Search

Your search keyword '"Johnson MP"' showing total 863 results
Start Over Author "Johnson MP"
863 results on '"Johnson MP"'

1. Palbociclib Adherence and Persistence in Patients with Hormone Receptor Positive/Human Epidermal Growth Factor Receptor 2 Negative (HR+/HER2-) Metastatic Breast Cancer

Author

Engel-Nitz NM, Johnson MG, Johnson MP, Cha-Silva AS, Kurosky SK, and Liu X

Subjects
breast cancer, palbociclib, adherence, persistence, metastatic, Medicine (General), R5-920
Abstract

Nicole M Engel-Nitz,1 Mary G Johnson,1 Michael P Johnson,1 Ashley S Cha-Silva,2 Samantha K Kurosky,2 Xianchen Liu2 1Optum, Eden Prairie, MN, 55344, USA; 2Pfizer Inc, New York, NY, 10017, USACorrespondence: Nicole M Engel-Nitz, HEOR | Optum Life Sciences, MN950-1000, 11000 Optum Circle, Eden Prairie, MN, 55344, USA, Tel +1 952-205-7770, Email Nicole.engel-nitz@optum.comPurpose: To assess adherence and persistence with palbociclib therapy in patients with HR+/HER2- metastatic breast cancer (mBC) in a US real-world setting.Methods: This retrospective study evaluated palbociclib dosing, adherence, and persistence using commercial and Medicare Advantage with Part D claims data from the Optum Research Database. Adult patients with mBC who had continuous enrollment 12 months prior to mBC diagnosis and initiated first-line palbociclib with aromatase inhibitor (AI) or fulvestrant between 02/03/2015 and 12/31/2019 were included. Demographic and clinical characteristics, palbociclib dosing and dose changes, adherence (medication possession ratio [MPR]), and persistence were measured. Adjusted logistic and Cox regression models were used to examine demographic and clinical factors associated with adherence and discontinuation.Results: Patients (n = 1066) with a mean age of 66 years were included; 76.1% received first-line palbociclib+AI and 23.9% palbociclib+fulvestrant. Most patients (85.7%) initiated palbociclib at 125 mg/day. Of the 34.0% of patients with a dose reduction, 82.6% reduced from 125 to 100 mg/day. Overall, 80.0% of patients were adherent (MPR), and 38.3% discontinued palbociclib during a mean (SD) follow-up of 16.0 (11.2) and 17.4 (13.4) months, for palbociclib+fulvestrant and palbociclib+AI, respectively. Annual income below $75,000 was significantly associated with poor adherence. Older age (age 65– 74 years (hazard ratio [HR] 1.57, 95% CI, 1.06, 2.33), age ≥ 75 years (HR 1.61, 95% CI: 1.08, 2.41)) and bone-only metastatic disease (HR 1.37, 95% CI, 1.06, 1.76) were significantly associated with palbociclib discontinuation.Conclusion: In this real-world study, > 85% of patients started palbociclib at 125 mg/day and 1 in 3 had dose reductions during the follow-up. Patients were generally adherent and persistent with palbociclib. Older age, bone-only disease, and low-income levels were associated with early discontinuation or non-adherence. Further studies are needed to understand the associations of clinical and economic outcomes with palbociclib adherence and persistence.Keywords: breast cancer, palbociclib, adherence, persistence, metastatic

Published
2023

2. Patient-reported treatment satisfaction and choice of dosing frequency with biologic treatment for moderate to severe plaque psoriasis

Author

Zhang M, Brenneman SK, Carter CT, Essoi BL, Farahi K, Johnson MP, Lee S, and Olson WH

Subjects
Medicine (General), R5-920
Abstract

Mingliang Zhang,1 Susan K Brenneman,2 Chureen T Carter,1 Breanna L Essoi,2 Kamyar Farahi,1 Michael P Johnson,2 Seina Lee,1 William H Olson3 1Health Economics and Outcomes Research, Janssen Scientific Affairs, LLC, Horsham, PA, 2Health Economics and Outcomes Research, Optum Life Sciences, Eden Prairie, MN, 3Research and Analysis Strategy, Janssen Scientific Affairs, LLC, Titusville, NJ, USA Background: Moderate to severe plaque psoriasis has a serious effect on health-related quality of life. Patients treated with biologic medications place importance on satisfaction and treatment frequency options. We assessed patient-reported treatment satisfaction and dosing frequency choice with biologics.Methods: We used a health care claims database to identify patients with moderate to severe plaque psoriasis. Participants completed the Treatment Satisfaction Questionnaire for Medication. Results were compared between patients experienced with biologics (adalimumab, etanercept, or ustekinumab) or not (cyclosporine or methotrexate). Participants were asked for their choices of dosing options of once every 1–2 weeks, 3–4 weeks, 1–2 months, or 2–3 months. Participants were also asked for their choices of dosing options of every 1, 2, 3, and so on up to every 12+ weeks.Results: A total of 426 patients completed the survey (263 biologic-experienced and 163 biologic-naïve patients). Patient satisfaction with psoriasis treatment was significantly higher in the biologic-experienced cohort. The most frequently chosen option (38.8% of all participating patients) was every 2–3 months; 37.3% chose once every 1–2 weeks. Significant differences were found in the percentage of biologic-naïve patients choosing 2–3-month (49.7%) over 1–2-week (20.9%) dosing (P

Published
2015

3. A Randomized Trial of Prenatal versus Postnatal Repair of Myelomeningocele

Author

Adzick, NS, primary, Thom, EA, additional, Spong, CY, additional, Brock, JW, additional, Burrows, PK, additional, Johnson, MP, additional, Howell, LJ, additional, Farrell, JA, additional, Dabrowiak, ME, additional, Sutton, LN, additional, Gupta, N, additional, Tulipan, NB, additional, D'Alton, ME, additional, and Farmer, DL, additional

Published
2023
Full Text
View/download PDF

6. Reply to 'Minimally invasive fetoscopic surgery for spina bifida aperta: learning and doing'

Author

Joyeux, Luc, Danzer, Enrico, De Bie, Felix, Russo, francesca, Javaux, Allan, Peralta, CFA, De salles, AAF, Pastuszka, A, Olejek, A, Van Mieghem, Tim, De Coppi, Paolo, Moldenhauer, Julie, Whitehead, William E, Belfort, Michael, Lapa, DA, Acacio, GL, Devlieger, Roland, Hirose, Shinjiro, Farmer, DL, Van Calenbergh, Frank, Adzick, NS, Johnson, MP, and Deprest, Jan

Abstract

ispartof: Ultrasound In Obstetrics & Gynecology vol:56 pages:634-655 status: published

Published
2020

8. Pathway Analysis Integrating Genome-Wide and Functional Data Identifies PLCG2 as a Candidate Gene for Age-Related Macular Degeneration

