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

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

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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

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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

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

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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%P<0.001,6 mo 73%vs 46%P<0.001,12 mo 66%vs 51%P=0.03).More Australian 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

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Efficiency of a Modular Cleanroom for Space Applications

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Fluid Dynamics & Materials Processing 2024年第3期20卷 547-562页

作者： Matthew R.Coburn Charlie Young Chris smith graham Schultz Miguel Robayo Zheng-Tong Xie Faculty of Engineering and Physical Sciences University of SouthamptonSouthamptonSO171BJUK Plastron UK Ltd. Westcott Venture ParkWestcottHP180XBUK Renewable Energy Group University of ExeterExeterTR109FEUK

A prototype cleanroom for hazardous testing and handling of satellites prior to launcher encapsulation,satisfying the ISO8 standard has been designed and analyzed in terms of *** Reynolds Averaged Navier-Stokes(URANS)models have been used to study the related flow field and particulate matter(PM)*** outcomes of the URANS models have been validated through comparison with equivalent large-eddy *** attention has been paid to the location and shape of the air intakes and their orientation in space,in order to balance the PM convection and diffusion inside the *** a cyclone-type flow pattern inside the cleanroom is a key to maintaining a high ventilation efficiency.

关键词： Diffuser LES PM RANS unsteady flow exponential decay

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Superior anti-corrosion and self-healing bi-functional polymer composite coatings with polydopamine modified mesoporous silica/graphene oxide

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Journal of Materials Science & Technology 2021年第36期95卷 95-104页

作者： Yanqi Ma Haowei Huang Hongda Zhou Michael graham James smith Xinxin Sheng Ying Chen Li Zhang Xinya Zhang Elena Shchukina Dmitry Shchukin Guangdong Provincial Key Laboratory of Functional Soft Condensed Matter School of Materials and EnergyGuangdong University of TechnologyGuangzhou 510006China School of Chemistry and Chemical Engineering Guangdong Provincial Key Lab of Green Chemical Product TechnologySouth China University of TechnologyGuangzhou 510640China Stephenson Institute for Renewable Energy Department of ChemistryUniversity of LiverpoolCrown StreetLiverpool L697ZDUK

In this article,graphene oxide(GO)and benzotriazole-loaded mesoporous silica nanoparticles(BTA/MSNs)are combined on micro scale through the in situ polymerization of polydopamine(PDA),preparing a selfhealing bi-functional GO(fGO)used as nano-fillers for anti-corrosion enhancement of waterborne epoxy(WEP)*** electronic microscopy(SEM)images show that the BTA/MSNs are uniformly distributed on the surface of high aspect ratio GO nanosheets to endow GO nanocontainer ***-vis profiles demonstrate that fGO has p H-controlled release *** at lowest frequency is generally used for comparing the corrosion resistance of organic *** at lowest frequency(1.42×10^(5)Ωcm^(2))after 30 days immersion in 3.5 wt.%Na Cl solution revealed 2 orders of magnitude higher that of blank WEP(1.17×10^(7)Ωcm^(2)).With artificial cracks on its coatings,fGO/WEP had no obvious rust compared with blank WEP after 240 h of *** anticipate that self-healing and physical barrier bi-functional nanocontainers improve the traditional anticorrosion coating efficiency with better,longer-lasting performance for shipping,oil drilling or bridge maintenance.

关键词： Mesoporous silica Graphene oxide Anti-corrosion Self-healing Functional composite coatings

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INCREASING CREATIVITY AND INNOVATION IN ENGLISH LANGUAGE TEACHING IN CHINA

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Chinese Journal of Applied Linguistics 2000年第3期23卷 2-4页

作者： Larry E.smith graham Crookes Frank Tang

Creativity and innovation in English language teaching(ELT)are frequently discussed and debated. Recently the Ministry of Education(MOE)of China has urged the development of a system,which en- hances creative ability in students at all levels. Hawaii’s East-West Center in collaboration with the Ohana Foundation implemented an educational re- search activity designed to assess the current needs and best practices for English language teaching and learn- ing at the middle school level in *** project focused on increasing creativity and innovation in English language education and used case studies of successful English language teaching/learning as the unit of analysis. Researchers from both China and the United States were involved with the analysis and made rec- ommendations for implementing innovative approach- es to English language instruction and on how to in- crease creativity in teacher training,curriculum de- velopment,and the use of appropriate technology.

