Search

Your search keyword '"Consortium, I"' showing total 46 results
Start Over Author "Consortium, I"
46 results on '"Consortium, I"'

1. Simulation-based Bayesian predictive probability of success for interim monitoring of clinical trials with competing event data: two case studies

Author

Micoli, Chiara, Crippa, Alessio, Connor, Jason T., Consortium, I-SPY COVID, Eklund, Martin, and Discacciati, Andrea

Subjects
Statistics - Methodology, Statistics - Applications
Abstract

Bayesian predictive probabilities of success (PPoS) use interim trial data to calculate the probability of trial success. These quantities can be used to optimize trial size or to stop for futility. In this paper, we describe a simulation-based approach to compute the PPoS for clinical trials with competing event data, for which no specific methodology is currently available. The proposed procedure hinges on modelling the joint distribution of time to event and event type by specifying Bayesian models for the cause-specific hazards of all event types. This allows the prediction of outcome data at the conclusion of the trial. The PPoS is obtained by numerically averaging the probability of success evaluated at fixed parameter values over the posterior distribution of the parameters. Our work is motivated by two randomised clinical trials: the I-SPY COVID phase II trial for the treatment of severe COVID-19 (NCT04488081) and the STHLM3 prostate cancer diagnostic trial (ISRCTN84445406), both of which are characterised by competing event data. We present different modelling alternatives for the joint distribution of time to event and event type and show how the choice of the prior distributions can be used to assess the PPoS under different scenarios. The role of the PPoS analyses in the decision making process for these two trials is also discussed., Comment: 13 pages, 2 tables, 2 figures, last two authors contributed equally to the work

Published
2024

2. Exome sequencing of ATP1A3-negative cases of alternating hemiplegia of childhood reveals SCN2A as a novel causative gene

Author

Panagiotakaki, Eleni, Tiziano, Francesco Danilo, Mikati, Mohamad A., Vijfhuizen, Lisanne S., Nicole5, Sophie, Lesca, Gaetan, Abiusi, Emanuela, Novelli, Agnese, Di Pietro, Lorena, AHC Consortium, I. B., Consortium, Iahcrc, Harder, Aster V. E., Walley, Nicole M., De Grandis, Elisa, Poulat, Anne-Lise, Des Portes, Vincent, Lépine, Anne, Nassogne, Marie-Cecile, Arzimanoglou, Alexi, Vavassori, Rosaria, Koenderink, Jan, Thompson, Christopher H., L. George Jr., Alfred, Gurrieri, Fiorella, van den Maagdenberg, Arn M. J. M., Heinzen, Erin L., Francesco D. Tiziano (ORCID:0000-0002-5545-6158), Emanuela Abiusi (ORCID:0000-0001-9028-012X), Agnese Novelli, Lorena Di Pietro (ORCID:0000-0001-5723-2169), Fiorella Gurrieri (ORCID:0000-0002-6775-5972), Panagiotakaki, Eleni, Tiziano, Francesco Danilo, Mikati, Mohamad A., Vijfhuizen, Lisanne S., Nicole5, Sophie, Lesca, Gaetan, Abiusi, Emanuela, Novelli, Agnese, Di Pietro, Lorena, AHC Consortium, I. B., Consortium, Iahcrc, Harder, Aster V. E., Walley, Nicole M., De Grandis, Elisa, Poulat, Anne-Lise, Des Portes, Vincent, Lépine, Anne, Nassogne, Marie-Cecile, Arzimanoglou, Alexi, Vavassori, Rosaria, Koenderink, Jan, Thompson, Christopher H., L. George Jr., Alfred, Gurrieri, Fiorella, van den Maagdenberg, Arn M. J. M., Heinzen, Erin L., Francesco D. Tiziano (ORCID:0000-0002-5545-6158), Emanuela Abiusi (ORCID:0000-0001-9028-012X), Agnese Novelli, Lorena Di Pietro (ORCID:0000-0001-5723-2169), and Fiorella Gurrieri (ORCID:0000-0002-6775-5972)

Published
2024
Full Text
View/download PDF

3. OP0102 IDENTIFICATION OF NEW RISK LOCI AND PATHWAYS INVOLVED IN GCA PATHOGENESIS BY A GENOME-WIDE STUDY

Author

Borrego-Yaniz, G., primary, Ortiz-Fernández, L., additional, Kerick, M., additional, Madrid-Paredes, A., additional, Vaglio, A., additional, Hernández-Rodríguez, J., additional, Mackie, S., additional, Castañeda, S., additional, Solans-Laqué, R., additional, Mestre, J., additional, Dasgupta, B., additional, Watts, R., additional, Khalidi, N., additional, Langford, C., additional, Ytterberg, S. R., additional, Beretta, L., additional, Govoni, M., additional, Emmi, G., additional, Cimmino, M. A., additional, Witte, T., additional, Neumann, T., additional, Holle, J., additional, Schönau, V., additional, Pugnet, G., additional, Papo, T., additional, Haroche, J., additional, Mahr, A., additional, Mouthon, L., additional, Molberg, Ø., additional, Diamantopoulos, A., additional, Voskuyl, A., additional, Daikeler, T., additional, Berger, C., additional, Molloy, E., additional, Blockmans, D., additional, Consortium, U. G., additional, Gca Consortium, I., additional, Ortego, N., additional, Brouwer, E., additional, Lamprecht, P., additional, Klapa, S., additional, Salvarani, C., additional, Merkel, P. A., additional, Cid, M. C., additional, González-Gay, M. A., additional, Morgan, A., additional, Martin Ibanez, J., additional, and Márquez, A., additional

Published
2023
Full Text
View/download PDF

5. MoCA in five Indian languages: A brief screening tool to diagnose dementia and MCI in a linguistically diverse setting

Author

Kaul, Subhash, primary, Paplikar, Avanthi, additional, Varghese, Feba, additional, Alladi, Suvarna, additional, Sharma, Meenakshi, additional, Dhaliwal, R. S., additional, Goyal, Sheetal, additional, Saroja, Aralikatte Onkarappa, additional, Arshad, Faheem, additional, Divyaraj, Gollahalli, additional, Ghosh, Amitabha, additional, Iyer, Gowri K., additional, J, Sunitha, additional, Khan, Arfa Banu, additional, Kandukuri, Rajmohan, additional, Mathew, Robert, additional, Mekala, Shailaja, additional, Menon, Ramshekhar, additional, Pauranik, Apoorva, additional, Nandi, Ranita, additional, Narayanan, Jwala, additional, Nehra, Ashima, additional, Padma, M. V., additional, Ramakrishnan, Subasree, additional, Sarath, Lekha, additional, Shah, Urvashi, additional, Tripathi, Manjari, additional, Sylaja, P. N., additional, Varma, Ravi Prasad, additional, Verma, Mansi, additional, Vishwanath, Yeshaswini, additional, and Consortium, I. C. M. R‐N. C. T. B, additional

