disorders are one of the most common mental health problems worldwide, but the exact pathophysiology remains largely unknown. It has been demonstrated previously that administration of exogenous ketone supplement KSMCT (ketone salt/KS + medium chain triglyceride/MCT oil) by intragastric gavage for 7 days decreased the anxiety level in genetically absence epileptic Wistar Albino Glaxo/Rijswijk (WAG/Rij) rats. To investigate the potential role of the adenosinergic system in the pathomechanism of anxiety we tested whether the inhibition of adenosine A 1 receptors (A 1 Rs) influence the anxiolytic effect of the exogenous ketone supplement. As A 1 Rs may mediate such an effect, in the present study we used a specific A 1 R antagonist, DPCPX (1,3-dipropyl-8-cyclopentylxanthine) to test whether it modulates the anxiolytic effect of sub-chronically (7 days) applied KSMCT in the previously tested animal model by using elevated plus maze (EPM) test. We administered KSMCT (2.5 g/kg/day) alone by intragastric gavage and in combination with intraperitoneally (i.p.) injected of DPCPX in two doses (lower: 0.15 mg/kg, higher: 0.25 mg/kg). Control groups represented i.p saline and water gavage with or without i.p. DPCPX administration (2.5 g/kg/day). After treatments, the level of blood glucose and beta-hydroxybutyrate (βHB), as well as body weight were recorded. KSMCT alone significantly increased the time spent in the open arms and decreased the time spent in the closed arms, supporting our previous results. Injection of lower dose of DPCPX decreased, while higher dose of DPCPX abolished the effect of KSMCT administration on EPM. Blood βHB levels were significantly increased after administration of KSMCT, while DPCPX did not change the KSMCT induced increase in blood βHB levels. These results demonstrate that A 1 R inhibition modified (decreased) the anti-anxiety effect of KSMCT administration implying that the adenosinergic system, likely via A 1 Rs, may modulate the

  19. Rival ecologies of global commerce: Adam Smith and the natural historians.

    PubMed

    Jonsson, Fredrik Albritton

    2010-01-01

    This essay explores how the defense of global commerce pioneered in the Enlightenment was tied to the improvement of the natural order. Two rival ecologies, one made by natural historians and the other developed by Adam Smith and his liberal successors, vied for intellectual precedence as well as for practical application in the metropole and the colonies. Together they constitute the beginnings of an ongoing quarrel over the environmental foundation of capitalism.

  20. [Occurrence of Solenopsis saevissima F Smith (Hymenoptera: Formicidae) damaging Schizolobium amazonicum].

    PubMed

    Lunz, Alexandre M; Harada, Ana Y; Aguiar, Tanice da S; Cardoso, Andreza S

    2009-01-01

    Injuries by Solenopsis saevissima F Smith in paricá (Schizolobium amazonicum) trees are described for the first time in Dom Eliseu County, Pará State, Brazil. This ant damages leaves and the shaft where holes and galleries are opened up to the plant shoot. Terminal and new shoots are attacked and destroyed, harming the development of upright and uniform trunks for commercialization. Arboreal nests constructed by this ant were also observed in some plants.

  1. LIFE HISTORY MONITORING OF SALMONIDS IN THE WEST FORK SMITH RIVER, UMPQUA BASIN, OREGON

    EPA Science Inventory

    As a life-cycle monitoring basin for the Oregon Salmon Plan, the Oregon Department of Fish and Wildlife has estimated adult returns, distribution and smolt outmigration of coho, chinook and winter steelhead in the West Fork Smith River since 1998. In 2001/2002, the Environmenta...