Author

Waksmunski, AR, Grunin, M, Kinzy, TG, Igo, RP, Haines, JL, Bailey, JNC, Fritsche, LG, Igl, W, Grassmann, F, Sengupta, S, Bragg-Gresham, JL, Burdon, KP, Hebbring, SJ, Wen, C, Gorski, M, Kim, IK, Cho, D, Zack, D, Souied, E, Scholl, HPN, Bala, E, Lee, KE, Hunter, DJ, Sardell, RJ, Mitchell, P, Merriam, JE, Cipriani, V, Hoffman, JD, Schick, T, Lechanteur, YTE, Guymer, RH, Johnson, MP, Jiang, Y, Stanton, CM, Buitendijk, GHS, Zhan, X, Kwong, AM, Boleda, A, Brooks, M, Gieser, L, Ratnapriya, R, Branham, KE, Foerster, JR, Heckenlively, JR, Othman, M, Vote, BJ, Liang, HH, Souzeau, E, McAllister, IL, Isaacs, T, Hall, J, Lake, S, Mackey, DA, Constable, IJ, Craig, JE, Kitchner, TE, Yang, Z, Su, Z, Luo, H, Chen, D, Ouyang, H, Flagg, K, Lin, D, Mao, G, Ferreyra, H, Stark, K, von Strachwitz, CN, Wolf, A, Brandl, C, Rudolph, G, Olden, M, Morrison, MA, Morgan, DJ, Schu, M, Ahn, J, Silvestri, G, Tsironi, EE, Park, KH, Farrer, LA, Orlin, A, Brucker, A, Li, M, Curcio, CA, Mohand-Said, S, Sahel, J-A, Audo, I, Benchaboune, M, Cree, AJ, Rennie, CA, Goverdhan, S, Hagbi-Levi, S, Campochiaro, P, Katsanis, N, Holz, FG, Blond, F, Blanche, H, Deleuze, J-F, Truitt, B, Peachey, NS, Meuer, SM, Myers, CE, Moore, EL, Klein, R, Hauser, MA, Postel, EA, Courtenay, MD, Schwartz, SG, Kovach, JL, Scott, WK, Liew, G, Tan, AG, Gopinath, B, Merriam, JC, Smith, RT, Khan, JC, Shahid, H, Moore, AT, McGrath, JA, Laux, R, Brantley, MA, Agarwal, A, Ersoy, L, Caramoy, A, Langmann, T, Saksens, NTM, de Jong, EK, Hoyng, CB, Cain, MS, Richardson, AJ, Martin, TM, Blangero, J, Weeks, DE, Dhillon, B, van Duijn, CM, Doheny, KF, Romm, J, Klaver, CCW, Hayward, C, Gorin, MB, Klein, ML, Baird, PN, den Hollander, A, Fauser, S, Yates, JRW, Allikmets, R, Wang, JJ, Schaumberg, DA, Klein, BEK, Hagstrom, SA, Chowers, I, Lotery, AJ, Leveillard, T, Zhang, K, Brilliant, MH, Hewitt, AW, Swaroop, A, Chew, EY, Pericak-Vance, MA, DeAngelis, M, Stambolian, D, Iyengar, SK, Weber, BHF, Abecasis, GR, Heid, IM, Waksmunski, AR, Grunin, M, Kinzy, TG, Igo, RP, Haines, JL, Bailey, JNC, Fritsche, LG, Igl, W, Grassmann, F, Sengupta, S, Bragg-Gresham, JL, Burdon, KP, Hebbring, SJ, Wen, C, Gorski, M, Kim, IK, Cho, D, Zack, D, Souied, E, Scholl, HPN, Bala, E, Lee, KE, Hunter, DJ, Sardell, RJ, Mitchell, P, Merriam, JE, Cipriani, V, Hoffman, JD, Schick, T, Lechanteur, YTE, Guymer, RH, Johnson, MP, Jiang, Y, Stanton, CM, Buitendijk, GHS, Zhan, X, Kwong, AM, Boleda, A, Brooks, M, Gieser, L, Ratnapriya, R, Branham, KE, Foerster, JR, Heckenlively, JR, Othman, M, Vote, BJ, Liang, HH, Souzeau, E, McAllister, IL, Isaacs, T, Hall, J, Lake, S, Mackey, DA, Constable, IJ, Craig, JE, Kitchner, TE, Yang, Z, Su, Z, Luo, H, Chen, D, Ouyang, H, Flagg, K, Lin, D, Mao, G, Ferreyra, H, Stark, K, von Strachwitz, CN, Wolf, A, Brandl, C, Rudolph, G, Olden, M, Morrison, MA, Morgan, DJ, Schu, M, Ahn, J, Silvestri, G, Tsironi, EE, Park, KH, Farrer, LA, Orlin, A, Brucker, A, Li, M, Curcio, CA, Mohand-Said, S, Sahel, J-A, Audo, I, Benchaboune, M, Cree, AJ, Rennie, CA, Goverdhan, S, Hagbi-Levi, S, Campochiaro, P, Katsanis, N, Holz, FG, Blond, F, Blanche, H, Deleuze, J-F, Truitt, B, Peachey, NS, Meuer, SM, Myers, CE, Moore, EL, Klein, R, Hauser, MA, Postel, EA, Courtenay, MD, Schwartz, SG, Kovach, JL, Scott, WK, Liew, G, Tan, AG, Gopinath, B, Merriam, JC, Smith, RT, Khan, JC, Shahid, H, Moore, AT, McGrath, JA, Laux, R, Brantley, MA, Agarwal, A, Ersoy, L, Caramoy, A, Langmann, T, Saksens, NTM, de Jong, EK, Hoyng, CB, Cain, MS, Richardson, AJ, Martin, TM, Blangero, J, Weeks, DE, Dhillon, B, van Duijn, CM, Doheny, KF, Romm, J, Klaver, CCW, Hayward, C, Gorin, MB, Klein, ML, Baird, PN, den Hollander, A, Fauser, S, Yates, JRW, Allikmets, R, Wang, JJ, Schaumberg, DA, Klein, BEK, Hagstrom, SA, Chowers, I, Lotery, AJ, Leveillard, T, Zhang, K, Brilliant, MH, Hewitt, AW, Swaroop, A, Chew, EY, Pericak-Vance, MA, DeAngelis, M, Stambolian, D, Iyengar, SK, Weber, BHF, Abecasis, GR, and Heid, IM

Abstract

PURPOSE: Age-related macular degeneration (AMD) is the worldwide leading cause of blindness among the elderly. Although genome-wide association studies (GWAS) have identified AMD risk variants, their roles in disease etiology are not well-characterized, and they only explain a portion of AMD heritability. METHODS: We performed pathway analyses using summary statistics from the International AMD Genomics Consortium's 2016 GWAS and multiple pathway databases to identify biological pathways wherein genetic association signals for AMD may be aggregating. We determined which genes contributed most to significant pathway signals across the databases. We characterized these genes by constructing protein-protein interaction networks and performing motif analysis. RESULTS: We determined that eight genes (C2, C3, LIPC, MICA, NOTCH4, PLCG2, PPARA, and RAD51B) "drive" the statistical signals observed across pathways curated in the Kyoto Encyclopedia of Genes and Genomes (KEGG), Reactome, and Gene Ontology (GO) databases. We further refined our definition of statistical driver gene to identify PLCG2 as a candidate gene for AMD due to its significant gene-level signals (P < 0.0001) across KEGG, Reactome, GO, and NetPath pathways. CONCLUSIONS: We performed pathway analyses on the largest available collection of advanced AMD cases and controls in the world. Eight genes strongly contributed to significant pathways from the three larger databases, and one gene (PLCG2) was central to significant pathways from all four databases. This is, to our knowledge, the first study to identify PLCG2 as a candidate gene for AMD based solely on genetic burden. Our findings reinforce the utility of integrating in silico genetic and biological pathway data to investigate the genetic architecture of AMD.