Published
2022
Full Text
View/download PDF

9. A novel Alzheimer disease locus located near the gene encoding tau protein

Author

Jun, G, Ibrahim-Verbaas, C A, Vronskaya, M, Lambert, J-C, Chung, J, Naj, A C, Kunkle, B W, Wang, L-S, Bis, J C, Bellenguez, C, Harold, D, Lunetta, K L, Destefano, A L, Grenier-Boley, B, Sims, R, Beecham, G W, Smith, A V, Chouraki, V, Hamilton-Nelson, K L, Ikram, M A, Fievet, N, Denning, N, Martin, E R, Schmidt, H, Kamatani, Y, Dunstan, M L, Valladares, O, Laza, A R, Zelenika, D, Ramirez, A, Foroud, T M, Choi, S-H, Boland, A, Becker, T, Kukull, W A, van der Lee, S J, Pasquier, F, Cruchaga, C, Beekly, D, Fitzpatrick, A L, Hanon, O, Gill, M, Barber, R, Gudnason, V, Campion, D, Love, S, Bennett, D A, Amin, N, Berr, C, Tsolaki, Magda, Buxbaum, J D, Lopez, O L, Deramecourt, V, Fox, N C, Cantwell, L B, Tárraga, L, Dufouil, C, Hardy, J, Crane, P K, Eiriksdottir, G, Hannequin, D, Clarke, R, Evans, D, Mosley, T H, Jr., Letenneur, L, Brayne, C, Maier, W, De Jager, P, Emilsson, V, Dartigues, J-F, Hampel, H, Kamboh, M I, de Bruijn, R FAG, Tzourio, C, Pastor, P, Larson, E B, Rotter, J I, OʼDonovan, M C, Montine, T J, Nalls, M A, Mead, S, Reiman, E M, Jonsson, P V, Holmes, C, St George-Hyslop, P H, Boada, M, Passmore, P, Wendland, J R, Schmidt, R, Morgan, K, Winslow, A R, Powell, J F, Carasquillo, M, Younkin, S G, Jakobsdóttir, J, Kauwe, J SK, Wilhelmsen, K C, Rujescu, D, Nöthen, M M, Hofman, A, Jones, L, Consortium, I GAP, Haines, J L, Psaty, B M, Van Broeckhoven, C, Holmans, P, Launer, L J, Mayeux, R, Lathrop, M, Goate, A M, Escott-Price, V, Seshadri, S, Pericak-Vance, M A, Amouyel, P, Williams, J, van Duijn, C M, Schellenberg, G D, and Farrer, L A

Published
2016
Full Text
View/download PDF

11. Cerebral small vessel disease genomics and its implications across the lifespan

Author

Sargurupremraj, M., Suzuki, H., Jian, X.Q., Sarnowski, C., Evans, T.E., Bis, J.C., Eiriksdottir, G., Sakaue, S., Terzikhan, N., Habes, M., Zhao, W., Armstrong, N.J., Hofer, E., Yanek, L.R., Hagenaars, S.P., Kumar, R.B., Akker, E.B. van den, McWhirter, R.E., Trompet, S., Mishra, A., Saba, Y., Satizabal, C.L., Beaudet, G., Petit, L., Tsuchida, A., Zago, L., Schilling, S., Sigurdsson, S., Gottesman, R.F., Lewis, C.E., Aggarwal, N.T., Lopez, O.L., Smith, J.A., Hernandez, M.C.V., Grond, J. van der, Wright, M.J., Knol, M.J., Dorr, M., Thomson, R.J., Bordes, C., Grand, Q. le, Duperron, M.G., Smith, A.V., Knopman, D.S., Schreiner, P.J., Evans, D.A., Rotter, J.I., Beiser, A.S., Maniega, S.M., Beekman, M., Trollor, J., Stott, D.J., Vernooij, M.W., Wittfeld, K., Niessen, W.J., Soumare, A., Boerwinkle, E., Sidney, S., Turner, S.T., Davies, G., Thalamuthu, A., Volker, U., Buchem, M.A. van, Bryan, R.N., Dupuis, J., Bastin, M.E., Ames, D., Teumer, A., Amouyel, P., Kwok, J.B., Bulow, R., Deary, I.J., Schofield, P.R., Brodaty, H., Jiang, J.Y., Tabara, Y., Setoh, K., Miyamoto, S., Yoshida, K., Nagata, M., Kamatani, Y., Matsuda, F., Psaty, B.M., Bennett, D.A., Jager, P.L. de, Mosley, T.H., Sachdev, P.S., Schmidt, R., Warren, H.R., Evangelou, E., Tregouet, D.A., Ikram, M.A., Wen, W., DeCarli, C., Srikanth, V.K., Jukema, J.W., Slagboom, E.P., Kardia, S.L.R., Okada, Y., Mazoyer, B., Wardlaw, J.M., Nyquist, P.A., Mather, K.A., Grabe, H.J., Schmidt, H., Duijn, C.M. van, Gudnason, V., Longstreth, W.T., Launer, L.J., Lathrop, M., Seshadri, S., Tzourio, C., Adams, H.H., Matthews, P.M., Fornage, M., Debette, S., Int Network Thrombosis INVENT Cons, and Int Headache Genomics Consortium I

Subjects
Adult, Male, Science, BLOOD-PRESSURE, Risk Assessment, behavioral disciplines and activities, GENETIC ARCHITECTURE, Young Adult, Alzheimer Disease, Risk Factors, mental disorders, WHITE-MATTER HYPERINTENSITIES, WIDE ASSOCIATION, Humans, International Headache Genomics Consortium (IHGC), CELL-TYPES, Medical History Taking, METAANALYSIS, AGING RESEARCH, Aged, RISK, Aged, 80 and over, Science & Technology, Mendelian Randomization Analysis, Middle Aged, COGNITIVE IMPAIRMENT, White Matter, Multidisciplinary Sciences, Stroke, Diffusion Tensor Imaging, Genetic Loci, Cerebral Small Vessel Diseases, Hypertension, MENDELIAN RANDOMIZATION, Science & Technology - Other Topics, Female, International Network against Thrombosis (INVENT) Consortium, Genome-Wide Association Study
Abstract

White matter hyperintensities (WMH) are the most common brain-imaging feature of cerebral small vessel disease (SVD), hypertension being the main known risk factor. Here, we identify 27 genome-wide loci for WMH-volume in a cohort of 50,970 older individuals, accounting for modification/confounding by hypertension. Aggregated WMH risk variants were associated with altered white matter integrity (p=2.5x10-7) in brain images from 1,738 young healthy adults, providing insight into the lifetime impact of SVD genetic risk. Mendelian randomization suggested causal association of increasing WMH-volume with stroke, Alzheimer-type dementia, and of increasing blood pressure (BP) with larger WMH-volume, notably also in persons without clinical hypertension. Transcriptome-wide colocalization analyses showed association of WMH-volume with expression of 39 genes, of which four encode known drug targets. Finally, we provide insight into BP-independent biological pathways underlying SVD and suggest potential for genetic stratification of high-risk individuals and for genetically-informed prioritization of drug targets for prevention trials. White matter hyperintensities (WMH) are a common brain-imaging feature of cerebral small vessel disease. Here, the authors carry out a GWAS and followup analyses for WMH-volume, implicating several variants with potential for risk stratification and drug targeting.