  2. Smith predictor-based robot control for ultrasound-guided teleoperated beating-heart surgery.

    PubMed

    Bowthorpe, Meaghan; Tavakoli, Mahdi; Becher, Harald; Howe, Robert

    2014-01-01

    Performing surgery on fast-moving heart structures while the heart is freely beating is next to impossible. Nevertheless, the ability to do this would greatly benefit patients. By controlling a teleoperated robot to continuously follow the heart's motion, the heart can be made to appear stationary. The surgeon will then be able to operate on a seemingly stationary heart when in reality it is freely beating. The heart's motion is measured from ultrasound images and thus involves a non-negligible delay due to image acquisition and processing, estimated to be 150 ms that, if not compensated for, can cause the teleoperated robot's end-effector (i.e., the surgical tool) to collide with and puncture the heart. This research proposes the use of a Smith predictor to compensate for this time delay in calculating the reference position for the teleoperated robot. The results suggest that heart motion tracking is improved as the introduction of the Smith predictor significantly decreases the mean absolute error, which is the error in making the distance between the robot's end-effector and the heart follow the surgeon's motion, and the mean integrated square error.

  3. A new species and key for Acanthocaudus Smith (Braconidae: Aphidiinae), with new host and distribution records for aphidiines associated with Silphium perfoliatum L. (Asterales: Asteraceae)

    USDA-ARS?s Scientific Manuscript database

    A new species, Acanthocaudus bicolor Kula (Braconidae: Aphidiinae), from the Nearctic Region is described and differ- entiated from all other species of Acanthocaudus Smith. Acanthocaudus schlingeri Muesebeck, 1958 is synonymized with Acanthocaudus tissoti (Smith, 1944). A key to the species of Acan...

  4. Childhood predictors of lung function trajectories and future COPD risk: a prospective cohort study from the first to the sixth decade of life.

    PubMed

    Bui, Dinh S; Lodge, Caroline J; Burgess, John A; Lowe, Adrian J; Perret, Jennifer; Bui, Minh Q; Bowatte, Gayan; Gurrin, Lyle; Johns, David P; Thompson, Bruce R; Hamilton, Garun S; Frith, Peter A; James, Alan L; Thomas, Paul S; Jarvis, Deborah; Svanes, Cecilie; Russell, Melissa; Morrison, Stephen C; Feather, Iain; Allen, Katrina J; Wood-Baker, Richard; Hopper, John; Giles, Graham G; Abramson, Michael J; Walters, Eugene H; Matheson, Melanie C; Dharmage, Shyamali C

    2018-04-05

    trajectory. We identified six potential FEV 1 trajectories, two of which were novel. Three trajectories contributed 75% of COPD burden and were associated with modifiable early-life exposures whose impact was aggravated by adult factors. We postulate that reducing maternal smoking, encouraging immunisation, and avoiding personal smoking, especially in those with smoking parents or low childhood lung function, might minimise COPD risk. Clinicians and patients with asthma should be made aware of the potential long-term implications of non-optimal asthma control for lung function trajectory throughout life, and the role and benefit of optimal asthma control on improving lung function should be investigated in future intervention trials. National Health and Medical Research Council of Australia; European Union's Horizon 2020; The University of Melbourne; Clifford Craig Medical Research Trust of Tasmania; The Victorian, Queensland & Tasmanian Asthma Foundations; The Royal Hobart Hospital; Helen MacPherson Smith Trust; and GlaxoSmithKline. Copyright © 2018 Elsevier Ltd. All rights reserved.

  5. Assessment of loaded squat jump height with a free-weight barbell and Smith machine: comparison of the take-off velocity and flight time procedures.

