Gotowa bibliografia na temat „Eyre and Spottiswoode Ltd”

InJohn Pfeiffer Pty. Ltd. v. Rogerson (2000) 201 C.L.R. 552, the High Court of Australia had reconsidered the choice of law rules for “intra-national torts”, i.e. torts involving elements occurring in more than one Australian state. There, the Court rejected the rule of double actionability derived from Phillips v. Eyre (1870) L.R. 6 Q.B. 1 in preference for the rule that all questions of substance should be governed by the lex loci delicti. In Régie National des Usines Renault v. Zhang (2002) 187 A.L.R. 1, the High Court was asked to extend this preference to international torts as well. It did so emphatically. Except as regards a limited number of specific torts, for which the Court expressly reserved its consideration, the Australian common law rule is now that the substantive elements of tort actions are to be determined in accordance with the law of the place of the act or omission giving rise to the action.

HISTORICAL GEOLOGY OF IRELAND. J. K. Charlesworth. 9×6 in. xxiii + 565 pp. Oliver and Boyd: Edinburgh and London. 1963. 84s.JACKSON, John N., Surveys for Town and Country Planning, London, Hutchinson University Library, 1963, 15s.THE IRISH BORDER AS A CULTURAL DIVIDE. M. W. Heslinga. 225 pp. Assen. 1962.SHELL GUIDE TO IRELAND, by Lord Killanin and Michael V. Duignan. London: The Ebury Press, 1962. 478 pp. 9 3/4 × 6 in. 45s.IRELAND BY THE IRISH, edited by Michael Gorman. London: Galley Press Ltd., 1963. 162 pp. 9 3/4 × 7 in. 30s.MARINE CARTOGRAPHY IN BRITAIN. A history of the sea chart to 1855. A. H. W. Robinson. 11¼ × 9 in. 222 pp., 30 text figures, 42 photographic plates. Leicester: Leicester University Press, 1962. £5. 5s.VEGETATION AND SOILS, A WORLD PICTURE, by S. R. Eyre. London: Edward Arnold, 1963. pp. 324. 36/‐.MORPHOGENESIS OF THE AGRARIAN CULTURAL LANDSCAPE, (ed.) S. Helmfrid. Published as Geografiska Annaler, Vol. XLIII, 1961, Number 1–2. Stockholm. Pp. 1–328.NOTIONS ESSENTIELLES DE GÉOGRAPHIE ÉCONOMIQUE, by Jean Mérigot and Roland Froment, Volume one, Sirey, Paris, 1963; 555 pp., 54 illustrations.THE MONSOON. Pierre Pédelaborde. 8 × 5½ in. xii + 196 pp. Methuen, London, 1963, 21s.ON THE MARGINS OF THE GOOD EARTH. The South Australian Wheat Frontier 1869–1894. D. W. Meinig. Murray, London, 1963. 231 pp. 35s.INDEX TO AUSTRALIAN RESOURCES MAPS OF 1940–59. Canberra : Dept. of National Development, 1961. 241 pp. 9 × 6½ in.BRITISH LANDSCAPES THROUGH MAPS. Numbers 1 to 5. The Geographical Association. Price 4/6 each.‘SAMPLE STUDIES’. The Geographical Association. 1962. Price 4/6.

Abstract Background: Patients (pts) with relapsed/refractory (R/R) follicular lymphoma (FL) remain an unmet need population. Monotherapy with mosunetuzumab (M), a CD20xCD3 bispecific antibody, has demonstrated high and consistent response rates in high-risk R/R FL subsets, with early evidence of response durability and a favorable benefit/risk profile (Assouline et al. ASH 2020). Lenalidomide (Len) is clinically active in pts with FL, and its potent immunomodulatory activity offers the potential for additive/synergistic efficacy when combined with M. Here, we present initial data from an ongoing Phase Ib study (NCT04246086) evaluating the safety and activity of M+Len in R/R FL pts who have received at least one prior line of therapy. Methods: Pts with R/R FL (Grade [Gr] 1-3a) and at least one prior systemic anti-cancer therapy were enrolled to receive 12 cycles of M+Len (cycle duration: Cycle [C] 1, 21 days; C2-12, 28 days). In C1, step-up doses of M (IV infusion) are given on C1 Day (D)1 (1mg) and C1D8 (2mg), with the target dose given on C1D15 (30mg) and on D1 of C2-12. Len (20mg orally) is administered on D1-21 of C2-12. No hospitalization is mandated by the protocol. The primary objective is to evaluate the safety of M+Len; secondary objectives include assessment of response and long-term efficacy outcomes. Cytokine release syndrome (CRS) is reported using ASTCT criteria (Lee et al. Biol Blood Marrow Transplant 2019). Responses are assessed by investigators with PET-CT using Lugano 2014 criteria (Cheson et al. J Clin Oncol 2014). Results: At data cut-off (May 31, 2021), 27 pts had been enrolled. Median age was 59 years (range: 31-79 years); 12 pts (44%) were male. All pts had an ECOG performance status of 0 (18 pts, 67%) or 1 (9 pts, 33%). Median number of prior lines of therapy was 1 (range: 1-4), and 3 pts (11%) had disease progression (PD) <24 months from the start of first-line therapy. At data cut-off, 16 pts (59%) had been on study for 0-3 months, 8 (30%) for 3-6 months, 2 (7%) for 6-9 months, and 1 for >9 months. All 27 pts were safety evaluable at data cut-off. Twenty pts (74%) experienced ≥1 adverse event (AE) of any Gr; the most common AE was CRS (8 pts, 30%). Gr 3-4 AEs occurred in 8 pts (30%) and serious AEs in 8 pts (30%). No Gr 5 (fatal) AEs were observed. AEs relating to M occurred in 20 pts (74%) and AEs relating to Len occurred in 10 pts (37%). There were no AEs leading to withdrawal of M or Len; 2 pts had M-related AEs leading to M dose delays, 6 pts (22%) had Len-related AEs leading to Len dose interruption and/or reduction. In all pts, CRS events were Gr 1 (7/8 pts) or Gr 2 (1/8 pts). For most pts (6/8), CRS events occurred C1D1-C1D7; 2 pts experienced Gr 1 CRS events in C2. Median time to CRS onset was 1 day after first study drug administration (range: 1-28 days), median CRS duration was 