Published
2020

12. A genomic catalog of Earth’s microbiomes

Author

Nayfach, S., Roux, S., Seshadri, R., Udwary, D., Varghese, N., Schulz, F., Wu, D., Paez-Espino, D., Chen, I., Huntemann, M., Palaniappan, K., Ladau, J., Mukherjee, S., Reddy, T., Nielsen, T., Kirton, E., Faria, J., Edirisinghe, J., Henry, C., Jungbluth, S., Chivian, D., Dehal, P., Wood-Charlson, E., Arkin, A., Tringe, S., Visel, A., Abreu, H., Acinas, S., Allen, E., Allen, M., Alteio, L., Andersen, G., Anesio, A., Attwood, G., Avila-Magaña, V., Badis, Y., Bailey, J., Baker, B., Baldrian, P., Barton, H., Beck, D., Becraft, E., Beller, H., Beman, J., Bernier-Latmani, R., Berry, T., Bertagnolli, A., Bertilsson, S., Bhatnagar, J., Bird, J., Blanchard, J., Blumer-Schuette, S., Bohannan, B., Borton, M., Brady, A., Brawley, S., Brodie, J., Brown, S., Brum, J., Brune, A., Bryant, D., Buchan, A., Buckley, D., Buongiorno, J., Cadillo-Quiroz, H., Caffrey, S., Campbell, A., Campbell, B., Carr, S., Carroll, J., Cary, S., Cates, A., Cattolico, R., Cavicchioli, R., Chistoserdova, L., Coleman, M., Constant, P., Conway, J., Mac Cormack, W., Crowe, S., Crump, B., Currie, C., Daly, R., DeAngelis, K., Denef, V., Denman, S., Desta, A., Dionisi, H., Dodsworth, J., Dombrowski, N., Donohue, T., Dopson, M., Driscoll, T., Dunfield, P., Dupont, C., Dynarski, K., Edgcomb, V., Edwards, E., Elshahed, M., Figueroa, I., Flood, B., Fortney, N., Fortunato, C., Francis, C., Gachon, C., Garcia, S., Gazitua, M., Gentry, T., Gerwick, L., Gharechahi, J., Girguis, P., Gladden, J., Gradoville, M., Grasby, S., Gravuer, K., Grettenberger, C., Gruninger, R., Guo, J., Habteselassie, M., Hallam, S., Hatzenpichler, R., Hausmann, B., Hazen, T., Hedlund, B., Henny, C., Herfort, L., Hernandez, M., Hershey, O., Hess, M., Hollister, E., Hug, L., Hunt, D., Jansson, J., Jarett, J., Kadnikov, V., Kelly, C., Kelly, R., Kelly, W., Kerfeld, C., Kimbrel, J., Klassen, J., Konstantinidis, K., Lee, L., Li, W., Loder, A., Loy, A., Lozada, M., MacGregor, B., Magnabosco, C., Maria da Silva, A., McKay, R., McMahon, K., McSweeney, C., Medina, M., Meredith, L., Mizzi, J., Mock, T., Momper, L., Moran, M., Morgan-Lang, C., Moser, D., Muyzer, G., Myrold, D., Nash, M., Nesbø, C., Neumann, A., Neumann, R., Noguera, D., Northen, T., Norton, J., Nowinski, B., Nüsslein, K., O’Malley, M., Oliveira, R., Maia de Oliveira, V., Onstott, T., Osvatic, J., Ouyang, Y., Pachiadaki, M., Parnell, J., Partida-Martinez, L., Peay, K., Pelletier, D., Peng, X., Pester, M., Pett-Ridge, J., Peura, S., Pjevac, P., Plominsky, A., Poehlein, A., Pope, P., Ravin, N., Redmond, M., Reiss, R., Rich, V., Rinke, C., Rodrigues, J., Rodriguez-Reillo, W., Rossmassler, K., Sackett, J., Salekdeh, G., Saleska, S., Scarborough, M., Schachtman, D., Schadt, C., Schrenk, M., Sczyrba, A., Sengupta, A., Setubal, J., Shade, A., Sharp, C., Sherman, D., Shubenkova, O., Sierra-Garcia, I., Simister, R., Simon, H., Sjöling, S., Slonczewski, J., Correa de Souza, R., Spear, J., Stegen, J., Stepanauskas, R., Stewart, F., Suen, G., Sullivan, M., Sumner, D., Swan, B., Swingley, W., Tarn, J., Taylor, G., Teeling, H., Tekere, M., Teske, A., Thomas, T., Thrash, C., Tiedje, J., Ting, C., Tully, B., Tyson, G., Ulloa, O., Valentine, D., Van Goethem, M., VanderGheynst, J., Verbeke, T., Vollmers, J., Vuillemin, A., Waldo, N., Walsh, D., Weimer, B., Whitman, T., van der Wielen, P., Wilkins, M., Williams, T., Woodcroft, B., Woolet, J., Wrighton, K., Ye, J., Young, E., Youssef, N., Yu, F., Zemskaya, T., Ziels, R., Woyke, T., Mouncey, N., Ivanova, N., Kyrpides, N., Eloe-Fadrosh, E., Consortium, I., and Agencia Estatal de Investigación (España)

Subjects
Resource, Life sciences, biology, Biomedical Engineering, FILOGENIA, Bioengineering, Genomics, Biology, Microbiology, Applied Microbiology and Biotechnology, Genome, purl.org/becyt/ford/1 [https], 03 medical and health sciences, ddc:570, EARTH MICROBIOME PROJECT, Microbiome, purl.org/becyt/ford/1.6 [https], 030304 developmental biology, 2. Zero hunger, 0303 health sciences, 030306 microbiology, Phylum, 15. Life on land, biology.organism_classification, Computational biology and bioinformatics, Phylogenetic diversity, Evolutionary biology, Earth Microbiome Project, Molecular Medicine, Evolutionary ecology, MAGS, GENOMICS, Biotechnology, Archaea, MICROBIAL DIVERSITY
Abstract

13 pages, 5 figures, supplementary information https://doi.org/10.1038/s41587-020-0718-6.-- Data availability: All available metagenomic data, bins and annotations are available through the IMG/M portal (https://img.jgi.doe.gov/). Bulk download for the 52,515 MAGs is available at https://genome.jgi.doe.gov/GEMs and https://portal.nersc.gov/GEM. Genome-scale metabolic models for the nonredundant, high-quality GEMs are summarized at https://doi.org/10.25982/53247.64/1670777 and available in KBase (https://narrative.kbase.us/#org/jgimags). IMG/M identifiers of all metagenomes binned, including detailed information for each metagenome, are available in Supplementary Table 1.-- The pipeline used to generate the metagenome bins is available at https://bitbucket.org/berkeleylab/metabat/src/master/, Publisher Correction: A genomic catalog of Earth’s microbiomes; Nature Biotechnology 39: 520 (2021); https://doi.org/10.1038/s41587-020-00769-4, The reconstruction of bacterial and archaeal genomes from shotgun metagenomes has enabled insights into the ecology and evolution of environmental and host-associated microbiomes. Here we applied this approach to >10,000 metagenomes collected from diverse habitats covering all of Earth’s continents and oceans, including metagenomes from human and animal hosts, engineered environments, and natural and agricultural soils, to capture extant microbial, metabolic and functional potential. This comprehensive catalog includes 52,515 metagenome-assembled genomes representing 12,556 novel candidate species-level operational taxonomic units spanning 135 phyla. The catalog expands the known phylogenetic diversity of bacteria and archaea by 44% and is broadly available for streamlined comparative analyses, interactive exploration, metabolic modeling and bulk download. We demonstrate the utility of this collection for understanding secondary-metabolite biosynthetic potential and for resolving thousands of new host linkages to uncultivated viruses. This resource underscores the value of genome-centric approaches for revealing genomic properties of uncultivated microorganisms that affect ecosystem processes, This work was conducted by the US DOE Joint Genome Institute, a DOE Office of Science User Facility (contract no. DE-AC02–05CH11231), and used resources of the National Energy Research Scientific Computing Center, which is supported by the Office of Science of the US DOE (contract no. DE-AC02–05CH11231). This work was also supported as part of the Genomic Sciences Program DOE Systems Biology KBase (award nos. DE-AC02-05CH11231, DE-AC02-06CH11357, DE-AC05-00OR22725, and DE-AC02-98CH10886).-- With the funding support of the ‘Severo Ochoa Centre of Excelle

