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3. POS0540 REDUCTION OF B CELL SUBSETS, AUTOANTIBODIES AND DISEASE-RELEVANT PATHWAYS IN IANALUMAB TREATED PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS: FINDINGS FROM A PHASE 2 CLINICAL TRIAL

Author

Dörner, T., primary, Santos Da Costa, A., additional, Avrameas, A., additional, Sommer, U., additional, Hillenbrand, R., additional, De Luca, V., additional, Ferrero, E., additional, Da Costa, A., additional, Sips, C., additional, Bonal, C., additional, Rowlands, M., additional, Isnardi, I., additional, and Oliver, S., additional

Published
2024
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7. Global Variability in Administrative Approval Prescription Criteria for Biologic Therapy in Severe Asthma

Author

Porsbjerg, C.M. Menzies-Gow, A.N. Tran, T.N. Murray, R.B. Unni, B. Audrey Ang, S.L. Alacqua, M. Al-Ahmad, M. Al-Lehebi, R. Altraja, A. Belevskiy, A.S. Björnsdóttir, U.S. Bourdin, A. Busby, J. Canonica, G.W. Christoff, G.C. Cosio, B.G. Costello, R.W. FitzGerald, J.M. Fonseca, J.A. Hansen, S. Heaney, L.G. Heffler, E. Hew, M. Iwanaga, T. Jackson, D.J. Kocks, J.W.H. Kallieri, M. Bruce Ko, H.-K. Koh, M.S. Larenas-Linnemann, D. Lehtimäki, L.A. Loukides, S. Lugogo, N. Maspero, J. Papaioannou, A.I. Perez-de-Llano, L. Pitrez, P.M. Popov, T.A. Rasmussen, L.M. Rhee, C.K. Sadatsafavi, M. Schmid, J. Siddiqui, S. Taillé, C. Taube, C. Torres-Duque, C.A. Ulrik, C. Upham, J.W. Wang, E. Wechsler, M.E. Bulathsinhala, L. Carter, V. Chaudhry, I. Eleangovan, N. Hosseini, N. Rowlands, M.-A. Price, D.B. van Boven, J.F.M.

Abstract

Background: Regulatory bodies have approved five biologics for severe asthma. However, regional differences in accessibility may limit the global potential for personalized medicine. Objective: To compare global differences in ease of access to biologics. Methods: In April 2021, national prescription criteria for omalizumab, mepolizumab, reslizumab, benralizumab, and dupilumab were reviewed by severe asthma experts collaborating in the International Severe Asthma Registry. Outcomes (per country, per biologic) were (1) country-specific prescription criteria and (2) development of the Biologic Accessibility Score (BACS). The BACS composite score incorporates 10 prescription criteria, each with a maximum score of 10 points. Referenced to European Medicines Agency marketing authorization specifications, a higher score reflects easier access. Results: Biologic prescription criteria differed substantially across 28 countries from five continents. Blood eosinophil count thresholds (usually ≥300 cells/μL) and exacerbations were key requirements for anti-IgE/anti–IL-5/5R prescriptions in around 80% of licensed countries. Most countries (40% for dupilumab to 54% for mepolizumab) require two or more moderate or severe exacerbations, whereas numbers ranged from none to four. Moreover, 0% (for reslizumab) to 21% (for omalizumab) of countries required long-term oral corticosteroid use. The BACS highlighted marked between-country differences in ease of access. For omalizumab, mepolizumab, benralizumab, and dupilumab, only two, one, four, and seven countries, respectively, scored equal or higher than the European Medicines Agency reference BACS. For reslizumab, all countries scored lower. Conclusions: Although some differences were expected in country-specific biologic prescription criteria and ease of access, the substantial differences found in the current study present a challenge to implementing precision medicine across the world. © 2022 The Authors

Published
2022

8. New Endocrine Agents for the Treatment of Breast Cancer

Author

Coombes, R. C., Jarman, M., Dowsett, M., Chander, S. K., Rowlands, M. G., Di Salle, E., Evans, T. J., Herfarth, Ch., editor, Senn, H.-J., editor, Baum, M., editor, Diehl, V., editor, Gutzwiller, F., editor, Rajewsky, M. F., editor, Wannenmacher, M., editor, Senn, Hans-Jörg, editor, Gelber, Richard D., editor, Goldhirsch, Aron, editor, and Thürlimann, Beat, editor

Published
1993
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10. Descriptive Statements, Covering Laws, and Theories in Archaeology [and Comments and Reply]