3 days (range: 2-5 days). All CRS events resolved without sequelae. No pt required tocilizumab, ICU admission, high flow oxygen, or vasopressor support. Five pts (19%) reported 14 events of Gr 3-4 neutropenia; all neutropenia events occurred between D41 and D218, with a duration of 6-16 days. All neutropenia events resolved, with 1 patient receiving primary G-CSF prophylaxis and 2 pts receiving G-CSF treatment. No febrile neutropenia events occurred. The efficacy-evaluable population included all pts who had been assessed for response at any time on study, who had withdrawn from treatment or study prior to reaching their first response assessment, or who had been on study long enough to have reached their first scheduled response assessment, planned per protocol for D15-21 of C3. Objective response rate in the 13 pts who were efficacy evaluable at data cut-off was 92%, with complete metabolic response observed in 10 pts (77%), partial metabolic response (PMR) in 2 pts (15%), and stable disease in 1 patient (8%). One pt who initially achieved PMR experienced PD after 8 cycles of treatment. Conclusions: M+Len appears to have an acceptable safety profile in pts with R/R FL who have received at least one prior line of therapy, with encouraging preliminary anti-lymphoma activity observed. These data support initiation of a randomized Phase III study of M+Len versus rituximab+Len. Updated safety, efficacy, and pharmacokinetic data will be presented at the meeting. Disclosures Morschhauser: AstraZenenca: Membership on an entity's Board of Directors or advisory committees; Epizyme: Consultancy, Membership on an entity's Board of Directors or advisory committees; Chugai: Honoraria; Janssen: Honoraria; Genmab: Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees; Genentech, Inc.: Consultancy; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Speakers Bureau; Servier: Consultancy. Bishton: Nottingham University Hospitals NHS Trust: Current Employment; Celltrion: Honoraria; Tevapharma: Honoraria; Bristol-Myers Squibb: Honoraria; Gilead: Honoraria; F. Hoffmann-La Roche Ltd: Membership on an entity's Board of Directors or advisory committees. Eyre: Oxford University Hospitals NHS Foundation Trust: Current Employment; LOXO Oncology: Consultancy, Honoraria; Incyte: Consultancy, Honoraria; BeiGene: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Speakers Bureau; KITE/Gilead: Consultancy, Honoraria, Speakers Bureau; Secura Bio: Consultancy, Honoraria; AstraZeneca: Consultancy, Honoraria, Research Funding, Speakers Bureau. Bachy: Kite, a Gilead Company: Honoraria; Novartis: Honoraria; Daiishi: Research Funding; Roche: Consultancy; Takeda: Consultancy; Incyte: Consultancy. Cartron: Roche, Celgene-BMS: Consultancy; Danofi, Gilead, Novartis, Jansen, Roche, Celgene-BMS, Abbvie, Takeda: Honoraria. Ysebaert: AbbVie: Consultancy, Honoraria, Speakers Bureau; AstraZeneca: Consultancy, Honoraria, Speakers Bureau; Gilead: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Speakers Bureau. Bobillo: F. Hoffmann-La Roche Ltd: Consultancy, Speakers Bureau; Gilead: Speakers Bureau. Budde: Kite Pharma: Consultancy; Genentech: Consultancy, Research Funding; AstraZeneca: Research Funding. Fox: F. Hoffmann-La Roche Ltd: Consultancy, Membership on an entity's Board of Directors or advisory committees. Knapp: F. Hoffmann-La Roche Ltd: Current Employment. Yaqub: Genentech, Inc./F. Hoffmann-La Roche Ltd: Current Employment. Wei: Genentech, Inc.: Current Employment; F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. O'Hear: Genentech, Inc.: Current Employment; F. Hoffmann-La Roche Ltd: Current holder of individual stocks in a privately-held company. Li: F. Hoffmann-La Roche Ltd: Current Employment. Townsend: F. Hoffmann-La Roche Ltd: Consultancy, Honoraria; Celgene (Bristol-Myers Squibb): Consultancy, Honoraria. OffLabel Disclosure: Mosunetuzumab is a CD20xCD3 bispecific antibody that redirects T cells to engage and eliminate malignant B cells. Mosunetuzumab is an investigational agent.

Background:Tocilizumab (TCZ) is a biological disease-modifying antirheumatic drug that blocks IL-6 signalling and is effective in ameliorating disease activity in rheumatoid arthritis (RA). However, approximately 50% of patients do not respond adequately to TCZ and some patients report adverse events. Considering there is growing evidence that DNA methylation is implicated in RA susceptibility and response to some biologics (1, 2), we investigated DNA methylation as a candidate biomarker for response to TCZ in RA.Objectives:To identify differential DNA methylation signatures in whole blood associated with TCZ response in patients with RA.Methods:Epigenome-wide DNA methylation patterns were measured using the Infinium EPIC BeadChip (Illumina) in whole blood-derived DNA samples from patients with RA. DNA was extracted from blood samples taken pre-treatment and following 3 months on therapy, and response was determined at 6 months using the Clinical Disease Activity Index (CDAI). Patients who had good response (n=10) or poor response (n=10) to TCZ by 6 months were selected. Samples from secondary poor responders (n=10) (patients who had an improvement of CDAI and were in remission at 3 months, followed by a worsening of CDAI at 6 months) were also analysed. Differentially methylated positions and regions (DMPs/DMRs) were identified using linear regression, adjusting for gender, age, cell composition, smoking