Published
2020

13. N-3 fatty acid biomarkers and incident type 2 diabetes: An individual participant-level pooling project of 20 prospective cohort studies.

Author

Qian F., Ardisson Korat A.V., Imamura F., Marklund M., Tintle N., Virtanen J.K., Zhou X., Bassett J.K., Lai H., Hirakawa Y., Chien K.-L., Wood A.C., Lankinen M., Murphy R.A., Samieri C., Pertiwi K., de Mello V.D., Guan W., Forouhi N.G., Wareham N., Consortium I., Hu F.B., Riserus U., Lind L., Harris W.S., Shadyab A.H., Robinson J.G., Steffen L.M., Hodge A., Giles G.G., Ninomiya T., Uusitupa M., Tuomilehto J., Lindstrom J., Laakso M., Siscovick D.S., Helmer C., Geleijnse J.M., Wu J.H.Y., Fretts A., Lemaitre R.N., Micha R., Mozaffarian D., Sun Q., Qian F., Ardisson Korat A.V., Imamura F., Marklund M., Tintle N., Virtanen J.K., Zhou X., Bassett J.K., Lai H., Hirakawa Y., Chien K.-L., Wood A.C., Lankinen M., Murphy R.A., Samieri C., Pertiwi K., de Mello V.D., Guan W., Forouhi N.G., Wareham N., Consortium I., Hu F.B., Riserus U., Lind L., Harris W.S., Shadyab A.H., Robinson J.G., Steffen L.M., Hodge A., Giles G.G., Ninomiya T., Uusitupa M., Tuomilehto J., Lindstrom J., Laakso M., Siscovick D.S., Helmer C., Geleijnse J.M., Wu J.H.Y., Fretts A., Lemaitre R.N., Micha R., Mozaffarian D., and Sun Q.

Abstract

OBJECTIVE Prospective associations between n-3 fatty acid biomarkers and type 2 diabetes (T2D) risk are not consistent in individual studies. We aimed to summarize the prospective associations of biomarkers of a-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) with T2D risk through an individual participant-level pooled analysis. RESEARCH DESIGN AND METHODS For our analysis we incorporated data from a global consortium of 20 prospective studies from 14 countries. We included 65,147 participants who had blood measurements of ALA, EPA, DPA, or DHA and were free of diabetes at baseline. De novo harmonized analyses were performed in each cohort following a prespecified protocol, and cohort-specific associations were pooled using inverse variance-weighted meta-analysis. RESULTS A total of 16,693 incident T2D cases were identified during follow-up (median follow-up ranging from 2.5 to 21.2 years). In pooled multivariable analysis, per interquintile range (difference between the 90th and 10th percentiles for each fatty acid), EPA, DPA, DHA, and their sum were associated with lower T2D incidence, with hazard ratios (HRs) and 95% CIs of 0.92 (0.87, 0.96), 0.79 (0.73, 0.85), 0.82 (0.76, 0.89), and 0.81 (0.75, 0.88), respectively (all P < 0.001). ALA was not associated with T2D (HR 0.97 [95% CI 0.92, 1.02]) per interquintile range. Associations were robust across prespecified subgroups as well as in sensitivity analyses. CONCLUSIONS Highercirculating biomarkers of seafood-derivedn-3 fattyacids, including EPA,DPA, DHA, and their sum, were associated with lower risk of T2D in a global consortium of prospective studies. The biomarker of plant-derived ALA was not significantly associated with T2D risk.Copyright © 2021 by the American Diabetes Association.

Published
2021

15. OC07.03: Automated cortical analysis from third‐dimensional second trimester ultrasound scans.

Author

Wyburd, M.K., Consortium, I., Jenkinson, M., and Namburete, A.

Subjects
*MACHINE learning, *TEMPORAL lobe, *DEEP learning, *INSULAR cortex, *SURFACE area
Abstract

This article, titled "OC07.03: Automated cortical analysis from third-dimensional second trimester ultrasound scans," describes a study that aimed to analyze the cortical development of healthy fetuses between 18+0 and 26+6 gestational weeks using a novel, fast, automated method. The researchers used a deep learning algorithm to extract the cortical plate from 3D ultrasound scans and measured global and local cortical properties. The results showed consistent measurements of cortical volume, surface area, and 3D Sylvian Fissure depth, with the insula showing the fastest rate of deepening and thickening. The study demonstrates the potential for characterizing the developing cortex in 3D from ultrasound scans and enables future cohort comparisons. [Extracted from the article]

Published
2024
Full Text
View/download PDF

16. Intimate Partner Violence Prior to and During COVID-19 Measures in 30 Countries: A Global Cross-Sectional Study From the I-SHARE Consortium

Author

Campbell, Linda, primary, Tan, Rayner K. J., additional, Uhlich, Maximiliane, additional, Francis, Joel M., additional, Mark, Kristen, additional, Miall, Naomi, additional, Eleuteri, Stefano, additional, Gabster, Amanda, additional, Shamu, Simukai, additional, Plášilová, Leona, additional, Kemigisha, Elizabeth, additional, Olumide, Adesola, additional, Kosana, Priya, additional, Hurtado-Murillo, Felipe, additional, Larsson, Elin C., additional, Cleeve, Amanda, additional, Calvo González, Soraya, additional, Perrotta, Gabriela, additional, Fernández Albamonte, Victoria, additional, Blanco, Lucía, additional, Schröder, Johanna, additional, Adebayo, Adedamola, additional, Hendriks, Jacqueline, additional, Saltis, Hanna, additional, Marks, Michael, additional, Wu, Dan, additional, Esho, Tammary, additional, Briken, Peer, additional, Hlatshwako, Takhona Grace, additional, Ryan, Rebecca, additional, Daliana Nik Farid, Nik, additional, Gomez Bravo, Raquel, additional, Van de Velde, Sarah, additional, Tucker, Joseph D., additional, and Consortium, I-SHARE Research, additional