Author

Read, Dwight W., LeBlanc, Steven A., Ammerman, Albert J., Bayard, Donn, Bertram, Jack B., Borillo, Mario, Demoule, Jean-Paul, Ferreira, J. V., Leone, Mark P., Malik, S. C., Matson, R. G., Morgan, Charles G., Paddock, John, Rowlands, M. J., Salmon, Merrilee H., Segraves, B. Abbott, Van Der Leeuw, Sander E., Voorrips, Albertus, and Zubrow, Ezra

Published
1978

13. Recidivism rates of sex offenders managed under the Dangerous Prisoners (Sexual Offenders) Act 2003: an evaluation of actuarial justice

Author

Rowlands, M. T., Palk, G., Young, R. Mc D., Rowlands, M. T., Palk, G., and Young, R. Mc D.

Abstract

According to the Dangerous Prisoners Sexual Offenders Act 2003 (DPSOA), an offender is considered ‘dangerous’ if there is an ‘unacceptable risk’ that he will commit ‘serious sexual harm’. Current legislation operates within an actuarial justice framework, whereby increasing resources are spent on those considered at greater risk. There is limited research on the efficacy of this approach. The current study examines sexual recidivism rates of a sample of DPSOA offenders. Court files of 104 community-supervised dangerous sex offenders (Mage = 50.7 SD = 10.8) were examined to determine date and type of re-offending. Recidivism was operationalised as time until arrest (for a sexual conviction/contravention). The overall level of sexual recidivism was low (7.69%). Kaplan–Meier analyses of survival curves identified no difference in rates between risk categories. While this likely suggests that they are not dangerous or an unacceptable risk, the strict conditions of supervision may be effective in preventing sexual re-offending. Further, limitations in empirically understanding the construct need to be considered.

Published
2021

14. The Sputum Transcriptome of Mild Atopic Asthma Following Bronchoprovocation and Inhaled Anti-TSLP Antibody Fragment Treatment

Author

Cabanski, M., primary, Xu, H., additional, Zhao, X., additional, Fernandez, A., additional, Khokhlovich, E., additional, Rowlands, M., additional, Schuhmann, I., additional, Grant, S.S., additional, Pertel, P., additional, Gauvreau, G.M., additional, O'Byrne, P., additional, Hohlfeld, J.M., additional, Vitaliti, A., additional, and Obeidat, M., additional

Published
2021
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16. Privileged structures and polypharmacology within and between protein families

Author

Meyers, J., Chessum, N.E.A., Ali, S., Mok, N.Y., Wilding, B., Pasqua, A.E., Rowlands, M., Tucker, M.J., Evans, L.E., Rye, C.S., O'Fee, L., Le Bihan, Y.V., Burke, R., Carter, M., Workman, P., Blagg, J., Brown, N., van Montfort, R.L.M., Jones, K., and Cheeseman, M.D.

Abstract

Polypharmacology is often a key contributor to the efficacy of a drug, but is also a potential risk. We investigated two hits discovered via a cell-based phenotypic screen, the CDK9 inhibitor CCT250006 (1) and the pirin ligand CCT245232 (2), to establish methodology to elucidate their secondary protein targets. Using computational pocket-based analysis, we discovered intrafamily polypharmacology for our kinase inhibitor, despite little overall sequence identity. The interfamily polypharmacology of 2 with B-Raf was used to discover a novel pirin ligand from a very small but privileged compound library despite no apparent ligand or binding site similarity. Our data demonstrates that in areas of drug discovery where intrafamily polypharmacology is often an issue, ligand dissimilarity cannot necessarily be used to assume different off-target profiles and that understanding interfamily polypharmacology will be important in the future to reduce the risk of idiopathic toxicity and in the design of screening libraries.

Published
2018

20. The future of Mali's past

Author

Bedaux, R.M.A and Rowlands, M.

Subjects
Mali -- Social aspects, Archaeology and state -- Mali -- Social aspects, Cultural property, Protection of -- Mali -- Social aspects, Excavations (Archaeology) -- Crimes against -- Mali, Anthropology/archeology/folklore, Social aspects, Crimes against
Abstract

Key-words: Cultural heritage, looting, protection, conservation, Mali, One of the greatest disasters for African archaeology is the systematic plundering of archaeological sites for the antiquities trade (e.g. Schmidt & McIntosh 1996; ICOM 1994). An eloquent proof of [...]