status, and glucocorticoid use. Gene Set Enrichment Analysis (GSEA) was used to identify significant pathways associated with response and Functional Epigenetic Module analysis of interactome hotspots in regions of differential methylation.Results:20 DMPs were significantly associated with response status at 6 months in the pre-treatment samples. Another 21 DMPs were associated with response in the 3 month samples. Within good responders, 10 DMPs showed significant change in methylation level between pre-treatment and the 3 month samples (unadjusted P-value <10-6). One DMP, cg03121467, was significantly less methylated in good responders compared to poor responders in the pre-treatment samples. This DMP is close toEPB41L4Aand thought to have a role in β–catenin signalling. GSEA of DMRs in non- and secondary non- responders identified histone acetyltransferase pathways and included theKAT2Agene, which is a repressor of NF-κB. Additional analysis of interaction hotspots of differential methylation identified significant interactions withSTAMBPandPTPN12associated with response status.Conclusion:These preliminary results provide evidence that DNA methylation patterns may predict response to TCZ. Validation of these findings in other larger data sets is required.References:[1]Liu,Y., Aryee,M.J., Padyukov,L., Fallin,M.D., Hesselberg,E., Runarsson,A., Reinius,L., Acevedo,N., Taub,M., Ronninger,M.,et al.(2013) Epigenome-wide association data implicate DNA methylation as an intermediary of genetic risk in rheumatoid arthritis.Nat. Biotechnol.,31, 142–147.[2]Plant,D., Webster,A., Nair,N., Oliver,J., Smith,S.L., Eyre,S., Hyrich,K.L., Wilson,A.G., Morgan,A.W., Isaacs,J.D.,et al.(2016) Differential Methylation as a Biomarker of Response to Etanercept in Patients With Rheumatoid Arthritis.Arthritis Rheumatol. (Hoboken, N.J.),68, 1353–60.Disclosure of Interests:Nisha Nair: None declared, Darren Plant: None declared, John Isaacs Consultant of: AbbVie, Bristol-Myers Squibb, Eli Lilly, Gilead, Janssen, Merck, Pfizer, Roche, Ann Morgan Grant/research support from: I have received a grant from Roche Products Ltd to establish a registry for GCA patients treated with tocilizumab., Consultant of: I have undertaken consultancy work for Roche, Chugai, Regeneron, Sanofi and GSK in the area of GCA therapeutics., Speakers bureau: I have presented on tocilizumab therapy for GCA and glucocorticoid toxicity on behalf of Roche products ltd., Kimme Hyrich Grant/research support from: Pfizer, UCB, BMS, Speakers bureau: Abbvie, Anne Barton Consultant of: AbbVie, Anthony G Wilson: None declared

NORTHERN IRELAND FROM THE AIR. Edited by R. Common, Belfast : Queen's University Geography Department, 1964. 104 pp., 44 plates, 1 folding map. 10 × 8 ins. 25s.THE CANALS OF THE NORTH OF IRELAND, by W. A. McCutcheon. Dawlish : David and Charles, and London : Macdonald and Co., 1965. 180 pp. 8 1/2 × 5 1/4 in. 36s.ULSTER AND OTHER IRISH MAPS c.1600. Edited by G. A. Hayes‐McCoy. Dublin : Irish Manuscripts Commission, 1964. 13 × 19 in. xv + 36 pp., 23. plates. £ 6.SOILS OF COUNTY WEXFORD. Edited by P. Ryan and M. J. Gardiner. Prepared and published by An Foras Talúntais (The Agricultural Institute), Dublin 1964. 171 pp. and three fold‐in maps. 30s.THE GEOGRAPHY OF SOIL, by Brian T. Bunting. London : Hutchinson's University Library, 1965. pp. 213. 14 figs. 12 tables. 7 1/2 × 5 in. 15s.THE HISTORY OF THE STUDY OF LANDFORMS. Vol. I : GEOMORPHOLOGY BEFORE DAVIS. Richard J. Chorley, Anthony J. Dunn and Robert P. Beckinsale. London : Methuen, 1964. 678 pp. 84s.A DICTIONARY OF GEOGRAPHY, by F. J. Monkhouse. London : Edward. Arnold Ltd., 1965. 344 pp. 8 1/2 × 5 1/2 in. 35s.LA REGION DE L'OUEST, by Pierre Flatrès. Collection ‘France de Demain ‘. Paris : Presses Universitaires de France, 1964. 31s. 6d.THE BRITISH ISLES : A SYSTEMATIC GEOGRAPHY. Edited by J. Wreford Watson and J. B. Sissons. Edinburgh : Thomas Nelson, 1964. 452 pp. 45s.SCANDINAVIAN LANDS, by Roy Millward. London : Macmillan, 1964. Pp. 448. 9 × 6 in. 45s.MERSEYSIDE, by R. Kay Gresswell and R. Lawton. British Landscapes Through Maps, No. 6. The Geographical Association, Sheffield, 1964. 36 pp. + 16 plates. 7 1/2 × 9 1/2 in. 5s.WALKING IN WICKLOW, by J. B. Malone. Dublin : Helicon Ltd., 1964. 172 pp. 7 × 4 #fr1/2> in. 7s.GREYSTONES 1864–1964. A parish centenary, 1964. 23 pp. 8 #fr1/4> × 5 1/2 in. 2s. 6d. Obtainable from the A.P.C.K., 37 Dawson Street, Dublin 2.DINNSEANCHAS. Vol. I, No. I. June 1964. An Cumann Logainmneacha, Baile Atha Cliath. Pp. 24. 5s.JOURNAL OF THE ASSOCIATION OF GEOGRAPHY TEACHERS OF IRELAND. Vol. I, Dublin. 1964.MAP READING FOR THE INTERMEDIATE CERTIFICATE, by Michael J. Turner. A. Folens : Dublin. 1964. 92 pp.MAP OF CORK CITY, 1: 15,000. Dublin : Ordnance Survey Office, 1964. 32 × 24 in. On paper, flat, 4s., or folded and covered, 5s.IRELAND, by T. W. Freeman. London : Methuen & Co. Ltd. Third edition, 1965. 5 1/2 × 8 #fr1/2> in. Pp. xx + 560. 65s.THE PLANNING AND FUTURE DEVELOPMENT OF THE DUBLIN REGION. PRELIMINARY REPORT. By Myles Wright. Dublin : Stationery Office, 1965. Pp.55. 8 ins. × 11 3/4 ins. 10s 6d.LIMERICK REGIONAL PLAN. Interim Report on the Limerick—Shannon— Ennis District by Nathaniel Litchfield. The Stationery Office, Dublin 1965. 8 × 12 ins. ; Pp. 83 ; 10s. 6d.ANTRIM NEW TOWN. Outline Plan. Belfast : H. M. Stationery Office, 1965. 10 1/2 × 8 1/2 in. 15s.HEPORT OF THE DEPUTY KEEPER OF THE RECORDS 1954–1959. Belfast : Her Majesty's Stationery Office. Cmd. 490. 