Search

Your search keyword '"Darby, C"' showing total 720 results
Start Over Author "Darby, C"
720 results on '"Darby, C"'

1. Title: Doctoral writing workshops: A preregistered, randomized controlled trial (PREPRINT)

Author

Sarnecka, Barbara, Silva, Paulina N, Coon, Jeff, Vickers, Darby C, Goldstein, Rena B, and Rouder, Jeffrey N

Subjects
Writing, Higher education, Graduate education, Doctoral training
Abstract

Doctoral students were randomly assigned to a five-week (30-hour) faculty-led writing workshop (the intervention) or to a waitlist control group. After completing the workshop, students enjoyed writing more, found it easier, and had more confidence in themselves as writers. They were able to write productively in shorter blocks of time, and they engaged in more planning of their writing and research. The intervention also increased the frequency with which students paused for reflection or positive thinking, and it elicited more new writing from participants about their research, relative to controls. Effects were maintained in a peer-led writing maintenance group after the workshop ended. This workshop model can be used across disciplines to support doctoral students’ training in academic and scientific writing.

Published
2023

4. Title: Doctoral writing workshops: A preregistered, randomized controlled trial (PREPRINT)

Author

Sarnecka, Barbara, Silva, Paulina N, Coon, Jeff, Vickers, Darby C, Goldstein, Rena B, and Rouder, Jeffrey N

Subjects
Writing, Higher education, Graduate education, Doctoral training
Abstract

Doctoral students were randomly assigned to a five-week (30-hour) faculty-led writing workshop (the intervention) or to a waitlist control group. After completing the workshop, students enjoyed writing more, found it easier, and had more confidence in themselves as writers. They were able to write productively in shorter blocks of time, and they engaged in more planning of their writing and research. The intervention also increased the frequency with which students paused for reflection or positive thinking, and it elicited more new writing from participants about their research, relative to controls. Effects were maintained in a peer-led writing maintenance group after the workshop ended. This workshop model can be used across disciplines to support doctoral students’ training in academic and scientific writing.

Published
2021

5. Doctoral Writing Workshops: A Pre-Registered, Randomized Controlled Trial

Author

Sarnecka, Barbara W., Silva, Paulina N., Coon, Jeff, Vickers, Darby C., Goldstein, Rena B., and Rouder, Jeffrey N.

Abstract

Doctoral students were randomly assigned to a five-week (30-h) faculty-led writing workshop intervention, either preceded by a five-week (waiting list) control phase or followed by a five-week maintenance phase. In the workshop, students wrote together, received instruction in genres of academic writing (literature reviews, scientific articles, funding proposals, and presentations), and exchanged feedback on drafts. As a result of the workshop students enjoyed writing more, found writing easier, and gained confidence in themselves as academic writers. They felt able to write productively in shorter blocks of time, and they engaged in more short-term, medium-term, and long-term planning of their research. The intervention also caused participants to pause more frequently for reflection or positive thinking and to generate more new writing. Effects were maintained in a peer-led writing maintenance group for at least five weeks after the intervention ended. This is the first randomized controlled trial of a doctoral-level writing intervention to date and has the potential to support doctoral training in academic and scientific writing across the Social Sciences, Education, and the Humanities.

Published
2022
Full Text
View/download PDF

7. Plasma Prostaglandin E2 Metabolite Levels Predict Type 2 Diabetes Status and One-Year Therapeutic Response Independent of Clinical Markers of Inflammation

Author

Rachel J. Fenske, Alicia M. Weeks, Michael Daniels, Randall Nall, Samantha Pabich, Allison L. Brill, Darby C. Peter, Margaret Punt, Elizabeth D. Cox, Dawn Belt Davis, and Michelle E. Kimple

Subjects
type 2 diabetes, prostaglandin E2, inflammation, diabetes control, biomarker, HbA1c, Microbiology, QR1-502
Abstract

Over half of patients with type 2 diabetes (T2D) are unable to achieve blood glucose targets despite therapeutic compliance, significantly increasing their risk of long-term complications. Discovering ways to identify and properly treat these individuals is a critical problem in the field. The arachidonic acid metabolite, prostaglandin E2 (PGE2), has shown great promise as a biomarker of β-cell dysfunction in T2D. PGE2 synthesis, secretion, and downstream signaling are all upregulated in pancreatic islets isolated from T2D mice and human organ donors. In these islets, preventing β-cell PGE2 signaling via a prostaglandin EP3 receptor antagonist significantly improves their glucose-stimulated and hormone-potentiated insulin secretion response. In this clinical cohort study, 167 participants, 35 non-diabetic, and 132 with T2D, were recruited from the University of Wisconsin Hospital and Clinics. At enrollment, a standard set of demographic, biometric, and clinical measurements were performed to quantify obesity status and glucose control. C reactive protein was measured to exclude acute inflammation/illness, and white cell count (WBC), erythrocyte sedimentation rate (ESR), and fasting triglycerides were used as markers of systemic inflammation. Finally, a plasma sample for research was used to determine circulating PGE2 metabolite (PGEM) levels. At baseline, PGEM levels were not correlated with WBC and triglycerides, only weakly correlated with ESR, and were the strongest predictor of T2D disease status. One year after enrollment, blood glucose management was assessed by chart review, with a clinically-relevant change in hemoglobin A1c (HbA1c) defined as ≥0.5%. PGEM levels were strongly predictive of therapeutic response, independent of age, obesity, glucose control, and systemic inflammation at enrollment. Our results provide strong support for future research in this area.

Published
2022
Full Text
View/download PDF

9. Celebrating Diversity: Approaching Families through Their Food.

Author

National Center for Education in Maternal and Child Health, Arlington, VA., Eliades, Darby C., Suitor, Carol West, Eliades, Darby C., Suitor, Carol West, and National Center for Education in Maternal and Child Health, Arlington, VA.

Abstract

This book is designed to help nutrition educators communicate with an increasingly diverse clientele on issues related to food and nutrition, presenting strategies and ideas that can be used with families from various cultural backgrounds. Chapter 1 addresses the changing cultural demographics in the United States and the relationship between culture and food. Chapter 2 focuses on techniques for using food stories and recipes to open dialogues about nutrition. Chapter 3 examines changing food patterns among immigrants and cultural groups, while Chapter 4 discusses food availability, family traditions, status foods, traditional preparation, seasonings, frequency of consumption, health beliefs, traditional celebrations, and economics. Chapter 5 focuses on communicating with clients from different cultural groups, stressing the need to listen and observe, combine nutrition with social events, reach the right family members, and acknowledge the importance of the age and experience of family members. Chapter 6 presents strategies for working within community groups, while Chapter 7 addresses the challenges of working in a multilingual environment. Chapter 8 provides practical advice for finding out what clients are eating, sharing important nutrition messages with them, and using resources available in the community. (Contains a list of 23 resource materials. (MDM)

Published
1994

10. Development and application of high-throughput screens for the discovery of compounds that disrupt ErbB4 signaling: Candidate cancer therapeutics.

Author

Richard L Cullum, Lauren M Lucas, Jared I Senfeld, John T Piazza, Logan T Neel, Kanupriya Whig, Ling Zhai, Mackenzie H Harris, Cristina C Rael, Darby C Taylor, Laura J Cook, David P Kaufmann, Christopher P Mill, Megan A Jacobi, Forrest T Smith, Mark Suto, Robert Bostwick, Ram B Gupta, Allan E David, and David J Riese Ii

Subjects
Medicine, Science
Abstract

Whereas recent clinical studies report metastatic melanoma survival rates high as 30-50%, many tumors remain nonresponsive or become resistant to current therapeutic strategies. Analyses of The Cancer Genome Atlas (TCGA) skin cutaneous melanoma (SKCM) data set suggests that a significant fraction of melanomas potentially harbor gain-of-function mutations in the gene that encodes for the ErbB4 receptor tyrosine kinase. In this work, a drug discovery strategy was developed that is based on the observation that the Q43L mutant of the naturally occurring ErbB4 agonist Neuregulin-2beta (NRG2β) functions as a partial agonist at ErbB4. NRG2β/Q43L stimulates tyrosine phosphorylation, fails to stimulate ErbB4-dependent cell proliferation, and inhibits agonist-induced ErbB4-dependent cell proliferation. Compounds that exhibit these characteristics likely function as ErbB4 partial agonists, and as such hold promise as therapies for ErbB4-dependent melanomas. Consequently, three highly sensitive and reproducible (Z' > 0.5) screening assays were developed and deployed for the identification of small-molecule ErbB4 partial agonists. Six compounds were identified that stimulate ErbB4 phosphorylation, fail to stimulate ErbB4-dependent cell proliferation, and appear to selectively inhibit ErbB4-dependent cell proliferation. Whereas further characterization is needed to evaluate the full therapeutic potential of these molecules, this drug discovery platform establishes reliable and scalable approaches for the discovery of ErbB4 inhibitors.