Published
2001

21. Biologic Utilization Patterns: Data from the International Severe Asthma Registry (ISAR)

Author

Menzies-Gow, A., primary, Wang, E., additional, Rowlands, M.-A., additional, Alacqua, M., additional, Al-Ahmad, M., additional, Bulathsinhala, L., additional, Carter, V., additional, Chaudhry, I., additional, Cheng, T.S., additional, Cosio, B.G., additional, Eleangovan, N., additional, Fitzgerald, J.M., additional, Heaney, L.G., additional, Hew, M., additional, Hosseini, N., additional, Jackson, D.J., additional, Kallieri, M., additional, Larenas-Linnemann, D., additional, Loukides, S., additional, Lugogo, N., additional, Murray, R., additional, Papaioannou, A., additional, Perez-de-Llano, L., additional, Porsbjerg, C., additional, Rasmussen, L., additional, Schmid, J., additional, Tran, T.N., additional, Ulrik, C.S., additional, Upham, J.W., additional, and Price, D.B., additional

Published
2020
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22. Global Access for Biologics in the Treatment of Severe Asthma: A Challenge to Personalized Medicine

Author

Menzies-Gow, A., primary, Tran, T.N., additional, Hosseini, N., additional, Eleangovan, N., additional, Rowlands, M.-A., additional, Bulathsinhala, L., additional, Hew, M., additional, Upham, J.W., additional, Heaney, L.G., additional, Ulrik, C., additional, Larenas-Linnemann, D., additional, Boven, J., additional, Fitzgerald, J.M., additional, Alacqua, M., additional, Wang, E., additional, Al-Ahmad, M., additional, Cosio, B.G., additional, Jackson, D.J., additional, Perez-de-Llano, L., additional, Porsbjerg, C., additional, Rasmussen, L.M., additional, Schmid, J., additional, Papaioannou, A.I.P., additional, Loukides, S., additional, Kallieri, M., additional, Lugogo, N., additional, Tan, A., additional, Chaudhry, I., additional, Carter, V., additional, Murray, R., additional, and Price, D.B., additional

Published
2020
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29. The associations of anthropometric, behavioural and sociodemographic factors with circulating concentrations of IGF‐I, IGF‐II, IGFBP‐1, IGFBP‐2 and IGFBP‐3 in a pooled analysis of 16,024 men from 22 studies

Author

Watts, EL, Perez-Cornago, A, Appleby, PN, Albanes, D, Ardanaz, E, Black, A, Bueno-De-Mesquita, HB, Chan, JM, Chen, C, Chubb, SAP, Cook, MB, Deschasaux, M, Donovan, JL, English, DR, Flicker, L, Freedman, ND, Galan, P, Giles, GG, Giovannucci, EL, Gunter, MJ, Habel, LA, Häggström, C, Haiman, C, Hamdy, FC, Hercberg, S, Holly, JM, Huang, J, Huang, W-Y, Johansson, M, Kaaks, R, Kubo, T, Lane, JA, Layne, TM, Le Marchand, L, Martin, RM, Metter, EJ, Mikami, K, Milne, RL, Morris, HA, Mucci, LA, Neal, DE, Neuhouser, ML, Oliver, SE, Overvad, K, Ozasa, K, Pala, V, Pernar, CH, Pollak, M, Rowlands, M-A, Schaefer, CA, Schenk, JM, Stattin, P, Tamakoshi, A, Thysell, E, Touvier, M, Trichopoulou, A, Tsilidis, KK, Van Den Eeden, SK, Weinstein, SJ, Wilkens, L, Yeap, BB, Key, TJ, Allen, NE, Travis, RC, Nuffield Department of Population Health [Oxford], University of Oxford [Oxford], National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Public Health Institute of Navarra, National Institute for Public Health and the Environment [Bilthoven] (RIVM), University of California [San Francisco] (UCSF), University of California, Fred Hutchinson Cancer Research Center [Seattle] (FHCRC), The University of Western Australia (UWA), Equipe 3: EREN- Equipe de Recherche en Epidémiologie Nutritionnelle (CRESS - U1153), Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Paris 13 (UP13)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Bristol [Bristol], Melbourne School of Population and Global Health [Melbourne], University of Melbourne, Harvard T.H. Chan School of Public Health, Harvard Medical School [Boston] (HMS), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Kaiser Permanente, Umeå University, Keck School of Medicine [Los Angeles], University of Southern California (USC), Nuffield (Nuffield), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), University of Occupational and Environmental Health [Kitakyushu] (UEOH), Icahn School of Medicine at Mount Sinai [New York] (MSSM), University of Hawai'i [Honolulu] (UH), The University of Tennessee Health Science Center [Memphis] (UTHSC), Japanese Red Cross Kyoto Daiichi Hospital, SA Pathology [Adelaide, SA, Australia], University of York [York, UK], Aarhus University [Aarhus], Radiation Effects Research Foundation, Fondazione IRCCS Istituto Nazionale Tumori - National Cancer Institute [Milan], McGill University = Université McGill [Montréal, Canada], Uppsala Universitet [Uppsala], Hokkaido University [Sapporo, Japan], Hellenic Health Foundation, Imperial College London, University of Ioannina, Deschasaux-Tanguy, Mélanie, University of Oxford, University of California [San Francisco] (UC San Francisco), University of California (UC), Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, Aging, Neoplasms, 80 and over, Prospective Studies, Insulin-Like Growth Factor I, POPULATION, Cancer, Aged, 80 and over, INSULIN-RESISTANCE, Tumor, Anthropometry, CARDIOVASCULAR RISK, SERUM-LEVELS, Middle Aged, Insulin-Like Growth Factor Binding Proteins, Oncology, Centre for Surgical Research, IGFBPs, ICEP, pooled analysis, Life Sciences & Biomedicine, Cancer Epidemiology, hormones, hormone substitutes, and hormone antagonists, Adult, Urologic Diseases, FACTOR-BINDING-PROTEIN, PROSTATE-CANCER RISK, Oncology and Carcinogenesis, and over, Young Adult, HORMONE, Insulin-Like Growth Factor II, GROWTH-FACTOR-I, Biomarkers, Tumor, Humans, 1112 Oncology and Carcinogenesis, Oncology & Carcinogenesis, METAANALYSIS, Aged, IGFs, Cancer och onkologi, Science & Technology, correlates, BODY-MASS INDEX, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Cross-Sectional Studies, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Cancer and Oncology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Biomarkers
Abstract