Published
2019

10. The antihypertensive MTHFR gene polymorphism rs17367504-G is a possible novel protective locus for preeclampsia

Author

Thomsen, LCV, McCarthy, NS, Melton, PE, Cadby, G, Austgulen, R, Nygard, OK, Johnson, MP, Brennecke, S, Moses, EK, Bjorge, L, Iversen, A-C, Thomsen, LCV, McCarthy, NS, Melton, PE, Cadby, G, Austgulen, R, Nygard, OK, Johnson, MP, Brennecke, S, Moses, EK, Bjorge, L, and Iversen, A-C

Abstract

OBJECTIVE: Preeclampsia is a complex heterogeneous disease commonly defined by new-onset hypertension and proteinuria in pregnancy. Women experiencing preeclampsia have increased risk for cardiovascular diseases (CVD) later in life. Preeclampsia and CVD share risk factors and pathophysiologic mechanisms, including dysregulated inflammation and raised blood pressure. Despite commonalities, little is known about the contribution of shared genes (pleiotropy) to these diseases. This study aimed to investigate whether genetic risk factors for hypertension or inflammation are pleiotropic by also being associated with preeclampsia. METHODS: We genotyped 122 single nucleotide polymorphisms (SNPs) in women with preeclampsia (n = 1006) and nonpreeclamptic controls (n = 816) from the Norwegian HUNT Study. SNPs were chosen on the basis of previously reported associations with either nongestational hypertension or inflammation in genome-wide association studies. The SNPs were tested for association with preeclampsia in a multiple logistic regression model. RESULTS: The minor (G) allele of the intronic SNP rs17367504 in the gene methylenetetrahydrofolate reductase (MTHFR) was associated with a protective effect on preeclampsia (odds ratio 0.65, 95% confidence interval 0.53-0.80) in the Norwegian cohort. This association did not replicate in an Australian preeclampsia case-control cohort (P = 0.68, odds ratio 1.05, 95% confidence interval 0.83-1.32, minor allele frequency = 0.15). CONCLUSION: MTHFR is important for regulating transmethylation processes and is involved in regulation of folate metabolism. The G allele of rs17367504 has previously been shown to protect against nongestational hypertension. Our study suggests a novel association between this allele and reduced risk for preeclampsia. This is the first study associating the minor (G) allele of a SNP within the MTHFR gene with a protective effect on preeclampsia, and in doing so identifying a possible pleiotropic protecti

Published
2017

12. Ecological priming of artificial aquaculture structures: kelp farms as an example.

Author

Walls, AM, Edwards, MD, Firth, LB, and Johnson, MP

Abstract

The continued development of the aquaculture industry is contributing to the proliferation of artificial structures in the marine environment. Observations of seaweed farms (infrastructure and biomass) suggest they act as a habitat for associated species. Seaweed farms differ from other forms of artificial infrastructure as the material deployed already has marine organisms (i.e. culture species) growing on it. This 'priming' of ropes with juvenile sporophytes may affect future development of communities by facilitating colonizing species or suppressing competitors. We call this process 'ecological priming': the provision of a biological platform that influences the successional development of specific communities. The communities that developed on ropes primed with Alaria esculenta individuals were compared with unprimed ropes to assess the ecological priming effect, at a commercial kelp farm in south-west Ireland. Species richness increased over two cultivation seasons and species composition was consistent between years, with distinct communities developing on primed and unprimed treatments. Timing of species occurrence on primed ropes was predictable with no predictable pattern occurring on unprimed ropes. Multivariate tests indicated distinct communities between treatments, with suppression of other algal species and potential facilitation of some species that have a particular association with A. esculenta on primed ropes. Communities from primed holdfasts contained a lower diversity of algal species compared with unprimed communities. Cultivated kelp holdfasts represent a habitat for distinct assemblages that reflect ecological priming of the substratum. [ABSTRACT FROM AUTHOR]

Published
2019
Full Text
View/download PDF

13. A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants

Author

Fritsche, LG, Igl, W, Bailey, JNC, Grassmann, F, Sengupta, S, Bragg-Gresham, JL, Burdon, KP, Hebbring, SJ, Wen, C, Gorski, M, Kim, IK, Cho, D, Zack, D, Souied, E, Scholl, HPN, Bala, E, Lee, KE, Hunter, DJ, Sardell, RJ, Mitchell, P, Merriam, JE, Cipriani, V, Hoffman, JD, Schick, T, Lechanteur, YTE, Guymer, RH, Johnson, MP, Jiang, Y, Stanton, CM, Buitendijk, GHS, Zhan, X, Kwong, AM, Boleda, A, Brooks, M, Gieser, L, Ratnapriya, R, Branham, KE, Foerster, JR, Heckenlively, JR, Othman, MI, Vote, BJ, Liang, HH, Souzeau, E, McAllister, IL, Isaacs, T, Hall, J, Lake, S, Mackey, DA, Constable, IJ, Craig, JE, Kitchner, TE, Yang, Z, Su, Z, Luo, H, Chen, D, Hong, O, Flagg, K, Lin, D, Mao, G, Ferreyra, H, Starke, K, von Strachwitz, CN, Wolf, A, Brandl, C, Rudolph, G, Olden, M, Morrison, MA, Morgan, DJ, Schu, M, Ahn, J, Silvestri, G, Tsironi, EE, Park, KH, Farrer, LA, Orlin, A, Brucker, A, Li, M, Curcio, CA, Mohand-Said, S, Sahel, J-M, Audo, I, Benchaboune, M, Cree, AJ, Rennie, CA, Goverdhan, SV, Grunin, M, Hagbi-Levi, S, Campochiaro, P, Katsanis, N, Holz, FG, Blond, F, Blanche, H, Deleuze, J-F, Igo, RP, Truitt, B, Peachey, NS, Meuer, SM, Myers, CE, Moore, EL, Klein, R, Hauser, MA, Postel, EA, Courtenay, MD, Schwartz, SG, Kovach, JL, Scott, WK, Liew, G, Tan, AG, Gopinath, B, Merriam, JC, Smith, RT, Khan, JC, Shahid, H, Moore, AT, McGrath, JA, Laux, R, Brantley, MA, Agarwal, A, Ersoy, L, Caramoy, A, Langmann, T, Saksens, NTM, de Jong, EK, Hoyng, CB, Cain, MS, Richardson, AJ, Martin, TM, Blangero, J, Weeks, DE, Dhillon, B, van Duijn, CM, Doheny, KF, Romm, J, Klaver, CCW, Hayward, C, Gorin, MB, Klein, ML, Baird, PN, den Hollander, AI, Fauser, S, Yates, JRW, Allikmets, R, Wang, JJ, Schaumberg, DA, Klein, BEK, Hagstrom, SA, Chowers, I, Lotery, AJ, Leveillard, T, Zhang, K, Brilliant, MH, Hewitt, AW, Swaroop, A, Chew, EY, Pericak-Vance, MA, DeAngelis, M, Stambolian, D, Haines, JL, Iyengar, SK, Weber, BHF, Abecasis, GR, Heid, IM, Fritsche, LG, Igl, W, Bailey, JNC, Grassmann, F, Sengupta, S, Bragg-Gresham, JL, Burdon, KP, Hebbring, SJ, Wen, C, Gorski, M, Kim, IK, Cho, D, Zack, D, Souied, E, Scholl, HPN, Bala, E, Lee, KE, Hunter, DJ, Sardell, RJ, Mitchell, P, Merriam, JE, Cipriani, V, Hoffman, JD, Schick, T, Lechanteur, YTE, Guymer, RH, Johnson, MP, Jiang, Y, Stanton, CM, Buitendijk, GHS, Zhan, X, Kwong, AM, Boleda, A, Brooks, M, Gieser, L, Ratnapriya, R, Branham, KE, Foerster, JR, Heckenlively, JR, Othman, MI, Vote, BJ, Liang, HH, Souzeau, E, McAllister, IL, Isaacs, T, Hall, J, Lake, S, Mackey, DA, Constable, IJ, Craig, JE, Kitchner, TE, Yang, Z, Su, Z, Luo, H, Chen, D, Hong, O, Flagg, K, Lin, D, Mao, G, Ferreyra, H, Starke, K, von Strachwitz, CN, Wolf, A, Brandl, C, Rudolph, G, Olden, M, Morrison, MA, Morgan, DJ, Schu, M, Ahn, J, Silvestri, G, Tsironi, EE, Park, KH, Farrer, LA, Orlin, A, Brucker, A, Li, M, Curcio, CA, Mohand-Said, S, Sahel, J-M, Audo, I, Benchaboune, M, Cree, AJ, Rennie, CA, Goverdhan, SV, Grunin, M, Hagbi-Levi, S, Campochiaro, P, Katsanis, N, Holz, FG, Blond, F, Blanche, H, Deleuze, J-F, Igo, RP, Truitt, B, Peachey, NS, Meuer, SM, Myers, CE, Moore, EL, Klein, R, Hauser, MA, Postel, EA, Courtenay, MD, Schwartz, SG, Kovach, JL, Scott, WK, Liew, G, Tan, AG, Gopinath, B, Merriam, JC, Smith, RT, Khan, JC, Shahid, H, Moore, AT, McGrath, JA, Laux, R, Brantley, MA, Agarwal, A, Ersoy, L, Caramoy, A, Langmann, T, Saksens, NTM, de Jong, EK, Hoyng, CB, Cain, MS, Richardson, AJ, Martin, TM, Blangero, J, Weeks, DE, Dhillon, B, van Duijn, CM, Doheny, KF, Romm, J, Klaver, CCW, Hayward, C, Gorin, MB, Klein, ML, Baird, PN, den Hollander, AI, Fauser, S, Yates, JRW, Allikmets, R, Wang, JJ, Schaumberg, DA, Klein, BEK, Hagstrom, SA, Chowers, I, Lotery, AJ, Leveillard, T, Zhang, K, Brilliant, MH, Hewitt, AW, Swaroop, A, Chew, EY, Pericak-Vance, MA, DeAngelis, M, Stambolian, D, Haines, JL, Iyengar, SK, Weber, BHF, Abecasis, GR, and Heid, IM