Published
2020
Full Text
View/download PDF

11. Choices of Stent and Cerebral Protection in the Ongoing ACST-2 Trial: A Descriptive Study

Author

Fraedrich, G., Rantner, B., Gizewski, E., Gruber, I., Hendriks, J., Cras, P., Lauwers, P., van Scheil, P., Vermassen, F., Van Herzeele, I., Geenens, M., Hemelsoet, D., Lerut, P., Lambrecht, B., Saad, G., Peeters, A., Bosiers, M., da Silva, E., de Luccia, N., Sitrangulo, J.C., Jr., Estenssoro, A.E.V., Presti, C., Casella, I., Monteiro, J.A.T., Campos, W., Jr., Puech-Leao, P., Petrov, V., Bachvarov, C., Hill, M., Mitha, A., Wong, J., Liu, C.-W., Bao, L., Yu, C., Cvjetko, I., Vidjak, V., Fiedler, J., Ostry, S., Sterba, L., Kostal, P., Staffa, R., Vlachovsky, R., Privara, M., Kriz, Z., Vojtisek, B., Krupa, P., Reif, M., Benes, V., Buchvald, P., Endrych, L., Prochazka, V., Kuliha, M., Otahal, D., Hrbac, T., Netuka, D., Mohapl, M., Kramier, F., Eldessoki, M., Heshmat, H., Abd-Allah, F., Palmiste, V., Margus, S., Toomsoo, T., Becquemin, J.-P., Bergeron, P., Abdulamit, T., Cardon, J.-M., Debus, S., Thomalla, G., Fiehler, J., Gerloss, C., Grzyska, U., Storck, M., LaMacchia, E., Eckstein, H.H., Söllner, H., Berger, H., Kallmayer, M., Popert, H., Zimmermann, A., Guenther, A., Klingner, C., Mayer, T., Schubert, J., Zanow, J., Scheinert, D., Banning-Eichenseer, U., Bausback, Y., Branzan, D., Braünilch, S., Lenzer, J., Schidt, A., Staab, H., Ulirch, M., Barlinn, J., Haase, K., Abramyuk, A., Bodechtel, U., Gerber, J., Reeps, C., Pfeiffer, T., Torello, G., Cöster, A., Giannoukas, A., Spanos, K., Matsagkas, M., Koutias, S., Vasdekis, S., Kakisis, J., Moulakakis, K., Lazaris, A., Liapas, C., Brountzos, E., Lazarides, M., Ioannou, N., Polydorou, A., Fulop, B., Fako, E., Voros, E., Bodosi, M., Nemeth, T., Barzo, P., Pazdernyik, S., Entz, L., Szeberin, Z., Dosa, E., Nemes, B., Jaranyi, Z., Pazdernyia, S., Madhaban, P., Hoffman, A., Nikolsky, E., Beyar, R., Casana, R., Tolva, V., Silingardi, R., Lauricella, A., Coppi, G., Nicoloci, E., Tusini, N., Strozzi, F., Vecchiati, E., Ferri, M., Ferrero, E., Psacharopulo, D., Gaggiano, A., Viazzo, A., Farchioni, L., Parlani, G., Caso, V., De Rangoy, P., Verzini, F., Castelli, P., DeLodovici, M.L., Carrafiello, G., Ierardi, A.M., Piffaretti, G., Nano, G., Occhiuto, M.T., Malacrida, G., Tealdi, D., Steghter, S., Stella, A., Pini, R., Faggioli, G., Sacca, S., Negri, M.D., Palombo, M., Perfumo, M.C., Fadda, G.F., Kasemi, H., Cernetti, C., Tonello, D., Visonà, A., Mangialardi, N., Ronchey, S., Altavista, M.C., Michelagnoli, S., Chisci, E., Speziale, F., Capoccia, L., Veroux, P., Giaquinta, A., Patti, F., Pulli, R., Boggia, P., Angiletta, D., Amatucci, G., Spinetti, F., Mascoli, F., Tsolaki, E., Civilini, E., Reimers, B., Setacci, C., Pogany, G., Odero, A., Accrocca, F., Bajardi, G., Takashi, I., Masayuki, E., Hidenori, E., Aidashova, B., Kospanov, N., Bakke, S., Skjelland, M., Czlonkowska, A., Kobayashi, A., Proczka, R., Dowzenko, A., Czepel, W., Polanski, J., Bialek, P., Ozkinis, G., Snoch-Ziólkiewicz, M., Gabriel, M., Stanisic, M., Iwanowski, W., Andziak, P., Gonçalves, F.B., Starodubtsev, V., Ignatenko, P., Karpenko, A., Radak, D., Aleksic, N., Sagic, D., Davidovic, L., Koncar, I., Tomic, I., Colic, M., Bartkoy, D., Rusnak, F., Gaspirini, M., Praczek, P., Milosevic, Z., Flis, V., Bergauer, A., Kobilica, N., Miksic, K., Matela, J., Blanco, E., Guerra, M., Riambau, V., Gillgren, P., Skioldebrand, C., Nymen, N., Berg, B., Delle, M., Formgren, J., Kally, T.B., Qvarfordt, P., Plate, G., Pärson, H., Lindgren, H., Bjorses, K., Gottsäter, A., Warvsten, M., Kristmundsson, T., Forssell, C., Malina, M., Holst, J., Kuhme, T., Sonesson, B., Lindblad, B., Kolbel, T., Acosta, S., Bonati, L., Traenka, C., Mueller, M., Lattman, T., Wasner, M., Mujagic, E., Von Hessling, A., Isaak, A., Stierli, P., Eugster, T., Mariani, L., Stippich, C., Wolff, T., Kahles, T., de Borst, G.J., Toorop, R., Moll, F., Lo, R., Meershoek, A., Jahrome, A.K., Vos, A.W.F., Schuiling, W., Keunen, R., Reijnen, M., Macsweeney, S., McConachie, N., Southam, A., Stansby, G., Lees, T., Lambert, D., Clarke, M., Wyatt, M., Kappadath, S., Wales, L., Jackson, R., Raudonaitis, A., MacDonald, S., Dunlop, P., Brown, A., Vetrivel, S., Bajoriene, M., Gopi, R., McCollum, C., Wolowczyk, L., Ghosh, J., Seriki, D., Ashleigh, R., Butterfield, J., Welch, M., Smyth, J.V., Briley, D., Schulz, U., Perkins, J., Hands, L., Kuker, W., Darby, C., Handa, A., Sekaran, L., Poskitt, K., Bulbulia, R., Morrison, J., Guyler, P., Grunwald, I., Brown, J., Jakeways, M., Tysoe, S., Hargroves, D., Gunathilagan, G., Insall, R., Senaratne, J., Beard, J., Cleveland, T., Nawaz, S., Lonsdale, R., Turner, D., Gaines, P., Nair, R., Chetter, I., Robinson, G., Akomolafe, B., Hatfield, J., Saastamoinen, K., Crinnion, J., Egun, A.A., Thomas, J., Drinkwater, S., D'Souza, S., Thomson, G., Gregory, B., Babu, S., Ashley, S., Joseph, T., Gibbs, R., Tebit, G., Mehrzad, A., Enevoldson, P., Mendalow, D., Parry, A., Tervitt, G., Clifton, A., Nazzel, M., Halliday, A., Peto, R., Pan, H., Potter, J., Bullbulia, R., Mihaylova, B., Flather, M., Mansfield, A., Simpson, D., Thomas, D., Gray, W., Farrell, B., Davies, C., Rahimi, K., Gough, M., Cao, P., Rothwell, P., Belli, A., Mafham, M., Herrington, W., Sandercock, P., Gray, R., Shearman, C., Molyneux, A., Gray, A., Clarke, A., Sneade, M., Tully, L., Brudlo, W., Lay, M., Munday, A., Berry, C., Tochlin, S., Cox, J., Kurien, R., Chester, J., de Waard, D.D., Huibers, A., and Bonati, L.H.

Published
2017
Full Text
View/download PDF

14. Learning in the COVID-19 pandemic and beyond: development and rapid uptake of an online learning platform for vascular surgery

Author

Nortley, MC, Bera, KD, Dixon, F, Warner, N-R, Sideso, E, and Darby, C

Subjects
Education, Distance, COVID-19, Humans, Vascular Surgery, Surgery, Curriculum, General Medicine, Pandemics, Vascular Surgical Procedures
Abstract

Introduction With the onset of the COVID-19 pandemic, alternative methods of delivering medical education were rapidly required. An online learning platform was developed with the aim of providing high-quality, accessible learning to vascular specialty trainees. We describe the design, delivery and analysis of the first 15 months of the platform. Although originally a regional initiative, we discuss how popularity and feedback led to a rapid expansion of the training programme internationally. Methods A fully online educational platform for vascular surgery specialist trainees was developed. The primary aims and ethos of the programme were that it should be easily accessible from any location, convenient, flexible, cooperative and collaborative, social and free financially to access. All learning resources were researched carefully and based on the UK vascular surgery curriculum and 20 seminal papers targeted in the Vascular Specialist Fellow of the Royal College of Surgeons (FRCSVasc) examination. Results The project demonstrated that it is feasible to design, build and deliver a postgraduate clinical teaching platform with minimal time requirement, resources and cost while creating and maintaining high-quality content. Rapid national and international uptake has proven there is demand – in addition to overwhelmingly positive feedback from educators and learners, this demonstrates that previously perceived barriers to online education can be overcome. At present, 53 educational sessions have been delivered and are available in the online library, and in the past year (8 December 2020 to 8 December 2021) the website has been accessed 3,877 times. Conclusions Although the programme has grown and evolved, a strong focus is being kept on its original ethos and aims – easily accessible, collaborative, free learning resources for all vascular professionals, based on the UK vascular surgery curriculum. Making learning convenient is key. The COVID-19 pandemic may be a watershed moment for a new era of learning. It is an opportunity for people from different backgrounds to share experiences and to develop cohesion within a hospital and network, nationally and worldwide.

Published
2022

15. Metformin Monotherapy Alters the Human Plasma Lipidome Independent of Clinical Markers of Glycemic Control and Cardiovascular Disease Risk in a Type 2 Diabetes Clinical Cohort

Author

Wancewicz, Benjamin, primary, Zhu, Yanlong, additional, Fenske, Rachel J., additional, Weeks, Alicia M., additional, Wenger, Kent, additional, Pabich, Samantha, additional, Daniels, Michael, additional, Punt, Margaret, additional, Nall, Randall, additional, Peter, Darby C., additional, Brasier, Allan, additional, Cox, Elizabeth D., additional, Davis, Dawn Belt, additional, Ge, Ying, additional, and Kimple, Michelle E., additional

Published
2023
Full Text
View/download PDF

16. Working Together

Author

Diane Yendol-Hoppey, Deborah Shanley, Darby C. Delane

Published
2017

17. Association of Serum Lipid Profile With Coronary Computed Tomographic Angiography–derived Morphologic and Functional Quantitative Plaque Markers

Author

Baumann, Stefan, Kryeziu, Philipp, Tesche, Christian, Shuler, Darby C., Becher, Tobias, Rutsch, Marlon, Behnes, Michael, Stach, Ksenija, Jacobs, Brian E., Renker, Matthias, Henzler, Thomas, Haubenreisser, Holger, Schoenberg, Stefan O., Weiss, Christel, Borggrefe, Martin, Schwemmer, Chris, Schoepf, U. Joseph, Akin, Ibrahim, and Lossnitzer, Dirk

Published
2019
Full Text
View/download PDF

20. Plasma Prostaglandin E2 Metabolite Levels Predict Type 2 Diabetes Status and One-Year Therapeutic Response Independent of Clinical Markers of Inflammation

Author

Fenske, Rachel J., primary, Weeks, Alicia M., additional, Daniels, Michael, additional, Nall, Randall, additional, Pabich, Samantha, additional, Brill, Allison L., additional, Peter, Darby C., additional, Punt, Margaret, additional, Cox, Elizabeth D., additional, Davis, Dawn Belt, additional, and Kimple, Michelle E., additional

Published
2022
Full Text
View/download PDF

21. Ogive characterisation in medium-term stock projections

Author

Needle, C. L., O’Brien, C. M., and Darby, C. D.

Subjects
Fisheries and aquaculture
Abstract

Under prevailing stock assessment methodologies, stochasticity is introduced into the simulation of future fish-stock population dynamics via random variation about a) an hypothesised spawner-recruitment model (possibly constrained to emulate the historical time-series of recruitment), and b) the initial population size. However, hindcast simulations suggest that the importance of appropriate characterisations of age-dependent measures of growth and reproductive potential may equal or exceed that of recruitment or starting numbers. This paper proposes a methodology modification by which such concerns might be addressed, through vector autoregressive moving-average (VARMA) modelling of maturity and weights-at-age ogives in stock projections. A number of technical points contingent on these modifications are raised. North Sea cod (Gadus morhua L.) is used as a test case for the new method, and implications for the management of this and other stocks are discussed.

Published
2023
Full Text
View/download PDF

23. Plasma Prostaglandin E

Author

Rachel J, Fenske, Alicia M, Weeks, Michael, Daniels, Randall, Nall, Samantha, Pabich, Allison L, Brill, Darby C, Peter, Margaret, Punt, Elizabeth D, Cox, Dawn Belt, Davis, and Michelle E, Kimple

Abstract

Over half of patients with type 2 diabetes (T2D) are unable to achieve blood glucose targets despite therapeutic compliance, significantly increasing their risk of long-term complications. Discovering ways to identify and properly treat these individuals is a critical problem in the field. The arachidonic acid metabolite, prostaglandin E

Published
2022

24. Human Islet Expression Levels of Prostaglandin E2 Synthetic Enzymes, But Not Prostaglandin EP3 Receptor, Are Positively Correlated with Markers of β-Cell Function and Mass in Nondiabetic Obesity

Author

Austin Reuter, Samantha Pabich, Rachel J. Fenske, Alicia M Weeks, Dawn Belt Davis, Chinmai Patibandla, Elizabeth D. Cox, Harpreet K Sandhu, Randall Nall, Cecilia E Kaiser, Margaret Punt, Nathan A. Truchan, Allison L. Brill, Michelle E. Kimple, Darby C. Peter, Benjamin Wancewicz, Ying Ge, Jeffrey M. Harrington, and Michael Daniels

Subjects
endocrine system, medicine.medical_specialty, Prostaglandin E2 receptor, medicine.medical_treatment, Prostaglandin, Type 2 diabetes, Biology, chemistry.chemical_compound, Insulin resistance, Downregulation and upregulation, Internal medicine, medicine, Pharmacology (medical), Prostaglandin E3, Prostaglandin E2, Receptor, Pharmacology, geography, geography.geographical_feature_category, Insulin, Islet, medicine.disease, Endocrinology, chemistry, lipids (amino acids, peptides, and proteins), medicine.drug
Abstract