Published
2021
Full Text
View/download PDF

17. International Guillain-Barré Syndrome Outcome Study

Author

Jacobs, B, van den Berg, B, Verboon, C, Chavada, G, Cornblath, D, Gorson, K, Harbo, T, Hartung, H, Hughes, R, Kusunoki, S, van Doorn, P, Willison, H, Consortium, I, van Woerkom, M, Roodbol, J, Reisin, R, Reddel, S, Islam, Z, Islam, B, Mohammad, Q, van den Bergh, P, Feasby, T, Wang, Y, Péréon, Y, Lehmann, H, Dardiotis, E, Nobile Orazio, E, Shahrizaila, N, Bateman, K, Illa, I, Querol, L, Hsieh, S, Davidson, A, Addington, J, Ajroud Driss, S, Andersen, H, Antonini, G, Attarian, S, Badrising, U, Barroso, F, Benedetti, L, Beronio, A, Bianco, M, Binda, D, Briani, C, Bürmann, J, Bella, I, Bertorini, T, Bhavaraju Sanka, R, Brannagan, T, Busby, M, Butterworth, S, Campagnolo, M, Casasnovas, C, Cavaletti, G, Chao, C, Chen, S, Chetty, S, Claeys, K, Cohen, J, Conti, M, Cosgrove, J, Dalakas, M, Dimachkie, M, Dillmann, U, Domínguez González, C, Doppler, K, Dornonville de la Cour, C, Echaniz Laguna, A, Eftimov, F, Faber, C, Fazio, R, Fokke, C, Fujioka, T, Fulgenzi, E, Galassi, G, Garcia, T, Garnero, M, Garssen, M, Gijsbers, C, Gilchrist, J, Gilhuis, H, Goldstein, J, Goyal, N, Granit, V, Grapperon, A, Gutiérrez Gutiérrez, G, Gutmann, L, Hadden, R, Holbech, J, Holt, J, Homedes Pedret, C, Htut, M, Jellema, K, Jericó Pascual, I, Kaida, K, Karafiath, S, Katzberg, H, Kiers, L, Kieseier, B, Kimpinski, K, Kleyweg, R, Kokubun, N, Kolb, N, Kuitwaard, K, Kuwabara, S, Kwan, J, Ladha, S, Landschoff Lassen, L, Lawson, V, Ledingham, D, Léon Cejas, L, Luciano, C, Lucy, S, Lunn, M, Magot, A, Manji, H, Marchesoni, C, Marfia, Ga, Márquez Infante, C, Martinez Hernandez, E, Mataluni, G, Mattiazi, M, Mcdermott, C, Meekins, G, Miller, J, Monges, M, Montero, M, Morís de la Tassa, G, Nascimbene, C, Neumann, C, Nowak, R, Orizaola Balaguer, P, Osei Bonsu, M, Pan, E, Pardo Fernandez, J, Pasnoor, M, Pulley, M, Rajabally, Y, Rinaldi, S, Ritter, C, Roberts, R, Rojas Marcos, I, Rudnicki, S, Sachs, G, Samijn, J, Santoro, L, Saperstein, D, Savransky, A, Schneider, H, Schenone, A, Sedano Tous, M, Sekiguchi, Y, Sheikh, K, Silvestri, N, Sindrup, S, Sommer, C, Stein, B, Stino, A, Spyropoulos, A, Srinivasan, J, Suzuki, H, Taylor, S, Tankisi, H, Tigner, D, Twydell, P, Valzania, F, van Damme, P, van der Kooi, A, van Dijk, G, van der Ree, T, van Koningsveld, R, Varrato, J, Vermeij, F, Verschuuren, J, Visser, L, Vytopil, M, Waheed, W, Wilken, M, Wilkerson, C, Wirtz, P, Yamagishi, Y, Yiu, E, Zhou, L, Zivkovic, S, Immunology, Neurology, Jacobs, B, van den Berg, B, Verboon, C, Chavada, G, Cornblath, D, Gorson, K, Harbo, T, Hartung, H, Hughes, R, Kusunoki, S, van Doorn, P, Willison, H, van Woerkom, M, Roodbol, J, Reisin, R, Reddel, S, Islam, Z, Islam, B, Mohammad, Q, van den Bergh, P, Feasby, T, Wang, Y, Pã©rã©on, Y, Lehmann, H, Dardiotis, E, Nobile Orazio, E, Shahrizaila, N, Bateman, K, Illa, I, Querol, L, Hsieh, S, Davidson, A, Addington, J, Ajroud Driss, S, Andersen, H, Antonini, G, Attarian, S, Badrising, U, Barroso, F, Benedetti, L, Beronio, A, Bianco, M, Binda, D, Briani, C, Bã¼rmann, J, Bella, I, Bertorini, T, Bhavaraju Sanka, R, Brannagan, T, Busby, M, Butterworth, S, Campagnolo, M, Casasnovas, C, Cavaletti, G, Chao, C, Chen, S, Chetty, S, Claeys, K, Cohen, J, Conti, M, Cosgrove, J, Dalakas, M, Dimachkie, M, Dillmann, U, Domínguez González, C, Doppler, K, Dornonville de la Cour, C, Echaniz Laguna, A, Eftimov, F, Faber, C, Fazio, R, Fokke, C, Fujioka, T, Fulgenzi, E, Galassi, G, Garcia, T, Garnero, M, Garssen, M, Gijsbers, C, Gilchrist, J, Gilhuis, H, Goldstein, J, Goyal, N, Granit, V, Grapperon, A, Gutiérrez Gutiérrez, G, Gutmann, L, Hadden, R, Holbech, J, Holt, J, Homedes Pedret, C, Htut, M, Jellema, K, Jericó Pascual, I, Kaida, K, Karafiath, S, Katzberg, H, Kiers, L, Kieseier, B, Kimpinski, K, Kleyweg, R, Kokubun, N, Kolb, N, Kuitwaard, K, Kuwabara, S, Kwan, J, Ladha, S, Landschoff Lassen, L, Lawson, V, Ledingham, D, Léon Cejas, L, Luciano, C, Lucy, S, Lunn, M, Magot, A, Manji, H, Marchesoni, C, Marfia, G, Márquez Infante, C, Martinez Hernandez, E, Mataluni, G, Mattiazi, M, Mcdermott, C, Meekins, G, Miller, J, Monges, M, Montero, M, Morís de la Tassa, G, Nascimbene, C, Neumann, C, Nowak, R, Orizaola Balaguer, P, Osei Bonsu, M, Pan, E, Pardo Fernandez, J, Pasnoor, M, Pulley, M, Rajabally, Y, Rinaldi, S, Ritter, C, Roberts, R, Rojas Marcos, I, Rudnicki, S, Sachs, G, Samijn, J, Santoro, L, Saperstein, D, Savransky, A, Schneider, H, Schenone, A, Sedano Tous, M, Sekiguchi, Y, Sheikh, K, Silvestri, N, Sindrup, S, Sommer, C, Stein, B, Stino, A, Spyropoulos, A, Srinivasan, J, Suzuki, H, Taylor, S, Tankisi, H, Tigner, D, Twydell, P, Valzania, F, van Damme, P, van der Kooi, A, van Dijk, G, van der Ree, T, van Koningsveld, R, Varrato, J, Vermeij, F, Verschuuren, J, Visser, L, Vytopil, M, Waheed, W, Wilken, M, Wilkerson, C, Wirtz, P, Yamagishi, Y, Yiu, E, Zhou, L, Zivkovic, S, Rehabilitation medicine, Internal medicine, and ANS - Neuroinfection & -inflammation