Abstract

Advanced age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, with limited therapeutic options. Here we report on a study of >12 million variants, including 163,714 directly genotyped, mostly rare, protein-altering variants. Analyzing 16,144 patients and 17,832 controls, we identify 52 independently associated common and rare variants (P < 5 × 10(-8)) distributed across 34 loci. Although wet and dry AMD subtypes exhibit predominantly shared genetics, we identify the first genetic association signal specific to wet AMD, near MMP9 (difference P value = 4.1 × 10(-10)). Very rare coding variants (frequency <0.1%) in CFH, CFI and TIMP3 suggest causal roles for these genes, as does a splice variant in SLC16A8. Our results support the hypothesis that rare coding variants can pinpoint causal genes within known genetic loci and illustrate that applying the approach systematically to detect new loci requires extremely large sample sizes.

Published
2016

14. Whole-genome sequencing to understand the genetic architecture of common gene expression and biomarker phenotypes

Author

Wood, AR, Tuke, MA, Nalls, M, Hernandez, D, Gibbs, JR, Lin, H, Xu, CS, Li, Q, Shen, J, Jun, G, Almeida, M, Tanaka, T, Perry, JR, Gaulton, K, Rivas, M, Pearson, R, Curran, JE, Johnson, MP, Göring, HH, Duggirala, R, Blangero, J, Mccarthy, MI, Bandinelli, S, Murray, A, Weedon, MN, Singleton, A, Melzer, D, Ferrucci, L, and Frayling, TM

Subjects
Adult, Genetic Markers, Male, Genotyping Techniques, Quantitative Trait Loci, and over, Medical and Health Sciences, Polymorphism, Single Nucleotide, Young Adult, Gene Frequency, 80 and over, Humans, Polymorphism, Genetic Association Studies, Aged, Genetics & Heredity, Aged, 80 and over, Genome, Genome, Human, Association Studies Articles, Genetic Variation, High-Throughput Nucleotide Sequencing, Single Nucleotide, Biological Sciences, Middle Aged, Phenotype, Female, Human
Abstract

Initial results from sequencing studies suggest that there are relatively few low-frequency (

Published
2014

16. The transcriptional landscape of age in human peripheral blood

Author

Peters, MJ, Joehanes, R, Pilling, LC, Schurmann, C, Conneely, KN, Powell, J, Reinmaa, E, Sutphin, GL, Zhernakova, A, Schramm, K, Wilson, YA, Kobes, S, Tukiainen, T, Ramos, YF, Göring, HHH, Fornage, M, Liu, Y, Gharib, SA, Stranger, BE, De Jager, PL, Aviv, A, Levy, D, Murabito, JM, Munson, PJ, Huan, T, Hofman, A, Uitterlinden, AG, Rivadeneira, F, Van Rooij, J, Stolk, L, Broer, L, Verbiest, MMPJ, Jhamai, M, Arp, P, Metspalu, A, Tserel, L, Milani, L, Samani, NJ, Peterson, P, Kasela, S, Codd, V, Peters, A, Ward-Caviness, CK, Herder, C, Waldenberger, M, Roden, M, Singmann, P, Zeilinger, S, Illig, T, Homuth, G, Grabe, HJ, Völzke, H, Steil, L, Kocher, T, Murray, A, Melzer, D, Yaghootkar, H, Bandinelli, S, Moses, EK, Kent, JW, Curran, JE, Johnson, MP, Williams-Blangero, S, Westra, HJ, McRae, AF, Smith, JA, Kardia, SLR, Hovatta, I, Perola, M, Ripatti, S, Salomaa, V, Henders, AK, Martin, NG, Smith, AK, Mehta, D, Binder, EB, Nylocks, KM, Kennedy, EM, Klengel, T, Ding, J, Suchy-Dicey, AM, Enquobahrie, DA, Brody, J, Rotter, JI, Chen, YDI, Houwing-Duistermaat, J, Kloppenburg, M, Slagboom, PE, Helmer, Q, Den Hollander, W, Bean, S, Raj, T, Bakhshi, N, Wang, QP, Oyston, LJ, Psaty, BM, Tracy, RP, Montgomery, GW, Turner, ST, Blangero, J, Peters, MJ, Joehanes, R, Pilling, LC, Schurmann, C, Conneely, KN, Powell, J, Reinmaa, E, Sutphin, GL, Zhernakova, A, Schramm, K, Wilson, YA, Kobes, S, Tukiainen, T, Ramos, YF, Göring, HHH, Fornage, M, Liu, Y, Gharib, SA, Stranger, BE, De Jager, PL, Aviv, A, Levy, D, Murabito, JM, Munson, PJ, Huan, T, Hofman, A, Uitterlinden, AG, Rivadeneira, F, Van Rooij, J, Stolk, L, Broer, L, Verbiest, MMPJ, Jhamai, M, Arp, P, Metspalu, A, Tserel, L, Milani, L, Samani, NJ, Peterson, P, Kasela, S, Codd, V, Peters, A, Ward-Caviness, CK, Herder, C, Waldenberger, M, Roden, M, Singmann, P, Zeilinger, S, Illig, T, Homuth, G, Grabe, HJ, Völzke, H, Steil, L, Kocher, T, Murray, A, Melzer, D, Yaghootkar, H, Bandinelli, S, Moses, EK, Kent, JW, Curran, JE, Johnson, MP, Williams-Blangero, S, Westra, HJ, McRae, AF, Smith, JA, Kardia, SLR, Hovatta, I, Perola, M, Ripatti, S, Salomaa, V, Henders, AK, Martin, NG, Smith, AK, Mehta, D, Binder, EB, Nylocks, KM, Kennedy, EM, Klengel, T, Ding, J, Suchy-Dicey, AM, Enquobahrie, DA, Brody, J, Rotter, JI, Chen, YDI, Houwing-Duistermaat, J, Kloppenburg, M, Slagboom, PE, Helmer, Q, Den Hollander, W, Bean, S, Raj, T, Bakhshi, N, Wang, QP, Oyston, LJ, Psaty, BM, Tracy, RP, Montgomery, GW, Turner, ST, and Blangero, J