138 pp. 10s.ECONOMIC GEOGRAPHY, by Ronald Hope. London : George Philip and Son Ltd., 4th edition, 1965. pp. 296. 15s. 6d.CLIMATE, SOILS AND VEGETATION, by D. C. Money. London : University Tutorial Press, 1965. pp. 272. 18s.TECHNIQUES IN GEOMORPHOLOGY, by Cuchlaine A. M. King. 9 × 5 1/2 in. 342 pp. London : Edward Arnold (Publishers) Ltd., 1966. 40s.BRITISH GEOMORPHOLOGICAL RESEARCH GROUP PUBLICATIONS :— 1. RATES OF EROSION AND WEATHERING IN THE BRITISH ISLES. Occasional Publication No. 2, 1965. Pp. 46. 13 × 8 in. 7s. 6d.2. DEGLACIATION. Occasional Publication No. 3, 1966. Pp. 37. 13 × 8 in. 7s.RECHERCHES DE GÉOMORPHOLOGIE EN ÉCOSSE DU NORD‐OUEST. By A. Godard. Publication de la Faculté des Lettres de l'Université de Strasbourg, 1965. 701 pp. 482 reís.ARTHUR'S SEAT: A HISTORY OF EDINBURGH'S VOLCANO, by G. P. Black. Edinburgh & London : Oliver & Boyd, 1966. 226 pp. 7 1/2 × 5 in. 35s.OFFSHORE GEOGRAPHY OF NORTHWESTERN EUROPE. The Political and Economic Problems of Delimitation and Control, by Lewis M. Alexander. London : Murray, 1966. 35s.GEOGRAPHICAL PIVOTS OF HISTORY. An Inaugural Lecture, by W. Kirk. Leicester University Press, 1965. 6s.THE GEOGRAPHY OF FRONTIERS AND BOUNDARIES, by J. R. V. Prescott. London : Hutchinson, 1965. 15s.THE READER'S DIGEST COMPLETE ATLAS OF THE BRITISH ISLES.. London : Reader's Digest Assoc., 1965. 230 pp. 15 1/4 × 10 1/2 in. £5. 10. 0.ULSTER DIALECTS. AN INTRODUCTORY SYMPOSIUM. Edited by G. B. Adams, Belfast : Ulster Folk Museum, 1964. 201 pp. 9 1/2 × 6 1/2 in. 20s.ULSTER FOLKLIFE, Volume 11. Belfast: The Ulster Folk Museum, 1965. Pp. 139. 9 1/2 × 7 in. 15s.GEOGRAPHICAL ABSTRACTS published and edited by K. M. Clayton, F. M Yates, F. E. Hamilton and C. Board.Obtainable from Geo. Abstracts, Dept. of Geography, London School of Economics, Aldwych, London, W.C.2. Subscription rates as below.THE CLIMATE OF LONDON. T. J. Chandler. London : Hutchinson and Co., 1965. 292 pp., 86 figs., 93 tables. 70/‐.MONSOON LANDS, Part I, by R. T. Cobb and L. J. M. Coleby. London : University Tutorial Press Ltd., 1966, constituting Book Six (Part 1 ) of the Advanced Level Geography Series. 303 pp. 8 1/4 × 5 1/4 in. 20s.PREHISTORIC AND EARLY CHRISTIAN IRELAND. A GUIDE, by Estyn Evans. London : B. T. Batsford Ltd., 1966. xii + 241 pp. 45s.A REGIONAL GEOGRAPHY OF IRELAND, by G. Fahy. Dublin : Browne and Nolan Ltd. No date. 238 pp. 12s.THE CANALS OF THE SOUTH OF IRELAND, by V. T. H. and D. R. Delany. Newton Abbot : David and Charles, 1966. 260 pp. + 20 plates. 8 1/2 × 5 1/2 in. 50s.THE COURSE OF IRISH HISTORY. Edited by T. W. Moody and F. X. Martin. Cork : The Mercier Press. 1967. 404 pp. 5 3/4 × 7 3/4 ins. Paperback, 21s. Hard cover, 40s.NORTH MUNSTER STUDIES. Edited by E. Rynne. Limerick : The Thomond Archaeological Society, 1967. 535 pp. 63s.SOILS OF COUNTY LIMERICK, by T. F. Finch and Pierce Ryan. Dublin: An Foras Talúntais, 1966. 199 pp. and four fold‐in maps. 9 1/2 × 7 1/4 in. 30s.THE FORESTS OF IRELAND. Edited by H. M. Fitzpatrick. Dublin : Society of Irish Foresters. No date. 153 pp. 9 3/4 × 7 1/4 in. 30s.PLANNING FOR AMENITY AND TOURISM. Specimen Development Plan Manual 2–3, Donegal. Dublin : An Foras Forbartha (The National Institute for Physical Planning and Construction Research), 1966. 110 pp. 8 × 11 in. 12s. 6d.NEW DIMENSIONS IN REGIONAL PLANNING. A CASE STUDY OF IRELAND, by Jeremiah Newman. Dublin : An Foras Forbartha, 1967. 128 pp. 8 1/2 × 6 in. 25s.TRAFFIC PLANNING FOR SMALLER TOWNS. Dublin : An Foras Forbartha (The National Institute for Regional Planning and Construction Research), 1966. 35 pp. 8 1/4 × 10 3/4 in. No price.LATE AND POST‐GLACIAL SHORELINES AND ICE LIMITS IN ARGYLL AND NORTH‐EAST ULSTER, by F. M. Synge and N. Stephens. Institute of British Geographers Transactions No. 59, 1966, pp. 101–125.QUATERNARY CHANGES OF SEA‐LEVEL IN IRELAND, by A. R. Orme. Institute of British Geographers Transactions No. 39, 1966, pp. 127–140.LIMESTONE PAVEMENTS (with special reference to Western Ireland), by Paul W. Williams. Institute of British Geographers Transactions No. 40, 1966, pp. 155–172. 50s. for 198 pages.IRISH SPELEOLOGY. Volume I, No. 2, 1966. Pp. 18. 10 × 8 in. 5s., free to members of the Irish Speleological Association.THE GEOGRAPHER'S CRAFT, by T. W. Freeman. Manchester University Press, 1967. pp.204. 8 1/4 × 5 in. 25s.GEOGRAPHY AS HUMAN ECOLOGY. Edited by S. R. Eyre and G. R. J. Jones. London : Edward Arnold Ltd., 1966. 308 pp. 45s.LOCATIONAL ANALYSIS IN HUMAN GEOGRAPHY, by Peter Haggett. London : Edward Arnold (Publishers) Ltd., 1965. 339 pp. 9 × 5 1/2 in. 40s.AGRICULTURAL GEOGRAPHY, by Leslie Symons. London : G. Bell and Sons, Ltd., 1967. 283 pp. 8 1/2 × 5 1/2 ins. 30s.THE GEOLOGY OF SCOTLAND, edited by Gordon Y. Craig. Edinburgh and London : Oliver & Boyd, 1965. Pp. 556. 9 3/4 × 7 1/2 in. 105s.MORPHOLOGY OF THE EARTH, by Lester C. King. Edinburgh : Oliver and Boyd, 2nd ed., 1967. 726 pp. 9 1/2 × 7 in. £5. 5. 0.INTERNATIONAL YEARBOOK OF CARTOGRAPHY, V, 1965. Edited by Eduard Imhof. London : George Philip and Son Ltd., 1965. 222 pp. + 9 plates. 9 3/4 × 6 1/2 in. 47s. 6d.IRISH FOLK WAYS, by E. Estyn Evans. London : Routledge and Kegan Paul, 1967. 324 pp. 16s.A HISTORY OF MEDIEVAL IRELAND, by A.J.Otway‐Ruthven. London: Ernest Benn Limited. New York : Barnes and Noble Inc., 1968. xv + 454 pp. 70s.IRISH AGRICULTURAL PRODUCTION, ITS VOLUME AND STRUCTURE, by Raymond D. Crotty. Cork University Press, 1966. 