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Associations between NOD2/CARD15 genotype andphenotype in Crohn’s disease-Are we there yet?

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World journal of Gastroenterology 2006年第44期12卷 7097-7103页

作者： Graham radford-Smith Nirmala Pandeya IBD Unit Department of Gastroenter-ology Royal Brisbane and Womens Hospital Brisbane Queensland 4029 Australia Cancer and Population studies group Queensland Institute of Medical Research Brisbane Australia

There have been multiple NOD2/CARD15 genotype- phenotype analyses undertaken in patients with Crohn’s disease since the gene’s discovery in 2001. This review focuses on the major published series based upon their size and on the presence of specific clinical and genetic information provided in the published material from 2001 to 2005. Twelve studies provided raw data to carry out comparisons of disease location while ten studies included analysis of NOD2/CARD15 genotypes. NOD2/CARD15 variant frequency in ileal disease did not differ significantly among studies, whereas a comparison of disease location demonstrated highly significant differences among studies. Meta-analysis confirmed significant associations between NOD2/CARD15 variants and both ileal and ileocolonic disease locations, and with both stricturing and penetrating forms of disease behavior. This review underlines the significant phenotypic differences that exist among populations, including similar ethnic groups, and has demonstrated the need for further studies of patients with long-term “inflammatory” Crohn’s disease.

关键词： Crohn's disease Phenotypic heterogeneity Genotype Inter-observer agreement Disease location Disease behavior

Dysregulation of innate immunity in ulcerative colitis patients who fail anti-tumor necrosis factor therapy

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World journal of Gastroenterology 2016年第41期22卷 9104-9116页

作者： Angela C Baird Dominic Mallon Graham radford-Smith julien Boyer Thierry Piche Susan L Prescott ian C Lawrance Meri K Tulic Faculty of Medicine and Dentistry School of Medicine and Pharmacology University of Western Australia Perth WA 6009 Australia Department of Immunology Fremantle Hospital Royal Brisbane and Women’s Hospital Perth WA 6160 Australia Royal Brisbane Queensland 4006 Australia University of Nice Sophia-Antipolis EA6302 06202 Nice France Department of Gastroenterology and Nutrition l’Archet Hospital 2 06202 Nice France School of Paediatrics and Child Health University of Western Australia Subiaco WA 6008 Australia International Inflammation network (in-FLAME) of the World Universities Network University of Western Australia Subiaco WA 6008 Australia Centre for Inflammatory Bowel Diseases St John of God Subiaco Hospital Perth WA 6009 Australia Mediterranean Center for Molecular Medicine (C3M)-INSERM U1065 Team 12 06204 Nice France

AIM To study the innate immune function in ulcerative colitis(UC) patients who fail to respond to anti-tumor necrosis factor(TNF) *** Effects of anti-TNF therapy, inflammation and medications on innate immune function were assessed by measuring peripheral blood mononuclear cell(PBMC) cytokine expression from 18 inflammatory bowel disease patients pre- and 3 mo post-anti-TNF therapy. Toll-like receptor(TLR) expression and cytokine production post TLR stimulation was assessed in UC "responders"(n = 12) and "non-responders"(n = 12) and compared to healthy controls(n = 12). Erythrocyte sedimentation rate(ESR) and C-reactive protein(CRP) levels were measured in blood to assess disease severity/activity and inflammation. Pro-inflammatory(TNF, IL-1β, IL-6), immuno-regulatory(IL-10), Th1(IL-12, IFNγ) and Th2(IL-9, IL-13, IL-17A) cytokine expression was measured with enzyme-linked immunosorbent assay while TLR cellular composition and intracellular signalling was assessed with *** Prior to anti-TNF therapy, responders and nonresponders had similar level of disease severity and activity. PBMC's ability to respond to TLR stimulation was not affected by TNF therapy, patient's severity of the disease and inflammation or their medication use. At baseline, non-responders had elevated innate but not adaptive immune responses compared to responders(P < 0.05). Following TLR stimulation, nonresponders had consistently reduced innate cytokine responses to all TLRs compared to healthy controls(P < 0.01) and diminished TNF(P < 0.001) and IL-1β(P < 0.01) production compared to responders. This innate immune dysfunction was associated with reduced number of circulating plasmacytoid dendritic cells(p DCs)(P < 0.01) but increased number of CD4+ regulatory T cells(Tregs)(P = 0.03) as well as intracellular accumulation of IRAK4 in non-responders following TLR-2,-4 and-7 activation(P < 0.001). CONCLUSION Reduced innate immunity in non-responders may explain reduced efficacy