We and others previously reported increased signaling through the Prostaglandin E3 Receptor (EP3), a G protein-coupled receptor (GPCR) for the arachidonic acid metabolite, prostaglandin E2 (PGE2), is associated with {beta}-cell dysfunction of type 2 diabetes (T2D). Yet, the relationship between PGE2 production and signaling and {beta}-cell function during the progression to T2D remains unclear. In this work, we assessed gene expression from a panel of cadaveric human islets from 40 non-diabetic donors with BMI values spanning the spectrum from lean to high-risk obesity. Interleukin-6 (gene symbol: IL6) and cyclooxygenase-2 (COX-2) (gene symbol: PTGS2) mRNA levels were positively correlated with donor body mass index (BMI), while EP3 (gene symbol: PTGER3) was not. IL6 was itself strongly correlated with PTGS2 and all but one of the other PGE2 synthetic pathway genes tested. About half of the islet preparations were used in glucose-stimulated- and incretin-potentiated insulin secretion assays using an EP3-specific antagonist, confirming functionally-relevant up-regulation of PGE2 production. Islets from obese donors showed no inherent {beta}-cell dysfunction and were at least equally as glucose- and incretin-responsive as islets from non-obese donors. Furthermore, insulin content, a marker of islet size known to be associated with donor BMI, was also significantly and positively correlated with islet PTGS2 expression. We conclude up-regulated islet PGE2 production and signaling may be a necessary part of the {beta}-cell adaption response, compensating for obesity and insulin resistance. Analysis of plasma PGE2 metabolite levels from a clinical cohort reveal these findings are not in conflict with the concept of further elevations in PGE2 production contributing to T2D-related {beta}-cell dysfunction where islet EP3 expression has also been up-regulated. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=126 HEIGHT=200 SRC="FIGDIR/small/429205v1_ufig1.gif" ALT="Figure 1"> View larger version (25K): org.highwire.dtl.DTLVardef@14056a7org.highwire.dtl.DTLVardef@f8fcf1org.highwire.dtl.DTLVardef@a66915org.highwire.dtl.DTLVardef@13ce208_HPS_FORMAT_FIGEXP M_FIG C_FIG

Published
2021

25. ERBB4 Mutant Alleles May Drive BRAF WT Melanomas

Author

Lauren M. Lucas, Richard L. Cullum, Jessica A. Markham, Joelle N. Woggerman, Vipasha Dwivedi, Rania H. Mohamedelhassan, Laura J. Cook, Connor M. Kelley, Elizabeth L. Knerr, David P. Kaufmann, Megan A. Jacobi, Darby C. Taylor, Cristina C. Rael, Damien S. Waits, Taraswi M. Ghosh, Kenneth M. Halanych, Ram B. Gupta, and David J. Riese

Abstract

Metastatic skin cutaneous melanomas that contain wild-type BRAF alleles (“BRAF WT melanomas”) remain a significant clinical challenge, primarily because of the paucity of targets for therapeutic intervention. In prior work, in silico analyses of The Cancer Genome Atlas Skin Cutaneous Melanoma (TCGA-SKCM) dataset suggested that elevated transcription of the gene that encodes the ERBB4 receptor tyrosine kinase may drive BRAF WT melanomas. Moreover, that prior work demonstrated that expression of the wild-type ERBB4 gene (WT ERBB4) stimulates clonogenic proliferation by the MEL-JUSO, MeWo, and IPC-298 human BRAF WT melanoma cell lines. Moreover, expression of a dominant-negative (K751M) ERBB4 mutant (ERBB4 DN) inhibits clonogenic proliferation by the MEL-JUSO and MeWo cell lines.Here we have extended these findings by investigating the role of ERBB4 mutant alleles in BRAF WT melanomas. In silico analyses of the TCGA-SKCM BRAF WT melanoma dataset indicates that ERBB4 missense mutant alleles occur in a non-random manner, suggesting that melanomagenesis selects for the ERBB4 missense mutant alleles. Specifically, ERBB4 missense mutant alleles affect amino acid residues that are weakly correlated with residues conserved in the ERBB3 extracellular domains and the EGFR tyrosine kinase domain. The occurrence of ERBB4 missense mutant alleles in the TCGA-SKCM BRAF WT melanoma dataset is weakly inversely correlated with events that cause ERBB4-independent PI3K pathway signaling and is strongly correlated with events that cause elevated RAS pathway signaling. Thus, the in silico analyses suggest that ERBB4 mutant alleles stimulate PI3K signaling, which cooperates with elevated RAS signaling to drive BRAF WT melanomas. Moreover, the in silico analyses have prioritized the ERBB4 mutant alleles as candidate drivers of BRAF WT melanomas. One of the prioritized ERBB4 mutant alleles (P759L) stimulates greater clonogenic proliferation of MEL-JUSO cells than does WT ERBB4. Thus, our in silico prioritization strategy may effectively identify ERBB4 mutants that drive BRAF WT melanomas. Finally, the results of our in silico analyses suggest that ERBB4-dependent, BRAF WT melanomas may be effectively treated by a combination of a PI3K pathway inhibitor and a RAS pathway inhibitor.

Published
2022

26. ERBB4 Mutant Alleles May Drive BRAF WT Melanomas

Author

Lucas, Lauren M, primary, Cullum, Richard L, additional, Markham, Jessica A, additional, Woggerman, Joelle N, additional, Dwivedi, Vipasha, additional, Mohamedelhassan, Rania H, additional, Cook, Laura J, additional, Kelley, Connor M, additional, Knerr, Elizabeth L, additional, Kaufmann, David P, additional, Jacobi, Megan A, additional, Taylor, Darby C, additional, Rael, Cristina C, additional, Waits, Damien S, additional, Ghosh, Taraswi M, additional, Halanych, Kenneth M, additional, Gupta, Ram B, additional, and Riese, David J, additional

Published
2022
Full Text
View/download PDF

29. Title: Doctoral writing workshops: A preregistered, randomized controlled trial (PREPRINT)

Author

Sarnecka, Barbara, Sarnecka, Barbara, Silva, Paulina N, Coon, Jeff, Vickers, Darby C, Goldstein, Rena B, Rouder, Jeffrey N, Sarnecka, Barbara, Sarnecka, Barbara, Silva, Paulina N, Coon, Jeff, Vickers, Darby C, Goldstein, Rena B, and Rouder, Jeffrey N

Abstract

Doctoral students were randomly assigned to a five-week (30-hour) faculty-led writing workshop (the intervention) or to a waitlist control group. After completing the workshop, students enjoyed writing more, found it easier, and had more confidence in themselves as writers. They were able to write productively in shorter blocks of time, and they engaged in more planning of their writing and research. The intervention also increased the frequency with which students paused for reflection or positive thinking, and it elicited more new writing from participants about their research, relative to controls. Effects were maintained in a peer-led writing maintenance group after the workshop ended. This workshop model can be used across disciplines to support doctoral students’ training in academic and scientific writing.

Published
2022

34. Plasma Prostaglandin E 2 Metabolite Levels Predict Type 2 Diabetes Status and One-Year Therapeutic Response Independent of Clinical Markers of Inflammation.

Author

Fenske, Rachel J., Weeks, Alicia M., Daniels, Michael, Nall, Randall, Pabich, Samantha, Brill, Allison L., Peter, Darby C., Punt, Margaret, Cox, Elizabeth D., Davis, Dawn Belt, and Kimple, Michelle E.

Subjects
TYPE 2 diabetes, BIOMARKERS, PROSTAGLANDIN receptors, PROSTAGLANDINS, BLOOD sedimentation, ORGANS (Anatomy), INSULIN receptors
Abstract

Over half of patients with type 2 diabetes (T2D) are unable to achieve blood glucose targets despite therapeutic compliance, significantly increasing their risk of long-term complications. Discovering ways to identify and properly treat these individuals is a critical problem in the field. The arachidonic acid metabolite, prostaglandin E2 (PGE2), has shown great promise as a biomarker of β-cell dysfunction in T2D. PGE2 synthesis, secretion, and downstream signaling are all upregulated in pancreatic islets isolated from T2D mice and human organ donors. In these islets, preventing β-cell PGE2 signaling via a prostaglandin EP3 receptor antagonist significantly improves their glucose-stimulated and hormone-potentiated insulin secretion response. In this clinical cohort study, 167 participants, 35 non-diabetic, and 132 with T2D, were recruited from the University of Wisconsin Hospital and Clinics. At enrollment, a standard set of demographic, biometric, and clinical measurements were performed to quantify obesity status and glucose control. C reactive protein was measured to exclude acute inflammation/illness, and white cell count (WBC), erythrocyte sedimentation rate (ESR), and fasting triglycerides were used as markers of systemic inflammation. Finally, a plasma sample for research was used to determine circulating PGE2 metabolite (PGEM) levels. At baseline, PGEM levels were not correlated with WBC and triglycerides, only weakly correlated with ESR, and were the strongest predictor of T2D disease status. One year after enrollment, blood glucose management was assessed by chart review, with a clinically-relevant change in hemoglobin A1c (HbA1c) defined as ≥0.5%. PGEM levels were strongly predictive of therapeutic response, independent of age, obesity, glucose control, and systemic inflammation at enrollment. Our results provide strong support for future research in this area. [ABSTRACT FROM AUTHOR]

Published
2022
Full Text
View/download PDF

39. Independent mechanisms underlie the protective effect of dietary polyunsaturated fatty acid supplementation and Gαz deficiency on the early type 1 diabetes phenotype of Non-obese diabetic (NOD) mice

Author

Michelle E. Kimple, Schaid, Pennati A, Galipeau J, Darby C. Peter, Rachel J. Fenske, and Haley Wienkes

Subjects
medicine.medical_specialty, Pancreatic islets, Prostaglandin, Nod, Biology, medicine.disease, chemistry.chemical_compound, Endocrinology, medicine.anatomical_structure, chemistry, Internal medicine, Diabetes mellitus, medicine, Arachidonic acid, Prostaglandin E2, Insulitis, medicine.drug, NOD mice
Abstract

Non-obese diabetic (NOD) mice deficient in Gz alpha subunit (Gαz) are protected from developing hyperglycemia, even with early islet insulitis similar to wild-type mice. Similarly, wild-type (WT) NOD mice are protected from glucose intolerance when fed a diet enriched in eicosapentaneoic acid (EPA). In the beta-cell, Prostaglandin EP3 receptor (EP3), whose primary endogenous ligand is the arachidonic acid (AA) metabolite, prostaglandin E2, is specifically coupled to Gαz. In this work, we tested whether dietary EPA supplementation, thereby reducing systemic PGE2 levels, would complement Gαz loss in the NOD mouse model. WT and Gαz-null NOD mice were fed an AA-enriched diet, EPA-enriched diet, or control diet upon weaning. After 12 weeks of diet feeding, glucose tolerance tests were performed and pancreatic islets and whole pancreas collected for ex vivo analyses, with the longer-term effect of an EPA-enriched diet on splenic T-cell populations quantified via flow cytometry. Our results reveal a polyunsaturated fatty acid-enriched diet, whether AA or EPA, improves wild-type NOD glucose tolerance by the same magnitude as Gαz loss, but through almost completely different physiological and cellular mechanisms. Our results shed critical light on future research into novel pharmacological and dietary adjuvant therapies for T1D.

Published
2021

42. Human Islet Expression Levels of Prostaglandin E2 Synthetic Enzymes, But Not Prostaglandin EP3 Receptor, Are Positively Correlated with Markers of β-Cell Function and Mass in Nondiabetic Obesity

Author

Truchan, Nathan A., primary, Fenske, Rachel J., additional, Sandhu, Harpreet K., additional, Weeks, Alicia M., additional, Patibandla, Chinmai, additional, Wancewicz, Benjamin, additional, Pabich, Samantha, additional, Reuter, Austin, additional, Harrington, Jeffrey M., additional, Brill, Allison L., additional, Peter, Darby C., additional, Nall, Randall, additional, Daniels, Michael, additional, Punt, Margaret, additional, Kaiser, Cecilia E., additional, Cox, Elizabeth D., additional, Ge, Ying, additional, Davis, Dawn B., additional, and Kimple, Michelle E., additional

Published
2021
Full Text
View/download PDF

44. FOREWORD

Author

Stapp, Darby C.