Insulin‐like growth factors (IGFs) and insulin‐like growth factor binding proteins (IGFBPs) have been implicated in the aetiology of several cancers. To better understand whether anthropometric, behavioural and sociodemographic factors may play a role in cancer risk via IGF signalling, we examined the cross‐sectional associations of these exposures with circulating concentrations of IGFs (IGF‐I and IGF‐II) and IGFBPs (IGFBP‐1, IGFBP‐2 and IGFBP‐3). The Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group dataset includes individual participant data from 16,024 male controls (i.e. without prostate cancer) aged 22–89 years from 22 prospective studies. Geometric means of protein concentrations were estimated using analysis of variance, adjusted for relevant covariates. Older age was associated with higher concentrations of IGFBP‐1 and IGFBP‐2 and lower concentrations of IGF‐I, IGF‐II and IGFBP‐3. Higher body mass index was associated with lower concentrations of IGFBP‐1 and IGFBP‐2. Taller height was associated with higher concentrations of IGF‐I and IGFBP‐3 and lower concentrations of IGFBP‐1. Smokers had higher concentrations of IGFBP‐1 and IGFBP‐2 and lower concentrations of IGFBP‐3 than nonsmokers. Higher alcohol consumption was associated with higher concentrations of IGF‐II and lower concentrations of IGF‐I and IGFBP‐2. African Americans had lower concentrations of IGF‐II, IGFBP‐1, IGFBP‐2 and IGFBP‐3 and Hispanics had lower IGF‐I, IGF‐II and IGFBP‐3 than non‐Hispanic whites. These findings indicate that a range of anthropometric, behavioural and sociodemographic factors are associated with circulating concentrations of IGFs and IGFBPs in men, which will lead to a greater understanding of the mechanisms through which these factors influence cancer risk., What's new? In many cancers, evidence points to insulin‐like growth factors and their associated binding proteins as a possible culprit. This study investigated how IGF and IGF binding proteins correlate with various other cancer‐associated factors. The authors obtained data from 16,000 cancer‐free males ranging in age from 22 to 89 years. Their analysis confirmed associations between circulating IGFs and IGFBPs and age, race/ethnicity and BMI. They also uncovered some new associations, including with height, drinking alcohol and smoking. IGFs and their binding proteins, they suggest, may be part of the mechanism by which these factors influence cancer risk.

Published
2019

37. Partnership with Schools: A Case Study of a Nature Field Course.

Author

Rowlands, M.