    PubMed

    Pérez-Castilla, Alejandro; McMahon, John J; Comfort, Paul; García-Ramos, Amador

    2017-07-31

    The aims of this study were to compare the reliability and magnitude of jump height between the two standard procedures of analysing force platform data to estimate jump height (take-off velocity [TOV] and flight time [FT]) in the loaded squat jump (SJ) exercise performed with a free-weight barbell and in a Smith machine. Twenty-three collegiate men (age 23.1 ± 3.2 years, body mass 74.7 ± 7.3 kg, height 177.1 ± 7.0 cm) were tested twice for each SJ type (free-weight barbell and Smith machine) with 17, 30, 45, 60, and 75 kg loads. No substantial differences in reliability were observed between the TOV (Coefficient of variation [CV]: 9.88%; Intraclass correlation coefficient [ICC]: 0.82) and FT (CV: 8.68%; ICC: 0.88) procedures (CV ratio: 1.14), while the Smith SJ (CV: 7.74%; ICC: 0.87) revealed a higher reliability than the free-weight SJ (CV: 9.88%; ICC: 0.81) (CV ratio: 1.28). The TOV procedure provided higher magnitudes of jump height than the FT procedure for the loaded Smith machine SJ (systematic bias: 2.64 cm; P<0.05), while no significant differences between the TOV and FT procedures were observed in the free-weight SJ exercise (systematic bias: 0.26 cm; P>0.05). Heteroscedasticity of the errors was observed for the Smith machine SJ (r: 0.177) with increasing differences in favour of the TOV procedure for the trials with lower jump height (i.e. higher external loads). Based on these results the use of a Smith machine in conjunction with the FT more accurately determine jump height during the loaded SJ.

  6. The futility of utility: how market dynamics marginalize Adam Smith

    NASA Astrophysics Data System (ADS)

    McCauley, Joseph L.

    2000-10-01

    Economic theorizing is based on the postulated, nonempiric notion of utility. Economists assume that prices, dynamics, and market equilibria are supposed to be derived from utility. The results are supposed to represent mathematically the stabilizing action of Adam Smith's invisible hand. In deterministic excess demand dynamics I show the following. A utility function generally does not exist mathematically due to nonintegrable dynamics when production/investment are accounted for, resolving Mirowski's thesis. Price as a function of demand does not exist mathematically either. All equilibria are unstable. I then explain how deterministic chaos can be distinguished from random noise at short times. In the generalization to liquid markets and finance theory described by stochastic excess demand dynamics, I also show the following. Market price distributions cannot be rescaled to describe price movements as ‘equilibrium’ fluctuations about a systematic drift in price. Utility maximization does not describe equilibrium. Maximization of the Gibbs entropy of the observed price distribution of an asset would describe equilibrium, if equilibrium could be achieved, but equilibrium does not describe real, liquid markets (stocks, bonds, foreign exchange). There are three inconsistent definitions of equilibrium used in economics and finance, only one of which is correct. Prices in unregulated free markets are unstable against both noise and rising or falling expectations: Adam Smith's stabilizing invisible hand does not exist, either in mathematical models of liquid market data, or in real market data.

  7. Speeding-up Bioinformatics Algorithms with Heterogeneous Architectures: Highly Heterogeneous Smith-Waterman (HHeterSW).

    PubMed

    Gálvez, Sergio; Ferusic, Adis; Esteban, Francisco J; Hernández, Pilar; Caballero, Juan A; Dorado, Gabriel

    2016-10-01

    The Smith-Waterman algorithm has a great sensitivity when used for biological sequence-database searches, but at the expense of high computing-power requirements. To overcome this problem, there are implementations in literature that exploit the different hardware-architectures available in a standard PC, such as GPU, CPU, and coprocessors. We introduce an application that splits the original database-search problem into smaller parts, resolves each of them by executing the most efficient implementations of the Smith-Waterman algorithms in different hardware architectures, and finally unifies the generated results. Using non-overlapping hardware allows simultaneous execution, and up to 2.58-fold performance gain, when compared with any other algorithm to search sequence databases. Even the performance of the popular BLAST heuristic is exceeded in 78% of the tests. The application has been tested with standard hardware: Intel i7-4820K CPU, Intel Xeon Phi 31S1P coprocessors, and nVidia GeForce GTX 960 graphics cards. An important increase in performance has been obtained in a wide range of situations, effectively exploiting the available hardware.