Published
1998

45. The protection of Gαz-null NOD mice from hyperglycemia is sexually dimorphic and only partially β-cell autonomous

Author

Schaid, Michelle E. Kimple, Haley Wienkes, Austin Reuter, Darby C. Peter, Kathryn A. Carbajal, and Rachel J. Fenske

Subjects
medicine.medical_specialty, Type 1 diabetes, Nod, Biology, medicine.disease, Phenotype, Endocrinology, Internal medicine, Heterotrimeric G protein, Knockout mouse, medicine, Beta (finance), Insulitis, NOD mice
Abstract

The mechanisms that underlie the β-cell pathophysiology of Type 1 Diabetes (T1D) are not fully understood. Our group has defined the unique heterotrimeric G protein alpha-subunit, Gαz, as a key negative regulator of β-cell signal transduction pathways. Non-obese diabetic (NOD) mice lacking Gαzthroughout the body are protected from developing T1D-like hyperglycemia. To determine whether this phenotype is β-cell autonomous, we generated and validated a β-cell-specific Gαzknockout (βKO) on the NOD background and characterized the phenotype of female and male cohorts. Long-term hyperglycemia incidence was lower in GαzβKO mice as compared to wild-type (WT) controls, but, unlike global Gαzknockout mice, this protection was incomplete. While young male and female GαzβKO NOD mice had improved glucose tolerance, WT NOD males were significantly less glucose tolerant than females, and only female GαzβKO mice retained improved glucose tolerance at 28-29 weeks of age. Conversely, β-cell-specific Gαzloss only influenced insulitis in 28-29-week old male NOD mice, a phenotype correlating directly with body burden of glucose during oral glucose challenge. Using surrogates for β-cell function and apoptosis, the partial penetrance of euglycemia in GαzβKO NOD was best explained by an early failure to up-regulate β-cell proliferation. We conclude β-cell Gαzis an important regulator of the sexually-dimorphic T1D-like phenotype of NOD mice. Yet, other factors must be important in imparting full protection from the disease.

Published
2021

46. Second asymptomatic carotid surgery trial (ACST-2): a randomised comparison of carotid artery stenting versus carotid endarterectomy