关键词： INCREASING CREATIVITY AND INNOVATION IN ENGLISH LANGUAGE TEACHING IN CHINA

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Sensing Properties of Femtosecond Laser-Inscribed Long Period Gratings in Photonic Crystal Fiber

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Photonic Sensors 2011年第3期1卷 228-233页

作者： Kyriacos KALLI Tom ALLSOP Kaimin ZHOU graham smith Michael KOMODROMOS David WEBB Ian BENNION Nanophotonics Research Laboratory Department of Electrical Engineering and Information Technology CyprusUniversity of Technology Limassol 3036 Cyprus photonics Research Group Aston University Birmingham B4 7ET United Kingdom Department of Electrical Engineering Frederick University Filokyprou 7 Nicosia Cyprus

The use of near infrared, high intensity femtosecond laser pulses for the inscription of long period fiber gratings in photonic crystal fiber is reported. The formation of grating structures in photonic crystal fiber is complicated by the fiber structure that allows wave-guidance but that impairs and scatters the femtosecond inscription beam. The effects of symmetric and asymmetric femtosecond laser inscriptions are compared and the polarization characteristics of long period gratings and their responses to external perturbations are reported.

关键词： Fiber gratings femtosecond laser inscription photonic crystal fiber

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南部非洲的发展走廊

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人类居住 2005年第1期 18-19页

作者： graham smith 王瀛

姆特瓦拉交通走廊是南部非洲发展共同体的南部非洲运输和通讯委员会于1 992年首创的.今天,这一交通走廊有力地证明了,不仅在一国内部而且在国家之间都可以发展城乡和地区的联系,并使之可持续发展.最初,这一项目还只是一条交通走廊,现在... 详细信息

姆特瓦拉交通走廊是南部非洲发展共同体的南部非洲运输和通讯委员会于1 992年首创的.今天,这一交通走廊有力地证明了,不仅在一国内部而且在国家之间都可以发展城乡和地区的联系,并使之可持续发展.最初,这一项目还只是一条交通走廊,现在,它已经成为一条涉及范围更广的发展走廊.

关键词：走廊南部非洲发展

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Performance of Bt-susceptible and -heterozygous dual-gene resistant genotypes of Spodoptera frugiperda (***) (Lepidoptera:Noctuidae) in seed blends of non-Bt and pyramided Bt maize

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Insect Science 2021年第4期28卷 1147-1158页

作者： Marcelo Dimase Sebe Brown graham P.Head Paula A.Price Wade Walker Wenbo Yu Fangneng Huang Department of Entomology Louisiana State University Agricultural CenterBaton RougeLouisianaUSA Dean Lee Research Station Louisiana State University Agricultural CenterAlexandriaLouisianaUSA Bayer Crop Science ChesterfieldMissouriUSA Macon Ridge Research Station Louisiana State University Agricultural CenterWinnsboroLouisianaUSA

A seed blend refuge has been implemented in the *** Belt for Bt maize resistance *** fall armyworm,Spodoptera frugiperda(***),is a target pest of Bt maize in the *** larvae of this pest are mobile,which may affect the efficacy of seed blend *** this study,field and greenhouse trials were conducted to determine the performance of Bt-susceptible(aabb)and-heterozygous dual-gene-resistant(AaBb)genotypes of *** in seed blends of non-Bt and pyramided Bt *** field trials evaluated larval survival,larval growth,and plant injury with aabb in seed blends of Bt maize expressing Cry1A.105/Cry2Ab2/Vip3A with 0–30%non-Bt *** tests investigated the performance of aabb and AaBb in seed blends of Cry1A.105/Cry2Ab2 with 0–30% non-Bt *** pure non-Bt maize plots,after 9–13 d of neonates being released on the plants,0.39 and 0.65 larvae/plant survived with leaf injury ratings of 4.7 and 5.9(Davis's 1–9 scale)in the field and greenhouse,*** contrast,live larvae and plant injury were virtually not observed on Bt plants across all planting *** occurrence and plant injury by aabb on non-Bt plants were similar between seed blends and pure non-Bt plantings,suggesting that the blended refuges could provide an equivalent susceptible population as structured refuge under the test *** the greenhouse,the two insect genotypes in seed blends performed similarly,indicating that the seed blends did not provide more favorable conditions for AaBb over *** information generated from this study should be useful in managing *** and evaluating if send blends could be suitable refuge options for Bt resistance management in the regions where the insect is a primary target pest.

关键词： Bt maize dual-gene resistance fall armyworm resistance management seed blend

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