  8. Design and implementation of a hybrid MPI-CUDA model for the Smith-Waterman algorithm.

    PubMed

    Khaled, Heba; Faheem, Hossam El Deen Mostafa; El Gohary, Rania

    2015-01-01

    This paper provides a novel hybrid model for solving the multiple pair-wise sequence alignment problem combining message passing interface and CUDA, the parallel computing platform and programming model invented by NVIDIA. The proposed model targets homogeneous cluster nodes equipped with similar Graphical Processing Unit (GPU) cards. The model consists of the Master Node Dispatcher (MND) and the Worker GPU Nodes (WGN). The MND distributes the workload among the cluster working nodes and then aggregates the results. The WGN performs the multiple pair-wise sequence alignments using the Smith-Waterman algorithm. We also propose a modified implementation to the Smith-Waterman algorithm based on computing the alignment matrices row-wise. The experimental results demonstrate a considerable reduction in the running time by increasing the number of the working GPU nodes. The proposed model achieved a performance of about 12 Giga cell updates per second when we tested against the SWISS-PROT protein knowledge base running on four nodes.

  9. 77 FR 51064 - Huntington Foam LLC, Fort Smith, AR; Notice of Affirmative Determination Regarding Application...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-23

    ... DEPARTMENT OF LABOR Employment and Training Administration [TA-W-81,475] Huntington Foam LLC, Fort Smith, AR; Notice of Affirmative Determination Regarding Application for Reconsideration By application dated May 21, 2012, the State Workforce Office requested administrative reconsideration of the negative...

  10. A 3D Human-Machine Integrated Design and Analysis Framework for Squat Exercises with a Smith Machine

    PubMed Central

    Lee, Haerin; Jung, Moonki; Lee, Ki-Kwang; Lee, Sang Hun

    2017-01-01

    In this paper, we propose a three-dimensional design and evaluation framework and process based on a probabilistic-based motion synthesis algorithm and biomechanical analysis system for the design of the Smith machine and squat training programs. Moreover, we implemented a prototype system to validate the proposed framework. The framework consists of an integrated human–machine–environment model as well as a squat motion synthesis system and biomechanical analysis system. In the design and evaluation process, we created an integrated model in which interactions between a human body and machine or the ground are modeled as joints with constraints at contact points. Next, we generated Smith squat motion using the motion synthesis program based on a Gaussian process regression algorithm with a set of given values for independent variables. Then, using the biomechanical analysis system, we simulated joint moments and muscle activities from the input of the integrated model and squat motion. We validated the model and algorithm through physical experiments measuring the electromyography (EMG) signals, ground forces, and squat motions as well as through a biomechanical simulation of muscle forces. The proposed approach enables the incorporation of biomechanics in the design process and reduces the need for physical experiments and prototypes in the development of training programs and new Smith machines. PMID:28178184

  11. A 3D Human-Machine Integrated Design and Analysis Framework for Squat Exercises with a Smith Machine.

    PubMed

    Lee, Haerin; Jung, Moonki; Lee, Ki-Kwang; Lee, Sang Hun

    2017-02-06

    In this paper, we propose a three-dimensional design and evaluation framework and process based on a probabilistic-based motion synthesis algorithm and biomechanical analysis system for the design of the Smith machine and squat training programs. Moreover, we implemented a prototype system to validate the proposed framework. The framework consists of an integrated human-machine-environment model as well as a squat motion synthesis system and biomechanical analysis system. In the design and evaluation process, we created an integrated model in which interactions between a human body and machine or the ground are modeled as joints with constraints at contact points. Next, we generated Smith squat motion using the motion synthesis program based on a Gaussian process regression algorithm with a set of given values for independent variables. Then, using the biomechanical analysis system, we simulated joint moments and muscle activities from the input of the integrated model and squat motion. We validated the model and algorithm through physical experiments measuring the electromyography (EMG) signals, ground forces, and squat motions as well as through a biomechanical simulation of muscle forces. The proposed approach enables the incorporation of biomechanics in the design process and reduces the need for physical experiments and prototypes in the development of training programs and new Smith machines.