Subjects
Male, Pediatrics, PROGNOSIS, diagnosis, International Cooperation, Guillain-Barré syndrome, biomarkers, outcome, prognosis, treatment, Guillain-Barre syndrome, Guillain-Barré syndrome, Neuroscience (all), Neurology (clinical), Cohort Studies, 0302 clinical medicine, Epidemiology, Outcome Assessment, Health Care, INFECTION, CRITERIA, 030212 general & internal medicine, General Neuroscience, Biobank, Observational Studies as Topic, diagnosi, Disease Progression, biomarker, Female, Settore MED/26 - Neurologia, medicine.symptom, prognosi, Cohort study, medicine.medical_specialty, Weakness, Guillain-Barre Syndrome, CLASSIFICATION, VALIDATION, 03 medical and health sciences, medicine, Humans, INTRAVENOUS IMMUNOGLOBULIN, Protocol (science), business.industry, Polyradiculoneuropathy, medicine.disease, ANTIBODIES, Observational study, business, COLLECTION, 030217 neurology & neurosurgery
Abstract

Guillain-Barré syndrome (GBS) is an acute polyradiculoneuropathy with a highly variable clinical presentation, course, and outcome. The factors that determine the clinical variation of GBS are poorly understood which complicates the care and treatment of individual patients. The protocol of the ongoing International GBS Outcome Study (IGOS), a prospective, observational, multicenter cohort study that aims to identify the clinical and biological determinants and predictors of disease onset, subtype, course and outcome of GBS is presented here. Patients fulfilling the diagnostic criteria for GBS, regardless of age, disease severity, variant forms, or treatment, can participate if included within 2 weeks after onset of weakness. Information about demography, preceding infections, clinical features, diagnostic findings, treatment, course, and outcome is collected. In addition, cerebrospinal fluid and serial blood samples for serum and DNA is collected at standard time points. The original aim was to include at least 1,000 patients with a follow-up of 1-3 years. Data are collected via a web-based data entry system and stored anonymously. IGOS started in May 2012 and by January 2017 included more than 1,400 participants from 143 active centers in 19 countries across 5 continents. The IGOS data/biobank is available for research projects conducted by expertise groups focusing on specific topics including epidemiology, diagnostic criteria, clinimetrics, electrophysiology, antecedent events, antibodies, genetics, prognostic modeling, treatment effects, and long-term outcome of GBS. The IGOS will help to standardize the international collection of data and biosamples for future research of GBS.

Published
2017
Full Text
View/download PDF

18. Low-frequency and rare-coding variation contributes to multiple sclerosis risk

Author

Consortium, I, Mitrovič, M, Patsopoulos, N, Beecham, A, Van Duijn, C, Karpe, F, and al., Et

Abstract

Multiple sclerosis is a complex neurological disease, with ∼20% of risk heritability attributable to common genetic variants, including >230 identified by genome-wide association studies. Multiple strands of evidence suggest that much of the remaining heritability is also due to additive effects of common variants rather than epistasis between these variants or mutations exclusive to individual families. Here, we show in 68,379 cases and controls that up to 5% of this heritability is explained by low-frequency variation in gene coding sequence. We identify four novel genes driving MS risk independently of common-variant signals, highlighting key pathogenic roles for regulatory T cell homeostasis and regulation, IFNγ biology, and NFκB signaling. As low-frequency variants do not show substantial linkage disequilibrium with other variants, and as coding variants are more interpretable and experimentally tractable than non-coding variation, our discoveries constitute a rich resource for dissecting the pathobiology of MS.

Published
2019
Full Text
View/download PDF

19. Abstract P2-11-04: Prognostic contribution of predicted sensitivity to endocrine therapy (SET) prior to neoadjuvant chemotherapy for stage II-III hormone receptor-positive and HER2-negative (HR+/HER2-) breast cancer

Author

Du, Lili, primary, Yau, Christina, additional, Brown-Swigart, Lamorna, additional, Gould, Rebekah, additional, Hirst, Gillian L, additional, Consortium, I-SPY, additional, van der Noordaa, Marieke, additional, Bedrosian, Isabelle, additional, Layman, Rachel M, additional, Valero, Vicente, additional, van't Veer, Laura, additional, Esserman, Laura, additional, and Symmans, W. Fraser, additional

Published
2020
Full Text
View/download PDF

20. Adherence to predefined dietary patterns and incident type 2 diabetes in European populations: EPIC-InterAct Study

Author

Kroeger, J, Schulze, MB, Romaguera, D, Guevara, M, Buijsse, B, Boeing, H, Beulens, JWJ, Feskens, EJM, Amiano, P, Ardanaz, E, Agnoli, C, Buckland, G, Clavel-Chapelon, F, Dahm, CC, Fagherazzi, G, Franks, PW, Kaaks, R, Key, TJ, Khaw, KT, Lajous, M, Mattiello, A, Menendez Garcia, V, Navarro, C, Nilsson, PM, Overvad, K, Palli, D, Ricceri, F, Rolandsson, O, Sanchez, M-J, Slimani, N, Spijkerman, AMW, Tjonneland, A, Tumino, R, van der A, DL, Langenberg, C, Sharp, SJ, Forouhi, NG, Riboli, E, Wareham, NJ, and Consortium, I

Subjects
Male, Questionnaires, Health Knowledge, Attitudes, Practice, Nutrition and Disease, Mediterranean diet, Endocrinology, Diabetes and Metabolism, Carbonated Beverages, Type 2 diabetes, Alternative Healthy Eating Index, Risk Factors, Voeding en Ziekte, Surveys and Questionnaires, Vegetables, Medicine, Prospective Studies, Dietary patterns, physical-activity, risk-factors, quality index, Incidence, Reduced rank regression, Middle Aged, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Europe, nutrition, Female, Dietary Proteins, Adult, medicine.medical_specialty, DASH diet, European Continental Ancestry Group, Case-cohort, Diet Surveys, Article, White People, dash diet, insulin-resistance, Beverages, Insulin resistance, Internal medicine, Diabetes mellitus, Dash, Internal Medicine, cancer, Humans, Refined grains, VLAG, Aged, business.industry, mediterranean diet, Feeding Behavior, fatty-acids, medicine.disease, Dietary Fats, Diet, Endocrinology, Diabetes Mellitus, Type 2, Case-Control Studies, Fruit, Sweetening Agents, Dairy Products, Food Habits, Energy Intake, business, chronic disease, Risk Reduction Behavior, Dietary Approaches to Stop Hypertension, Demography
Abstract

Aims/hypothesis Few studies have investigated the relationship between predefined dietary patterns and type 2 diabetes incidence; little is known about the generalisability of these associations. We aimed to assess the association between predefined dietary patterns and type 2 diabetes risk in European populations. Methods From among a case-cohort of 12,403 incident diabetes cases and 16,154 subcohort members nested within the prospective European Prospective Investigation into Cancer and Nutrition study, we used data on 9,682 cases and 12,595 subcohort participants from seven countries. Habitual dietary intake was assessed at baseline with country-specific dietary questionnaires. Two diet-quality scores (alternative Healthy Eating Index [aHEI], Dietary Approaches to Stop Hypertension [DASH] score) and three reduced rank regression (RRR)-derived dietary-pattern scores were constructed. Country-specific HRs were calculated and combined using a random-effects meta-analysis. Results After multivariable adjustment, including body size, the aHEI and DASH scores were not significantly associated with diabetes, although for the aHEI there was a tendency towards an inverse association in countries with higher mean age. We observed inverse associations of the three RRR-derived dietary-pattern scores with diabetes: HRs (95% CIs) for a 1-SD difference were 0.91 (0.86, 0.96), 0.92 (0.84, 1.01) and 0.87 (0.82, 0.92). Random-effects meta-analyses revealed heterogeneity between countries that was explainable by differences in the age of participants or the distribution of dietary intake. Conclusions/interpretation Adherence to specific RRR-derived dietary patterns, commonly characterised by high intake of fruits or vegetables and low intake of processed meat, sugar-sweetened beverages and refined grains, may lower type 2 diabetes risk. Electronic supplementary material The online version of this article (doi:10.1007/s00125-013-3092-9) contains peer-reviewed but unedited supplementary material, which is available to authorised users.