384 pp. 42s.PLANNING IN IRELAND. Edited by F. Rogerson and P. O hUiginn. Dublin : The Irish Branch of the Town Planning Institute and An Foras Forbartha, 1907. 199 pp.THE SHELL GUIDE TO IRELAND, by Lord Killanin and Michael V. Duignan. London : Ebury Press and George Rainbird (distributed by Michael Joseph) : 2nd edition, 1967. 512 pp. 50s.THE CLIMATE OF NORTH MUNSTER, by P. K. Rohan. Dublin : Department of Transport and Power, Meteorological Service, 1968. 72 pp. 10s. 6d.SOILS OF COUNTY CARLOW, by M.J. Conry and Pierce Ryan. Dublin : An Foras Talúntais, 1967. 204 pp. and four fold‐in maps. 30s.MOURNE COUNTRY, by E. Estyn Evans. Dundalk : Dundalgan Press (W. Tempest) Ltd., 2nd ed., 1967. 244 pp. 63s.THE DUBLIN REGION. Advisory Plan and Final Report, by Myles Wright. Dublin : The Stationery Office, 1967. Part One, pp. 64. 20s. Part Two, pp. 224. 80s.BELFAST : THE ORIGIN AND GROWTH OF AN INDUSTRIAL CITY. Edited by J. C. Beckett and R. E. Glasscock. London : The British Broadcasting Corporation, 1967. 204 pp. 25s.REPORT ON SKIBBEREEN SOCIAL SURVEY, by John Jackson. Dublin : Human Sciences Committee of the Irish National Productivity Committee, 1967. 63 pp. 12s. 6d.AN OUTLINE PLAN FOR GALWAY CITY, by Breandan S. MacAodha. Dublin : Scepter Publishers Ltd., 1966. 15 pp.COASTAL PASSENGER STEAMERS AND INLAND NAVIGATIONS IN THE SOUTH OF IRELAND, by D.B. McNeill. Belfast : The Transport Museum (Transport Handbook No. 6), 1965 (issued in 1967). 44 pp. (text) + 12 pp. (plates). 3s. 6d.CANALIANA, the annual bulletin of Robertstown Muintir na Tire. Robertstown, Co. Kildare : Muintir na Tire, n.d. (issued in 1967). 60 pp. 2s. 6d.CONACRE IN IRELAND, by Breandan S. MacAodha (Social Sciences Research Centre, Galway). Dublin : Scepter Publishers Ltd., 1967, 15 pp. No price.PROCESSES OF COASTAL DEVELOPMENT, by V.P. Zenkovich, edited by J.A. Steers, translated by D.G. Fry. 738 pp. Edinburgh and London : Oliver and Boyd, 1967. £12. 12s.CONGRESS PROCEEDINGS. 20th International Geographical Congress. Edited by J. Wreford Watson. London : Nelson, 1967. 401 pp. 70s.REGIONAL GEOGRAPHY, by Roger Minshull. London : Hutchinson University Library, 1967. 168 pp. 10s. 6d.ATMOSPHERE, WEATHER AND CLIMATE, by R.G. Barry and R.J. Chorley. London : University Paperback, Methuen, 1967. 25s.THE EVOLUTION OF SCOTLAND'S SCENERY, by J.B. Sissons. Edinburgh and London : Oliver and Boyd, 1967. 259 pp. 63s.WEST WICKLOW. BACKGROUND FOR DEVELOPMENT, by F.H.A. Aalen, D.A. Gillmor and P.W. Williams. Dublin : Geography Department, Trinity College, 1966. 323 pp. Unpublished : copy available in the Society's Library.

BackgroundWe recently performed the largest juvenile idiopathic arthritis (JIA) genome-wide association study (GWAS) to date 1. Disease-associated loci contain multiple single nucleotide polymorphism (SNPs), and the majority map to non-coding enhancers, making it challenging to define causal variants and genes.Functional genomics datasets in disease-relevant tissues have shown to be essential for the functional interpretation of GWAS loci. In particular, capture Hi-C (CHi-C) has been successful in detecting chromosomal interactions linking GWAS loci to their target genes. However, such datasets are lacking in JIA.ObjectivesThe aim of this study is to bridge this gap and advance the knowledge of the biological mechanisms that underpin susceptibility to JIA, by integrating GWAS with public epigenomics datasets and in-house generated CHi-C from JIA patients. We focus on CD4+ T-cells, which have been shown to be one of the most relevant cell types in JIA. In addition, we use CRISPR-Cas9 to validate the regulatory effect of prioritised variants on their predicted target genes.MethodsCredible SNP sets for the top JIA risk loci (P < 5x10-6) were annotated using EpiMap data 2. Low input whole genome promoter CHi-C (PCHi-C) was performed on CD4+ T-cells isolated from blood from 3 JIA oligoarthritis patients, and data was analysed using CHiCAGO 3. GWAS and PCHi-C data were combined to prioritise causal genes using the Capture Hi-C Omnibus Gene Score (COGS) pipeline 4. We subsequently employed CRISPR activation (CRISPRa) and CRISPR interference (CRISPRi) in Jurkats to assess whether prioritized JIA variants were capable of regulating the expression of the interacting genes.Results614 credible SNPs (out of 735) were found to overlap active enhancers in CD4+ T-cells, and were prioritized for further analysis.We identified numerous significant chromatin interactions in 19 out of 44 non-MHC JIA associated loci, linking JIA SNPs mapping to T-cell enhancers to a total of 61 target genes and revealing potential novel disease pathways. Moreover, COGS prioritised a total of 7 genes (RGS14, ERAP2, HIPK1, CCR4, CCRL2, CCR2, CCR3).A JIA associated locus on chromosome 3 contains 39 SNPs. It maps to an intergenic region and the causal gene/s are unclear. Our PCHi-C data revealed that this JIA locus presents chromatin interactions with the promoters of several genes, such as CCRL2, CCR2, CCR3 and CCR5, three of which were prioritised by COGS. Two variants were selected for further analysis: rs79815064, which had the highest posterior probability, and rs8005404,the only variant within a CD4+ T-cell enhancer linked to surrounding gene activity.When both SNPs were targeted with CRISPRa and CRISPRi, we observed an increased and decreased expression, respectively, of CCRL2, CCR2, CCR3 and CCR5, confirming their role in disease. These genes belong to the chemokine receptor family and are important regulators of the inflammatory response.ConclusionOur work shows how functional genomics can help identify biological mechanisms by which GWAS variants increase risk of JIA, which in turn will benefit patients through personalised medicine and the identification of therapeutic targets.References[1]López-Isac, E. et al. Combined genetic analysis of juvenile idiopathic arthritis clinical subtypes identifies novel risk loci, target genes and key regulatory mechanisms. Ann. Rheum. Dis.80, 321–328 (2021).