  12. Immune complex-mediated autoimmunity in a patient With Smith-Magenis syndrome (del 17p11.2).

    PubMed

    Yang, Jianying; Chandrasekharappa, Settara C; Vilboux, Thierry; Smith, Ann C M; Peterson, Erik J

    2014-08-01

    Smith-Magenis syndrome (SMS) is a sporadic congenital disorder involving multiple organ systems caused by chromosome 17p11.2 deletions. Smith-Magenis syndrome features craniofacial and skeletal anomalies, cognitive impairment, and neurobehavioral abnormalities. In addition, some SMS patients may exhibit hypogammaglobulinemia. We report the first case of SMS-associated autoimmunity in a woman who presented with adult onset of multiple autoimmune disorders, including systemic lupus erythematosus, antiphospholipid antibody syndrome, and autoimmune hepatitis. Molecular analysis using single-nucleotide polymorphism array confirmed a de novo 3.8-Mb deletion (breakpoints, chr17: 16,660,721-20,417,975), resulting in haploinsufficiency for TACI (transmembrane activator and CAML interactor). Our data are consistent with potential loss of function for the BAFF (B cell-activating factor) receptor TACI as a contributing factor to human autoimmune phenomena.

  13. Ebonics and Dr. Ernie Adolphus Smith toward Acomparative and Holistic Paradigm in Black Linguistics

    ERIC Educational Resources Information Center

    Minamoto, Kunihiko

    2017-01-01

    One African-centered linguistic paradigm argues the primary language of most descendants of enslaved Africans in the United States is not English but an African language. The language is called "Ebonics." Clinical linguist Dr. Ernie Adolphus Smith (1938-) is the most conspicuous figure in the history of the paradigm. The reconstructed…

  14. 160-fold acceleration of the Smith-Waterman algorithm using a field programmable gate array (FPGA)

    PubMed Central

    Li, Isaac TS; Shum, Warren; Truong, Kevin

    2007-01-01

    Background To infer homology and subsequently gene function, the Smith-Waterman (SW) algorithm is used to find the optimal local alignment between two sequences. When searching sequence databases that may contain hundreds of millions of sequences, this algorithm becomes computationally expensive. Results In this paper, we focused on accelerating the Smith-Waterman algorithm by using FPGA-based hardware that implemented a module for computing the score of a single cell of the SW matrix. Then using a grid of this module, the entire SW matrix was computed at the speed of field propagation through the FPGA circuit. These modifications dramatically accelerated the algorithm's computation time by up to 160 folds compared to a pure software implementation running on the same FPGA with an Altera Nios II softprocessor. Conclusion This design of FPGA accelerated hardware offers a new promising direction to seeking computation improvement of genomic database searching. PMID:17555593

  15. 160-fold acceleration of the Smith-Waterman algorithm using a field programmable gate array (FPGA).

    PubMed

    Li, Isaac T S; Shum, Warren; Truong, Kevin

    2007-06-07

    To infer homology and subsequently gene function, the Smith-Waterman (SW) algorithm is used to find the optimal local alignment between two sequences. When searching sequence databases that may contain hundreds of millions of sequences, this algorithm becomes computationally expensive. In this paper, we focused on accelerating the Smith-Waterman algorithm by using FPGA-based hardware that implemented a module for computing the score of a single cell of the SW matrix. Then using a grid of this module, the entire SW matrix was computed at the speed of field propagation through the FPGA circuit. These modifications dramatically accelerated the algorithm's computation time by up to 160 folds compared to a pure software implementation running on the same FPGA with an Altera Nios II softprocessor. This design of FPGA accelerated hardware offers a new promising direction to seeking computation improvement of genomic database searching.

  16. Neurodevelopment of children under 3 years of age with Smith-Magenis syndrome.

    PubMed

    Wolters, Pamela L; Gropman, Andrea L; Martin, Staci C; Smith, Michaele R; Hildenbrand, Hanna L; Brewer, Carmen C; Smith, Ann C M