Published
2013
Full Text
View/download PDF

22. Clinical-Risk Factors that Influence an Optimal Hypomethylating Agents Treatment in Myelodysplastic Syndromes and Chronic Myelomonocytic Leukemia

Author

Iastrebner, M., primary, Lazzarino, C., additional, Nucifora, E., additional, Penchasky, D., additional, Fernandez, I., additional, Gusmao Moreno, B.G.M., additional, Rivas, M.M., additional, Espinosa, D., additional, Abello Polo, V., additional, Boada, M., additional, Enrico, A., additional, Araujo Schuster, S., additional, Agra, M., additional, Sarmiento, M., additional, Flores, G., additional, Alfonso, G., additional, Crisp, R., additional, Gusmao Moreno, B., additional, and Consortium, I., additional

Published
2017
Full Text
View/download PDF

23. Lower-Risk Patients that Required Hypomethylating Agents. A Multicentric Experience from Latin America

Author

Iastrebner, M., primary, Belli, C., additional, Lazzarino, C., additional, Fantl, D., additional, Pintos, N., additional, Bengio, R., additional, Prates, M.V., additional, Rosenhain, M., additional, Pose, J., additional, Celebrin, L., additional, Moro, D., additional, Garcia Rivello, H., additional, Grille, S., additional, Flores, G., additional, Rivas, M.M., additional, Enrico, A., additional, Abello Polo, V., additional, Araujo Schuster, S., additional, Arbelbide, J., additional, and Consortium, I., additional

Published
2017
Full Text
View/download PDF

25. Non-type I cystinuria caused by mutations in SLC7A9, encoding a subunit (bo,+AT) of rBAT

Author

Feliubadaló, L., Font, M., Purroy, J., Rousaud, F., Estivill, X., Nunes, V., Golomb, E., Centola, M., Aksentijevich, I., Kreiss, Y., Goldman, B., Pras, M., Kastner, D. L., Pras, E., Gasparini, P., Bisceglia, L., Beccia, E., Gallucci, M., Sanctis, L. d., Ponzone, A., Rizzoni, G. F., Zelante, L., Bassi, M. T., George, A. L., Manzoni, Marta, Grandi, A. D., Riboni, M., Endsley, J. K., Ballabio, A., Borsani, Giuseppe, Reig, N., Fernández, E., Estévez, R., Pineda, M., Torrents, D., Camps, M., Lloberas, J., Zorzano, A., Palacín, M., and Consortium, I. C.

Subjects
Male, Amino Acid Transport Systems, Sequence Homology, chemistry.chemical_compound, Models, Complementary, Missense mutation, Tissue Distribution, Frameshift Mutation, Genetics, Membrane Glycoproteins, COS cells, Cystinuria, Basic, Carrier Proteins, Mutation, Missense, Pedigree, Amino Acid, Italy, COS Cells, Female, Human, DNA, Complementary, Protein subunit, Molecular Sequence Data, Mutation, Missense, Cystine, Libya, Biology, Models, Biological, Chromosomes, Frameshift mutation, medicine, Animals, Humans, Amino Acid Sequence, Amino acid transporter, Gene, Pair 19, DNA, Jews, Biological, North America, Spain, Sequence Homology, Amino Acid, medicine.disease, Molecular biology, chemistry, Amino Acid Transport Systems, Basic, Chromosomes, Human, Pair 19
Abstract

Cystinuria (MIM 220100) is a common recessive disorder of renal reabsorption of cystine and dibasic amino acids. Mutations in SLC3A1, encoding rBAT, cause cystinuria type I (ref. 1), but not other types of cystinuria (ref. 2). A gene whose mutation causes non-type I cystinuria has been mapped by linkage analysis to 19q12-13.1 (Refs 3,4). We have identified a new transcript, encoding a protein (bo, +AT, for bo,+ amino acid transporter) belonging to a family of light subunits of amino acid transporters, expressed in kidney, liver, small intestine and placenta, and localized its gene (SLC7A9) to the non-type I cystinuria 19q locus. Co-transfection of bo,+AT and rBAT brings the latter to the plasma membrane, and results in the uptake of L-arginine in COS cells. We have found SLC7A9 mutations in Libyan-Jews, North American, Italian and Spanish non-type I cystinuria patients. The Libyan Jewish patients are homozygous for a founder missense mutation (V170M) that abolishes b o,+AT amino-acid uptake activity when co-transfected with rBAT in COS cells. We identified four missense mutations (G105R, A182T, G195R and G295R) and two frameshift (520insT and 596delTG) mutations in other patients. Our data establish that mutations in SLC7A9 cause non-type I cystinuria, and suggest that bo,+AT is the light subunit of rBAT.

Published
1999
Full Text
View/download PDF

26. Gene-set and multivariate genome-wide association analysis of oppositional defiant behavior subtypes in attention-deficit/hyperactivity disorder

Author

Aebi, M., Donkelaar, M.M.J. van, Poelmans, G.J.V., Buitelaar, J.K., Sonuga-Barke, E.J., Stringaris, A., Consortium, I., Faraone, S.V, Franke, B., Steinhausen, H.C., Hulzen, K.J.E. van, Aebi, M., Donkelaar, M.M.J. van, Poelmans, G.J.V., Buitelaar, J.K., Sonuga-Barke, E.J., Stringaris, A., Consortium, I., Faraone, S.V, Franke, B., Steinhausen, H.C., and Hulzen, K.J.E. van

Abstract

Contains fulltext : 167822.pdf (publisher's version ) (Open Access), Oppositional defiant disorder (ODD) is a frequent psychiatric disorder seen in children and adolescents with attention-deficit-hyperactivity disorder (ADHD). ODD is also a common antecedent to both affective disorders and aggressive behaviors. Although the heritability of ODD has been estimated to be around 0.60, there has been little research into the molecular genetics of ODD. The present study examined the association of irritable and defiant/vindictive dimensions and categorical subtypes of ODD (based on latent class analyses) with previously described specific polymorphisms (DRD4 exon3 VNTR, 5-HTTLPR, and seven OXTR SNPs) as well as with dopamine, serotonin, and oxytocin genes and pathways in a clinical sample of children and adolescents with ADHD. In addition, we performed a multivariate genome-wide association study (GWAS) of the aforementioned ODD dimensions and subtypes. Apart from adjusting the analyses for age and sex, we controlled for "parental ability to cope with disruptive behavior." None of the hypothesis-driven analyses revealed a significant association with ODD dimensions and subtypes. Inadequate parenting behavior was significantly associated with all ODD dimensions and subtypes, most strongly with defiant/vindictive behaviors. In addition, the GWAS did not result in genome-wide significant findings but bioinformatics and literature analyses revealed that the proteins encoded by 28 of the 53 top-ranked genes functionally interact in a molecular landscape centered around Beta-catenin signaling and involved in the regulation of neurite outgrowth. Our findings provide new insights into the molecular basis of ODD and inform future genetic studies of oppositional behavior. (c) 2015 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by Wiley Periodicals, Inc.