关键词： Ulcerative colitis Innate immunity Antitumor necrosis factor therapy Toll-like receptor IRAK4 Inflammatory bowel disease

Hygiene hypothesis in inflammatory bowel disease: A criticalreview of the literature

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World journal of Gastroenterology 2008年第2期14卷 165-173页

作者： Natasha A Koloski Laurel Bret Graham radford-Smith Department of Gastroenterology Royal Brisbane & Women'sHospital Herston Queensland 4072Australia Department of Gastroenterology Royal Brisbane & Women’sHospitalHerston Queensland 4072Australia

The hygiene hypothesis is thought to be a significant contributor to the growing incidence of inflammatory bowel disease (IBD) around the world, although the evidence for specific factors that underlie the hygiene hypothesis in IBD is unclear. We aimed to systematically review the literature to determine which hygiene-related factors are associated with the development of IBD. Publications identified from a broad based MEDLINE and Current Contents search between 1966 and 2007 on key terms relevant to the 'hygiene hypothesis' and IBD including H pylori exposure, helminths, cold chain hypothesis, measles infection and vaccination, antibiotic use, breastfeeding, family size, sibship, urban upbringing, day care attendance and domestic hygiene were reviewed. The literature suggests that the hygiene hypothesis and its association with decreased microbial exposure in childhood probably plays an important role in the development of IBD, although the strength of the supporting data for each of the factors varies considerably. The most promising factors that may potentially be associated with development of IBD include H pylori exposure, helminths, breastfeeding and sibship. However, the vast majority of studies in this area are plagued by serious methodological shortcomings, particularly the reliance on retrospective recall of information making it difficult to truly ascertain the importance of a 'hygiene hypothesis' in IBD. The 'hygiene hypothesis' in IBD is an important area of research that may give clues to the aetiology of this disease. Directions for future research are recommended.

关键词： Inflammatory bowel disease Hygiene hypothesis Microbial exposure Cold chain hypothesis H pylori Helminths Measles Antibiotic Breastfeeding Child care

Evaluating Behavioural Modelling Predictions in the Blue Shark (Prionace glauca) Enables Greater Insight on Habitat Use from Location only Argos Data

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Research in Ecology 2023年第3期5卷 31-48页

作者： Riley Elliott jingjing Zhang Todd Dennis john Montgomery Craig radford Institute of Marine Science Waipapa Tuamata Rau The University of AucklandWarkworth0985New Zealand School of Biological Sciences Waipapa Tuamata Rau The University of AucklandAuckland1142New Zealand Department of Biology School of Pure Sciences Fiji National UniversityP.O.Box 5529LautokaFiji

The relationship between habitat and behaviour provides important information for species *** large,free roaming,marine animals satellite tags provide high resolution information on movement,but such datasets are restricted due to *** additional biologically important information from these data would increase utilisation and *** modelling approaches have been developed to identify behavioural states in tracking *** objective of this study was to evaluate a behavioural state prediction model for blue shark(Prionace glauca)ARGOS surface location-only *** novel nature of the six SPLASH satellite tags used enabled behavioural events to be identified in blue shark dive data and accurately mapped spatio-temporally along respective surface location-only *** states modelled along the six surface location-only tracks were then tested against observed behavioural events to evaluate the model’s *** showed that the Behavioural Change Point Analysis(BCPA)model augmented with K means clustering analysis performed well for predicting foraging behaviour(correct 86%of the time).Prediction accuracy was lower for searching(52%)and travelling(63%)behaviour,likely related to the numerical dominance of foraging events in dive *** model’s validation for predicting foraging behaviour justified its application to nine additional surface location-only(SPOT tag)tracks,substantially increasing the utilisation of expensive and rare *** enabled the critical behavioural state of foraging,to be mapped throughout the entire home range of blue sharks,allowing drivers of critical habitat to be *** validation strengthens the use of such modelling to interpret historic and future datasets,for blue sharks but also other species,contributing to conservational management.