Author

Halliday, A., Bulbulia, R., Bonati, L. H., Chester, J., Cradduck-Bamford, A., Peto, R., Pan, H., Potter, J., Henning Eckstein, H., Farrell, B., Flather, M., Mansfield, A., Mihaylova, B., Rahimi, K., Simpson, D., Thomas, D., Sandercock, P., Gray, R., Molyneux, A., Shearman, C. P., Rothwell, P., Belli, A., Herrington, W., Judge, P., Leopold, P., Mafham, M., Gough, M., Cao, P., Macdonald, S., Bari, V., Berry, C., Bradshaw, S., Brudlo, W., Clarke, A., Cox, R., Fathers, S., Gaba, K., Gray, M., Hayter, E., Holliday, C., Kurien, R., Lay, M., le Conte, S., Mcmanus, J., Madgwick, Z., Morris, D., Munday, A., Pickworth, S., Ostasz, W., Poorthuis, M., Richards, S., Teixeira, L., Tochlin, S., Tully, L., Wallis, C., Willet, M., Young, A., Casana, R., Malloggi, C., Odero, A., Silani, V., Parati, G., Malchiodi, G., Malferrari, G., Strozzi, F., Tusini, N., Vecchiati, E., Coppi, G., Lauricella, A., Moratto, R., Silingardi, R., Veronesi, J., Zini, A., Ferrero, E., Ferri, M., Gaggiano, A., Labate, C., Nessi, F., Psacharopulo, D., Viazzo, A., Malacrida, G., Mazzaccaro, D., Meola, G., Modafferi, A., Nano, G., Occhiuto, M. T., Righini, P., Stegher, S., Chiarandini, S., Griselli, F., Lepidi, S., Pozzi Mucelli, F., Naccarato, M., D'Oria, M., Ziani, B., Stella, A., Dieng, M., Faggioli, G., Gargiulo, M., Palermo, S., Pini, R., Puddu, G. M., Vacirca, A., Angiletta, D., Desantis, C., Marinazzo, D., Mastrangelo, G., Regina, G., Pulli, R., Bianchi, P., Cireni, L., Coppi, E., Pizzirusso, R., Scalise, F., Sorropago, G., Tolva, V., Caso, V., Cieri, E., Derango, P., Farchioni, L., Isernia, G., Lenti, M., Parlani, G. B., Pupo, G., Pula, G., Simonte, G., Verzini, F., Carimati, F., Delodovici, M. L., Fontana, F., Piffaretti, G., Tozzi, M., Civilini, E., Poletto, G., Reimers, B., Praquin, B., Ronchey, S., Capoccia, L., Mansour, W., Sbarigia, E., Speziale, F., Sirignano, P., Toni, D., Galeotti, R., Gasbarro, V., Mascoli, F., Rocca, T., Tsolaki, E., Bernardini, G., Demarco, E., Giaquinta, A., Patti, F., Veroux, M., Veroux, P., Virgilio, C., Mangialardi, N., Orrico, M., Di Lazzaro, V., Montelione, N., Spinelli, F., Stilo, F., Cernetti, C., Irsara, S., Maccarrone, G., Tonello, D., Visona, A., Zalunardo, B., Chisci, E., Michelagnoli, S., Troisi, N., Masato, M., Dei Negri, M., Pacchioni, A., Sacca, S., Amatucci, G., Cannizzaro, A., Accrocca, F., Ambrogi, C., Barbazza, R., Marcucci, G., Siani, A., Bajardi, G., Savettieri, G., Argentieri, A., Corbetta, R., Quaretti, P., Thyrion, F. Z., Cappelli, A., Benevento, D., De Donato, G., Mele, M. A., Palasciano, G., Pieragalli, D., Rossi, A., Setacci, C., Setacci, F., Palombo, D., Perfumo, M. C., Martelli, E., Paolucci, A., Trimarchi, S., Grassi, V., Grimaldi, L., La Rosa, G., Mirabella, D., Scialabba, M., Sichel, L., D'Angelo, C. L., Fadda, G. F., Kasemi, H., Marino, M., Burzotta, Francesco, Codispoti, F. A., Ferrante, A., Tinelli, Giovanni, Tshomba, Yamume, Vincenzoni, Claudio, Amis, D., Anderson, D., Catterson, M., Clarke, M., Davis, M., Dixit, A., Dyker, A., Ford, G., Jackson, R., Kappadath, S., Lambert, D., Lees, T., Louw, S., Mccaslin, J., Parr, N., Robson, R., Stansby, G., Wales, L., Wealleans, V., Wilson, L., Wyatt, M., Baht, H., Balogun, I., Burger, I., Cosier, T., Cowie, L., Gunathilagan, G., Hargroves, D., Insall, R., Jones, S., Rudenko, H., Schumacher, N., Senaratne, J., Thomas, G., Thomson, A., Webb, T., Brown, E., Esisi, B., Mehrzad, A., Macsweeney, S., Mcconachie, N., Southam, A., Sunman, W., Abdul-Hamiq, A., Bryce, J., Chetter, I., Ettles, D., Lakshminarayan, R., Mitchelson, K., Rhymes, C., Robinson, G., Scott, P., Vickers, A., Ashleigh, R., Butterfield, S., Gamble, E., Ghosh, J., Mccollum, C. N., Welch, M., Welsh, S., Wolowczyk, L., Donnelly, M., D'Souza, S., Egun, A. A., Gregary, B., Joseph, T., Kelly, C., Punekar, S., Rahi, M. A., Raj, S., Seriki, D., Thomson, G., Brown, J., Durairajan, R., Grunwald, I., Guyler, P., Harman, P., Jakeways, M., Khuoge, C., Kundu, A., Loganathan, T., Menon, N., Prabakaran, R. O., Sinha, D., Thompson, V., Tysoe, S., Briley, D., Darby, C., Hands, L., Howard, D., Kuker, W., Schulz, U., Teal, R., Barer, D., Brown, A., Crawford, S., Dunlop, P., Krishnamurthy, R., Majmudar, N., Mitchell, D., Myint, M. P., O'Brien, R., O'Connell, J., Sattar, N., Vetrivel, S., Beard, J., Cleveland, T., Gaines, P., Humphreys, J., Jenkins, A., King, C., Kusuma, D., Lindert, R., Lonsdale, R., Nair, R., Nawaz, S., Okhuoya, F., Turner, D., Venables, G., Dorman, P., Hughes, A., Jones, D., Mendelow, D., Rodgers, H., Raudoniitis, A., Enevoldson, P., Nahser, H., O'Brien, I., Torella, F., Watling, D., White, R., Brown, P., Dutta, D., Emerson, L., Hilltout, P., Kulkarni, S., Morrison, J., Poskitt, K., Slim, F., Smith, S., Tyler, A., Waldron, J., Whyman, M., Bajoriene, M., Baker, L., Colston, A., Eliot-Jones, B., Gramizadeh, G., Lewis-Clarke, C., Mccafferty, L., Oliver, D., Palmer, D., Patil, A., Pegler, S., Ramadurai, G., Roberts, A., Sargent, T., Siddegowda, S., Singh-Ranger, R., Williams, A., Williams, L., Windebank, S., Zuromskis, T., Alwis, L., Angus, J., Asokanathan, A., Fornolles, C., Hardy, D., Hunte, S., Justin, F., Phiri, D., Mitabouana-Kibou, M., Sekaran, L., Sethuraman, S., Tate, M. L., Akyea-Mensah, J., Ball, S., Chrisopoulou, A., Keene, E., Phair, A., Rogers, S., Smyth, J. V., Bicknell, C., Chataway, J., Cheshire, N., Clifton, A., Eley, C., Gibbs, R., Hamady, M., Hazel, B., James, A., Jenkins, M., Khanom, N., Lacey, A., Mireskandari, M., O'Reilly, J., Pereira, A., Sachs, T., Wolfe, J., Davey, P., Rogers, G., Smith, G., Tervit, G., Nichol, I., Parry, A., Young, G., Ashley, S., Barwell, J., Dix, F., Nor, A. M., Parry, C., Birt, A., Davies, P., George, J., Graham, A., Jonker, L., Kelsall, N., Potts, C., Wilson, T., Crinnion, J., Cuenoud, L., Aleksic, N., Babic, S., Ilijevski, N., Radak, Sagic, D., Tanaskovic, S., Colic, M., Cvetic, V., Davidovic, L., Jovanovic, D. R., Koncar, I., Mutavdzic, P., Sladojevic, M., Tomic, I., Debus, E. S., Grzyska, U., Otto, D., Thomalla, G., Barlinn, J., Gerber, J., Haase, K., Hartmann, C., Ludwig, S., Putz, V., Reeps, C., Schmidt, C., Weiss, N., Werth, S., Winzer, S., Gemper, J., Gunther, A., Heiling, B., Jochmann, E., Karvouniari, P., Klingner, C., Mayer, T., Schubert, J., Schulze-Hartung, F., Zanow, J., Bausback, Y., Borger, F., Botsios, S., Branzan, D., Braunlich, S., Holzer, H., Lenzer, J., Piorkowski, C., Richter, N., Schuster, J., Scheinert, D., Schmidt, A., Staab, H., Ulrich, M., Werner, M., Berger, H., Biro, G., Eckstein, H. -H., Kallmayer, M., Kreiser, K., Zimmermann, A., Berekoven, B., Frerker, K., Gordon, V., Torsello, G., Arnold, S., Dienel, C., Storck, M., Biermaier, B., Gissler, H. M., Klotzsch, C., Pfeiffer, T., Schneider, R., Sohl, L., Wennrich, M., Alonso, A., Keese, M., Groden, C., Coster, A., Engelhardt, A., Ratusinski, C. -M., Berg, B., Delle, M., Formgren, J., Gillgren, P., Jarl, L., Kall, T. B., Konrad, P., Nyman, N., Skioldebrand, C., Steuer, J., Takolander, R., Malmstedt, J., Acosta, S., Bjorses, K., Brandt, K., Dias, N., Gottsater, A., Holst, J., Kristmundsson, T., Kuhme, T., Kolbel, T., Lindblad, B., Lindh, M., Malina, M., Ohrlander, T., Resch, T., Ronnle, V., Sonesson, B., Warvsten, M., Zdanowski, Z., Campbell, E., Kjellin, P., Lindgren, H., Nyberg, J., Petersen, B., Plate, G., Parsson, H., Qvarfordt, P., Ignatenko, P., Karpenko, A., Starodubtsev, V., Chernyavsky, M. A., Golovkova, M. S., Komakha, B. B., Zherdev, N. N., Belyasnik, A., Chechulov, P., Kandyba, D., Stepanishchev, I., Csobay-Novak, C., Dosa, E., Entz, L., Nemes, B., Szeberin, Z., Barzo, P., Bodosi, M., Fako, E., Fulop, B., Nemeth, T., Pazdernyik, S., Skoba, K., Voros, E., Chatzinikou, E., Giannoukas, A., Karathanos, C., Koutsias, S., Kouvelos, G., Matsagkas, M., Ralli, S., Rountas, C., Rousas, N., Spanos, K., Brountzos, E., Kakisis, J. D., Lazaris, A., Moulakakis, K. G., Stefanis, L., Tsivgoulis, G., Vasdekis, S., Antonopoulos, C. N., Bellenis, I., Maras, D., Polydorou, A., Polydorou, V., Tavernarakis, A., Ioannou, N., Terzoudi, M., Lazarides, M., Mantatzis, M., Vadikolias, K., Dzieciuchowicz, L., Gabriel, M., Krasinski, Z., Oszkinis, G., Pukacki, F., Slowinski, M., Stanisic, M. -G., Staniszewski, R., Tomczak, J., Zielinski, M., Myrcha, P., Rozanski, D., Drelichowski, S., Iwanowski, W., Koncewicz, K., Bialek, P., Biejat, Z., Czepel, W., Czlonkowska, A., Dowzenko, A., Jedrzejewska, J., Kobayashi, A., Leszczynski, J., Malek, A., Polanski, J., Proczka, R., Skorski, M., Szostek, M., Andziak, P., Dratwicki, M., Gil, R., Nowicki, M., Pniewski, J., Rzezak, J., Seweryniak, P., Dabek, P., Juszynski, M., Madycki, G., Pacewski, B., Raciborski, W., Slowinski, P., Staszkiewicz, W., Bombic, M., Chlouba, V., Fiedler, J., Hes, K., Kostal, P., Sova, J., Kriz, Z., Privara, M., Reif, M., Staffa, R., Vlachovsky, R., Vojtisek, B., Hrbac, T., Kuliha, M., Prochazka, V., Roubec, M., Skoloudik, D., Netuka, D., Steklacova, A., Benes III, V., Buchvald, P., Endrych, L., Sercl, M., Campos, W., Casella, I. B., de Luccia, N., Estenssoro, A. E. V., Presti, C., Puech-Leao, P., Neves, C. R. B., da Silva, E. S., Sitrangulo, C. J., Monteiro, J. A. T., Tinone, G., Bellini Dalio, M., Joviliano, E. E., Pontes Neto, O. M., Serra Ribeiro, M., Cras, P., Hendriks, J. M. H., Hoppenbrouwers, M., Lauwers, P., Loos, C., Yperzeele, L., Geenens, M., Hemelsoet, D., van Herzeele, I., Vermassen, F., Astarci, P., Hammer, F., Lacroix, V., Peeters, A., Verhelst, R., Cirelli, S., Dormal, P., Grimonprez, A., Lambrecht, B., Lerut, P., Thues, E., De Koster, G., Desiron, Q., Maertens de Noordhout, A., Malmendier, D., Massoz, M., Saad, G., Bosiers, M., Callaert, J., Deloose, K., Blanco Canibano, E., Garcia Fresnillo, B., Guerra Requena, M., Morata Barrado, P. C., Muela Mendez, M., Yusta Izquierdo, A., Aparici Robles, F., Blanes Orti, P., Garcia Dominguez, L., Martinez Lopez, R., Miralles Hernandez, M., Tembl Ferrairo, J. I., Chamorro, A., Macho, J., Obach, V., Riambau, V., San Roman, L., Ahlhelm, F. J., Blackham, K., Engelter, S., Eugster, T., Gensicke, H., Gurke, L., Lyrer, P., Mariani, L., Maurer, M., Mujagic, E., Muller, M., Psychogios, M., Stierli, P., Stippich, C., Traenka, C., Wolff, T., Wagner, B., Wiegert, M. M., Clarke, S., Diepers, M., Grochenig, E., Gruber, P., Isaak, A., Kahles, T., Marti, R., Nedeltchev, K., Remonda, L., Tissira, N., Valenca Falcao, M., de Borst, G. J., Lo, R. H., Moll, F. L., Toorop, R., van der Worp, B. H., Vonken, E. J., Kappelle, J. L., Jahrome, O., Vos, F., Schuiling, W., van Overhagen, H., Keunen, R. W. M., Knippenberg, B., Wever, J. J., Lardenoije, J. W., Reijnen, M., Smeets, L., van Sterkenburg, S., Fraedrich, G., Gizewski, E., Gruber, I., Knoflach, M., Kiechl, S., Rantner, B., Abdulamit, T., Bergeron, P., Padovani, R., Trastour, J. -C., Cardon, J. -M., Le Gallou-Wittenberg, A., Allaire, E., Becquemin, J. -P., Cochennec-Paliwoda, F., Desgranges, P., Hosseini, H., Kobeiter, H., Marzelle, J., Almekhlafi, M. A., Bal, S., Barber, P. A., Coutts, S. B., Demchuk, A. M., Eesa, M., Gillies, M., Goyal, M., Hill, M. D., Hudon, M. E., Jambula, A., Kenney, C., Klein, G., Mcclelland, M., Mitha, A., Menon, B. K., Morrish, W. F., Peters, S., Ryckborst, K. J., Samis, G., Save, S., Smith, E. E., Stys, P., Subramaniam, S., Sutherland, G. R., Watson, T., Wong, J. H., Zimmel, L., Flis, V., Matela, J., Miksic, K., Milotic, F., Mrdja, B., Stirn, B., Tetickovic, E., Gasparini, M., Grad, A., Kompara, I., Milosevic, Z., Palmiste, V., Toomsoo, T., Aidashova, B., Kospanov, N., Lyssenko, R., Mussagaliev, D., Beyar, R., Hoffman, A., Karram, T., Kerner, A., Nikolsky, E., Nitecki, S., Andonova, S., Bachvarov, C., Petrov, V., Cvjetko, I., Vidjak, V., Haluzan, D., Petrunic, M., Liu, B., Liu, C. -W., Bartko, D., Beno, P., Rusnak, F., Zelenak, K., Ezura, M., Inoue, T., Kimura, N., Kondo, R., Matsumoto, Y., Shimizu, H., Endo, H., Furui, E., Bakke, S., Krohg-Sorensen, K., Nome, T., Skjelland, M., Tennoe, B., Albuquerque e Castro, J., Alves, G., Bastos Goncalves, F., de Aragao Morais, J., Garcia, A. C., Valentim, H., Vasconcelos, L., Belcastro, F., Cura, F., Zaefferer, P., Abd-Allah, F., Eldessoki, M. H., Heshmat Kassem, H., Soliman Gharieb, H., Colgan, M. P., Haider, S. N., Harbison, J., Madhavan, P., Moore, D., Shanik, G., Kazan, V., Nazzal, M., Ramsey-Williams, V., Burzotta F. (ORCID:0000-0002-6569-9401), Tinelli G. (ORCID:0000-0002-2212-3226), Tshomba Y. (ORCID:0000-0001-7304-7553), Vincenzoni