Abstract

Disease incidences increase with age, but the molecular characteristics of ageing that lead to increased disease susceptibility remain inadequately understood. Here we perform a whole-blood gene expression meta-analysis in 14,983 individuals of European ancestry (including replication) and identify 1,497 genes that are differentially expressed with chronological age. The age-associated genes do not harbor more age-associated CpG-methylation sites than other genes, but are instead enriched for the presence of potentially functional CpG-methylation sites in enhancer and insulator regions that associate with both chronological age and gene expression levels. We further used the gene expression profiles to calculate the 'transcriptomic age' of an individual, and show that differences between transcriptomic age and chronological age are associated with biological features linked to ageing, such as blood pressure, cholesterol levels, fasting glucose, and body mass index. The transcriptomic prediction model adds biological relevance and complements existing epigenetic prediction models, and can be used by others to calculate transcriptomic age in external cohorts.

Published
2015

17. Genome-Wide Transcriptome Directed Pathway Analysis of Maternal Pre-Eclampsia Susceptibility Genes

Author

Shankar, K, Yong, HEJ, Melton, PE, Johnson, MP, Freed, KA, Kalionis, B, Murthi, P, Brennecke, SP, Keogh, RJ, Moses, EK, Shankar, K, Yong, HEJ, Melton, PE, Johnson, MP, Freed, KA, Kalionis, B, Murthi, P, Brennecke, SP, Keogh, RJ, and Moses, EK

Abstract

BACKGROUND: Preeclampsia (PE) is a serious hypertensive pregnancy disorder with a significant genetic component. Numerous genetic studies, including our own, have yielded many susceptibility genes from distinct functional groups. Additionally, transcriptome profiling of tissues at the maternal-fetal interface has likewise yielded many differentially expressed genes. Often there is little overlap between these two approaches, although genes identified in both approaches are significantly associated with PE. We have thus taken a novel integrative bioinformatics approach of analysing pathways common to the susceptibility genes and the PE transcriptome. METHODS: Using Illumina Human Ht12v4 and Wg6v3 BeadChips, transcriptome profiling was conducted on n = 65 normotensive and n = 60 PE decidua basalis tissues collected at delivery. The R software package libraries lumi and limma were used to preprocess transcript data for pathway analysis. Pathways were analysed and constructed using Pathway Studio. We examined ten candidate genes, which are from these functional groups: activin/inhibin signalling-ACVR1, ACVR1C, ACVR2A, INHA, INHBB; structural components-COL4A1, COL4A2 and M1 family aminopeptidases-ERAP1, ERAP2 and LNPEP. RESULTS/CONCLUSION: Major common regulators/targets of these susceptibility genes identified were AGT, IFNG, IL6, INHBA, SERPINE1, TGFB1 and VEGFA. The top two categories of pathways associated with the susceptibility genes, which were significantly altered in the PE decidual transcriptome, were apoptosis and cell signaling (p < 0.001). Thus, susceptibility genes from distinct functional groups share similar downstream pathways through common regulators/targets, some of which are altered in PE. This study contributes to a better understanding of how susceptibility genes may interact in the development of PE. With this knowledge, more targeted functional analyses of PE susceptibility genes in these key pathways can be performed to examine their contributi

Published
2015

18. The transcriptional landscape of age in human peripheral blood

Author

Peters, Marjolein, Joehanes, R, Pilling, LC, Schurmann, C, Conneely, KN, Powell, J, Reinmaa, E, Sutphin, GL, Zhernakova, A, Schramm, K, Wilson, YA, Kobes, S, Tukiainen, T, Ramos, YF, Goring, HHH, Fornage, M, Liu, YM, Gharib, SA, Stranger, BE, De Jager, PL, Aviv, A, Levy, D, Murabito, JM, Munson, PJ, Huan, T, Hofman, Bert, Uitterlinden, André, Rivadeneira, Fernando, van Rooij, J, Stolk, Lisette, Broer, Linda, Verbiest, Michael, Jhamai, M, Arp, Pascal, Metspalu, A, Tserel, L, Milani, L, Samani, NJ, Peterson, P, Kasela, S, Codd, V, Peters, A, Ward-Caviness, CK, Herder, Cindy, Waldenberger, M, Roden, M, Singmann, P, Zeilinger, S, Illig, T, Homuth, G, Grabe, HJ, Voelzke, H, Steil, L, Kocher, T, Murray, A, Melzer, D, Yaghootkar, H, Bandinelli, S, Moses, EK, Kent, JW, Curran, JE, Johnson, MP, Williams-Blangero, S, Westra, HJ, Mcrae, AF, Smith, JA, Kardia, SLR, Hovatta, I, Perola, M, Ripatti, S, Salomaa, V, Henders, AK, Martin, NG, Smith, AK, Mehta, D, Binder, EB, Nylocks, KM, Kennedy, EM, Klengel, T, Ding, J, Suchy-Dicey, AM, Enquobahrie, DA, Brody, J, Rotter, JI, Chen, YDI, Houwing-Duistermaat, J, Kloppenburg, M, Slagboom, PE (Eline), Helmer, Q, den Hollander, W, Bean, S, Raj, T, Bakhshi, N, Wang, QP, Oyston, LJ, Psaty, BM, Tracy, RP, Montgomery, GW, Turner, ST, Blangero, J, Meulenbelt, I, Ressler, KJ, Yang, Jiaqi, Franke, L, Kettunen, J, Visscher, PM, Neely, GG, Korstanje, R, Hanson, RL, Prokisch, H, Ferrucci, L, Esko, T, Teumer, A, van Meurs, Joyce, Andrew, D, Peters, Marjolein, Joehanes, R, Pilling, LC, Schurmann, C, Conneely, KN, Powell, J, Reinmaa, E, Sutphin, GL, Zhernakova, A, Schramm, K, Wilson, YA, Kobes, S, Tukiainen, T, Ramos, YF, Goring, HHH, Fornage, M, Liu, YM, Gharib, SA, Stranger, BE, De Jager, PL, Aviv, A, Levy, D, Murabito, JM, Munson, PJ, Huan, T, Hofman, Bert, Uitterlinden, André, Rivadeneira, Fernando, van Rooij, J, Stolk, Lisette, Broer, Linda, Verbiest, Michael, Jhamai, M, Arp, Pascal, Metspalu, A, Tserel, L, Milani, L, Samani, NJ, Peterson, P, Kasela, S, Codd, V, Peters, A, Ward-Caviness, CK, Herder, Cindy, Waldenberger, M, Roden, M, Singmann, P, Zeilinger, S, Illig, T, Homuth, G, Grabe, HJ, Voelzke, H, Steil, L, Kocher, T, Murray, A, Melzer, D, Yaghootkar, H, Bandinelli, S, Moses, EK, Kent, JW, Curran, JE, Johnson, MP, Williams-Blangero, S, Westra, HJ, Mcrae, AF, Smith, JA, Kardia, SLR, Hovatta, I, Perola, M, Ripatti, S, Salomaa, V, Henders, AK, Martin, NG, Smith, AK, Mehta, D, Binder, EB, Nylocks, KM, Kennedy, EM, Klengel, T, Ding, J, Suchy-Dicey, AM, Enquobahrie, DA, Brody, J, Rotter, JI, Chen, YDI, Houwing-Duistermaat, J, Kloppenburg, M, Slagboom, PE (Eline), Helmer, Q, den Hollander, W, Bean, S, Raj, T, Bakhshi, N, Wang, QP, Oyston, LJ, Psaty, BM, Tracy, RP, Montgomery, GW, Turner, ST, Blangero, J, Meulenbelt, I, Ressler, KJ, Yang, Jiaqi, Franke, L, Kettunen, J, Visscher, PM, Neely, GG, Korstanje, R, Hanson, RL, Prokisch, H, Ferrucci, L, Esko, T, Teumer, A, van Meurs, Joyce, and Andrew, D