关键词： Blue shark Behavioural state modelling Satellite tracking Foraging behaviour Habitat use

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先天性心脏病与免疫缺陷

国外医学（儿科学分册） 1989年第6期16卷 318-320,336页

作者： radford D j 徐大地

先天性心脏病(先心病)患儿易患某些严重的感染,特别是呼吸道感染,感染性心内膜炎及脑脓肿。习惯上认为系血流动力学和机械性因素与之有关。然而我们最近证实,先心病儿有程度不等的免疫缺陷。25%的先心病儿免疫球蛋白水平低下,而某些园... 详细信息

先天性心脏病(先心病)患儿易患某些严重的感染,特别是呼吸道感染,感染性心内膜炎及脑脓肿。习惯上认为系血流动力学和机械性因素与之有关。然而我们最近证实,先心病儿有程度不等的免疫缺陷。25%的先心病儿免疫球蛋白水平低下,而某些园锥总干畸形(conotruncal malformation)的患儿缺乏淋巴细胞。

关键词：先天性心脏病免疫缺陷儿童

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语言学教程 1

Vedolizumab for ulcerative colitis: Real world outcomes from a multicenter observational cohort of Australia and Oxford

丛书名：当代国外语言学与应用语言学文库

2000年

作者： Andrew radford等周流溪导读

本书的总体结构是语音、词汇、句法三个部分。作者们介绍了发展语言学、心理语言学、神经语言学和社会语言学，并且力图将这些分支(交叉)学科的研究思路和成果糅合进语音、词汇和句法的探讨。

ISBN: (纸本)7560020089

关键词：语言学

来源：汇雅图书（南通市图书馆... 评论

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World journal of Gastroenterology 2020年第30期26卷 4428-4441页

作者： Samba Siva Reddy Pulusu Ashish Srinivasan Krupa Krishnaprasad Daniel Cheng jakob Begun CharlotteKeung Daniel Van Langenberg Lena Thin Tamara Mogilevski Peter De Cruz Graham radford-Smith Emma Flanagan Sally Bell Soleiman Kashkooli Miles Sparrow Simon Ghaly Peter Bampton Elise Sawyer Susan Connor Quart-ul-ain Rizvi jane M Andrews Gillian Mahy Paola Chivers Simon Travis ian Craig Lawrance Centre for Inflammatory Bowel Diseases St John of God HospitalSubiaco 6008Western AustraliaAustralia Translational Gastroenterology Unit NIHR Oxford Biomedical Research CentreOxford University Hospitals NHS Foundation TrustJohn Radcliffe HospitalOxford OX39DUUnited Kingdom Inflammatory Bowel Disease Research Group Queensland institute of Medical ResearchHerston 4006QueenslandAustralia Department of Gastroenterology Mater HospitalBrisbane 4101QueenslandAustralia Department of Gastroenterology Mater HospitalSouth Brisbane 4101QueenslandAustralia of Gastroenterology Eastern HealthBox Hill 3128VictoriaAustralia Department of Gastroenterology Fiona Stanley HospitalMurdoch 6150Western AustraliaAustralia Department of Gastroenterology Austin HealthHeidelberg 3084VictoriaAustralia Department of Gastroenterology St Vincent’s HospitalFitzroy 3065VictoriaAustralia Department of Gastroenterology Northern HealthEpping 3076VictoriaAustralia Department of Gastroenterology The Alfred HospitalMelbourne 3004VictoriaAustralia Department of Gastroenterology St Vincent’s HospitalDarlinghurst 2010New South WalesAustralia Department of Gastroenterology Flinders Medical CentreBedford Park 5042South AustraliaAustralia Department of Gastroenterology Liverpool HospitalSydney 2170New South WalesAustralia Department of Gastroenterology Royal Adelaide Hospital&University of AdelaideAdelaide 5000South AustraliaAustralia Department of Gastroenterology Townsville HospitalDouglas 4814QueenslandAustralia Institute for Health Research University of Notre DameFremantle 6160Western AustraliaAustralia School of Medicine and Pharmacology University of Western AustraliaCrawley 6009Western AustraliaAustralia