C., Halliday, A., Bulbulia, R., Bonati, L. H., Chester, J., Cradduck-Bamford, A., Peto, R., Pan, H., Potter, J., Henning Eckstein, H., Farrell, B., Flather, M., Mansfield, A., Mihaylova, B., Rahimi, K., Simpson, D., Thomas, D., Sandercock, P., Gray, R., Molyneux, A., Shearman, C. P., Rothwell, P., Belli, A., Herrington, W., Judge, P., Leopold, P., Mafham, M., Gough, M., Cao, P., Macdonald, S., Bari, V., Berry, C., Bradshaw, S., Brudlo, W., Clarke, A., Cox, R., Fathers, S., Gaba, K., Gray, M., Hayter, E., Holliday, C., Kurien, R., Lay, M., le Conte, S., Mcmanus, J., Madgwick, Z., Morris, D., Munday, A., Pickworth, S., Ostasz, W., Poorthuis, M., Richards, S., Teixeira, L., Tochlin, S., Tully, L., Wallis, C., Willet, M., Young, A., Casana, R., Malloggi, C., Odero, A., Silani, V., Parati, G., Malchiodi, G., Malferrari, G., Strozzi, F., Tusini, N., Vecchiati, E., Coppi, G., Lauricella, A., Moratto, R., Silingardi, R., Veronesi, J., Zini, A., Ferrero, E., Ferri, M., Gaggiano, A., Labate, C., Nessi, F., Psacharopulo, D., Viazzo, A., Malacrida, G., Mazzaccaro, D., Meola, G., Modafferi, A., Nano, G., Occhiuto, M. T., Righini, P., Stegher, S., Chiarandini, S., Griselli, F., Lepidi, S., Pozzi Mucelli, F., Naccarato, M., D'Oria, M., Ziani, B., Stella, A., Dieng, M., Faggioli, G., Gargiulo, M., Palermo, S., Pini, R., Puddu, G. M., Vacirca, A., Angiletta, D., Desantis, C., Marinazzo, D., Mastrangelo, G., Regina, G., Pulli, R., Bianchi, P., Cireni, L., Coppi, E., Pizzirusso, R., Scalise, F., Sorropago, G., Tolva, V., Caso, V., Cieri, E., Derango, P., Farchioni, L., Isernia, G., Lenti, M., Parlani, G. B., Pupo, G., Pula, G., Simonte, G., Verzini, F., Carimati, F., Delodovici, M. L., Fontana, F., Piffaretti, G., Tozzi, M., Civilini, E., Poletto, G., Reimers, B., Praquin, B., Ronchey, S., Capoccia, L., Mansour, W., Sbarigia, E., Speziale, F., Sirignano, P., Toni, D., Galeotti, R., Gasbarro, V., Mascoli, F., Rocca, T., Tsolaki, E., Bernardini, G., Demarco, E., Giaquinta, A., Patti, F., Veroux, M., Veroux, P., Virgilio, C., Mangialardi, N., Orrico, M., Di Lazzaro, V., Montelione, N., Spinelli, F., Stilo, F., Cernetti, C., Irsara, S., Maccarrone, G., Tonello, D., Visona, A., Zalunardo, B., Chisci, E., Michelagnoli, S., Troisi, N., Masato, M., Dei Negri, M., Pacchioni, A., Sacca, S., Amatucci, G., Cannizzaro, A., Accrocca, F., Ambrogi, C., Barbazza, R., Marcucci, G., Siani, A., Bajardi, G., Savettieri, G., Argentieri, A., Corbetta, R., Quaretti, P., Thyrion, F. Z., Cappelli, A., Benevento, D., De Donato, G., Mele, M. A., Palasciano, G., Pieragalli, D., Rossi, A., Setacci, C., Setacci, F., Palombo, D., Perfumo, M. C., Martelli, E., Paolucci, A., Trimarchi, S., Grassi, V., Grimaldi, L., La Rosa, G., Mirabella, D., Scialabba, M., Sichel, L., D'Angelo, C. L., Fadda, G. F., Kasemi, H., Marino, M., Burzotta, Francesco, Codispoti, F. A., Ferrante, A., Tinelli, Giovanni, Tshomba, Yamume, Vincenzoni, Claudio, Amis, D., Anderson, D., Catterson, M., Clarke, M., Davis, M., Dixit, A., Dyker, A., Ford, G., Jackson, R., Kappadath, S., Lambert, D., Lees, T., Louw, S., Mccaslin, J., Parr, N., Robson, R., Stansby, G., Wales, L., Wealleans, V., Wilson, L., Wyatt, M., Baht, H., Balogun, I., Burger, I., Cosier, T., Cowie, L., Gunathilagan, G., Hargroves, D., Insall, R., Jones, S., Rudenko, H., Schumacher, N., Senaratne, J., Thomas, G., Thomson, A., Webb, T., Brown, E., Esisi, B., Mehrzad, A., Macsweeney, S., Mcconachie, N., Southam, A., Sunman, W., Abdul-Hamiq, A., Bryce, J., Chetter, I., Ettles, D., Lakshminarayan, R., Mitchelson, K., Rhymes, C., Robinson, G., Scott, P., Vickers, A., Ashleigh, R., Butterfield, S., Gamble, E., Ghosh, J., Mccollum, C. N., Welch, M., Welsh, S., Wolowczyk, L., Donnelly, M., D'Souza, S., Egun, A. A., Gregary, B., Joseph, T., Kelly, C., Punekar, S., Rahi, M. A., Raj, S., Seriki, D., Thomson, G., Brown, J., Durairajan, R., Grunwald, I., Guyler, P., Harman, P., Jakeways, M., Khuoge, C., Kundu, A., Loganathan, T., Menon, N., Prabakaran, R. O., Sinha, D., Thompson, V., Tysoe, S., Briley, D., Darby, C., Hands, L., Howard, D., Kuker, W., Schulz, U., Teal, R., Barer, D., Brown, A., Crawford, S., Dunlop, P., Krishnamurthy, R., Majmudar, N., Mitchell, D., Myint, M. P., O'Brien, R., O'Connell, J., Sattar, N., Vetrivel, S., Beard, J., Cleveland, T., Gaines, P., Humphreys, J., Jenkins, A., King, C., Kusuma, D., Lindert, R., Lonsdale, R., Nair, R., Nawaz, S., Okhuoya, F., Turner, D., Venables, G., Dorman, P., Hughes, A., Jones, D., Mendelow, D., Rodgers, H., Raudoniitis, A., Enevoldson, P., Nahser, H., O'Brien, I., Torella, F., Watling, D., White, R., Brown, P., Dutta, D., Emerson, L., Hilltout, P., Kulkarni, S., Morrison, J., Poskitt, K., Slim, F., Smith, S., Tyler, A., Waldron, J., Whyman, M., Bajoriene, M., Baker, L., Colston, A., Eliot-Jones, B., Gramizadeh, G., Lewis-Clarke, C., Mccafferty, L., Oliver, D., Palmer, D., Patil, A., Pegler, S., Ramadurai, G., Roberts, A., Sargent, T., Siddegowda, S., Singh-Ranger, R., Williams, A., Williams, L., Windebank, S., Zuromskis, T., Alwis, L., Angus, J., Asokanathan, A., Fornolles, C., Hardy, D., Hunte, S., Justin, F., Phiri, D., Mitabouana-Kibou, M., Sekaran, L., Sethuraman, S., Tate, M. L., Akyea-Mensah, J., Ball, S., Chrisopoulou, A., Keene, E., Phair, A., Rogers, S., Smyth, J. V., Bicknell, C., Chataway, J., Cheshire, N., Clifton, A., Eley, C., Gibbs, R., Hamady, M., Hazel, B., James, A., Jenkins, M., Khanom, N., Lacey, A., Mireskandari, M., O'Reilly, J., Pereira, A., Sachs, T., Wolfe, J., Davey, P., Rogers, G., Smith, G., Tervit, G., Nichol, I., Parry, A., Young, G., Ashley, S., Barwell, J., Dix, F., Nor, A. M., Parry, C., Birt, A., Davies, P., George, J., Graham, A., Jonker, L., Kelsall, N., Potts, C., Wilson, T., Crinnion, J., Cuenoud, L., Aleksic, N., Babic, S., Ilijevski, N., Radak, Sagic, D., Tanaskovic, S., Colic, M., Cvetic, V., Davidovic, L., Jovanovic, D. R., Koncar, I., Mutavdzic, P., Sladojevic, M., Tomic, I., Debus, E. S., Grzyska, U., Otto, D., Thomalla, G., Barlinn, J., Gerber, J., Haase, K., Hartmann, C., Ludwig, S., Putz, V., Reeps, C., Schmidt, C., Weiss, N., Werth, S., Winzer, S., Gemper, J., Gunther, A., Heiling, B., Jochmann, E., Karvouniari, P., Klingner, C., Mayer, T., Schubert, J., Schulze-Hartung, F., Zanow, J., Bausback, Y., Borger, F., Botsios, S., Branzan, D., Braunlich, S., Holzer, H., Lenzer, J., Piorkowski, C., Richter, N., Schuster, J., Scheinert, D., Schmidt, A., Staab, H., Ulrich, M., Werner, M., Berger, H., Biro, G., Eckstein, H. -H., Kallmayer, M., Kreiser, K., Zimmermann, A., Berekoven, B., Frerker, K., Gordon, V., Torsello, G., Arnold, S., Dienel, C., Storck, M., Biermaier, B., Gissler, H. M., Klotzsch, C., Pfeiffer, T., Schneider, R., Sohl, L., Wennrich, M., Alonso, A., Keese, M., Groden, C., Coster, A., Engelhardt, A., Ratusinski, C. -M., Berg, B., Delle, M., Formgren, J., Gillgren, P., Jarl, L., Kall, T. B., Konrad, P., Nyman, N., Skioldebrand, C., Steuer, J., Takolander, R., Malmstedt, J., Acosta, S., Bjorses, K., Brandt, K., Dias, N., Gottsater, A., Holst, J., Kristmundsson, T., Kuhme, T., Kolbel, T., Lindblad, B., Lindh, M., Malina, M., Ohrlander, T., Resch, T., Ronnle, V., Sonesson, B., Warvsten, M., Zdanowski, Z., Campbell, E., Kjellin, P., Lindgren, H., Nyberg, J., Petersen, B., Plate, G., Parsson, H., Qvarfordt, P., Ignatenko, P., Karpenko, A., Starodubtsev, V., Chernyavsky, M. A., Golovkova, M. S., Komakha, B. B., Zherdev, N. N., Belyasnik, A., Chechulov, P., Kandyba, D., Stepanishchev, I., Csobay-Novak, C., Dosa, E., Entz, L., Nemes, B., Szeberin, Z., Barzo, P., Bodosi, M., Fako, E., Fulop, B., Nemeth, T., Pazdernyik, S., Skoba, K., Voros, E., Chatzinikou, E., Giannoukas, A., Karathanos, C., Koutsias, S., Kouvelos, G., Matsagkas, M., Ralli, S., Rountas, C., Rousas, N., Spanos, K., Brountzos, E., Kakisis, J. D., Lazaris, A., Moulakakis, K. G., Stefanis, L., Tsivgoulis, G., Vasdekis, S., Antonopoulos, C. N., Bellenis, I., Maras, D., Polydorou, A., Polydorou, V., Tavernarakis, A., Ioannou, N., Terzoudi, M., Lazarides, M., Mantatzis, M., Vadikolias, K., Dzieciuchowicz, L., Gabriel, M., Krasinski, Z., Oszkinis, G., Pukacki, F., Slowinski, M., Stanisic, M. -G., Staniszewski, R., Tomczak, J., Zielinski, M., Myrcha, P., Rozanski, D., Drelichowski, S., Iwanowski, W., Koncewicz, K., Bialek, P., Biejat, Z., Czepel, W., Czlonkowska, A., Dowzenko, A., Jedrzejewska, J., Kobayashi, A., Leszczynski, J., Malek, A., Polanski, J., Proczka, R., Skorski, M., Szostek, M., Andziak, P., Dratwicki, M., Gil, R., Nowicki, M., Pniewski, J., Rzezak, J., Seweryniak, P., Dabek, P., Juszynski, M., Madycki, G., Pacewski, B., Raciborski, W., Slowinski, P., Staszkiewicz, W., Bombic, M., Chlouba, V., Fiedler, J., Hes, K., Kostal, P., Sova, J., Kriz, Z., Privara, M., Reif, M., Staffa, R., Vlachovsky, R., Vojtisek, B., Hrbac, T., Kuliha, M., Prochazka, V., Roubec, M., Skoloudik, D., Netuka, D., Steklacova, A., Benes III, V., Buchvald, P., Endrych, L., Sercl, M., Campos, W., Casella, I. B., de Luccia, N., Estenssoro, A. E. V., Presti, C., Puech-Leao, P., Neves, C. R. B., da Silva, E. S., Sitrangulo, C. J., Monteiro, J. A. T., Tinone, G., Bellini Dalio, M., Joviliano, E. E., Pontes Neto, O. M., Serra Ribeiro, M., Cras, P., Hendriks, J. M. H., Hoppenbrouwers, M., Lauwers, P., Loos, C., Yperzeele, L., Geenens, M., Hemelsoet, D., van Herzeele, I., Vermassen, F., Astarci, P., Hammer, F., Lacroix, V., Peeters, A., Verhelst, R., Cirelli, S., Dormal, P., Grimonprez, A., Lambrecht, B., Lerut, P., Thues, E., De Koster, G., Desiron, Q., Maertens de Noordhout, A., Malmendier, D., Massoz, M., Saad, G., Bosiers, M., Callaert, J., Deloose, K., Blanco Canibano, E., Garcia Fresnillo, B., Guerra Requena, M., Morata Barrado, P. C., Muela Mendez, M., Yusta Izquierdo, A., Aparici Robles, F., Blanes Orti, P., Garcia Dominguez, L., Martinez Lopez, R., Miralles Hernandez, M., Tembl Ferrairo, J. I., Chamorro, A., Macho, J., Obach, V., Riambau, V., San Roman, L., Ahlhelm, F. J., Blackham, K., Engelter, S., Eugster, T., Gensicke, H., Gurke, L., Lyrer, P., Mariani, L., Maurer, M., Mujagic, E., Muller, M., Psychogios, M., Stierli, P., Stippich, C., Traenka, C., Wolff, T., Wagner, B., Wiegert, M. M., Clarke, S., Diepers, M., Grochenig, E., Gruber, P., Isaak, A., Kahles, T., Marti, R., Nedeltchev, K., Remonda, L., Tissira, N., Valenca Falcao, M., de Borst, G. J., Lo, R. H., Moll, F. L., Toorop, R., van der Worp, B. H., Vonken, E. J., Kappelle, J. L., Jahrome, O., Vos, F., Schuiling, W., van Overhagen, H., Keunen, R. W. M., Knippenberg, B., Wever, J. J., Lardenoije, J. W., Reijnen, M., Smeets, L., van Sterkenburg, S., Fraedrich, G., Gizewski, E., Gruber, I., Knoflach, M., Kiechl, S., Rantner, B., Abdulamit, T., Bergeron, P., Padovani, R., Trastour, J. -C., Cardon, J. -M., Le Gallou-Wittenberg, A., Allaire, E., Becquemin, J. -P., Cochennec-Paliwoda, F., Desgranges, P., Hosseini, H., Kobeiter, H., Marzelle, J., Almekhlafi, M. A., Bal, S., Barber, P. A., Coutts, S. B., Demchuk, A. M., Eesa, M., Gillies, M., Goyal, M., Hill, M. D., Hudon, M. E., Jambula, A., Kenney, C., Klein, G., Mcclelland, M., Mitha, A., Menon, B. K., Morrish, W. F., Peters, S., Ryckborst, K. J., Samis, G., Save, S., Smith, E. E., Stys, P., Subramaniam, S., Sutherland, G. R., Watson, T., Wong, J. H., Zimmel, L., Flis, V., Matela, J., Miksic, K., Milotic, F., Mrdja, B., Stirn, B., Tetickovic, E., Gasparini, M., Grad, A., Kompara, I., Milosevic, Z., Palmiste, V., Toomsoo, T., Aidashova, B., Kospanov, N., Lyssenko, R., Mussagaliev, D., Beyar, R., Hoffman, A., Karram, T., Kerner, A., Nikolsky, E., Nitecki, S., Andonova, S., Bachvarov, C., Petrov, V., Cvjetko, I., Vidjak, V., Haluzan, D., Petrunic, M., Liu, B., Liu, C. -W., Bartko, D., Beno, P., Rusnak, F., Zelenak, K., Ezura, M., Inoue, T., Kimura, N., Kondo, R., Matsumoto, Y., Shimizu, H., Endo, H., Furui, E., Bakke, S., Krohg-Sorensen, K., Nome, T., Skjelland, M., Tennoe, B., Albuquerque e Castro, J., Alves, G., Bastos Goncalves, F., de Aragao Morais, J., Garcia, A. C., Valentim, H., Vasconcelos, L., Belcastro, F., Cura, F., Zaefferer, P., Abd-Allah, F., Eldessoki, M. H., Heshmat Kassem, H., Soliman Gharieb, H., Colgan, M. P., Haider, S. N., Harbison, J., Madhavan, P., Moore, D., Shanik, G., Kazan, V., Nazzal, M., Ramsey-Williams, V., Burzotta F. (ORCID:0000-0002-6569-9401), Tinelli G. (ORCID:0000-0002-2212-3226), Tshomba Y. (ORCID:0000-0001-7304-7553), and Vincenzoni C.