Abstract

Disease incidences increase with age, but the molecular characteristics of ageing that lead to increased disease susceptibility remain inadequately understood. Here we perform a whole-blood gene expression meta-analysis in 14,983 individuals of European ancestry (including replication) and identify 1,497 genes that are differentially expressed with chronological age. The age-associated genes do not harbor more age-associated CpG-methylation sites than other genes, but are instead enriched for the presence of potentially functional CpG-methylation sites in enhancer and insulator regions that associate with both chronological age and gene expression levels. We further used the gene expression profiles to calculate the 'transcriptomic age' of an individual, and show that differences between transcriptomic age and chronological age are associated with biological features linked to ageing, such as blood pressure, cholesterol levels, fasting glucose, and body mass index. The transcriptomic prediction model adds biological relevance and complements existing epigenetic prediction models, and can be used by others to calculate transcriptomic age in external cohorts.

Published
2015

19. In utero Fetal Muscle Biopsy Alters Diagnosis and Carrier Risks in Duchenne and Becker Muscular Dystrophy

Author

Evans, Mi, Krivchenia, El, Johnson, Mp, Quintero, Ra, King, M, Pegoraro, Elena, Hoffman, Ep, Dubrovsky, Al, Taratuto, Al, Sevlever, G, Schultz, M, and Hoop, Rc

Subjects
Adult, Male, musculoskeletal diseases, Heterozygote, Embryology, medicine.medical_specialty, Pathology, Biopsy, Duchenne muscular dystrophy, Genetic Counseling, Prenatal diagnosis, Muscular Dystrophies, Dystrophin, Pregnancy, Prenatal Diagnosis, Internal medicine, medicine, Humans, Radiology, Nuclear Medicine and imaging, Diagnostic Errors, Muscular dystrophy, Muscle, Skeletal, Fetus, Muscle biopsy, biology, medicine.diagnostic_test, business.industry, fungi, food and beverages, Obstetrics and Gynecology, Abortion, Induced, General Medicine, medicine.disease, Fetal Diseases, Endocrinology, In utero, Pediatrics, Perinatology and Child Health, biology.protein, Female, business
Abstract

We have previously shown that Duchenne muscular dystrophy (DMD) can be diagnosed by fetal muscle biopsy and immunohistochemical staining showing the absence of dystrophin. In Becker muscular dystrophy (BMD), there is a variable dystrophin staining pattern.A 26-year-old, gravida 5, para 1, SAB 2, VIP 1, white female had a son with the diagnosis of BMD, with no other affected family members. In the current pregnancy, the male fetus inherited the same X chromosome.Fetal muscle biopsy revealed no dystrophin, consistent with the diagnosis of DMD, prompting re-analysis of the sibling whose diagnosis was then changed to DMD.Molecular techniques in prenatal diagnosis in this case not only led to the diagnosis of a severe disorder in the current pregnancy, but changed the diagnosis in another child, allowing for more appropriate counseling of this couple.

Published
1995
Full Text
View/download PDF

20. Identification of a rare coding variant in complement 3 associated with age-related macular degeneration

Author

Zhan, X, Larson, DE, Wang, C, Koboldt, DC, Sergeev, YV, Fulton, RS, Fulton, LL, Fronick, CC, Branham, KE, Bragg-Gresham, J, Jun, G, Hu, Y, Kang, HM, Liu, D, Othman, M, Brooks, M, Ratnapriya, R, Boleda, A, Grassmann, F, von Strachwitz, C, Olson, LM, Buitendijk, GHS, Hofman, A, van Duijn, CM, Cipriani, V, Moore, AT, Shahid, H, Jiang, Y, Conley, YP, Morgan, DJ, Kim, IK, Johnson, MP, Cantsilieris, S, Richardson, AJ, Guymer, RH, Luo, H, Ouyang, H, Licht, C, Pluthero, FG, Zhang, MM, Zhang, K, Baird, PN, Blangero, J, Klein, ML, Farrer, LA, DeAngelis, MM, Weeks, DE, Gorin, MB, Yates, JRW, Klaver, CCW, Pericak-Vance, MA, Haines, JL, Weber, BHF, Wilson, RK, Heckenlively, JR, Chew, EY, Stambolian, D, Mardis, ER, Swaroop, A, Abecasis, GR, Zhan, X, Larson, DE, Wang, C, Koboldt, DC, Sergeev, YV, Fulton, RS, Fulton, LL, Fronick, CC, Branham, KE, Bragg-Gresham, J, Jun, G, Hu, Y, Kang, HM, Liu, D, Othman, M, Brooks, M, Ratnapriya, R, Boleda, A, Grassmann, F, von Strachwitz, C, Olson, LM, Buitendijk, GHS, Hofman, A, van Duijn, CM, Cipriani, V, Moore, AT, Shahid, H, Jiang, Y, Conley, YP, Morgan, DJ, Kim, IK, Johnson, MP, Cantsilieris, S, Richardson, AJ, Guymer, RH, Luo, H, Ouyang, H, Licht, C, Pluthero, FG, Zhang, MM, Zhang, K, Baird, PN, Blangero, J, Klein, ML, Farrer, LA, DeAngelis, MM, Weeks, DE, Gorin, MB, Yates, JRW, Klaver, CCW, Pericak-Vance, MA, Haines, JL, Weber, BHF, Wilson, RK, Heckenlively, JR, Chew, EY, Stambolian, D, Mardis, ER, Swaroop, A, and Abecasis, GR

Abstract

Macular degeneration is a common cause of blindness in the elderly. To identify rare coding variants associated with a large increase in risk of age-related macular degeneration (AMD), we sequenced 2,335 cases and 789 controls in 10 candidate loci (57 genes). To increase power, we augmented our control set with ancestry-matched exome-sequenced controls. An analysis of coding variation in 2,268 AMD cases and 2,268 ancestry-matched controls identified 2 large-effect rare variants: previously described p.Arg1210Cys encoded in the CFH gene (case frequency (fcase) = 0.51%; control frequency (fcontrol) = 0.02%; odds ratio (OR) = 23.11) and newly identified p.Lys155Gln encoded in the C3 gene (fcase = 1.06%; fcontrol = 0.39%; OR = 2.68). The variants suggest decreased inhibition of C3 by complement factor H, resulting in increased activation of the alternative complement pathway, as a key component of disease biology.