[2]Boix, C. A., James, B. T., Park, Y. P., Meuleman, W. & Kellis, M. Regulatory genomic circuitry of human disease loci by integrative epigenomics. Nat. 2021 5907845590, 300–307 (2021).[3]Cairns, J. et al. CHiCAGO: Robust detection of DNA looping interactions in Capture Hi-C data. Genome Biol.17, 1–17 (2016).[4]Javierre, B. M. et al. Lineage-Specific Genome Architecture Links Enhancers and Non-coding Disease Variants to Target Gene Promoters. Cell167, 1369 (2016).Disclosure of InterestsAntonio Frantzesko: None declared, Valeriya Malysheva: None declared, Chenfu Shi: None declared, James Ding: None declared, John Bowes: None declared, Wendy Thomson: None declared, Stephen Eyre: None declared, Mikhail Spivakov Shareholder of: co-founder and shareholder of Enhanc3D Genomics Ltd, Gisela Orozco: None declared

Abstract Introduction Central nervous system relapse (secondary central nervous system lymphoma -SCNS) is an uncommon but devastating complication of aggressive B-cell lymphoma. Patients (Pts) with CNS-IPI 4-6 are at greatest risk (10.2% at 2 years). Intravenous high-dose methotrexate (HD-MTX) is widely used to mitigate SCNS risk but data supporting this practice are limited. Methods We performed a multicentre, retrospective study at 21 sites in Australia, Asia, North America and Europe. Chart or registry review was performed for consecutively diagnosed pts with diffuse large B-cell lymphoma (DLBCL) and CNS-IPI 4-6, high grade B-cell lymphoma (HGBL) with rearrangements of MYC+BCL2 and/or BCL6 and primary breast/testicular DLBCL irrespective of CNS-IPI. Pts were diagnosed between 2000-2020, 18-80 years at diagnosis, and treated with curative intent anti-CD20 based chemo-immunotherapy. Pts with CNS involvement at diagnosis were excluded. HD-MTX was defined as at least one cycle of intravenous MTX at any dose. Time to SCNS was calculated from date of diagnosis (all-pts), and from the end of frontline systemic lymphoma therapy, defined as 6x21 days from diagnosis (complete response (CR-pts)), until SCNS, systemic relapse, death, or censoring, whichever came first. Cumulative risk of SCNS was computed using the Aalen-Johansen estimator treating death and systemic relapses as competing events. Adjusted cumulative risks were obtained by using an inverse probability of treatment weighting approach. The average treatment effect was computed as the difference in adjusted 5-year risk of SCNS. Results - 2300 and 1455 pts were included in the all-pts and CR-pts analyses, respectively. Baseline demographics and details of therapy are summarised in Table 1. Except for a predominance of males, pts ≤60 years and pts with ECOG 0-1 in the HD-MTX vs no HD-MTX groups, the demographics and treatments were well balanced. At a median follow up of 5.9 years (range 0.0-19.1) and 5.5 years from diagnosis (range 0.0-18.7), 201/2300 and 84/1455 pts experienced CNS events in the all-pts and CR-pts analyses respectively. For all-pts(n=2300), CNS-IPI was 4-6 in 2052(89.2%), with R-CHOP-like therapy given to 93.8%. 410 pts (17.8%) received HD-MTX (265 HD-MTX alone, 145 in combination with intrathecal methotrexate (IT-MTX);435 received IT-MTX alone;1455 received neither. There were 32/410 and 169/1890 SCNS events, with median time from diagnosis to SCNS of 8.8 and 6.7 months in the HD-MTX and no HD-MTX groups respectively. 5-year OS was 70% (95% CI, 65-76%) and 55% (95% CI 53-57%) in HD-MTX and no HD-MTX groups respectively. There was no difference in the adjusted 5-year risk of SCNS between the HD-MTX and no HD-MTX groups (8.4% vs 9.1%, adjusted hazard ratio [HR] 0.71, p=0.100) (Figure 1). For CR-pts(n=1455), CNS-IPI was 4-6 in 1267(87.0%), with R-CHOP-like therapy given to 93.3%. 284 pts (19.5%) received HD-MTX (170 HD-MTX alone, 114 with IT-MTX);298 received IT-MTX alone;873 received neither. There were 16/284 and 68/1171 SCNS events, with median time from diagnosis to SCNS of 11.0 and 10.3 months in the HD-MTX and no HD-MTX groups respectively. 5-year OS was 74%(95% CI 67-81%) and 75%(95% CI 72-78%) in the HD-MTX groups and no HD-MTX groups respectively (adjusted HR 1.08, p=0.622). There was no difference in the 5-year risk of CNS relapse between the HD-MTX and no HD-MTX groups 5.0% vs 6.0% (adjusted HR 1.03, p=0.903) (Figure 2). Exploratory analysis of the impact of HD-MTX among the highest risk groups CNS IPI 5 (n=368), CNS-IPI 6 (n=59) and CNS-IPI 6 plus all pts with testicular, renal or adrenal involvement (n=349) did not reveal differences in SCNS rates in HD-MTX treated pts. Additional subgroup analyses will be presented at the meeting. Conclusions To our knowledge, this is the largest study of the efficacy of HD-MTX in reducing SCNS events focusing exclusively on high-risk pts. The overall incidence of CNS relapse observed was consistent with previous reports in similar patient cohorts at 9%. The use of HD-MTX