Abstract

Background: Among asymptomatic patients with severe carotid artery stenosis but no recent stroke or transient cerebral ischaemia, either carotid artery stenting (CAS) or carotid endarterectomy (CEA) can restore patency and reduce long-term stroke risks. However, from recent national registry data, each option causes about 1% procedural risk of disabling stroke or death. Comparison of their long-term protective effects requires large-scale randomised evidence. Methods: ACST-2 is an international multicentre randomised trial of CAS versus CEA among asymptomatic patients with severe stenosis thought to require intervention, interpreted with all other relevant trials. Patients were eligible if they had severe unilateral or bilateral carotid artery stenosis and both doctor and patient agreed that a carotid procedure should be undertaken, but they were substantially uncertain which one to choose. Patients were randomly allocated to CAS or CEA and followed up at 1 month and then annually, for a mean 5 years. Procedural events were those within 30 days of the intervention. Intention-to-treat analyses are provided. Analyses including procedural hazards use tabular methods. Analyses and meta-analyses of non-procedural strokes use Kaplan-Meier and log-rank methods. The trial is registered with the ISRCTN registry, ISRCTN21144362. Findings: Between Jan 15, 2008, and Dec 31, 2020, 3625 patients in 130 centres were randomly allocated, 1811 to CAS and 1814 to CEA, with good compliance, good medical therapy and a mean 5 years of follow-up. Overall, 1% had disabling stroke or death procedurally (15 allocated to CAS and 18 to CEA) and 2% had non-disabling procedural stroke (48 allocated to CAS and 29 to CEA). Kaplan-Meier estimates of 5-year non-procedural stroke were 2·5% in each group for fatal or disabling stroke, and 5·3% with CAS versus 4·5% with CEA for any stroke (rate ratio [RR] 1·16, 95% CI 0·86–1·57; p=0·33). Combining RRs for any non-procedural stroke in all CAS versus CEA

Published
2021

47. National scientific medical meeting 1995 abstracts: Oral presentations

Author

Norris, S., Collins, C., Hegarty, J., O’Farrelly, C., Carton, J., Madrigal, L., O’Donoghue, D. P., O’Farrelly, C., Holloway, H., Fielding, J. F., Mullins, W., Hone, S. W., Donnelly, M., Powell, F., Blayney, A. W., Cahill, E. A., Daly, S. F., Turner, M. J., Sullivan, P. A., McLoughlin, M., Skelly, M. M., Mulcahy, H. E., Connell, T., O’Donoghue, D. P., Duggan, C., Duffy, M. J., Troy, A., Sheahan, K., Whelan, A., Herra, C. M., Keane, C. T., Johnson, H., Lee, B., Doherty, E., McDonnell, T., Mulherin, D., FitzGerald, O., Bresnihan, B., Hassett, H. M., Boyce, A., Greig, V., O’Herlihy, C., Smyth, P. P. A., Roche, E. F., McCormack, I., Tempany, E., Cullen, M. J., Smith, D. F., Smyth, P. P. A., McBrinn, Y., Murray, B., Freaney, R., Keating, D., McKenna, M. J., O’Hare, J. A., Alam, H., Raza, Q., Geoghegan, M., Killalea, S., Hall, M., Feely, J., Kyne, L., O’Hara, B., Cullen, M., Rea, I. M., Donnelly, J. P., Stout, R. W., Lacey, P., Donnelly, M. J., McGrath, J., Hennessy, T. P., Timon, C. V. I., Hyde, D., Xia, H. X., Keane, C. T., Buckley, M., O’Morain, C., Buckley, M., Keating, S., Xia, H., Hyde, D., O’Morain, C., McGrath, J. P., Stuart, R. C., Lawlor, P., Byrne, P. J., Walsh, T. N., Hennessy, T. P. J., Skelly, M. M., Mulcahy, H. E., Connell, T., O’Donoghue, D. P., Duggan, C., Duffy, M., Troy, A., Sheahan, K., Norris, S., Tubridy, M., Redmond, J., Hegarty, J., Holloway, H., Fielding, J. F., Mullins, W., Monahan, K., Murphy, R. P., Headon, D. R., O’Gorman, T., O’Reilly, F. M., Darby, C., Fielding, J. F., Murphy, G. M., Murphy, A., Codd, M., Powell, F., Dervan, P., Lawlor, D., Loughlin, S. O., Flanagan, N., Watson, R., Barnes, L., Flanagan, N., Watson, R., Kilgallen, C., Sweeney, E., Mynes, A., Mooney, D., Donoghue, I., Browne, O., Kirrane, J. A., Murphy, G. M., McKenna, D., Young, M., McKenna, D., Young, M., O’Toole, E., Young, M., O’Briain, S., Srinivasan, U., Feighery, C., Leonard, N., Jones, E., O’Farrelly, C., Moloney, M. A., O’Farrelly, C., Weir, D. G., Lawler, M., O’Neill, A., Gowing, H., Pamphilon, D., McCann, S. R., O’Toole, G., Orren, A., Seifer, C. M., Crowley, D. C., Sheehan, G. J., Deignan, T., Kelly, J., O’Farrelly, C., Tormey, V. J., Faul, J., Leonard, C., Burke, C. M., Poulter, L. W., Collins, C., Lynch, S., Madrigal, L., Norris, S., McEntee, G., Traynor, O., Hegarty, J., O’Farrelly, C., Barry, E., Collins, C., Costello, P., Keavney, A., O’Donoghue, D. P., O’Farrelly, C., Willoughby, R., Feighery, C., O’Donnell, C., Cahill, M., Earley, A., Eustace, P., Osborne, R., Cahill, M., Saidlear, C., Holmes, B., Early, A., Eustace, P., Moran, A. P., Neisser, A., Polt, R. J., Bernheimer, H., Kainz, M., Schwerer, B., Gallagher, L., Cahill, M., Saidlear, C., Early, A., Firth, R., Eustace, P., Kennedy, N., McGilloway, E., Redmond, J., McGilloway, E., Kennedy, N., Tubridy, N., Shields, K., Cullen, W. K., Rowan, M. J., Moore, A. R., Rowan, M., Feely, J., Coakley, D., Lawlor, B., Swanwick, G., Al-Naeemi, R., Redmond, J., Murphy, R., Feely, J., Codd, N. M., Goggins, M., Kennedy, N. P., Mallon, B. L., Kennedy, N. P., Mulherin, D., FitzGerald, O., Bresnihan, B., Mulcahy, H., Skelly, M., Donoghue, D. O., McCarthy, D., Saunders, A., Mulherin, D., Bresnihan, B., FitzGerald, O., Veale, D. J., Belch, J. J. F., Mulherin, D., Bresnihan, B., FitzGerald, O., Veale, D. J., Belch, J. J. F., Mulherin, D., FitzGerald, O., Bresnihan, B., Costello, P., Breathnach, D., Murphy, E., Mulherin, D., FitzGerald, O., Bresnihan, B., Breathnach, D., Costello, P., Mulherin, D., Bresnihan, B., FitzGerald, O., Breathnach, D., Mulherin, D., Costello, P., Bresnihan, B., FitzGerald, O., Kernohan, G., Gibson, K., Wilson, A. G., Duff, G. W., de Vries, N., van de Putte, L. B. A., Donoghue, J., O’Kelly, F., Johnson, Z., Maher, T., Kyne, L., Moran, A., Keane, C., O’Neill, D., Horgan, N., Barragry, J. M., O’Neill, D., O’Herlihy, C., Campbell, D. M., Behan, M., O’Connell, P. R., Donnelly, V. S., Crowley, D., Geary, M., Boylan, P., Geary, M., Fanagan, M., Boylan, P., Hickey, K., Teoh, T., Doyle, M., Harrison, R., Hickey, K., Lyons, D., Shenouda, Y., Coughlan, M., McKenna, P., Hickey, K., Shenouda, Y., Lyons, D., McKenna, P., Coughlan, M., Lenehan, P., Foley, M., Kelehan, P., Ravichandran, P., Kelly, M., Conroy, A., Fitzpatrick, C., Egan, D., Regan, C. L., McAdam, B. V., McParland, P., Boylan, P., FitzGerald, G. A., Fitzgerald, D. J., Sharma, S. C., Foran, K., Barry-Kinsella, C., Harrison, R. F., Gillespie, F. J., O’Mahony, P., Boyle, M., White, M. J., Donohoe, F., Birrane, Y., Naughton, M., Tempany, E., Fitzsimons, R. B., Piracha, M., McConkey, S., Griffin, E., Hayes, E., Clarke, T., Parfrey, N., Butler, K., Fitzpatrick, C., Malone, A. J., Kearney, P. J., Duggan, P. F., Lane, A., Keville, R., Turner, M., Barry, S., Sloan, D., Gallagher, S., Darby, M., Galligan, P., Stack, J., Walsh, N., O’Sullivan, M., Fitzgerald, M., O’Sullivan, M., Meagher, D., Sloan, D., Browne, S., Meagher, D., Larkin, C., Lane, A., Casey, P., O’Callaghan, E., Walsh, N., Rooney, S., Walsh, E., Morris, M., Lane, A., Burke, T., Larkin, C., O’Callaghan, E., Browne, S., Roe, M., Lane, A., Larkin, C., O’Callaghan, E., Maher, C., Wrigley, M., Gill, M., Burgess, M., Corcoran, E., Walsh, D., Gilmer, B., Johnson, H., Hayes, C. B., Thornton, L., Fogarty, J., Lyons, R., O’Connor, M., Delaney, V., Buckley, K., Johnson, Z., Johnson, Z., Lillis, D., Delany, V., Hayes, C., Dack, P., Igoe, D., Gilmer, B., O’Neill, H. J., Johnson, H., Igoe, D., Delaney, V., Johnson, Z., Kelly, P., McKeown, D., Clancy, L., Varghese, G., Hennessy, S., Codd, M., Gilmartin, J. J., Birthistle, K., Carrington, D., Maguire, H., Atkinson, P., Foley-Nolan, C., Lynch, M., Cryan, B., Whyte, D., Cryan, B., Conlon, C., Foley-Nolan, C., Johnson, Z., Hayes, C., Delany, V., Kucinskas, V., Usinskiene, U., Sakalyte, I., Johnson, Z., Hayes, C., Delaney, V., Dack, P., Gill, M., Dawson, E., Molloy, K., Goulden, N., Lawler, M., McCann, S. R., Doyle, J., Lawlor, E., Lawler, M., Harrington, M. G., El-Nageh, N., Nolan, M. -L., El-Nageh, N., Nolan, M. -L., Harrington, M. G., Lawlor, E., O’Riordan, J., McCann, S. R., Judge, G., Crotty, G., Finch, T., Borton, M., Barnes, T., Gilligan, O., Lee, G., Limmer, R., Madden, M., Whyte, D., Cryan, B., Bergin, C., O’Leary, A., Keating, S., Mulcahy, F., Wallis, F., Glennon, M., Cormican, M., NiRiain, U., Heiginbothom, M., Gannon, F., Smith, T., O’Sullivan, C., Hone, R., Orren, A., Caugant, D. A., Fijen, C. A. P., Van Schalkwyk, E. J., Coetzee, G. J., Lynch, M., Cryan, B., Riain, U. Ni, Cormican, M. G., Park, L., Flynn, J., Glennon, M., O’Connor, M., Regazzoli, V., O’Connor, M., Hayes, M., Nicholson, G., Higgins, P., NiRiain, U., Flynn, N., Corbett-Feeney, G., Conway, D. J., Sheahan, K., O’Higgins, N. J., Smyth, P. P. A., Rajendiran, S., Byrne, J., Kilfeather, E., Dingle, P., Hunter, M., Kelehan, P., Al-Ghazal, S. K., Stanley, P., Palmer, J., Hong, A., Al-Ghazal, S. K., Saxby, P., Al-Ghazal, S. K., Saxby, P., McConkey, S., Sheehan, D., Regan, I., O’Mullane, J., Chaoimh, M. Ni, Leahy, M., Heffron, J. J., Lehane, M., Keohane, C., O’Leary, N., Sheehan, M., Renny-Walsh, E., Whelton, M. J., Doyle, C. T., Webster, J., Benjamin, N., Lyons, D., FitzGerald, S., Chadha, J. S., FitzGerald, M. G., FitzGerald, G. R., Hemeryck, L., McGettigan, P., Feely, J., McGettigan, P., Feely, J., McGettigan, P., Golden, J., Feely, J., Arthur, N., Wen, S. Y., Killalea, S., Deegan, P., McGettigan, P., Feely, J., Cooke, T., Adebayo, G. I., Feely, J., Gaffney, P., Sinnot, M., O’Riordan, D., Hayes, T., O’Connor, C. M., FitzGerald, M. X., Costello, C., Finlay, G., Hayes, J., O’Connor, C., FitzGerald, M. X., McMahon, K., O’Farrelly, C., O’Connor, C., FitzGerald, M. X., Donnelly, M. J., Hone, S., Robertson, J., Coakley, R., O’Neill, S., Walsh, M., McCarthy, J., Lannon, D., Wood, A. E., Sharkey, R., Mulloy, E., Long, M., Kilgallen, I., O’Neill, S., Faul, J., Tormey, V., Leonard, C., Burke, C. M., Poulter, L. W., Horne, S., Tormey, V. J., Faul, J., Leonard, C., Burke, C. M., Feeney, T., Muiré, Ó. Ó, Gilmartin, J. J., Griffin, M. J., Hughes, D., Knaggs, A., Magee, D., Donnelly, M., McCrory, C., March, B., Hone, R., Phelan, D., White, M., Fabry, J., Lynch, M., Buggy, D., Cooney, C., Hughes, D., McCrory, C., Aziz, E., O’Herlihy, C., Kelly, J., O’Keefe, D., McShane, A. J., Boylan, J., Tobin, E., Smith, T., Motherway, C., Colreavy, F., Denish, N., Dwyer, R., Bergin, A., O’Brien, K., MacSullivan, R., Carson, K. D., Blunnie, W. P., Moriarty, D. C., Carson, K. D., Blunnie, W. P., Moriarty, D. C., Kinirons, B., Lyons, B., Cregg, N., Casey, W., Moore, K. P., Colbert, S. A., Ecoffey, C., O’Gorman, D., Fitzgerald, J., Phelan, D., Diamond, P., Codd, M. B., Sugrue, D. D., Kellett, J., Tighe, M., McKenna, C. J., Galvin, J., McCann, H. A., Sugrue, D. D., McKenna, C. J., Codd, M. B., McCann, H. A., Sugrue, D. D., Scallon, A., Buckley, M., Fraser, A., Norton, M., Tomkin, G., Graham, I., Byrne, A., Maher, M., Moran, N., Fitzgerald, D., O’Callaghan, D., Coyle, D., Nugent, A. G., McGurk, C., Johnston, G. D., McGurk, C., Nugent, A., Silke, B., Nugent, A. G., Johnston, G. D., Murphy, N., Jennings, L., Pratico, D., Doyle, C., Fitzgerald, D., Hennessy, T., McCann, H., Sugrue, D., Hennessy, T., Codd, M., Donnelly, S., Hennessy, A., Hartigan, C., McCann, H., Sugrue, D., Hennessy, T., Codd, M., Donnelly, S., Hennessy, A., Hartigan, C., McCann, H., Sugrue, D., Hennessy, T., MacDonald, D., Blake, S., McCann, H., Sugrue, D., Hennessy, T., Sugrue, D., McCann, H., Hennessy, T., McCann, H., Sugrue, D., Hennessy, T., McDonald, D., Blake, S., Dominque, D., Sugrue, D., McMechan, S. R., MacKenzie, G., Allen, J., Wright, G. T., Dempsey, G. J., Crawley, M., Anderson, J., Adgey, A. A. J., Harbinson, M. T., Campbell, N. P. S., Wilson, C. M., Ellis, P. K., McIlrath, E. M., Freaney, R., McShane, A., Keaveny, T. V., McKenna, M. J., Rabenstein, K., Scheller, F., Pfeiffer, D., Urban, C., Moser, I., Jobst, G., Manz, A., Verpoorte, S., Dempsey, F., Diamond, D., Smyth, M., Rabenstein, K., Dempsey, E., McShane, A., Keaveny, T. V., McKenna, M. J., Freaney, R., Hamilton, V., Dwyer, R., Twomey, J., Crowley, R., Fenelon, L., Walsh, F., McCann, J., McDonagh, P., White, M., McGovern, E., Luke, D., Phelan, D., McCrory, C., Crowley, K., Lyons, B., Mannion, D., Wood, A. E., Casey, W., Murphy, D., Clarkson, K., Carton, E., Higgins, P., Leonard, I., O’Toole, D., Staunton, M., Phelan, D., Srinivasan, U., Leonard, N., Jones, E., Moloney, M. A., Weir, D. G., O’Farrelly, C., Feighery, C., Griffin, M., Owens, D., Collins, P., Johnson, A., Tomkin, G. H., Herity, N. A., Allen, J. D., Silke, B., Adgey, A. A. J., O’Reilly, F. M., Darby, C., O’Moore, R., Fielding, J. F., Murphy, G. M., Crotty, G. M., Judge, G., McCann, S. R., DeArce, M., Nugent, A. G., McGurk, C., Johnston, G. D., Nikookam, K., Keenan, P., Cregan, D., Firth, R., O’Meara, N., Forman, S., Cusack, D. A., and Farrell, B.