    2009-10-01

    Systematic data regarding early neurodevelopmental functioning in Smith-Magenis syndrome are limited. Eleven children with Smith-Magenis syndrome less than 3 years of age (mean, 19 months; range, 5-34 months) received prospective multidisciplinary assessments using standardized measures. The total sample scored in the moderately to severely delayed range in cognitive functioning, expressive language, and motor skills and exhibited generalized hypotonia, oral-motor abnormalities, and middle ear dysfunction. Socialization skills were average, and significantly higher than daily living, communication, and motor abilities, which were below average. Mean behavior ratings were in the nonautistic range. According to exploratory analyses, the toddler subgroup scored significantly lower than the infant subgroup in cognition, expressive language, and adaptive behavior, suggesting that the toddlers were more delayed than the infants relative to their respective peers. Infants aged approximately 1 year or younger exhibited cognitive, language, and motor skills that ranged from average to delayed, but with age-appropriate social skills and minimal maladaptive behaviors. At ages 2 to 3 years, the toddlers consistently exhibited cognitive, expressive language, adaptive behavior, and motor delays and mildly to moderately autistic behaviors. Combining age groups in studies may mask developmental and behavioral differences. Increased knowledge of these early neurodevelopmental characteristics should facilitate diagnosis and appropriate intervention.

  17. Water-quality assessment of the Smith River drainage basin, California and Oregon

    USGS Publications Warehouse

    Iwatsubo, Rick T.; Washabaugh, Donna S.

    1982-01-01

    A water-quality assessment of the Smith River drainage basin was made to provide a summary of the water-quality conditions including known or potential water-quality problems. Results of the study showed that the water quality of the Smith River is excellent and generally meets the water-quality objectives for the beneficial uses identified by the California Regional Water Quality Control Board, North Coast Region. Known and potential problems related to water quality include: Sedimentation resulting from both natural erosional processes and land-use activities such as timber harvest, road construction, and mining that accelerate the erosional processes; bacterial contamination of surface and ground waters from inundated septic tanks and drainfields, and grazing activities; industrial spills which have resulted in fish kills and oil residues; high concetrations of iron in ground water; log and debris jams creating fish migration barriers; and pesticide and trace-element contamination from timber-harvest and mining activities, respectively. Future studies are needed to establish: (1) a sustained long-term monitoring program to provide a broad coverage of water-quality conditions in order to define long-term water-quality trends; and (2) interpretive studies to determine the source of known and potential water-quality problems. (USGS)

  18. GPU-based cloud service for Smith-Waterman algorithm using frequency distance filtration scheme.

    PubMed

    Lee, Sheng-Ta; Lin, Chun-Yuan; Hung, Che Lun

    2013-01-01

    As the conventional means of analyzing the similarity between a query sequence and database sequences, the Smith-Waterman algorithm is feasible for a database search owing to its high sensitivity. However, this algorithm is still quite time consuming. CUDA programming can improve computations efficiently by using the computational power of massive computing hardware as graphics processing units (GPUs). This work presents a novel Smith-Waterman algorithm with a frequency-based filtration method on GPUs rather than merely accelerating the comparisons yet expending computational resources to handle such unnecessary comparisons. A user friendly interface is also designed for potential cloud server applications with GPUs. Additionally, two data sets, H1N1 protein sequences (query sequence set) and human protein database (database set), are selected, followed by a comparison of CUDA-SW and CUDA-SW with the filtration method, referred to herein as CUDA-SWf. Experimental results indicate that reducing unnecessary sequence alignments can improve the computational time by up to 41%. Importantly, by using CUDA-SWf as a cloud service, this application can be accessed from any computing environment of a device with an Internet connection without time constraints.

  19. 75 FR 37462 - Official Trail Marker for the Captain John Smith Chesapeake National Historic Trail

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-29

    ... DEPARTMENT OF THE INTERIOR National Park Service Official Trail Marker for the Captain John Smith Chesapeake National Historic Trail AGENCY: National Parks Service, Interior. ACTION: Official Insignia, Designation. Authority: National Trails System Act, 16 U.S.C. 124(a) and 1246(c) and Protection of Official...

  20. Attraction of Diabrotica barberi Smith and Lawrence (Coleoptera: Chrysomelidae) to eugenol-baited traps in soybean

    USDA-ARS?s Scientific Manuscript database

    Diabrotica barberi Smith and Lawrence (the northern corn rootworm) is a native North American leaf beetle and a major pest of corn. However, adult D. barberi forage in various habitats outside of corn, including soybean, roadside vegetation, and prairie. Eugenol is a common floral volatile that ha...