did not lower SCNS rates overall or when analysis was confined to CR pts at completion of curative intent therapy to compensate for potential immortal bias associated with HD-MTX therapy. Despite the limitations of the non-randomized and retrospective design, it appears unlikely that HD-MTX is associated with a clinically meaningful reduction in SCNS rates in pts with high risk for SCNS. Figure 1 Figure 1. Disclosures Lewis: AstraZeneca: Consultancy, Honoraria; Novartis: Patents & Royalties: Conference attendance; Janssen: Honoraria, Patents & Royalties: Conference attendance; Roche: Consultancy, Honoraria. Villa: Janssen: Honoraria; Gilead: Honoraria; AstraZeneca: Honoraria; AbbVie: Honoraria; Seattle Genetics: Honoraria; Celgene: Honoraria; Lundbeck: Honoraria; Roche: Honoraria; NanoString Technologies: Honoraria. Bobillo: F. Hoffmann-La Roche Ltd: Consultancy, Speakers Bureau; Gilead: Speakers Bureau. Ekstroem Smedby: Takeda: Consultancy; Janssen Cilag: Research Funding. Savage: Merck: Consultancy, Honoraria, Other: Institutional clinical trial funding; BMS: Consultancy, Honoraria, Other: Institutional clinical trial funding; AbbVie: Consultancy, Honoraria; Roche: Research Funding; Takeda: Other: Institutional clinical trial funding; Servier: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Astra-Zeneca: Consultancy, Honoraria; Beigene: Other: Institutional clinical trial funding; Genentech: Research Funding. Eyre: Beigene: Honoraria, Research Funding; Incyte: Consultancy; Secura Bio: Consultancy, Honoraria; Janssen: Honoraria; Gilead/KITE: Honoraria, Other: Travel support for conferences, Research Funding, Speakers Bureau; Loxo Oncology: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Honoraria, Other: Travel to conferences; AstraZeneca: Honoraria, Research Funding; Roche: Consultancy, Honoraria. Cwynarski: Incyte: Consultancy, Speakers Bureau; Gilead: Consultancy, Speakers Bureau; Atara: Consultancy; Celgene: Consultancy; Takeda: Consultancy, Other: travel to scientific conferences, Speakers Bureau; Kite, a Gilead Company: Consultancy, Other: travel to scientific conferences, Speakers Bureau; Janssen: Consultancy, Other: travel to scientific conferences; Roche: Consultancy, Other: travel to scientific conferences, Speakers Bureau; BMS/Celgene: Other: travel to scientific conferences. Stewart: Teva: Honoraria; Sandoz: Honoraria; Amgen: Honoraria; AstraZeneca: Honoraria; Novartis: Honoraria; Celgene: Honoraria; Gilead: Honoraria; Abbvie: Honoraria; Janssen: Honoraria; Roche: Honoraria. Bishton: Gilead: Honoraria, Other: Travel grants; AbbVie: Honoraria, Other: Travel grants; Celgene/BMS: Honoraria, Other: travel grants; Celltrion: Honoraria, Other: Travel grants; Takeda.: Honoraria, Other: Travel grants . Fox: F. Hoffmann-La Roche Ltd: Consultancy, Membership on an entity's Board of Directors or advisory committees. Joffe: Epizyme: Consultancy; AstraZeneca: Consultancy. Eloranta: Janssen Pharmaceutical NV: Other: NV. Sehn: Genmab: Consultancy; Novartis: Consultancy; Debiopharm: Consultancy. Manos: Bristol-Myers Squibb: Other: Travel and meetings. Hawkes: Specialised Therapeutics: Consultancy; Gilead: Membership on an entity's Board of Directors or advisory committees; Merck Sharpe Dohme: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Antigene: Membership on an entity's Board of Directors or advisory committees; Regeneron: Speakers Bureau; Bristol Myers Squib/Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck KgA: Research Funding; Astra Zeneca: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Other: Travel and accommodation expenses, Research Funding, Speakers Bureau; Janssen: Speakers Bureau. Minson: Novartis: Research Funding; Hoffman La Roche: Research Funding. Dickinson: Celgene: Research Funding; Amgen: Honoraria; Takeda: Research Funding; Gilead Sciences: Consultancy, Honoraria, Speakers Bureau; MSD: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Roche: Consultancy, Honoraria, Other: travel, accommodation, expenses, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau. Øvlisen: Abbvie: Other: Travel expenses. Gregory: Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel fees, Speakers Bureau; Janssen: Consultancy; Novartis: Consultancy. Ku: Roche: Consultancy; Antegene: Consultancy; Genor Biopharma: Consultancy. Talaulikar: Roche: Honoraria, Research Funding; Jansenn: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; EUSA Pharma: Honoraria, Research Funding. Maurer: Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding; Genentech: Research Funding; Kite Pharma: Membership on an entity's Board of Directors or advisory committees; Morphosys: Membership on an entity's Board of Directors or advisory committees, Research Funding; Nanostring: Research Funding. El-Galaly: Abbvie: Other: Speakers fee; ROCHE Ltd: Ended employment in the past 24 months. Cheah: Roche: Consultancy, Honoraria, Other: advisory and travel expenses, Research Funding; Janssen: Consultancy, Honoraria, Other: advisory; MSD: Consultancy, Honoraria, Other: advisory, Research Funding; Gilead: Consultancy, Honoraria, Other: advisory; Ascentage pharma: Consultancy, Honoraria, Other: advisory; Beigene: Consultancy, Honoraria, Other: advisory; AbbVie: Research Funding; Celgene: Research Funding; AstraZeneca: Consultancy, Honoraria, Other: advisory; Loxo/Lilly: Consultancy, Honoraria, Other: advisory; TG Therapeutics: Consultancy, Honoraria, Other: advisory.