Abstract

A teacher education field experience which emphasizes a collaborative partnership among supervisors, student teachers, teachers, and pupils, is described. Aspects discussed include student teachers' perceptions of the course's effectiveness, course activities, and links between the university and the schools. (Author/CB)

Published
1987

41. Exploiting Protein Conformational Change to Optimize Adenosine-Derived Inhibitors of HSP70

Author

Cheeseman, MD, Westwood, IM, Barbeau, O, Rowlands, M, Dobson, S, Jones, AM, Jeganathan, F, Burke, R, Kadi, N, Workman, P, Collins, I, van Montfort, RL, and Jones, K

Abstract

HSP70 is a molecular chaperone and a key component of the heat-shock response. Because of its proposed importance in oncology, this protein has become a popular target for drug discovery, efforts which have as yet brought little success. This study demonstrates that adenosine-derived HSP70 inhibitors potentially bind to the protein with a novel mechanism of action, the stabilization by desolvation of an intramolecular salt-bridge which induces a conformational change in the protein, leading to high affinity ligands. We also demonstrate that through the application of this mechanism, adenosine-derived HSP70 inhibitors can be optimized in a rational manner.

Published
2016

43. Assessing the role of insulin-like growth factors and binding proteins in prostate cancer using Mendelian randomization: Genetic variants as instruments for circulating levels

Author

Bonilla, C, Lewis, SJ, Rowlands, M-A, Gaunt, TR, Smith, GD, Gunnell, D, Palmer, T, Donovan, JL, Hamdy, FC, Neal, DE, Eeles, R, Easton, D, Kote-Jarai, Z, Al Olama, AA, Benlloch, S, Muir, K, Giles, GG, Wiklund, F, Groenberg, H, Haiman, CA, Schleutker, J, Nordestgaard, BG, Travis, RC, Pashayan, N, Khaw, K-T, Stanford, JL, Blot, WJ, Thibodeau, S, Maier, C, Kibel, AS, Cybulski, C, Cannon-Albright, L, Brenner, H, Park, J, Kaneva, R, Batra, J, Teixeira, MR, Pandha, H, Lathrop, M, Martin, RM, Holly, JMP, Bonilla, C, Lewis, SJ, Rowlands, M-A, Gaunt, TR, Smith, GD, Gunnell, D, Palmer, T, Donovan, JL, Hamdy, FC, Neal, DE, Eeles, R, Easton, D, Kote-Jarai, Z, Al Olama, AA, Benlloch, S, Muir, K, Giles, GG, Wiklund, F, Groenberg, H, Haiman, CA, Schleutker, J, Nordestgaard, BG, Travis, RC, Pashayan, N, Khaw, K-T, Stanford, JL, Blot, WJ, Thibodeau, S, Maier, C, Kibel, AS, Cybulski, C, Cannon-Albright, L, Brenner, H, Park, J, Kaneva, R, Batra, J, Teixeira, MR, Pandha, H, Lathrop, M, Martin, RM, and Holly, JMP

Abstract

Circulating insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) are associated with prostate cancer. Using genetic variants as instruments for IGF peptides, we investigated whether these associations are likely to be causal. We identified from the literature 56 single nucleotide polymorphisms (SNPs) in the IGF axis previously associated with biomarker levels (8 from a genome-wide association study [GWAS] and 48 in reported candidate genes). In ∼700 men without prostate cancer and two replication cohorts (N ∼ 900 and ∼9,000), we examined the properties of these SNPS as instrumental variables (IVs) for IGF-I, IGF-II, IGFBP-2 and IGFBP-3. Those confirmed as strong IVs were tested for association with prostate cancer risk, low (< 7) vs. high (≥ 7) Gleason grade, localised vs. advanced stage, and mortality, in 22,936 controls and 22,992 cases. IV analysis was used in an attempt to estimate the causal effect of circulating IGF peptides on prostate cancer. Published SNPs in the IGFBP1/IGFBP3 gene region, particularly rs11977526, were strong instruments for IGF-II and IGFBP-3, less so for IGF-I. Rs11977526 was associated with high (vs. low) Gleason grade (OR per IGF-II/IGFBP-3 level-raising allele 1.05; 95% CI: 1.00, 1.10). Using rs11977526 as an IV we estimated the causal effect of a one SD increase in IGF-II (∼265 ng/mL) on risk of high vs. low grade disease as 1.14 (95% CI: 1.00, 1.31). Because of the potential for pleiotropy of the genetic instruments, these findings can only causally implicate the IGF pathway in general, not any one specific biomarker.

Published
2016

45. Animal Rights

Author

Wissenburg, M.L.J., Rowlands, M., and Rowlands, M.

Subjects
Internationalisering van Europa
Abstract

Item does not contain fulltext M. Rowlands Animal Rights London:Macmillan ,1998 0 333 71131 9

Published
1999

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