Published
1995
Full Text
View/download PDF

49. Development and application of high-throughput screens for the discovery of compounds that disrupt ErbB4 signaling: Candidate cancer therapeutics

Author

Laura J. Cook, Ram B. Gupta, Christopher P. Mill, Richard L. Cullum, Cristina C. Rael, Megan A. Jacobi, Logan Neel, Ling Zhai, Mark J. Suto, Allan E. David, Robert Bostwick, Jared I. Senfeld, Lauren M. Lucas, Forrest Smith, Kanupriya Whig, David J. Riese, Darby C. Taylor, Mackenzie H. Harris, John T. Piazza, and David P. Kaufmann

Subjects
0301 basic medicine, Partial Agonists, Receptor, ErbB-4, Biochemistry, Receptor tyrosine kinase, chemistry.chemical_compound, Aromatic Amino Acids, 0302 clinical medicine, Drug Discovery, Medicine and Health Sciences, Enzyme assays, Colorimetric assays, Post-Translational Modification, Phosphorylation, Amino Acids, Enzyme-Linked Immunoassays, Bioassays and physiological analysis, Melanoma, ERBB4, MTT assay, Multidisciplinary, Organic Compounds, Drug discovery, Drugs, Chemistry, Optical Equipment, Cell Processes, Gain of Function Mutation, 030220 oncology & carcinogenesis, Physical Sciences, Engineering and Technology, Medicine, Research Article, Biotechnology, Signal Transduction, Agonist, medicine.drug_class, Science, Equipment, Bioengineering, Biology, Partial agonist, Small Molecule Libraries, 03 medical and health sciences, Hydroxyl Amino Acids, Cell Line, Tumor, medicine, Humans, Nerve Growth Factors, Immunoassays, Cell Proliferation, Pharmacology, Cell growth, Organic Chemistry, Chemical Compounds, Biology and Life Sciences, Proteins, Prisms, Tyrosine phosphorylation, Cell Biology, Research and analysis methods, 030104 developmental biology, chemistry, Small Molecules, Biochemical analysis, Immunologic Techniques, Cancer research, biology.protein, Tyrosine
Abstract

Whereas recent clinical studies report metastatic melanoma survival rates high as 30–50%, many tumors remain nonresponsive or become resistant to current therapeutic strategies. Analyses of The Cancer Genome Atlas (TCGA) skin cutaneous melanoma (SKCM) data set suggests that a significant fraction of melanomas potentially harbor gain-of-function mutations in the gene that encodes for the ErbB4 receptor tyrosine kinase. In this work, a drug discovery strategy was developed that is based on the observation that the Q43L mutant of the naturally occurring ErbB4 agonist Neuregulin-2beta (NRG2β) functions as a partial agonist at ErbB4. NRG2β/Q43L stimulates tyrosine phosphorylation, fails to stimulate ErbB4-dependent cell proliferation, and inhibits agonist-induced ErbB4-dependent cell proliferation. Compounds that exhibit these characteristics likely function as ErbB4 partial agonists, and as such hold promise as therapies for ErbB4-dependent melanomas. Consequently, three highly sensitive and reproducible (Z’ > 0.5) screening assays were developed and deployed for the identification of small-molecule ErbB4 partial agonists. Six compounds were identified that stimulate ErbB4 phosphorylation, fail to stimulate ErbB4-dependent cell proliferation, and appear to selectively inhibit ErbB4-dependent cell proliferation. Whereas further characterization is needed to evaluate the full therapeutic potential of these molecules, this drug discovery platform establishes reliable and scalable approaches for the discovery of ErbB4 inhibitors.

Published
2020

50. Integrating Indigenous Values into Federal Agency Impact Assessments to Reduce Conflicts—A Role for Anthropologists

Author

Darby C. Stapp

Subjects
Action (philosophy), Impact assessment, Political science, media_common.quotation_subject, Agency (sociology), Cultural impact, Quality (business), Public administration, Indigenous, media_common
Abstract

Conflicts surrounding the development of public lands are on the rise around the world. In the United States, where laws require federal agencies to conduct environmental and cultural impact assessments before approving or permitting development projects, conflicts still occur. This is especially true for projects that impact indigenous lands, resources, and communities, as the recent controversy surrounding Dakota Access Pipeline project so well illustrates. The purpose of this article is to highlight some of the problems I have encountered as an anthropologist conducting cultural impact assessments for federal agencies and for indigenous communities. Central among the problems encountered are the lack of awareness and appreciation for indigenous values by project proponents, agencies, and sometimes even the analysts hired to conduct the assessments. Recommendations for improving the quality of cultural impact assessments, which are based on the tenets of Action Anthropology, are explained.

Published
2018

Catalog

Books, media, physical & digital resources
See catalog results