Published
2013

21. Genome-Wide Association Scan Identifies a Risk Locus for Preeclampsia on 2q14, Near the Inhibin, Beta B Gene

Author

Grant, SFA, Johnson, MP, Brennecke, SP, East, CE, Goering, HHH, Kent, JW, Dyer, TD, Said, JM, Roten, LT, Iversen, A-C, Abraham, LJ, Heinonen, S, Kajantie, E, Kere, J, Kivinen, K, Pouta, A, Laivuori, H, Austgulen, R, Blangero, J, Moses, EK, Grant, SFA, Johnson, MP, Brennecke, SP, East, CE, Goering, HHH, Kent, JW, Dyer, TD, Said, JM, Roten, LT, Iversen, A-C, Abraham, LJ, Heinonen, S, Kajantie, E, Kere, J, Kivinen, K, Pouta, A, Laivuori, H, Austgulen, R, Blangero, J, and Moses, EK

Abstract

Elucidating the genetic architecture of preeclampsia is a major goal in obstetric medicine. We have performed a genome-wide association study (GWAS) for preeclampsia in unrelated Australian individuals of Caucasian ancestry using the Illumina OmniExpress-12 BeadChip to successfully genotype 648,175 SNPs in 538 preeclampsia cases and 540 normal pregnancy controls. Two SNP associations (rs7579169, p = 3.58×10(-7), OR = 1.57; rs12711941, p = 4.26×10(-7), OR = 1.56) satisfied our genome-wide significance threshold (modified Bonferroni p<5.11×10(-7)). These SNPs reside in an intergenic region less than 15 kb downstream from the 3' terminus of the Inhibin, beta B (INHBB) gene on 2q14.2. They are in linkage disequilibrium (LD) with each other (r(2) = 0.92), but not (r(2)<0.80) with any other genotyped SNP ±250 kb. DNA re-sequencing in and around the INHBB structural gene identified an additional 25 variants. Of the 21 variants that we successfully genotyped back in the case-control cohort the most significant association observed was for a third intergenic SNP (rs7576192, p = 1.48×10(-7), OR = 1.59) in strong LD with the two significant GWAS SNPs (r(2)>0.92). We attempted to provide evidence of a putative regulatory role for these SNPs using bioinformatic analyses and found that they all reside within regions of low sequence conservation and/or low complexity, suggesting functional importance is low. We also explored the mRNA expression in decidua of genes ±500 kb of INHBB and found a nominally significant correlation between a transcript encoded by the EPB41L5 gene, ∼250 kb centromeric to INHBB, and preeclampsia (p = 0.03). We were unable to replicate the associations shown by the significant GWAS SNPs in case-control cohorts from Norway and Finland, leading us to conclude that it is more likely that these SNPs are in LD with as yet unidentified causal variant(s).

Published
2012

22. Genetic and Molecular Functional Characterization of Variants within TNFSF13B, a Positional Candidate Preeclampsia Susceptibility Gene on 13q

Author

Brandstaetter, A, Fenstad, MH, Johnson, MP, Roten, LT, Aas, PA, Forsmo, S, Klepper, K, East, CE, Abraham, LJ, Blangero, J, Brennecke, SP, Austgulen, R, Moses, EK, Brandstaetter, A, Fenstad, MH, Johnson, MP, Roten, LT, Aas, PA, Forsmo, S, Klepper, K, East, CE, Abraham, LJ, Blangero, J, Brennecke, SP, Austgulen, R, and Moses, EK

Abstract

BACKGROUND: Preeclampsia is a serious pregnancy complication, demonstrating a complex pattern of inheritance. The elucidation of genetic liability to preeclampsia remains a major challenge in obstetric medicine. We have adopted a positional cloning approach to identify maternal genetic components, with linkages previously demonstrated to chromosomes 2q, 5q and 13q in an Australian/New Zealand familial cohort. The current study aimed to identify potential functional and structural variants in the positional candidate gene TNFSF13B under the 13q linkage peak and assess their association status with maternal preeclampsia genetic susceptibility. METHODOLOGY/PRINCIPAL FINDINGS: The proximal promoter and coding regions of the positional candidate gene TNFSF13B residing within the 13q linkage region was sequenced using 48 proband or founder individuals from Australian/New Zealand families. Ten sequence variants (nine SNPs and one single base insertion) were identified and seven SNPs were successfully genotyped in the total Australian/New Zealand family cohort (74 families/480 individuals). Borderline association to preeclampsia (p = 0.0153) was observed for three rare SNPs (rs16972194, rs16972197 and rs56124946) in strong linkage disequilibrium with each other. Functional evaluation by electrophoretic mobility shift assays showed differential nuclear factor binding to the minor allele of the rs16972194 SNP, residing upstream of the translation start site, making this a putative functional variant. The observed genetic associations were not replicated in a Norwegian case/control cohort (The Nord-Trøndelag Health Study (HUNT2), 851 preeclamptic and 1,440 non-preeclamptic women). CONCLUSION/SIGNIFICANCE: TNFSF13B has previously been suggested to contribute to the normal immunological adaption crucial for a successful pregnancy. Our observations support TNFSF13B as a potential novel preeclampsia susceptibility gene. We discuss a possible role for TNFSF13B in preeclampsia patho

Published
2010

29. Carbon black and fullerenes: New discoveries in early formation mechanisms and nucleation

Author

UCL - FSA/MAPR - Département des sciences des matériaux et des procédés, Johnson, MP, Locke, RW, Donnet, JB, Wang, TK, Wang, CC, Bertrand, Patrick, UCL - FSA/MAPR - Département des sciences des matériaux et des procédés, Johnson, MP, Locke, RW, Donnet, JB, Wang, TK, Wang, CC, and Bertrand, Patrick

Abstract

Recent studies on the formation of carbon black have resulted in the previously unreported finding of buckminster-fullerene, C-60, in trace quantities in the toluene extractable materials.(1,2) High-resolution transmission electron microscopy (HRTEM) experiments indicate the molecule may be functioning as a nucleation site in the formation of primary particles of carbon black.(1-4) Time-of-flight secondary ion mass spectroscopy (ToF-SIMS) and X-ray photoelectron spectroscopy (XPS) provided the surface chemical analysis of conventional and experimental carbon blacks. The toluene extracts represented the precursor compounds present in the gaseous phase at the time of quench. The extracts were analyzed by Fourier transform infrared (FTIR) spectroscopy, liquid chromatography (LC)/mass spectroscopy (MS) and elemental composition. The data, taken as a whole, have led to a more clear understanding of the competitive chemical pathways occurring during the inception and nucleation of a primary particle of carbon black. Direct observation of nucleation sites and types are possible with HRTEM analysis.

Published
2000

40. Transitions of Care in Patients Receiving Oral Anticoagulants: General Principles, Procedures, and Impact of New Oral Anticoagulants.

Author

Johnson MP.