Abstract Introduction: Central nervous system (CNS) relapse in diffuse large B-cell lymphoma (DLBCL) is uncommon but is associated with poor outcomes. In selected high risk patients (pts), high dose methotrexate (HDMTX) is often used as CNS prophylaxis with frontline (1L) DLBCL therapy despite uncertain efficacy, optimum dose and timing of delivery. A recent UK study (Wilson et al 2020) showed that intercalated HDMTX (i-HDMTX) was associated with increased toxicity and R-CHOP delays compared to end of treatment (EOT) delivery. Although hypothesis generating, the study size was insufficient to determine whether EOT was non-inferior in terms of CNS relapse risk. Methods: We conducted an international, multicentre retrospective analysis of consecutive DLBCL or high grade BCL pts between 2007-20 from 47 centers in Europe, Australia and N. America. Pts were included if they received R-CHOP or R-CHOP-like 1L therapy with curative intent as well as HDMTX CNS prophylaxis (≥1 cycle). Concurrent intrathecal (IT) prophylaxis was permitted. Pts with known CNS involvement at baseline and those treated with more intensive protocols (e.g. R-DA-EPOCH) were excluded. i-HDMTX was defined as any pt receiving a HD-MTX cycle before the final R-CHOP cycle. CNS relapse events were excluded if occurring after first systemic lymphoma relapse/progression. Time to event endpoints were measured from diagnosis to first event or censor and analysed using Kaplan-Meier and Cox regression methods. Time to CNS relapse was analysed using competing risk Fine and Gray method (for death and non-synchronous systemic relapse). To mitigate for possible immortality bias in the EOT arm, a landmark analysis for pts alive and free from progression at 6 months was conducted. We aimed to exclude a 5% difference in 2-year (y) CNS relapse rates. Results: 1,384 pts were analysed. 750 received i-HDMTX and 634 received EOT HDMTX. Key baseline characteristics are summarised in Table 1. Median follow up was 37.9 months. 44.2% had high CNS IPI (4-6) with no significant difference between i-HDMTX and EOT groups (45.1% vs 43.1%, p=0.087). ≥2 cycles of HDMTX were used in 86.6% with no difference between groups (85.6% vs 87.9%, p=0.22). Concurrent IT prophylaxis use was higher for EOT pts (55.6% vs 38.1% p&lt;0.0001). 78 CNS relapses (42 i-HDMTX, 36 EOT) were observed: parenchymal in 41 (53%), parenchymal and leptomeningeal in 16 (21%) and isolated leptomeningeal in 21 (27%). There was no significant difference in 2y CNS relapse rates between i-HDMTX and EOT in all pts: 5.2% vs 3.9%, adjusted hazard ratio (HR) 0.92 (95% CI 0.58-1.47), p=0.74, 2y difference -0.2% (-2.0-2.5) or landmark analysis: 2.8% vs 4.1%, HR: 0.93 (0.56-1.55), p=0.79, 2y difference: -0.3% (-1.8-2.2%) (Fig 1a/b). Exploratory analyses focusing on pts with isolated CNS relapse (n=57) demonstrated similar results (2y rates 3.6% vs 3.0%, p=0.99). On multivariable analysis (MVA) of risk factors for CNS relapse, renal/adrenal involvement was the only variable associated with increased CNS relapse risk (adjusted HR 1.74 (1.03-2.92), p=0.038). Notably, IT prophylaxis was not associated with reduction in CNS relapse. In 600 high CNS IPI (4-6) pts, there was no difference in CNS relapse risk between i-HD-MTX and EOT (3y rates 9.4% vs 8.6%, HR 0.92 (95% CI 0.52-1.62)). In a composite high risk group including CNS IPI 4-6 and/or any of the following: ≥3 extranodal sites, renal, adrenal, testicular or breast involvement (n=885) there was no difference in 3y CNS relapse rates between groups (i-HDMTX 7.6% vs EOT 7.4%, HR 0.94 (0.58-1.53)). Progression-free survival (PFS) and overall survival (OS) in the i-HDMTX and EOT groups were as follows: 3y PFS 70.7% vs 76.7% (p=0.098), 3y OS 79.9% vs 87.0% (p=0.0016). However, there were no PFS/OS differences between groups on landmark analysis (n=1259) (Fig 1c). On analysis of pts experiencing ≥1 R-CHOP delay of ≥7 days, use of i-HDMTX was the only factor on MVA associated with increased delays (p&lt;0.0001). Discussion: We found no evidence that EOT delivery increases CNS relapse risk when compared to i-HDMTX in this large analysis of pts treated with 1L R-CHOP. Delays to R-CHOP cycles were increased with i-HDMTX. Findings in a high risk subgroup were unchanged and rates of CNS relapse in this HDMTX treated group were similar to published comparable high risk cohorts receiving infrequent CNS prophylaxis. Where HDMTX prophylaxis is used, delivery could be deferred until R-CHOP completion. Figure 1 Figure 1. Disclosures Wilson: Takeda: Other: Conference fees; Janssen: Other: Conference fees; Abbvie: Honoraria. Eyre: Janssen: Honoraria; Secura Bio: Consultancy, Honoraria; Gilead/KITE: Honoraria, Other: Travel support for conferences, Research Funding, Speakers Bureau; Roche: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria, Other: Travel to conferences; AstraZeneca: Honoraria, Research Funding; Loxo Oncology: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy; Beigene: Honoraria, Research Funding. Ahearne: Pfizer: Research Funding; Takeda: Honoraria; Roche: Honoraria. Schorb: Roche: Research Funding; Riemser Pharma GmbH: Honoraria, Research Funding; AbbVie: Research Funding. Ku: Antegene: Consultancy; Roche: Consultancy; Genor Biopharma: Consultancy. Narkhede: Genentech/Roche: Research Funding; Gilead: Research Funding; Genmab: Other: Medical writing support, Research Funding; TG Therapeautics: Research Funding. Lewis: AstraZeneca: Consultancy, Honoraria; Janssen: Honoraria, Patents & Royalties; Novartis: Patents & Royalties; Roche: Consultancy, Honoraria. Øvlisen: Abbvie: Other: Travel expenses. Santarsiere: Janssen: Honoraria. Shah: Abbvie, Janssen and Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees. Roulin: Janssen: Other: Travel and meetings. Manos: Bristol-Myers Squibb: Other: Travel and meetings. Hamad: Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Lopez-Garcia: Roche: Other: Speaker Honoraria, Travel and accommodation grants; Janssen: Other: Speaker Honoraria, Advisor, Travel and accommodation grants, Research Funding; Abbvie: Other: Speaker Honoraria, Advisor, Travel and accommodation grants; Celgene: Other: Speaker Honoraria; Fresenius: Other: Speaker Honoraria; Novonordisk: Other: Speaker Honoraria. El-Galaly: ROCHE Ltd: Ended employment in the past 24 months; Abbvie: Other: Speakers fee. Cheah: Beigene: Consultancy, Honoraria, Other: advisory; AbbVie: Research Funding; Celgene: Research Funding; AstraZeneca: Consultancy, Honoraria, Other: advisory; Loxo/Lilly: Consultancy, Honoraria, Other: advisory; TG Therapeutics: Consultancy, Honoraria, Other: advisory; Roche: Consultancy, Honoraria, Other: advisory and travel expenses, Research Funding; Janssen: Consultancy, Honoraria, Other: advisory; MSD: Consultancy, Honoraria, Other: advisory, Research Funding; Gilead: Consultancy, Honoraria, Other: advisory; Ascentage pharma: Consultancy, Honoraria, Other: advisory. Ferreri: Gilead, Novartis, Juno, PletixaPharm, Roche, Incyte: Membership on an entity's Board of Directors or advisory committees; BMS, Beigene, Pharmacyclics, Hutchison Medipharma, Amgen, Genmab, ADC Therapeutics, Gilead, Novartis, Pfizer: Research Funding. Fox: Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Other: speaker fees. Cwynarski: Gilead: Consultancy, Speakers Bureau; Incyte: Consultancy, Speakers Bureau; Atara: Consultancy; Celgene: Consultancy; Takeda: Consultancy, Other: travel to scientific conferences, Speakers Bureau; Kite, a Gilead Company: Consultancy, Other: travel to scientific conferences, Speakers Bureau; Janssen: Consultancy, Other: travel to scientific conferences; Roche: Consultancy, Other: travel to scientific conferences, Speakers Bureau; BMS/Celgene: Other: travel to scientific conferences. McKay: Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Other: Travel Support; KITE: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support; Janssen: Honoraria, Other: Travel Support; Beigene: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS/Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees.