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12. The Multiple Sclerosis Genomic Map: Role of peripheral immune cells and resident microglia in susceptibility

Author

Ashley Beecham, David A. Hafler, Colombe J, Ublick K, Stephen Sawcer, Marcus C. S. Lee, Adam Santaniello, An Goris, Frank Seibold, Xavier Montalban, G. Comi, Christiane Gasperi, Sandra D'Alfonso, Federica Esposito, Laurent Peyrin-Biroulet, Frauke Zipp, Ioanna Konidari, Elisabeth Gulowsen Celius, Achim Berthele, Amoroso A, Rogier Q. Hintzen, Johan Van Limbergen, Marieme Dembele, Fredrik Karpe, Zhang W, Robbins A, Moiola L, Annette Bang Oturai, Cristin McCabe, Filippo Martinelli-Boneschi, M Lindén, Keith R Edwards, Hanne F. Harbo, Zuccalà M, Marc Lémann, Felix Luessi, Noriko Isobe, Nadia Barizzone, Renata D'Incà, Croft A, Ioannis S. Vlachos, Frohlich I, Martinelli, Daniela Galimberti, Efthimios Dardiotis, Lisa F. Barcellos, Brendan T. Keenan, Maja Jagodic, Ferdinando Clarelli, Bénédicte Dubois, Nicholas A. Kennedy, Lohith Madireddy, Grant W. Montgomery, Tommy Olsson, Phil De Jager, Lo A, Peter A. Calabresi, Brandes A, Chris Cotsapas, Bakker Pd, Steffan D. Bos, Christina M. Lill, Karban A, Thoerner Lw, Tojo James, Wong G, Harald Peeters, M.-M. Hoshi, Roberts R, Fredrik Piehl, Lars Alfredsson, Giorgos M. Hadjigeorgiou, Bertrand Fontaine, Melissa Sorosina, Benedetti M, Maria Ban, Jorge R. Oksenberg, Howard L. Weiner, Ingrid Kockum, Mireia Sospedra, Taylor Km, Henrik Ullum, Izaura Lima Bomfim, Stronati L, Molyneux P, Replogle J, Stacy J. Caillier, Zhang H, Till F. M. Andlauer, Margaret A. Pericak-Vance, Jan Hillert, Luisa Bernardinelli, Taibo Li, Helle Bach Søndergaard, Ilijas Jelcic, Nikolaos A. Patsopoulos, Silvia Delgado, Cathy Schaefer, Thomas Korn, Laura Piccio, Mark Mühlau, Deborah D. Proctor, B. Hemmer, Elizabeth M. Bradshaw, Hysi P, Megan C Neville, Mary F. Davis, Dorlan J. Kimbrough, Jyoti Khadake, Jean-Pierre Hugot, David Gomez-Cabrero, Murray L. Barclay, Anne H. Cross, Kasper Lage, Stephen L. Hauser, A Compston, Zimmer A, Ivinson A, Anne Spurkland, Jonas Halfvarson, Charles C. White, Biberacher, Zarzycki O, Kathryn C. Fitzgerald, Finn Sellebjerg, Ellis Patrick, Andrea Zauli, Bruce V. Taylor, Maurizio Leone, Genevieve Lachance, Marta Olah, B. Cree, Manuel Comabella, Arie Levine, Domizia Vecchio, Mathias Chamaillard, Mark Lathrop, Clara Guaschino, Roland Martin, Hanigan K, Pierre-Antoine F. D. Gourraud, Maria Cimpean, Jonathan L. Haines, Dorothea Buck, Marco Salvetti, Per Soelberg Sørensen, Noel Lg, Mitja Mitrovic, Graeme J. Stewart, Benjamin Knier, Ellen Lathi, Cottone M, Laura Ferrè, Winn P, Duijn Cv, Monica Milla, Tune H. Pers, I. Oikonomou, An D, David R. Booth, Rebeix Ic, Clara P. Manrique, Massey D, Evelyn Ng Sm, Törkvist L, Daniele Cusi, Shoostari P, Vatn Mh, Paola Cavalla, Silvia Santoro, Gossum Av, Seema Kalra, Paul Rutgeerts, Clive Hawkins, Sandra Vukusik, Khan Ma, Hakon Hakonarson, Paul Henderson, Christiane Graetz, Julia Y Mescheriakova, Jean-François Rahier, Panteliadis I, Cristina Agliardi, Grummel, Jacob L. McCauley, Amie Baker, Janna Saarela, Sergio E. Baranzini, J W Thorpe, and Damotte

Subjects
0303 health sciences, Microglia, Multiple sclerosis, Central nervous system, Biology, medicine.disease, Major histocompatibility complex, 03 medical and health sciences, 0302 clinical medicine, Immune system, medicine.anatomical_structure, Autoimmune Process, Immunology, medicine, biology.protein, Gene, 030217 neurology & neurosurgery, X chromosome, 030304 developmental biology
Abstract

We assembled and analyzed genetic data of 47,351 multiple sclerosis (MS) subjects and 68,284 control subjects and establish a reference map of the genetic architecture of MS that includes 200 autosomal susceptibility variants outside the major histocompatibility complex (MHC), one chromosome X variant, and 32 independent associations within the extended MHC. We used an ensemble of methods to prioritize up to 551 potentially associated MS susceptibility genes, that implicate multiple innate and adaptive pathways distributed across the cellular components of the immune system. Using expression profiles from purified human microglia, we do find enrichment for MS genes in these brain - resident immune cells. Thus, while MS is most likely initially triggered by perturbation of peripheral immune responses the functional responses of microglia and other brain cells are also altered and may have a role in targeting an autoimmune process to the central nervous system.One Sentence Summary:We report a detailed genetic and genomic map of multiple sclerosis, and describe the role of putatively affected genes in the peripheral immune system and brain resident microglia.

Published
2017

13. Inherited determinants of Crohn's disease and ulcerative colitis phenotypes:a genetic association study

Author

Cleynen, Isabelle, Boucher, Gabrielle, Jostins, Luke, Schumm, L. Philip, Zeissig, Sebastian, Ahmad, Tariq, Andersen, Vibeke, Andrews, Jane M., Annese, Vito, Brand, Stephan, Brant, Steven R., Cho, Judy H., Daly, Mark J., Dubinsky, Marla, Duerr, Richard H., Ferguson, Lynnette R., Franke, Andre, Gearry, Richard B., Goyette, Philippe, Hakonarson, Hakon, Halfvarson, Jonas, Hov, Johannes R., Huang, Hailang, Kennedy, Nicholas A., Kupcinskas, Limas, Lawrance, Ian C., Lee, James C., Satsangi, Jack, Schreiber, Stephan, Théâtre, Emilie, Van Der Meulen De Jong, Andrea E, Weersma, Rinse K., Wilson, David C., Parkes, Miles, Vermeire, Severine, Rioux, John D., Mansfield, John, Silverberg, Mark S., Radford Smith, Graham, Mcgovern, Dermot P. B., Barrett, Jeffrey C., Lees, Charlie W, Abraham, C, Achkar, Jp, Ahmad, T, Amininejad, L, Ananthakrishnan, An, Andersen, V, Anderson, Ca, Andrews, Jm, Annese, V, Aumais, G, Baidoo, L, Baldassano, Rn, Bampton, Pa, Barclay, M, Barrett, Jc, Bayless, Tm, Bethge, J, Bis, Jc, Bitton, A, Boucher, G, Brand, S, Brandt, B, Brant, Sr, Büning, C, Chew, A, Cho, Jh, Cleynen, I, Cohain, A, Croft, A, Daly, Mj, D'Amato, M, Danese, S, De Jong, D, De Vos, M, Denapiene, G, Denson, La, Devaney, K, Dewit, O, D'Inca, R, Dubinsky, M, Duerr, Rh, Edwards, C, Ellinghaus, D, Essers, J, Ferguson, Lr, Festen, Ea, Fleshner, P, Florin, T, Franchimont, D, Franke, A, Fransen, K, Gearry, R, Georges, M, Gieger, C, Glas, J, Goyette, P, Green, T, Griffiths, Am, Guthery, Sl, Hakonarson, H, Halfvarson, J, Hanigan, K, Haritunians, T, Hart, A, Hawkey, C, Hayward, Nk, Hedl, M, Henderson, P, Hu, X, Huang, H, Hui, Ky, Imielinski, M, Ippoliti, A, Jonaitis, L, Jostins, L, Karlsen, Th, Kennedy, Na, Khan, Ma, Kiudelis, G, Krishnaprasad, K, Kugathasan, S, Kupcinskas, L, Latiano, A, Laukens, D, Lawrance, Ic, Lee, Jc, Lees, Cw, Leja, M, Van Limbergen, J, Lionetti, P, Liu, Jz, Louis, E, Mahy, G, Mansfield, J, Massey, D, Mathew, Cg, Mcgovern, Dp, Milgrom, R, Mitrovic, M, Montgomery, Gw, Mowat, C, Newman, W, Ng, A, Ng, Sc, Ng, Sm, Nikolaus, S, Ning, K, Nöthen, M, Oikonomou, I, Palmieri, O, Parkes, M, Phillips, A, Ponsioen, Cy, Potocnik, U, Prescott, Nj, Proctor, Dd, Radford Smith, G, Rahier, Jf, Raychaudhuri, S, Regueiro, M, Rieder, F, Rioux, Jd, Ripke, S, Roberts, R, Russell, Rk, Sanderson, Jd, Sans, M, Satsangi, J, Schadt, Ee, Schreiber, S, Schumm, Lp, Scott, R, Seielstad, M, Sharma, Y, Silverberg, Ms, Simms, La, Skieceviciene, J, Spain, Sl, Steinhart, A, Stempak, Jm, Stronati, Laura, Sventoraityte, J, Targan, Sr, Taylor, Km, ter Velde, A, Theatre, E, Torkvist, L, Tremelling, M, van der Meulen, A, van Sommeren, S, Vasiliauskas, E, Vermeire, S, Verspaget, Hw, Walters, T, Wang, K, Wang, Mh, Weersma, Rk, Wei, Z, Whiteman, D, Wijmenga, C, Wilson, Dc, Winkelmann, J, Xavier, Rj, Zeissig, S, Zhang, B, Zhang, Ck, Zhang, H, Zhang, W, Zhao, H, Zhao, Zz, UCL - SSS/IREC/GAEN - Pôle d'Hépato-gastro-entérologie, UCL - (MGD) Service de gastro-entérologie, and Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI)

Subjects
Male, 0301 basic medicine, CLINICAL-COURSE, Nod2 Signaling Adaptor Protein, Disease, SUSCEPTIBILITY, Inflammatory bowel disease, Major Histocompatibility Complex, 0302 clinical medicine, Crohn Disease, Maintenance therapy, NOD2, Medicine and Health Sciences, POPULATION, Immunoassay, RISK, Medicine(all), education.field_of_study, Crohn's disease, Hepatocyte Growth Factor, Medicine (all), INDUCTION, Articles, General Medicine, PRIMARY SCLEROSING CHOLANGITIS, Ulcerative colitis, 3. Good health, Phenotype, Female, 030211 gastroenterology & hepatology, Adult, medicine.medical_specialty, MAINTENANCE THERAPY, Genotype, Population, Polymorphism, Single Nucleotide, Risk Assessment, CLASSIFICATION, Primary sclerosing cholangitis, Young Adult, 03 medical and health sciences, inflammatory bowel disease, Proto-Oncogene Proteins, Internal medicine, medicine, Humans, Genetic Predisposition to Disease, education, Alleles, Genetic Association Studies, business.industry, medicine.disease, digestive system diseases, 030104 developmental biology, Immunology, Colitis, Ulcerative, business, FOLLOW-UP, HLA-DRB1 Chains, INFLAMMATORY-BOWEL-DISEASE
Abstract

Background: Crohn's disease and ulcerative colitis are the two major forms of inflammatory bowel disease; treatment strategies have historically been determined by this binary categorisation. Genetic studies have identified 163 susceptibility loci for inflammatory bowel disease, mostly shared between Crohn's disease and ulcerative colitis. We undertook the largest genotype association study, to date, in widely used clinical subphenotypes of inflammatory bowel disease with the goal of further understanding the biological relations between diseases.Methods: This study included patients from 49 centres in 16 countries in Europe, North America, and Australasia. We applied the Montreal classification system of inflammatory bowel disease subphenotypes to 34 819 patients (19 713 with Crohn's disease, 14 683 with ulcerative colitis) genotyped on the Immunochip array. We tested for genotype–phenotype associations across 156 154 genetic variants. We generated genetic risk scores by combining information from all known inflammatory bowel disease associations to summarise the total load of genetic risk for a particular phenotype. We used these risk scores to test the hypothesis that colonic Crohn's disease, ileal Crohn's disease, and ulcerative colitis are all genetically distinct from each other, and to attempt to identify patients with a mismatch between clinical diagnosis and genetic risk profile.Findings: After quality control, the primary analysis included 29 838 patients (16 902 with Crohn's disease, 12 597 with ulcerative colitis). Three loci (NOD2, MHC, and MST1 3p21) were associated with subphenotypes of inflammatory bowel disease, mainly disease location (essentially fixed over time; median follow-up of 10·5 years). Little or no genetic association with disease behaviour (which changed dramatically over time) remained after conditioning on disease location and age at onset. The genetic risk score representing all known risk alleles for inflammatory bowel disease showed strong association with disease subphenotype (p=1·65 × 10−78), even after exclusion of NOD2, MHC, and 3p21 (p=9·23 × 10−18). Predictive models based on the genetic risk score strongly distinguished colonic from ileal Crohn's disease. Our genetic risk score could also identify a small number of patients with discrepant genetic risk profiles who were significantly more likely to have a revised diagnosis after follow-up (p=6·8 × 10−4).Interpretation: Our data support a continuum of disorders within inflammatory bowel disease, much better explained by three groups (ileal Crohn's disease, colonic Crohn's disease, and ulcerative colitis) than by Crohn's disease and ulcerative colitis as currently defined. Disease location is an intrinsic aspect of a patient's disease, in part genetically determined, and the major driver to changes in disease behaviour over time.Funding: International Inflammatory Bowel Disease Genetics Consortium members funding sources (see Acknowledgments for full list).

Published
2016
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20. Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease

Author

Jostins, Luke, Ripke, Stephan, Weersma, Rinse K., Duerr, Richard H., Mcgovern, Dermot P., Hui, Ken Y., Lee, James C., Philip Schumm, L., Sharma, Yashoda, Anderson, Carl A., Essers, Jonah, Mitrovic, Mitja, Ning, Kaida, Cleynen, Isabelle, Theatre, Emilie, Spain, Sarah L., Raychaudhuri, Soumya, Goyette, Philippe, Wei, Zhi, Abraham, Clara, Achkar, Jean Paul, Ahmad, Tariq, Amininejad, Leila, Ananthakrishnan, Ashwin N., Andersen, Vibeke, Andrews, Jane M., Baidoo, Leonard, Balschun, Tobias, Bampton, Peter A., Bitton, Alain, Boucher, Gabrielle, Brand, Stephan, Büning, Carsten, Cohain, Ariella, Cichon, Sven, D'Amato, Mauro, De Jong, Dirk, Devaney, Kathy L., Dubinsky, Marla, Edwards, Cathryn, Ellinghaus, David, Ferguson, Lynnette R., Franchimont, Denis, Fransen, Karin, Gearry, Richard, Georges, Michel, Gieger, Christian, Glas, Jürgen, Haritunians, Talin, Hart, Ailsa, Hawkey, Chris, Hedl, Matija, Xinli, Hu, Karlsen, Tom H., Kupcinskas, Limas, Kugathasan, Subra, Latiano, Anna, Laukens, Debby, Lawrance, Ian C., Lees, Charlie W., Louis, Edouard, Mahy, Gillian, Mansfield, John, Morgan, Angharad R., Mowat, Craig, Newman, William, Palmieri, Orazio, Ponsioen, Cyriel Y., Potocnik, Uros, Prescott, Natalie J., Regueiro, Miguel, Rotter, Jerome I., Russell, Richard K., Sanderson, Jeremy D., Sans, Miquel, Satsangi, Jack, Schreiber, Stefan, Simms, Lisa A., Sventoraityte, Jurgita, Targan, Stephan R., Taylor, Kent D., Tremelling, Mark, Verspaget, Hein W., De Vos, Martine, Wijmenga, Cisca, Wilson, David C., Winkelmann, Juliane, Xavier, Ramnik J., Zeissig, Sebastian, Zhang, Bin, Zhang, Clarence K., Zhao, Hongyu, Silverberg, Mark S., Annese, Vito, Hakonarson, Hakon, Brant, Steven R., Radford Smith, Graham, Mathew, Christopher G., Rioux, John D., Schadt, Eric E., Daly, Mark J., Franke, Andre, Parkes, Miles, Vermeire, Severine, Barrett, Jeffrey C., Cho, Judy H., Barclay, M, Peyrin Biroulet, L, Chamaillard, M, Colombel, Jf, Cottone, M, Croft, A, D'Incà, R, Halfvarson J, Hanigan K, Henderson, P, Hugot, Jp, Karban, A, Kennedy, Na, Khan, Ma, Lémann, M, Levine, A, Massey, D, Milla, M, Montgomery, Gw, Ng, Sm, Oikonomou, I, Peeters, H, Proctor, Dd, Rahier, Jf, Roberts, R, Rutgeerts, P, Seibold, F, Stronati, Laura, Taylor, Km, Törkvist, L, Ublick, K, Van Limbergen, J, Van Gossum, A, Vatn, Mh, Zhang, H, Zhang, W, Andrews, Jm, Bampton, Pa, Florin, Th, Gearry, R, Krishnaprasad, K, Lawrance, Ic, Mahy, G, Radford Smith, G, Roberts, Rl, Simms, La, Amininijad, L, Cleynen, I, Dewit, O, Franchimont, D, Georges, M, Laukens, D, Theatre, E, Vermeire, S, Aumais, G, Baidoo, L, Barrie AM 3rd, Beck, K, Bernard, Ej, Binion, Dg, Bitton, A, Brant, Sr, Cho, Jh, Cohen, A, Croitoru, K, Daly, Mj, Datta, Lw, Deslandres, C, Duerr, Rh, Dutridge, D, Ferguson, J, Fultz, J, Goyette, P, Greenberg, Gr, Haritunians, T, Jobin, G, Katz, S, Lahaie, Rg, Mcgovern, Dp, Nelson, L, Ning, K, Paré, P, Regueiro, Md, Rioux, Jd, Ruggiero, E, Schumm, L, Schwartz, M, Scott, R, Sharma, Y, Silverberg, Ms, Spears, D, Steinhart, A, Stempak, Jm, Swoger, Jm, Tsagarelis, C, Zhang, C, Zhao, H, Aerts, J, Ahmad, T, Arbury, H, Attwood, A, Auton, A, Ball, Sg, Balmforth, Aj, Barnes, C, Barrett, Jc, Barroso, I, Barton, A, Bennett, Aj, Bhaskar, S, Blaszczyk, K, Bowes, J, Brand, Oj, Braund, Ps, Bredin, F, Breen, G, Brown, Mj, Bruce, In, Bull, J, Burren, Os, Burton, J, Byrnes, J, Caesar, S, Cardin, N, Clee, Cm, Coffey, Aj, Connell, Jm, Conrad, Df, Cooper, Jd, Dominiczak, Af, Downes, K, Drummond, He, Dudakia, D, Dunham, A, Ebbs, B, Eccles, D, Edkins, S, Edwards, C, Elliot, A, Emery, P, Evans, Dm, Evans, G, Eyre, S, Farmer, A, Ferrier, In, Flynn, E, Forbes, A, Forty, L, Franklyn, Ja, Frayling, Tm, Freathy, Rm, Giannoulatou, E, Gibbs, P, Gilbert, P, Gordon Smith, K, Gray, E, Green, E, Groves, Cj, Grozeva, D, Gwilliam, R, Hall, A, Hammond, N, Hardy, M, Harrison, P, Hassanali, N, Hebaishi, H, Hines, S, Hinks, A, Hitman, Ga, Hocking, L, Holmes, C, Howard, E, Howard, P, Howson, Jm, Hughes, D, Hunt, S, Isaacs, Jd, Jain, M, Jewell, Dp, Johnson, T, Jolley, Jd, Jones, Ir, Jones, La, Kirov, G, Langford, Cf, Lango Allen, H, Lathrop, Gm, Lee, J, Lee, Kl, Lees, C, Lewis, K, Lindgren, Cm, Maisuria Armer, M, Maller, J, Mansfield, J, Marchini, Jl, Martin, P, Massey, Dc, Mcardle, Wl, Mcguffin, P, Mclay, Ke, Mcvean, G, Mentzer, A, Mimmack, Ml, Morgan, Ae, Morris, Ap, Mowat, C, Munroe, Pb, Myers, S, Newman, W, Nimmo, Er, O'Donovan, Mc, Onipinla, A, Ovington, Nr, Owen, Mj, Palin, K, Palotie, A, Parnell, K, Pearson, R, Pernet, D, Perry, Jr, Phillips, A, Plagnol, V, Prescott, Nj, Prokopenko, I, Quail, Ma, Rafelt, S, Rayner, Nw, Reid, Dm, Renwick, A, Ring, Sm, Robertson, N, Robson, S, Russell, E, St Clair, D, Sambrook, Jg, Sanderson, Jd, Sawcer, Sj, Schuilenburg, H, Scott, Ce, Seal, S, Shaw Hawkins, S, Shields, Bm, Simmonds, Mj, Smyth, Dj, Somaskantharajah, E, Spanova, K, Steer, S, Stephens, J, Stevens, He, Stirrups, K, Stone, Ma, Strachan, Dp, Su, Z, Symmons, Dp, Thompson, Jr, Thomson, W, Tobin, Md, Travers, Me, Turnbull, C, Vukcevic, D, Wain, Lv, Walker, M, Walker, Nm, Wallace, C, Warren Perry, M, Watkins, Na, Webster, J, Weedon, Mn, Wilson, Ag, Woodburn, M, Wordsworth, Bp, Yau, C, Young, Ah, Zeggini, E, Brown, Ma, Burton, Pr, Caulfield, Mj, Compston, A, Farrall, M, Gough, Sc, Hall, As, Hattersley, At, Hill, Av, Mathew, Cg, Pembrey, M, Satsangi, J, Stratton, Mr, Worthington, J, Hurles, Me, Duncanson, A, Ouwehand, Wh, Parkes, M, Rahman, N, Todd, Ja, Samani, Nj, Kwiatkowski, Dp, Mccarthy, Mi, Craddock, N, Deloukas, P, Donnelly, P, Blackwell, Jm, Bramon, E, Casas, Jp, Corvin, A, Jankowski, J, Markus, Hs, Palmer, Cn, Plomin, R, Rautanen, A, Trembath, Rc, Viswanathan, Ac, Wood, Nw, Spencer, Cc, Band, G, Bellenguez, C, Freeman, C, Hellenthal, G, Pirinen, M, Strange, A, Blackburn, H, Bumpstead, Sj, Dronov, S, Gillman, M, Jayakumar, A, Mccann, Ot, Liddle, J, Potter, Sc, Ravindrarajah, R, Ricketts, M, Waller, M, Weston, P, Widaa, S, Whittaker, P., AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Gastroenterology and Hepatology, and Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI)

Subjects
Genome-wide association study, Disease, SUSCEPTIBILITY, Inflammatory bowel disease, NUMBER, 0302 clinical medicine, Crohn Disease, NETWORK, Genetics, 0303 health sciences, Multidisciplinary, Genomics, Ulcerative colitis, 3. Good health, Colitis, Ulcerative, Genetic Predisposition to Disease, Genome, Human, Haplotypes, Humans, Inflammatory Bowel Diseases, Mycobacterium, Mycobacterium Infections, Mycobacterium tuberculosis, Phenotype, Polymorphism, Single Nucleotide, Reproducibility of Results, Genome-Wide Association Study, Host-Pathogen Interactions, IRGM, Medical genetics, 030211 gastroenterology & hepatology, EXPRESSION, medicine.medical_specialty, Immunology, Biology, Molecular gastro-enterology and hepatology Pathogenesis and modulation of inflammation [IGMD 2], TUBERCULOSIS, 03 medical and health sciences, Medical research, medicine, Allele, METAANALYSIS, 030304 developmental biology, HYPER-IGE SYNDROME, MUTATIONS, medicine.disease, RISK LOCI, Genetic architecture, digestive system diseases
Abstract

Crohn's disease and ulcerative colitis, the two common forms of inflammatory bowel disease (IBD), affect over 2.5 million people of European ancestry, with rising prevalence in other populations(1). Genome-wide association studies and subsequent meta-analyses of these two diseases(2,3) as separate phenotypes have implicated previously unsuspected mechanisms, such as autophagy(4), in their pathogenesis and showed that some IBD loci are shared with other inflammatory diseases(5). Here we expand on the knowledge of relevant pathways by undertaking a meta-analysis of Crohn's disease and ulcerative colitis genome-wide association scans, followed by extensive validation of significant findings, with a combined total of more than 75,000 cases and controls. We identify 71 new associations, for a total of 163 IBD loci, that meet genome-wide significance thresholds. Most loci contribute to both phenotypes, and both directional (consistently favouring one allele over the course of human history) and balancing (favouring the retention of both alleles within populations) selection effects are evident. Many IBD loci are also implicated in other immune-mediated disorders, most notably with ankylosing spondylitis and psoriasis. We also observe considerable overlap between susceptibility loci for IBD and mycobacterial infection. Gene co-expression network analysis emphasizes this relationship, with pathways shared between host responses to mycobacteria and those predisposing to IBD.

Published
2012
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23. A genome-wide scan of ashkenazi jewish crohn's disease suggests novel susceptibility loci

Author

Kenny, EE, Pe'er, I, Karban, A, Ozelius, L, Mitchell, AA, Ng, SM, Erazo, M, Ostrer, H, Abraham, C, Abreu, MT, Atzmon, G, Barzilai, N, Brant, SR, Bressman, S, Burns, ER, Chowers, Y, Clark, LN, Darvasi, A, Doheny, D, Duerr, RH, Eliakim, R, Giladi, N, Gregersen, PK, Hakonarson, H, Jones, MR, Marder, K, McGovern, DPB, Mulle, J, Orr-Urtreger, A, Proctor, DD, Pulver, A, Rotter, JI, Silverberg, MS, Ullman, T, Warren, ST, Waterman, M, Zhang, W, Bergman, A, Mayer, L, Katz, S, Desnick, RJ, Cho, JH, Peter, I, Kenny, EE, Pe'er, I, Karban, A, Ozelius, L, Mitchell, AA, Ng, SM, Erazo, M, Ostrer, H, Abraham, C, Abreu, MT, Atzmon, G, Barzilai, N, Brant, SR, Bressman, S, Burns, ER, Chowers, Y, Clark, LN, Darvasi, A, Doheny, D, Duerr, RH, Eliakim, R, Giladi, N, Gregersen, PK, Hakonarson, H, Jones, MR, Marder, K, McGovern, DPB, Mulle, J, Orr-Urtreger, A, Proctor, DD, Pulver, A, Rotter, JI, Silverberg, MS, Ullman, T, Warren, ST, Waterman, M, Zhang, W, Bergman, A, Mayer, L, Katz, S, Desnick, RJ, Cho, JH, and Peter, I

Abstract

Crohn's disease (CD) is a complex disorder resulting from the interaction of intestinal microbiota with the host immune system in genetically susceptible individuals. The largest meta-analysis of genome-wide association to date identified 71 CD-susceptibility loci in individuals of European ancestry. An important epidemiological feature of CD is that it is 2-4 times more prevalent among individuals of Ashkenazi Jewish (AJ) descent compared to non-Jewish Europeans (NJ). To explore genetic variation associated with CD in AJs, we conducted a genome-wide association study (GWAS) by combining raw genotype data across 10 AJ cohorts consisting of 907 cases and 2,345 controls in the discovery stage, followed up by a replication study in 971 cases and 2,124 controls. We confirmed genome-wide significant associations of 9 known CD loci in AJs and replicated 3 additional loci with strong signal (p<5×10 -6). Novel signals detected among AJs were mapped to chromosomes 5q21.1 (rs7705924, combined p = 2×10 -8; combined odds ratio OR = 1.48), 2p15 (rs6545946, p = 7×10 -9; OR = 1.16), 8q21.11 (rs12677663, p = 2×10 -8; OR = 1.15), 10q26.3 (rs10734105, p = 3×10 -8; OR = 1.27), and 11q12.1 (rs11229030, p = 8×10 -9; OR = 1.15), implicating biologically plausible candidate genes, including RPL7, CPAMD8, PRG2, and PRG3. In all, the 16 replicated and newly discovered loci, in addition to the three coding NOD2 variants, accounted for 11.2% of the total genetic variance for CD risk in the AJ population. This study demonstrates the complementary value of genetic studies in the Ashkenazim. © 2012 Kenny et al.

Published
2012

24. The Strength-Focused and Meaning-Oriented Approach to Resilience and Transformation (SMART): A body-mind-spirit approach to trauma management.

Author

Chan, CLW, Chan, THY, Ng, SM, Chan, CLW, Chan, THY, and Ng, SM

Abstract

This article introduces the Strength-focused and Meaning- oriented Approach to Resilience and Transformation (SMART) as a model of crisis intervention, which aims at discovering inner strengths through meaning reconstruction. Limitations of conventional crisis management and current findings in post-traumatic growth research are discussed. Instead of adopting a pathological framework, the SMART approach holds a holistic view of health, employs facilitative strategies, and promotes dynamic coping. Intervention components include Eastern spiritual teachings, physical techniques such as yoga and meditation, and psycho-education that promotes meaning reconstruction. Efficacy of the SMART model is assessed with reference to two pilot studies conducted in Hong Kong at the time when the SARS pandemic caused widespread fear and anxiety in the community. Response to potential criticisms of the SMART model is attempted.

Published
2006

25. The measurement of body-mind-spirit well-being toward multidimensionality and transcultural applicability.

Author

Ng, SM, Yau, JKY, Chan, CLW, Chan, CHY, Ho, DYF, Ng, SM, Yau, JKY, Chan, CLW, Chan, CHY, and Ho, DYF

Abstract

The Body-Mind-Spirit model of health promotion (Chan, Ho&Chow, 2002) guided the construction of a multidimensional inventory for assessing holistic health. Named Body-Mind-Spirit Well-Being Inventory (BMSWBI), it comprises four scales: Physical Distress, Daily Functioning, Affect, and Spirituality (differentiated from religiosity and conceived as ecumenical). Respondents (674 Chinese adults from Hong Kong) completed the BMSWBI via the Internet. Results indicate that all four scales have high reliability, with alpha coefficients ranging from .87 to .92, and concurrent validity. Factor analysis indicates that (a) positive and negative affect form two distinct factors; and (b) spirituality comprises three distinct aspects, tranquility, resistance to disorientation, and resilience. Spirituality is positively associated with mental well-being, positive affect, satisfaction with life, and hope; but negatively associated with negative affect and perceived stress. These results suggest that the inventory may be used to assess different dimensions of health satisfactorily.

Published
2005

29. A heuristic-based procedure for the weighted production-cell formation problem

Author

Lin, TL, Dessouky, MM, Kumar, KR, Ng, SM, Lin, TL, Dessouky, MM, Kumar, KR, and Ng, SM

Abstract

A key issue in the design of a cellular manufacturing system is the formation of the machines and parts into groups or production cells. The production cells are designed to minimize the costs of inter-cell part movements and intra-cell processing, while balancing the workload within each cell. Most of the prior research represents the cell formation problem as a binary machine-part incidence matrix. The workload balance within each production cen can be precisely calculated only if the processing times and demand rates are included in the analysis. For this reason, a heuristic-based procedure that uses processing times and demand rates to form the production cells is proposed. The procedure considers the cell imbalance costs as well as the costs associated with the inter-cell part movements and intra-cell processing. The efficiency and effectiveness of the heuristic is compared with other methods, and an industrial application of the proposed heuristic is presented.

Published
1996

30. On the characterization and measure of machine cells in group technology

Author

Ng, SM and Ng, SM

Abstract

Group technology plays an important role in the design of an automated manufacturing system. The ideal situation is to partition the machines into machine cells and the parts into part families so that each machine cell together with the part family for the cell is independent of the rest of the system. We will give a characterization of the independent cells for an arbitrary manufacturing system. An efficient algorithm to identify these independent cells will also be discussed. An effective policy for subcell formation (not necessarily independent) from larger cells will also be discussed. Computational results show that our algorithms always obtain solutions with higher grouping efficiency compared with some of the existing algorithms. We also discuss the effectiveness of grouping efficiency as a measure for group technology.

Published
1996

31. WORST-CASE ANALYSIS OF AN ALGORITHM FOR CELLULAR MANUFACTURING

Author

NG, SM and NG, SM

Abstract

Two measures for the efficiency of grouping in cellular manufacturing are discussed in this paper. We first analyze the effectiveness of the first measure, grouping efficiency. A worst case bound is then derived for the minimum spanning tree algorithm with respect to this measure. We then show a newly proposed measure, grouping efficacy, is not suitable from an algorithmic point of view. A weighted grouping efficacy is then proposed and worst case bounds are derived with respect to this new measure. We also propose several policies to improve grouping efficiency and grouping efficacy during the decomposition of larger machine cells. Computational results will also be presented to demonstrate the effectiveness of these measures and the worst case bounds.

Published
1993

33. The Strength-Focused and Meaning-Oriented Approach to Resilience and Transformation (SMART): a body-mind-spirit approach to trauma management.

Author

Chan CL, Chan THY, and Ng SM

Abstract

This article introduces the Strength-focused and Meaning-oriented Approach to Resilience and Transformation (SMART) as a model of crisis intervention, which aims at discovering inner strengths through meaning reconstruction. Limitations of conventional crisis management and current findings in post-traumatic growth research are discussed. Instead of adopting a pathological framework, the SMART approach holds a holistic view of health, employs facilitative strategies, and promotes dynamic coping. Intervention components include Eastern spiritual teachings, physical techniques such as yoga and meditation, and psycho-education that promotes meaning reconstruction. Efficacy of the SMART model is assessed with reference to two pilot studies conducted in Hong Kong at the time when the SARS pandemic caused widespread fear and anxiety in the community. Response to potential criticisms of the SMART model is attempted. [ABSTRACT FROM AUTHOR]

Published
2006
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34. Group debriefing for people with chronic diseases during the SARS pandemic: Strength-Focused and Meaning-Oriented Approach for Resilience and Transformation (SMART)

Author

Ng SM, Chan THY, Chan CL, Lee AM, Yau JKY, Chan CHY, and Lau J

Abstract

This study presented preliminary results on the efficacy of a novel group debriefing model called Strength-Focused and Meaning-Oriented Approach for Resilience and Transformation (SMART). The SMART debriefing (1) aimed at boosting resilience and catalyzing transformation among persons undergoing stressful events, (2) adopted a growth-oriented and holistic approach of health promotion, and (3) employed methods drawn from various indigenous sources (e.g. Asian philosophies and Traditional Chinese Medicine). Participants (N=51) were people with chronic diseases recruited about 1 month (August 2003) after the Severe Acute Respiratory Syndrome (SARS) outbreak was eventually under control, after causing widespread panic in Hong Kong. After the one-day group debriefing, participants showed significant decrease in depression level, as measured by Brief Symptom Inventory (Derogatis & Melisaratos, 1983, Psychological Medicine, 13(3), 595-605) and changes in cognitive appraisal towards SARS. Such changes were sustained in a 1-month follow-up. Clinical implications and directions for further study were discussed. [ABSTRACT FROM AUTHOR]

Published
2006
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35. Short communication: the effect of a one-hour Eastern stress management session on salivary cortisol.

Author

Chan CLW, Tso IF, Ho RTH, Ng SM, Chan CHY, Chan JCN, Lai JCL, and Evans PD

Abstract

Body-Mind-Spirit (BMS) model by Chan (2001) have been applied to interventions for a variety of clienteles and the effectiveness has been supported by positive psychological outcomes. This study aims to complement these studies by evaluating the efficacy of a one-hour Eastern stress management session in reducing salivary cortisol levels in working adults in Hong Kong. Pre- and post-test salivary cortisol levels were measured and a significant drop after the session when compared with local normative data was evident. The efficacy of the stress management session, limitations of this study and suggestions for further research are discussed. Copyright © 2006 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Published
2006
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36. The measurement of body-mind-spirit well-being: toward multidimensionality and transcultural applicability.

Author

Ng SM, Yau JKY, Chan CLW, Chan CHY, and Ho DYF

Abstract

The Body-Mind-Spirit model of health promotion (Chan, Ho&Chow, 2002) guided the construction of a multidimensional inventory for assessing holistic health. Named Body-Mind-Spirit Well-Being Inventory (BMSWBI), it comprises four scales: Physical Distress, Daily Functioning, Affect, and Spirituality (differentiated from religiosity and conceived as ecumenical). Respondents (674 Chinese adults from Hong Kong) completed the BMSWBI via the Internet. Results indicate that all four scales have high reliability, with alpha coefficients ranging from .87 to .92, and concurrent validity. Factor analysis indicates that (a) positive and negative affect form two distinct factors; and (b) spirituality comprises three distinct aspects, tranquility, resistance to disorientation, and resilience. Spirituality is positively associated with mental well-being, positive affect, satisfaction with life, and hope; but negatively associated with negative affect and perceived stress. These results suggest that the inventory may be used to assess different dimensions of health satisfactorily. [ABSTRACT FROM AUTHOR]

Published
2005
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37. The social work practitioner-researcher-educator: encouraging innovations and empowerment in the 21st century.

Author

Chan CLW and Ng SM

Abstract

Teaching, practice and research are the three integral missions of social work educators. This article uses examples of the empowerment curriculum and problem-based learning to illustrate how social work teachers can play the role of a practitioner-researcher-educator to promote social justice and anti-discrimination in the globalization process. [ABSTRACT FROM AUTHOR]

Published
2004
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38. Ninety-minute accelerated critical pathway for chest pain evaluation.

Author

Ng SM, Krishnaswamy P, Morissey R, Clopton P, Fitzgerald R, Maisel AS, Ng, S M, Krishnaswamy, P, Morissey, R, Clopton, P, Fitzgerald, R, and Maisel, A S

Abstract

Rapid, efficient, and accurate evaluation of chest pain patients in the emergency department optimizes patient care from public health, economic, and liability perspectives. To evaluate the performance of an accelerated critical pathway for patients with suspected coronary ischemia that utilizes clinical history, electrocardiographic findings, and triple cardiac marker testing (cardiac troponin I [cTnI], myoglobin, and creatine kinase-MB [CK-MB]), we performed an observational study of a chest pain critical pathway in the setting of a large Emergency Department at the Veterans Affairs Medical Center in 1,285 consecutive patients with signs and symptoms of cardiac ischemia. The accelerated critical pathway for chest pain evaluation was analyzed for: (1) accuracy in triaging of patients within 90 minutes of presentation, (2) sensitivity, specificity, positive predictive value, and negative predictive value of cTnI, myoglobin, and CK-MB in diagnosing acute myocardial infarction (MI) within 90 minutes, and (3) impact on Coronary Care Unit (CCU) admissions. All MIs were diagnosed within 90 minutes of presentation (sensitivity 100%, specificity 94%, positive predictive value 47%, negative predictive value 100%). CCU admissions decreased by 40%. Ninety percent of patients with negative cardiac markers and a negative electrocardiogram at 90 minutes were discharged home with 1 patient returning with an MI (0.2%) within the next 30 days. Thus, a simple, inexpensive, yet aggressive critical pathway that utilizes high-risk features from clinical history, electrocardiographic changes, and rapid point-of-care testing of 3 cardiac markers allows for accurate triaging of chest pain patients within 90 minutes of presenting to the emergency department. [ABSTRACT FROM AUTHOR]

Published
2001

42. PTU-028 Adequate bowel preparation in small bowel capsule endoscopy: has it been a clearer future?

Author

Liu, J Yin, Kumar, M Nanda, Ng, SM, Wong, M, McNair, A, and Pee, L

Abstract

IntroductionCapsule endoscopy (CE) relies on adequate bowel preparation to ensure good luminal views. Studies have given variable results on the efficacy of bowel preparation1,2. Our department moved from a regimen of 24 hour of clear fluids only (NP) to 24 hour of clear fluids and the addition of one sachet of polyethylene glycol (PEG1) after a retrospective audit of results3. As our results indicated PEG1 improved lesion detection compared to NP, we changed preparation to 24 hour of clear fluid combined with 2 sachets of PEG (PEG2). We present a retrospective look at our findings.MethodPatients who underwent CE from January 2016 till July 2016 were identified via Rapid capsule endoscopy software. Data collected included indication for test, total lesions detected (TL) and lesions excluding aphthous ulcers (EL). 3 independent assessors reviewed images at 20 min intervals to determine adequacy of bowel preparation. Overall adequacy was determined by majority opinion. Data from our previous analysis using the same methods was added and data comparison of lesion detection in each arm was compared by Fisher’s test chi squared analysis.ResultsA total of 31 patients were identified in this timeframe but only 30 patients were included due to failure of one procedure. All patients received PEG2. Our results are shown in figure 1.The only result which showed statistical significance was between PEG1 and PEG2 when comparing all lesions identified (p=0.045) although it appears that PEG1 was better than PEG2; and that PEG2 detected less lesions overall than NP. However, when normal examinations were discounted from all three arms and the subsequent results compared, there were statistically significant results between NP(36%) and PEG2(70%) showing PEG2 was better at detecting significant lesions.(x25.790,p=0.0161).[Figure]ConclusionIn our study, it appears that bowel preparation with PEG is better than NP in detecting significant lesions, but that PEG2 is inferior to PEG1. This goes against recent larger scale prospective studies4,5which suggest that clear fluid preparation is not inferior to full bowel preparation; and it is unusual that half dose preparation seems more effective than full dose. However, our numbers are small and it is a retrospective analysis. Additionally, in our dataset, there were more normal studies in the PEG2 arm than the other two, which may have skewed results. Further large scale prospective studies need to be carried out to clarify this difficult question.References. Nivet al. World J Gastroenterol.2013Feb 28;19(8):1264–70.. Rosaet al. World J Gastrointest Endosc.2013Feb 16;5(2):67–73.. Omeret al. Poster - United European Gastroenterology Week,Barcelona 2015 Oct.. Hookey et al. Gastrointest Endosc.2017Jan;85(1):187–193.. Kleinet al. Ann Gastroenterol.2016Apr-Jun;29(2):196–200.Disclosure of InterestNone Declared

Published
2017
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45. Efficacy of a brief intervention for carers of people with first-episode psychosis: a waiting list controlled study.

Author

So HW, Chen EYH, Chan RCK, Wong CW, Hung SF, Chung DWS, Ng SM, and Chan CLW

Abstract

Objectives: While family psycho-education for schizophrenia is well-supported, the efficacy of family intervention for first-episode psychosis is less studied. This waiting list controlled study set out to evaluate the effectiveness of a 6-week intervention for carers of people with first-episode psychosis. Participants and Methods: Carers were randomised into experimental or waiting list categories. Study 1 compared various outcome measures in the 2 categories. Study 2 evaluated the treatment effects. Results: After the intervention, carers showed increased knowledge about psychosis and a reduction in negative ways of coping. The improvement in knowledge was maintained at 6-month follow-up, and trends towards improved caregiving burden and coping were also evident.Conclusions: A brief intervention programme can be effective in improving important variables such as knowledge, coping, and caregiving burden. The implications for selecting 'core components' for an effective intervention were discussed. [ABSTRACT FROM AUTHOR]

Published
2006

46. Comparative performances of machine learning methods for classifying Crohn Disease patients using genome-wide genotyping data

Author

Romagnoni, A., Jegou, S., Van Steen, K., Wainrib, G., Hugot, J. -P., Peyrin-Biroulet, L., Chamaillard, M., Colombel, J. -F., Cottone, M., D'Amato, M., D'Inca, R., Halfvarson, J., Henderson, P., Karban, A., Kennedy, N. A., Khan, M. A., Lemann, M., Levine, A., Massey, D., Milla, M., S. M. E., Ng, Oikonomou, I., Peeters, H., Proctor, D. D., Rahier, J. -F., Rutgeerts, P., Seibold, F., Stronati, L., Taylor, K. M., Torkvist, L., Ublick, K., Van Limbergen, J., Van Gossum, A., Vatn, M. H., Zhang, H., Zhang, W., Andrews, J. M., Bampton, P. A., Barclay, M., Florin, T. H., Gearry, R., Krishnaprasad, K., Lawrance, I. C., Mahy, G., Montgomery, G. W., Radford-Smith, G., Roberts, R. L., Simms, L. A., Hanigan, K., Croft, A., Amininijad, L., Cleynen, I., Dewit, O., Franchimont, D., Georges, M., Laukens, D., Theatre, E., Vermeire, S., Aumais, G., Baidoo, L., Barrie, A. M., Beck, K., Bernard, E. -J., Binion, D. G., Bitton, A., Brant, S. R., Cho, J. H., Cohen, A., Croitoru, K., Daly, M. J., Datta, L. W., Deslandres, C., Duerr, R. H., Dutridge, D., Ferguson, J., Fultz, J., Goyette, P., Greenberg, G. R., Haritunians, T., Jobin, G., Katz, S., Lahaie, R. G., Mcgovern, D. P., Nelson, L., S. M., Ng, Ning, K., Pare, P., Regueiro, M. D., Rioux, J. D., Ruggiero, E., Schumm, L. P., Schwartz, M., Scott, R., Sharma, Y., Silverberg, M. S., Spears, D., Steinhart, A. H., Stempak, J. M., Swoger, J. M., Tsagarelis, C., Zhang, C., Zhao, H., Aerts, J., Ahmad, T., Arbury, H., Attwood, A., Auton, A., Ball, S. G., Balmforth, A. J., Barnes, C., Barrett, J. C., Barroso, I., Barton, A., Bennett, A. J., Bhaskar, S., Blaszczyk, K., Bowes, J., Brand, O. J., Braund, P. S., Bredin, F., Breen, G., Brown, M. J., Bruce, I. N., Bull, J., Burren, O. S., Burton, J., Byrnes, J., Caesar, S., Cardin, N., Clee, C. M., Coffey, A. J., MC Connell, J., Conrad, D. F., Cooper, J. D., Dominiczak, A. F., Downes, K., Drummond, H. E., Dudakia, D., Dunham, A., Ebbs, B., Eccles, D., Edkins, S., Edwards, C., Elliot, A., Emery, P., Evans, D. M., Evans, G., Eyre, S., Farmer, A., Ferrier, I. N., Flynn, E., Forbes, A., Forty, L., Franklyn, J. A., Frayling, T. M., Freathy, R. M., Giannoulatou, E., Gibbs, P., Gilbert, P., Gordon-Smith, K., Gray, E., Green, E., Groves, C. J., Grozeva, D., Gwilliam, R., Hall, A., Hammond, N., Hardy, M., Harrison, P., Hassanali, N., Hebaishi, H., Hines, S., Hinks, A., Hitman, G. A., Hocking, L., Holmes, C., Howard, E., Howard, P., Howson, J. M. M., Hughes, D., Hunt, S., Isaacs, J. D., Jain, M., Jewell, D. P., Johnson, T., Jolley, J. D., Jones, I. R., Jones, L. A., Kirov, G., Langford, C. F., Lango-Allen, H., Lathrop, G. M., Lee, J., Lee, K. L., Lees, C., Lewis, K., Lindgren, C. M., Maisuria-Armer, M., Maller, J., Mansfield, J., Marchini, J. L., Martin, P., Massey, D. C., Mcardle, W. L., Mcguffin, P., Mclay, K. E., Mcvean, G., Mentzer, A., Mimmack, M. L., Morgan, A. E., Morris, A. P., Mowat, C., Munroe, P. B., Myers, S., Newman, W., Nimmo, E. R., O'Donovan, M. C., Onipinla, A., Ovington, N. R., Owen, M. J., Palin, K., Palotie, A., Parnell, K., Pearson, R., Pernet, D., Perry, J. R., Phillips, A., Plagnol, V., Prescott, N. J., Prokopenko, I., Quail, M. A., Rafelt, S., Rayner, N. W., Reid, D. M., Renwick, A., Ring, S. M., Robertson, N., Robson, S., Russell, E., Clair, D. S., Sambrook, J. G., Sanderson, J. D., Sawcer, S. J., Schuilenburg, H., Scott, C. E., Seal, S., Shaw-Hawkins, S., Shields, B. M., Simmonds, M. J., Smyth, D. J., Somaskantharajah, E., Spanova, K., Steer, S., Stephens, J., Stevens, H. E., Stirrups, K., Stone, M. A., Strachan, D. P., Su, Z., Symmons, D. P. M., Thompson, J. R., Thomson, W., Tobin, M. D., Travers, M. E., Turnbull, C., Vukcevic, D., Wain, L. V., Walker, M., Walker, N. M., Wallace, C., Warren-Perry, M., Watkins, N. A., Webster, J., Weedon, M. N., Wilson, A. G., Woodburn, M., Wordsworth, B. P., Yau, C., Young, A. H., Zeggini, E., Brown, M. A., Burton, P. R., Caulfield, M. J., Compston, A., Farrall, M., Gough, S. C. L., Hall, A. S., Hattersley, A. T., Hill, A. V. S., Mathew, C. G., Pembrey, M., Satsangi, J., Stratton, M. R., Worthington, J., Hurles, M. E., Duncanson, A., Ouwehand, W. H., Parkes, M., Rahman, N., Todd, J. A., Samani, N. J., Kwiatkowski, D. P., Mccarthy, M. I., Craddock, N., Deloukas, P., Donnelly, P., Blackwell, J. M., Bramon, E., Casas, J. P., Corvin, A., Jankowski, J., Markus, H. S., Palmer, C. N., Plomin, R., Rautanen, A., Trembath, R. C., Viswanathan, A. C., Wood, N. W., Spencer, C. C. A., Band, G., Bellenguez, C., Freeman, C., Hellenthal, G., Pirinen, M., Strange, A., Blackburn, H., Bumpstead, S. J., Dronov, S., Gillman, M., Jayakumar, A., Mccann, O. T., Liddle, J., Potter, S. C., Ravindrarajah, R., Ricketts, M., Waller, M., Weston, P., Widaa, S., Whittaker, P., Romagnoni, A., Jegou, S., Van Steen, K., Wainrib, G., Hugot, J. -P., Peyrin-Biroulet, L., Chamaillard, M., Colombel, J. -F., Cottone, M., D'Amato, M., D'Inca, R., Halfvarson, J., Henderson, P., Karban, A., Kennedy, N. A., Khan, M. A., Lemann, M., Levine, A., Massey, D., Milla, M., Ng, S. M. E., Oikonomou, I., Peeters, H., Proctor, D. D., Rahier, J. -F., Rutgeerts, P., Seibold, F., Stronati, L., Taylor, K. M., Torkvist, L., Ublick, K., Van Limbergen, J., Van Gossum, A., Vatn, M. H., Zhang, H., Zhang, W., Andrews, J. M., Bampton, P. A., Barclay, M., Florin, T. H., Gearry, R., Krishnaprasad, K., Lawrance, I. C., Mahy, G., Montgomery, G. W., Radford-Smith, G., Roberts, R. L., Simms, L. A., Hanigan, K., Croft, A., Amininijad, L., Cleynen, I., Dewit, O., Franchimont, D., Georges, M., Laukens, D., Theatre, E., Vermeire, S., Aumais, G., Baidoo, L., Barrie, A. M., Beck, K., Bernard, E. -J., Binion, D. G., Bitton, A., Brant, S. R., Cho, J. H., Cohen, A., Croitoru, K., Daly, M. J., Datta, L. W., Deslandres, C., Duerr, R. H., Dutridge, D., Ferguson, J., Fultz, J., Goyette, P., Greenberg, G. R., Haritunians, T., Jobin, G., Katz, S., Lahaie, R. G., Mcgovern, D. P., Nelson, L., Ng, S. M., Ning, K., Pare, P., Regueiro, M. D., Rioux, J. D., Ruggiero, E., Schumm, L. P., Schwartz, M., Scott, R., Sharma, Y., Silverberg, M. S., Spears, D., Steinhart, A. H., Stempak, J. M., Swoger, J. M., Tsagarelis, C., Zhang, C., Zhao, H., Aerts, J., Ahmad, T., Arbury, H., Attwood, A., Auton, A., Ball, S. G., Balmforth, A. J., Barnes, C., Barrett, J. C., Barroso, I., Barton, A., Bennett, A. J., Bhaskar, S., Blaszczyk, K., Bowes, J., Brand, O. J., Braund, P. S., Bredin, F., Breen, G., Brown, M. J., Bruce, I. N., Bull, J., Burren, O. S., Burton, J., Byrnes, J., Caesar, S., Cardin, N., Clee, C. M., Coffey, A. J., MC Connell, J., Conrad, D. F., Cooper, J. D., Dominiczak, A. F., Downes, K., Drummond, H. E., Dudakia, D., Dunham, A., Ebbs, B., Eccles, D., Edkins, S., Edwards, C., Elliot, A., Emery, P., Evans, D. M., Evans, G., Eyre, S., Farmer, A., Ferrier, I. N., Flynn, E., Forbes, A., Forty, L., Franklyn, J. A., Frayling, T. M., Freathy, R. M., Giannoulatou, E., Gibbs, P., Gilbert, P., Gordon-Smith, K., Gray, E., Green, E., Groves, C. J., Grozeva, D., Gwilliam, R., Hall, A., Hammond, N., Hardy, M., Harrison, P., Hassanali, N., Hebaishi, H., Hines, S., Hinks, A., Hitman, G. A., Hocking, L., Holmes, C., Howard, E., Howard, P., Howson, J. M. M., Hughes, D., Hunt, S., Isaacs, J. D., Jain, M., Jewell, D. P., Johnson, T., Jolley, J. D., Jones, I. R., Jones, L. A., Kirov, G., Langford, C. F., Lango-Allen, H., Lathrop, G. M., Lee, J., Lee, K. L., Lees, C., Lewis, K., Lindgren, C. M., Maisuria-Armer, M., Maller, J., Mansfield, J., Marchini, J. L., Martin, P., Massey, D. C., Mcardle, W. L., Mcguffin, P., Mclay, K. E., Mcvean, G., Mentzer, A., Mimmack, M. L., Morgan, A. E., Morris, A. P., Mowat, C., Munroe, P. B., Myers, S., Newman, W., Nimmo, E. R., O'Donovan, M. C., Onipinla, A., Ovington, N. R., Owen, M. J., Palin, K., Palotie, A., Parnell, K., Pearson, R., Pernet, D., Perry, J. R., Phillips, A., Plagnol, V., Prescott, N. J., Prokopenko, I., Quail, M. A., Rafelt, S., Rayner, N. W., Reid, D. M., Renwick, A., Ring, S. M., Robertson, N., Robson, S., Russell, E., Clair, D. S., Sambrook, J. G., Sanderson, J. D., Sawcer, S. J., Schuilenburg, H., Scott, C. E., Seal, S., Shaw-Hawkins, S., Shields, B. M., Simmonds, M. J., Smyth, D. J., Somaskantharajah, E., Spanova, K., Steer, S., Stephens, J., Stevens, H. E., Stirrups, K., Stone, M. A., Strachan, D. P., Su, Z., Symmons, D. P. M., Thompson, J. R., Thomson, W., Tobin, M. D., Travers, M. E., Turnbull, C., Vukcevic, D., Wain, L. V., Walker, M., Walker, N. M., Wallace, C., Warren-Perry, M., Watkins, N. A., Webster, J., Weedon, M. N., Wilson, A. G., Woodburn, M., Wordsworth, B. P., Yau, C., Young, A. H., Zeggini, E., Brown, M. A., Burton, P. R., Caulfield, M. J., Compston, A., Farrall, M., Gough, S. C. L., Hall, A. S., Hattersley, A. T., Hill, A. V. S., Mathew, C. G., Pembrey, M., Satsangi, J., Stratton, M. R., Worthington, J., Hurles, M. E., Duncanson, A., Ouwehand, W. H., Parkes, M., Rahman, N., Todd, J. A., Samani, N. J., Kwiatkowski, D. P., Mccarthy, M. I., Craddock, N., Deloukas, P., Donnelly, P., Blackwell, J. M., Bramon, E., Casas, J. P., Corvin, A., Jankowski, J., Markus, H. S., Palmer, C. N., Plomin, R., Rautanen, A., Trembath, R. C., Viswanathan, A. C., Wood, N. W., Spencer, C. C. A., Band, G., Bellenguez, C., Freeman, C., Hellenthal, G., Pirinen, M., Strange, A., Blackburn, H., Bumpstead, S. J., Dronov, S., Gillman, M., Jayakumar, A., Mccann, O. T., Liddle, J., Potter, S. C., Ravindrarajah, R., Ricketts, M., Waller, M., Weston, P., Widaa, S., Whittaker, P., Daly, Mark J. [0000-0002-0949-8752], Apollo - University of Cambridge Repository, Hugot, Jean-Pierre [0000-0002-8446-6056], UCL - SSS/IREC/GAEN - Pôle d'Hépato-gastro-entérologie, UCL - (MGD) Service de gastro-entérologie, Romagnoni, A, Jegou, S, VAN STEEN, Kristel, Wainrib, G, Hugot, JP, Peyrin-Biroulet, L, Chamaillard, M, Colombel, JF, Cottone, M, D'Amato, M, D'Inca, R, Halfvarson, J, Henderson, P, Karban, A, Kennedy, NA, Khan, MA, Lemann, M, Levine, A, Massey, D, Milla, M, Ng, SME, Oikonomou, I, Peeters, H, Proctor, DD, Rahier, JF, Rutgeerts, P, Seibold, F, Stronati, L, Taylor, KM, Torkvist, L, Ublick, K, Van Limbergen, J, Van Gossum, A, Vatn, MH, Zhang, H, Zhang, W, Andrews, JM, Bampton, PA, Barclay, M, Florin, TH, Gearry, R, Krishnaprasad, K, Lawrance, IC, Mahy, G, Montgomery, GW, Radford-Smith, G, Roberts, RL, Simms, LA, Hanigan, K, Croft, A, Amininijad, L, Cleynen, I, Dewit, O, Franchimont, D, Georges, M, Laukens, D, Theatre, E, Vermeire, S, Aumais, G, Baidoo, L, Barrie, AM, Beck, K, Bernard, EJ, Binion, DG, Bitton, A, Brant, SR, Cho, JH, Cohen, A, Croitoru, K, Daly, MJ, Datta, LW, Deslandres, C, Duerr, RH, Dutridge, D, Ferguson, J, Fultz, J, Goyette, P, Greenberg, GR, Haritunians, T, Jobin, G, Katz, S, Lahaie, RG, McGovern, DP, Nelson, L, Ng, SM, Ning, K, Pare, P, Regueiro, MD, Rioux, JD, Ruggiero, E, Schumm, LP, Schwartz, M, Scott, R, Sharma, Y, Silverberg, MS, Spears, D, Steinhart, AH, Stempak, JM, Swoger, JM, Tsagarelis, C, Zhang, C, Zhao, HY, AERTS, Jan, Ahmad, T, Arbury, H, Attwood, A, Auton, A, Ball, SG, Balmforth, AJ, Barnes, C, Barrett, JC, Barroso, I, Barton, A, Bennett, AJ, Bhaskar, S, Blaszczyk, K, Bowes, J, Brand, OJ, Braund, PS, Bredin, F, Breen, G, Brown, MJ, Bruce, IN, Bull, J, Burren, OS, Burton, J, Byrnes, J, Caesar, S, Cardin, N, Clee, CM, Coffey, AJ, Mc Connell, J, Conrad, DF, Cooper, JD, Dominiczak, AF, Downes, K, Drummond, HE, Dudakia, D, Dunham, A, Ebbs, B, Eccles, D, Edkins, S, Edwards, C, Elliot, A, Emery, P, Evans, DM, Evans, G, Eyre, S, Farmer, A, Ferrier, IN, Flynn, E, Forbes, A, Forty, L, Franklyn, JA, Frayling, TM, Freathy, RM, Giannoulatou, E, Gibbs, P, Gilbert, P, Gordon-Smith, K, Gray, E, Green, E, Groves, CJ, Grozeva, D, Gwilliam, R, Hall, A, Hammond, N, Hardy, M, Harrison, P, Hassanali, N, Hebaishi, H, Hines, S, Hinks, A, Hitman, GA, Hocking, L, Holmes, C, Howard, E, Howard, P, Howson, JMM, Hughes, D, Hunt, S, Isaacs, JD, Jain, M, Jewell, DP, Johnson, T, Jolley, JD, Jones, IR, Jones, LA, Kirov, G, Langford, CF, Lango-Allen, H, Lathrop, GM, Lee, J, Lee, KL, Lees, C, Lewis, K, Lindgren, CM, Maisuria-Armer, M, Maller, J, Mansfield, J, Marchini, JL, Martin, P, Massey, DCO, McArdle, WL, McGuffin, P, McLay, KE, McVean, G, Mentzer, A, Mimmack, ML, Morgan, AE, Morris, AP, Mowat, C, Munroe, PB, Myers, S, Newman, W, Nimmo, ER, O'Donovan, MC, Onipinla, A, Ovington, NR, Owen, MJ, Palin, K, Palotie, A, Parnell, K, Pearson, R, Pernet, D, Perry, JRB, Phillips, A, Plagnol, V, Prescott, NJ, Prokopenko, I, Quail, MA, Rafelt, S, Rayner, NW, Reid, DM, Renwick, A, Ring, SM, Robertson, N, Robson, S, Russell, E, St Clair, D, Sambrook, JG, Sanderson, JD, Sawcer, SJ, Schuilenburg, H, Scott, CE, Seal, S, Shaw-Hawkins, S, Shields, BM, Simmonds, MJ, Smyth, DJ, Somaskantharajah, E, Spanova, K, Steer, S, Stephens, J, Stevens, HE, Stirrups, K, Stone, MA, Strachan, DP, Su, Z, Symmons, DPM, Thompson, JR, Thomson, W, Tobin, MD, Travers, ME, Turnbull, C, Vukcevic, D, Wain, LV, Walker, M, Walker, NM, Wallace, C, Warren-Perry, M, Watkins, NA, Webster, J, Weedon, MN, Wilson, AG, Woodburn, M, Wordsworth, BP, Yau, C, Young, AH, Zeggini, E, Brown, MA, Burton, PR, Caulfield, MJ, Compston, A, Farrall, M, Gough, SCL, Hall, AS, Hattersley, AT, Hill, AVS, Mathew, CG, Pembrey, M, Satsangi, J, Stratton, MR, Worthington, J, Hurles, ME, Duncanson, A, Ouwehand, WH, Parkes, M, Rahman, N, Todd, JA, Samani, NJ, Kwiatkowski, DP, McCarthy, MI, Craddock, N, Deloukas, P, Donnelly, P, Blackwell, JM, Bramon, E, Casas, JP, Corvin, A, Jankowski, J, Markus, HS, Palmer, CNA, Plomin, R, Rautanen, A, Trembath, RC, Viswanathan, AC, Wood, NW, Spencer, CCA, Band, G, Bellenguez, C, Freeman, C, Hellenthal, G, Pirinen, M, Strange, A, Blackburn, H, Bumpstead, SJ, Dronov, S, Gillman, M, Jayakumar, A, McCann, OT, Liddle, J, Potter, SC, Ravindrarajah, R, Ricketts, M, Waller, M, Weston, P, Widaa, S, Whittaker, P, and Kwiatkowski, D

Subjects
Male, 692/4020/1503/257/1402, Genotype, Genotyping Techniques, LOCI, 45/43, lcsh:Medicine, Polymorphism, Single Nucleotide, Crohn's disease, genetics, genome wide association, Article, Deep Learning, Crohn Disease, INDEL Mutation, Genetics research, Humans, genetics, Genetic Predisposition to Disease, 129, lcsh:Science, Alleles, Science & Technology, genome wide association, RISK PREDICTION, 45, Models, Genetic, lcsh:R, Decision Trees, 692/308/2056, ASSOCIATION, Multidisciplinary Sciences, Crohn's disease, Logistic Models, Nonlinear Dynamics, ROC Curve, Area Under Curve, Science & Technology - Other Topics, lcsh:Q, Female, Neural Networks, Computer, INFLAMMATORY-BOWEL-DISEASE, Genome-Wide Association Study
Abstract

Crohn Disease (CD) is a complex genetic disorder for which more than 140 genes have been identified using genome wide association studies (GWAS). However, the genetic architecture of the trait remains largely unknown. The recent development of machine learning (ML) approaches incited us to apply them to classify healthy and diseased people according to their genomic information. The Immunochip dataset containing 18,227 CD patients and 34,050 healthy controls enrolled and genotyped by the international Inflammatory Bowel Disease genetic consortium (IIBDGC) has been re-analyzed using a set of ML methods: penalized logistic regression (LR), gradient boosted trees (GBT) and artificial neural networks (NN). The main score used to compare the methods was the Area Under the ROC Curve (AUC) statistics. The impact of quality control (QC), imputing and coding methods on LR results showed that QC methods and imputation of missing genotypes may artificially increase the scores. At the opposite, neither the patient/control ratio nor marker preselection or coding strategies significantly affected the results. LR methods, including Lasso, Ridge and ElasticNet provided similar results with a maximum AUC of 0.80. GBT methods like XGBoost, LightGBM and CatBoost, together with dense NN with one or more hidden layers, provided similar AUC values, suggesting limited epistatic effects in the genetic architecture of the trait. ML methods detected near all the genetic variants previously identified by GWAS among the best predictors plus additional predictors with lower effects. The robustness and complementarity of the different methods are also studied. Compared to LR, non-linear models such as GBT or NN may provide robust complementary approaches to identify and classify genetic markers. Tis work was supported by Fondation pour la Recherche Médical (ref DEI20151234405) and Investissements d’Avenir programme ANR-11-IDEX-0005-02, Sorbonne Paris Cite, Laboratoire d’excellence INFLAMEX. Te authors thank the students that participated to the wisdom of the crowd exercise.

Published
2019

47. Comparative Effects of Durian and Banana Consumption on Thermic Effect of Food and Metabolic Responses in Healthy Adults.

Author

Ling CY, Yeo MTY, Kang Y, Ng SM, Bi X, and Henry CJ

Abstract

Objective: In traditional Chinese philosophy, durian is classified as a "yang" food with heaty properties, believed to raise body temperature and blood pressure (BP) after consumption. In contrast, bananas are considered as "yin," possessing cooling effect. However, scientific evidence supporting these concepts is limited. This study aims to compare the metabolic effects in response to durian and banana ingestion., Methods: This randomized cross-over clinical study recruited 16 young, healthy Chinese participants (8 males and 8 females). All participants ingested isocaloric portion (367.5 kcal) of durian and banana with a wash-out period of at least 5 days. 3-h thermic effect of food (TEF) and substrate oxidation were assessed by indirect calorimetry. Postprandial vital signs and metabolic responses were measured over a period of 3 h., Results: Durian induced a higher and longer-lasting TEF than banana in most participants. Additionally, durian significantly lowered BP and increased triglyceride (TG) levels during 3 h after consumption, whereas bananas had no significant effects on these measures. Despite containing much fewer carbohydrates, durian prompted a comparable postprandial rise in blood glucose concentrations to that of banana., Conclusion: While durian offers nutritional benefits and a BP-lowering effect, moderation is recommended due to its high sugar and fat content, which can elevate blood glucose and lipid levels, and its "heatiness" may cause digestive discomforts and a sore throat according to anecdotal experiences.

Published
2024
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48. Artificial intelligence for diagnosing exudative age-related macular degeneration.

Author

Kang C, Lo JE, Zhang H, Ng SM, Lin JC, Scott IU, Kalpathy-Cramer J, Liu SA, and Greenberg PB

Subjects
Humans, Bias, Tomography, Optical Coherence methods, Artificial Intelligence, Macular Degeneration diagnosis, Sensitivity and Specificity
Abstract

Background: Age-related macular degeneration (AMD) is a retinal disorder characterized by central retinal (macular) damage. Approximately 10% to 20% of non-exudative AMD cases progress to the exudative form, which may result in rapid deterioration of central vision. Individuals with exudative AMD (eAMD) need prompt consultation with retinal specialists to minimize the risk and extent of vision loss. Traditional methods of diagnosing ophthalmic disease rely on clinical evaluation and multiple imaging techniques, which can be resource-consuming. Tests leveraging artificial intelligence (AI) hold the promise of automatically identifying and categorizing pathological features, enabling the timely diagnosis and treatment of eAMD., Objectives: To determine the diagnostic accuracy of artificial intelligence (AI) as a triaging tool for exudative age-related macular degeneration (eAMD)., Search Methods: We searched CENTRAL, MEDLINE, Embase, three clinical trials registries, and Data Archiving and Networked Services (DANS) for gray literature. We did not restrict searches by language or publication date. The date of the last search was April 2024., Selection Criteria: Included studies compared the test performance of algorithms with that of human readers to detect eAMD on retinal images collected from people with AMD who were evaluated at eye clinics in community or academic medical centers, and who were not receiving treatment for eAMD when the images were taken. We included algorithms that were either internally or externally validated or both., Data Collection and Analysis: Pairs of review authors independently extracted data and assessed study quality using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool with revised signaling questions. For studies that reported more than one set of performance results, we extracted only one set of diagnostic accuracy data per study based on the last development stage or the optimal algorithm as indicated by the study authors. For two-class algorithms, we collected data from the 2x2 table whenever feasible. For multi-class algorithms, we first consolidated data from all classes other than eAMD before constructing the corresponding 2x2 tables. Assuming a common positivity threshold applied by the included studies, we chose random-effects, bivariate logistic models to estimate summary sensitivity and specificity as the primary performance metrics., Main Results: We identified 36 eligible studies that reported 40 sets of algorithm performance data, encompassing over 16,000 participants and 62,000 images. We included 28 studies (78%) that reported 31 algorithms with performance data in the meta-analysis. The remaining nine studies (25%) reported eight algorithms that lacked usable performance data; we reported them in the qualitative synthesis. Study characteristics and risk of bias Most studies were conducted in Asia, followed by Europe, the USA, and collaborative efforts spanning multiple countries. Most studies identified study participants from the hospital setting, while others used retinal images from public repositories; a few studies did not specify image sources. Based on four of the 36 studies reporting demographic information, the age of the study participants ranged from 62 to 82 years. The included algorithms used various retinal image types as model input, such as optical coherence tomography (OCT) images (N = 15), fundus images (N = 6), and multi-modal imaging (N = 7). The predominant core method used was deep neural networks. All studies that reported externally validated algorithms were at high risk of bias mainly due to potential selection bias from either a two-gate design or the inappropriate exclusion of potentially eligible retinal images (or participants). Findings Only three of the 40 included algorithms were externally validated (7.5%, 3/40). The summary sensitivity and specificity were 0.94 (95% confidence interval (CI) 0.90 to 0.97) and 0.99 (95% CI 0.76 to 1.00), respectively, when compared to human graders (3 studies; 27,872 images; low-certainty evidence). The prevalence of images with eAMD ranged from 0.3% to 49%. Twenty-eight algorithms were reportedly either internally validated (20%, 8/40) or tested on a development set (50%, 20/40); the pooled sensitivity and specificity were 0.93 (95% CI 0.89 to 0.96) and 0.96 (95% CI 0.94 to 0.98), respectively, when compared to human graders (28 studies; 33,409 images; low-certainty evidence). We did not identify significant sources of heterogeneity among these 28 algorithms. Although algorithms using OCT images appeared more homogeneous and had the highest summary specificity (0.97, 95% CI 0.93 to 0.98), they were not superior to algorithms using fundus images alone (0.94, 95% CI 0.89 to 0.97) or multimodal imaging (0.96, 95% CI 0.88 to 0.99; P for meta-regression = 0.239). The median prevalence of images with eAMD was 30% (interquartile range [IQR] 22% to 39%). We did not include eight studies that described nine algorithms (one study reported two sets of algorithm results) to distinguish eAMD from normal images, images of other AMD, or other non-AMD retinal lesions in the meta-analysis. Five of these algorithms were generally based on smaller datasets (range 21 to 218 participants per study) yet with a higher prevalence of eAMD images (range 33% to 66%). Relative to human graders, the reported sensitivity in these studies ranged from 0.95 and 0.97, while the specificity ranged from 0.94 to 0.99. Similarly, using small datasets (range 46 to 106), an additional four algorithms for detecting eAMD from other retinal lesions showed high sensitivity (range 0.96 to 1.00) and specificity (range 0.77 to 1.00)., Authors' Conclusions: Low- to very low-certainty evidence suggests that an algorithm-based test may correctly identify most individuals with eAMD without increasing unnecessary referrals (false positives) in either the primary or the specialty care settings. There were significant concerns for applying the review findings due to variations in the eAMD prevalence in the included studies. In addition, among the included algorithm-based tests, diagnostic accuracy estimates were at risk of bias due to study participants not reflecting real-world characteristics, inadequate model validation, and the likelihood of selective results reporting. Limited quality and quantity of externally validated algorithms highlighted the need for high-certainty evidence. This evidence will require a standardized definition for eAMD on different imaging modalities and external validation of the algorithm to assess generalizability., (Copyright © 2024 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Published
2024
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49. Childhood emotional abuse and alcohol use disorders in a national Nepali women sample: The mediating role of borderline personality traits.

Author

Xie W, Emery CR, Liu AY, Ng SM, Choi AW, and Chui CH

Subjects
Humans, Female, Nepal, Adult, Alcoholism psychology, Alcoholism epidemiology, Emotional Abuse psychology, Emotional Abuse statistics & numerical data, Adult Survivors of Child Abuse psychology, Adult Survivors of Child Abuse statistics & numerical data, Middle Aged, Young Adult, Child, Borderline Personality Disorder psychology, Borderline Personality Disorder epidemiology
Abstract

While many studies have found an association between childhood emotional abuse and alcohol use disorders (AUD) during adulthood, underlying psychological mechanisms linking the two remain inadequately understood. Drawing on the developmental psychopathology perspective, this study examined the relationship between childhood emotional abuse and AUD during adulthood with a national sample of women in Nepal ( N = 1,100, M age = 37.73), focusing on the mediating role of borderline personality traits. Mediation analyses were performed using the Karlson-Holm-Breen (KHB) method and bootstrapping confidence intervals. Results indicated that Nepali women's borderline personality traits significantly mediated the relationship between childhood emotional abuse and AUD. Hence, emotional abuse in childhood increases the risk for AUD during adulthood for Nepali women by increasing the risk of borderline personality traits. Findings underscore the necessity of continued emphasis on developing and implementing early interventions for childhood emotional abuse and therapeutic interventions for borderline personality traits in reducing AUD among vulnerable women in Nepal.

Published
2024
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50. Mindfulness-based family psychoeducation intervention for caregivers of young adults with first-episode psychosis: results at 9-month follow-up.

Author

Zhang ZJ, Lo HHM, Ho WC, Lau ENS, Ng SM, Mak WWS, Wong SYS, Hung KSY, Lai IYS, Lo CSL, Wong JOY, Lui SSY, Siu CMW, Yan EWC, Chan SHW, Lin E, Wong GOC, Mak JWH, Tam HSW, and Tse IHH

Abstract

Objectives: To investigate the effects of a mindfulness-based family psychoeducation (MBFPE) intervention on caregivers and the young adults with first-episode psychosis in mental health care., Methods: Sixty-five caregivers were randomly assigned to the MBFPE program (n = 33) or an ordinary family psychoeducation (FPE) program (n = 32). Eighteen young adults in recovery (YAIR) also participated in the study. All of the participants completed the assessments before participating in the intervention (T1), after the intervention (T2), and at 9-month follow-up (T3)., Results: Intention-to-treat analyses were conducted. The caregivers reported a significant and large effect size on positive caregiving experiences based on a Time × Group analysis ( g = 0.862, p = 0.006). Among the YAIR participants, between-group differences were significant in their perceptions of caregivers' expressed emotions, including large effect sizes of perceived criticism ( g = 1.396, p = 0.049) and hostility ( g = 1.444, p = 0.043). Caregiver demographics, including age, education level, socioeconomic status, and number of family members, were found to moderate the effect sizes of the variables studied., Conclusion: This study provides evidence of the effects of MBFPE programs on the outcomes of caregivers and the young adults with first-episode psychosis in their care. Specifically, the MBFPE program in this study played a greater role in promoting positive caregiving experiences and changing caregivers' expressed emotions, especially their expressed criticism of YAIR, compared with the regular FPE program. Therefore, the application of mindfulness training to promote family care and YAIR recovery should be encouraged., Clinical Trial Registration: ClinicalTrials.gov, identifier NCT03688009., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Zhang, Lo, Ho, Lau, Ng, Mak, Wong, Hung, Lai, Lo, Wong, Lui, Siu, Yan, Chan, Lin, Wong, Mak, Tam and Tse.)

Published
2024
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