Abstract

BACKGROUND:: Most patients requiring anticoagulation therapy while hospitalized will continue this therapy as outpatients. This transition can be associated with gaps in care related to anticoagulation therapy that increase the risk of adverse events, rehospitalizations, and death. Warfarin, the most commonly used oral anticoagulant, presents distinct management challenges, including drug-food and drug-drug interactions, a narrow therapeutic window, and the requirements for periodic blood monitoring and dose adjustments, particularly during the hospital discharge process. PURPOSE:: This review explores clinical challenges and potential solutions surrounding anticoagulation therapy with warfarin during transitions of care, as well as discusses newer anticoagulants that are approved or are in late stages of development for the prevention of thromboembolic events. CONCLUSIONS:: Diligence, careful planning, and close communication between patients and healthcare providers during and after discharge are required to ensure that patients remain adequately and safely anticoagulated with warfarin in the outpatient setting. New oral anticoagulants may offer the possibility of safer and simpler care for patients requiring anticoagulation. CLINICAL IMPLICATIONS:: We summarize the latest guidelines and recommendations for safe hospital discharge and apply them to the specific case of discharging a warfarin-treated patient. In addition, we discuss the new oral anticoagulants and their potential to offer more efficacious and easier-to-manage anticoagulation. [ABSTRACT FROM AUTHOR]

Published
2013
Full Text
View/download PDF

44. Paradoxical effects of the cannabinoid CB2 receptor agonist GW405833 on rat osteoarthritic knee joint pain.

Author

Schuelert N, Zhang C, Mogg AJ, Broad LM, Hepburn DL, Nisenbaum ES, Johnson MP, McDougall JJ, Schuelert, N, Zhang, C, Mogg, A J, Broad, L M, Hepburn, D L, Nisenbaum, E S, Johnson, M P, and McDougall, J J

Abstract

Objective: The present study examined whether local administration of the cannabinoid-2 (CB(2)) receptor agonist GW405833 could modulate joint nociception in control rat knee joints and in an animal model of osteoarthritis (OA).Method: OA was induced in male Wistar rats by intra-articular injection of sodium monoiodo-acetate with a recovery period of 14 days. Immunohistochemistry was used to evaluate the expression of CB(2) and transient receptor potential vanilloid channel-1 (TRPV1) receptors in the dorsal root ganglion (DRG) and synovial membrane of sham- and sodium mono-iodoacetate (MIA)-treated animals. Electrophysiological recordings were made from knee joint primary afferents in response to rotation of the joint both before and following close intra-arterial injection of different doses of GW405833. The effect of intra-articular GW405833 on joint pain perception was determined by hindlimb incapacitance. An in vitro neuronal release assay was used to see if GW405833 caused release of an inflammatory neuropeptide (calcitonin gene-related peptide - CGRP).Results: CB(2) and TRPV1 receptors were co-localized in DRG neurons and synoviocytes in both sham- and MIA-treated animals. Local application of the GW405833 significantly reduced joint afferent firing rate by up to 31% in control knees. In OA knee joints, however, GW405833 had a pronounced sensitising effect on joint mechanoreceptors. Co-administration of GW405833 with the CB(2) receptor antagonist AM630 or pre-administration of the TRPV1 ion channel antagonist SB366791 attenuated the sensitising effect of GW405833. In the pain studies, intra-articular injection of GW405833 into OA knees augmented hindlimb incapacitance, but had no effect on pain behaviour in saline-injected control joints. GW405833 evoked increased CGRP release via a TRPV1 channel-dependent mechanism.Conclusion: These data indicate that GW405833 reduces the mechanosensitivity of afferent nerve fibres in control joints but causes nociceptive responses in OA joints. The observed pro-nociceptive effect of GW405833 appears to involve TRPV1 receptors. [ABSTRACT FROM AUTHOR]

Published
2010
Full Text
View/download PDF

46. OEIS sequence--a rare congenital anomaly with prenatal evaluation and postnatal outcome in six cases.

Author

Tiblad E, Wilson RD, Carr M, Flake AW, Hedrick H, Johnson MP, Bebbington MW, Mann S, Adzick NS, Tiblad, Eleonor, Wilson, R Douglas, Carr, Michael, Flake, Alan W, Hedrick, Holly, Johnson, Mark P, Bebbington, Michael W, Mann, Stephanie, and Adzick, N Scott

Abstract

Objective: To describe the outcome of children prenatally diagnosed with omphalocele, exstrophy of the cloaca, imperforate anus and spinal defects (OEIS). Method: A retrospective study identified six fetuses diagnosed with OEIS from 2001 to 2007 and data were collected from pre- and postnatal charts. Results: Prenatal findings included an infraumbilical wall defect, omphalocele, no visible bladder and spinal defects. Abnormalities of the upper urinary tract were seen in all cases and ambiguous genitalia in four. Four women continued the pregnancy after prenatal counseling and these fetuses were liveborn at a mean gestational age of 36 weeks. Postnatal evaluation confirmed the prenatal findings in the neonates. The children have required multiple surgeries. Common complications are recurrent urinary tract infections and failure to thrive. Neurodevelopment and motor function are normal in all children, except for one child with lower extremity paralysis and global developmental delay. Conclusion: Prenatal diagnosis of OEIS is reliable and no significant differences in pre- and postnatal findings in the children were found. Correct diagnosis of abnormalities of external and internal genitalia remains a challenge and abnormalities of the upper urinary tract are common. Postnatal survival is good but associated with considerable morbidity and psychosocial consequences. [ABSTRACT FROM AUTHOR]

Published
2008
Full Text
View/download PDF

47. Conflict and control: gender symmetry and asymmetry in domestic violence.

Author

Johnson MP

Abstract

Four types of individual partner violence are identified based on the dyadic control context of the violence. In intimate terrorism, the individual is violent and controlling, the partner is not. In violent resistance, the individual is violent but not controlling; the partner is the violent and controlling one. In situational couple violence, although the individual is violent, neither the individual nor the partner is violent and controlling. In mutual violent control, the individual and the partner are violent and controlling. Evidence is presented that situational couple violence dominates in general surveys, intimate terrorism and violent resistance dominate in agency samples, and this is the source of differences across studies with respect to the gender symmetry of partner violence. An argument is made that if we want to understand partner violence, intervene effectively in individual cases, or make useful policy recommendations, we must make these distinctions in our research. [ABSTRACT FROM AUTHOR]

Published
2006
Full Text
View/download PDF

48. Verbal labeling as an assimilation mnemonic for abstract visual stimuli: the sample case of recognition memory for Chinese characters.

Author

Verhaeghen P, Palfai T, and Johnson MP

Abstract

In four experiments, we examined the effect that presenting a verbal stimulus (viz., an English noun) alongside an abstract visual stimulus (viz., a Chinese character) enhances recognition memory for the abstract visual stimulus. Experiment 1 demonstrated that the character-plus-word combination at both encoding and retrieval results in better recognition than does a character-alone presentation or presenting the combination at encoding only. Experiment 2 demonstrated that presenting the word first and then the character results in better performance than does the opposite order. Experiment 3 showed that the concreteness value of the word, not familiarity, is the critical factor. In Experiment 4, presentation time was varied. More time was needed for liftoff from chance level for the word-character combination than for the character-alone presentation. Together, the results suggest that subjects spontaneously assimilate stimulus and word into a single representation by building asymmetric effortful imagery associations, going from the English word to the Chinese character. [ABSTRACT FROM AUTHOR]

Published
2006
Full Text
View/download PDF

49. Apples and oranges in child custody disputes: intimate terrorism vs. situational couple violence.

Author

Johnson MP

Abstract

In response to Dutton's (this issue) critique of feminist theories of domestic violence, the author of this article makes three points relevant to the debate about the gender asymmetry of intimate partner violence. First, there are three major types of intimate partner violence, only one of which (intimate terrorism) is the kind of violence that we all think of when we hear the term 'domestic violence.' Second, both major types of sampling designs in domestic violence research are seriously biased, and those biases account for the fact that both sides of this debate have been able to marshal ostensibly contradictory empirical evidence for their position. Third, intimate terrorism (also know as domestic violence, spouse abuse, wife-beating, etc.) is, indeed, primarily male-perpetrated and, in the case of heterosexual relationships, probably best understood through some version of a feminist theory of domestic violence. The author then discusses the implications of these points for assessment of risk in child custody deliberations. [ABSTRACT FROM AUTHOR]

Published
2005

Catalog

Books, media, physical & digital resources
See catalog results