BACKGROUND Vedolizumab(VDZ),a humanised monoclonal antibody that selectively inhibits alpha4-beta7 integrins is approved for use in adult moderate to severe ulcerative colitis(UC)*** To assess the efficacy and safety of VDZ in the real-world management of UC in a large multicenter cohort involving two countries and to identify predictors of achieving *** A retrospective review of Australian and Oxford,United Kingdom data for UC *** response at 3 mo,endoscopic remission at 6 mo and clinical remission at 3,6 and 12 mo were *** regression models and Kaplan Meier curves were performed to assess the time to remission,time to failure and the covariates influencing *** outcomes were *** Three hundred and three UC patients from 14 centres in Australia and United Kingdom,[60%n=182,anti-TNF naïve]were *** clinical response was 79%at 3 mo with more Australian patients achieving clinical response compared to Oxford(83%vs 70%P=0.01).Clinical remission for all patients was 56%,62%and 60%at 3,6 and 12 mo ***-TNF naive patients were more likely to achieve remission than exposed patients at all the time points(3 mo 66%vs 40%Pian patients achieved endoscopic remission at 6 mo compared to Oxford(69%vs 43%P=0.01).On multi-variate analysis,anti-TNF naïve patients were 1.8(95%CI:1.3-2.3)times more likely to achieve remission than anti-TNF exposed(P<0.001).32 patients(11%)had colectomy by 12 *** VDZ was safe and effective with 60%of UC patients achieving clinical remission at 12 mo and prior anti-TNF exposure influenced this outcome.

关键词： Vedolizumab Ulcerative colitis Outcomes

Genetic and Demographic Outcomes in a Population of Patients with Headache and Facial Pain

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journal of Behavioral and Brain Science 2018年第6期8卷 339-350页

作者： jonathan Eskenazi Miriam Nuno Steven Graff-radford Oana M. Dumitrascu Department of Neurology Cedars-Sinai Medical Center Los Angeles CA USA Department of Public Health Sciences Division of Biostatistics University of California Davis Davis CA USA The Pain Center Cedars-Sinai Medical Center Los Angeles CA USA

Background: Pharmacogenetics information about cytochrome p450 (CYP450) polymorphism in patients with headaches is limitedly reported. Similarly, the genetic factors linking various headache types and vascular disorders are poorly described. We aimed to characterize the genetic profile of a cohort of headache and facial pain subjects. Methods: Medical records of consecutive headache subjects that underwent PersonaGeneTM testing were reviewed. PersonaGeneTM panel assessed CYP450, apolipoprotein E (ApoE), methylene tetrahydrofolate reductase (MTHFR), Factor II, Factor V Leiden and Vitamin K epoxide reductase complex subunit 1 (VKORC1). Demographic information, headache diagnosis and genetic profiling were analyzed and compared with data obtained from the general population. Results: Out of 130 headache patients, 91.3% were Caucasian and 70.8% had migraine. Compared to the general Caucasian population, our Caucasian headache patients were significantly different for CYP3A4/A5 and CYP2D6 (p ian headache cohort. These results may impact headache subjects’ pharmacological treatment options and vascular risk ascertainment.

关键词： Headache Pharmacogenetics Cytochrome P450 Cerebrovascular Risk Cardiovascular Risk

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为何左撇子容易见木不见林?

当代外语研究 2005年第5期 41-42页

作者： Tim radford 金蕾

今天发表的一项研究表明,左撇子看世界的方法的确与常人不同。伯明翰大学的一个研究小组发现,在观看同样的图像时,左撇子与习惯用右手者使用大脑的部分不同。他们在《自然·神经科学》杂志上发表报告称,习惯用右手者使用大脑的右半边来... 详细信息

今天发表的一项研究表明,左撇子看世界的方法的确与常人不同。伯明翰大学的一个研究小组发现,在观看同样的图像时,左撇子与习惯用右手者使用大脑的部分不同。他们在《自然·神经科学》杂志上发表报告称,习惯用右手者使用大脑的右半边来摄取图象的整体信息,比如一片森林,而左撇子却使用大脑的右半边来关注细节,比如树木。

关键词：左撇子惯用右手伯明翰大学神经科学研究小组树木图象图像女同性恋者溃疡性肠炎