Published
2016

28. Genetic Testing for TMEM154 Mutations Associated with Lentivirus Susceptibility in Sheep

Author

Heaton, M. P., Kalbfleisch, T. S., Petrik, D. T., Simpson, B., Kijas, J. W., Clawson, M. L., Chitko-McKown, C. G., Harhay, G. P., Leymaster, K. A., and Consortium, I. S. G.

Abstract

In sheep, small ruminant lentiviruses cause an incurable, progressive, lymphoproliferative disease that affects millions of animals worldwide. Known as ovine progressive pneumonia virus (OPPV) in the U.S., and Visna/Maedi virus (VMV) elsewhere, these viruses reduce an animal’s health, productivity, and lifespan. Genetic variation in the ovine transmembrane protein 154 gene (TMEM154) has been previously associated with OPPV infection in U.S. sheep. Sheep with the ancestral TMEM154 haplotype encoding glutamate (E) at position 35, and either form of an N70I variant, were highly-susceptible compared to sheep homozygous for the K35 missense mutation. Our current overall aim was to characterize TMEM154 in sheep from around the world to develop an efficient genetic test for reduced susceptibility. The average frequency of TMEM154 E35 among 74 breeds was 0.51 and indicated that highly-susceptible alleles were present in most breeds around the world. Analysis of whole genome sequences from an international panel of 75 sheep revealed more than 1,300 previously unreported polymorphisms in a 62 kb region containing TMEM154 and confirmed that the most susceptible haplotypes were distributed worldwide. Novel missense mutations were discovered in the signal peptide (A13V) and the extracellular domains (E31Q, I74F, and I102T) of TMEM154. A matrix-assisted laser desorption/ionization–time-of flight mass spectrometry (MALDI-TOF MS) assay was developed to detect these and six previously reported missense and two deletion mutations in TMEM154. In blinded trials, the call rate for the eight most common coding polymorphisms was 99.4% for 499 sheep tested and 96.0% of the animals were assigned paired TMEM154 haplotypes (i.e., diplotypes). The widespread distribution of highly-susceptible TMEM154 alleles suggests that genetic testing and selection may improve the health and productivity of infected flocks.

Published
2013

29. Physical activity reduces the risk of incident type 2 diabetes in general and in abdominally lean and obese men and women: the EPIC-InterAct Study

Author

Ekelund, U, Palla, L, Brage, S, Franks, PW, Peters, T, Balkau, B, Diaz, MJT, Huerta, JM, Agnoli, C, Arriola, L, Ardanaz, E, Boeing, H, Clavel-Chapelon, F, Crowe, F, Fagherazzi, G, Groop, L, Hainaut, P, Johnsen, NF, Kaaks, R, Khaw, KT, Key, TJ, de Lauzon-Guillain, B, May, A, Monninkhof, E, Navarro, C, Nilsson, P, Ostergaard, JN, Norat, T, Overvad, K, Palli, D, Panico, S, Redondo, ML, Ricceri, F, Rolandsson, O, Romaguera, D, Romieu, I, Sanchez Perez, MJ, Slimani, N, Spijkerman, A, Teucher, B, Tjonneland, A, Travier, N, Tumino, R, Vos, W, Vigl, M, Sharp, S, Langenberg, C, Forouhi, N, Riboli, E, Feskens, E, Wareham, NJ, and Consortium, I

Subjects
Male, Nutrition and Disease, Endocrinology, Diabetes and Metabolism, body-mass index, Type 2 diabetes, Body Mass Index, Cohort Studies, Risk Factors, Surveys and Questionnaires, Voeding en Ziekte, Abdominal obesity, adiposity, Incidence, improves, Middle Aged, 10 european countries, Europe, fat distribution, Cohort, Female, Waist Circumference, medicine.symptom, medicine.medical_specialty, Waist, life-style, Motor Activity, Article, Internal medicine, Diabetes mellitus, Internal Medicine, medicine, accelerometry, Humans, insulin sensitivity, Case–cohort study, Genetic Predisposition to Disease, Obesity, heart-rate, Life Style, VLAG, Physical activity, business.industry, medicine.disease, Physical activity level, Diabetes Mellitus, Type 2, Incident diabetes, Physical therapy, business, Body mass index, Follow-Up Studies, mellitus
Abstract

Aims/hypothesis We examined the independent and combined associations of physical activity and obesity with incident type 2 diabetes in men and women. Methods The InterAct case–cohort study consists of 12,403 incident type 2 diabetes cases and a randomly selected subcohort of 16,154 individuals, drawn from a total cohort of 340,234 participants with 3.99 million person-years of follow-up. Physical activity was assessed by a four-category index. Obesity was measured by BMI and waist circumference (WC). Associations between physical activity, obesity and case-ascertained incident type 2 diabetes were analysed by Cox regression after adjusting for educational level, smoking status, alcohol consumption and energy intake. In combined analyses, individuals were stratified according to physical activity level, BMI and WC. Results A one-category difference in physical activity (equivalent to approximately 460 and 365 kJ/day in men and women, respectively) was independently associated with a 13% (HR 0.87, 95% CI 0.80, 0.94) and 7% (HR 0.93, 95% CI 0.89, 0.98) relative reduction in the risk of type 2 diabetes in men and women, respectively. Lower levels of physical activity were associated with an increased risk of diabetes across all strata of BMI. Comparing inactive with active individuals, the HRs were 1.44 (95% CI 1.11, 1.87) and 1.38 (95% CI 1.17, 1.62) in abdominally lean and obese inactive men, respectively, and 1.57 (95% CI 1.19, 2.07) and 1.19 (95% CI 1.01, 1.39) in abdominally lean and obese inactive women, respectively. Conclusions/interpretation Physical activity is associated with a reduction in the risk of developing type 2 diabetes across BMI categories in men and women, as well as in abdominally lean and obese men and women. Electronic supplementary material The online version of this article (doi:10.1007/s00125-012-2532-2) contains peer-reviewed but unedited supplementary material, which is available to authorised users.

Published
2012
Full Text
View/download PDF

33. Angiogenic, neurotrophic, and inflammatory system SNPs moderate the association between birth weight and ADHD symptom severity

Author

Smith, T.F., Anastopoulos, A.D., Garrett, M.E., Arias Vasquez, A., Franke, B., Oades, R.D., Sonuga-Barke, E., Asherson, P., Gill, M., Buitelaar, J.K., Sergeant, J.A., Kollins, S.H., Faraone, S.V., Ashley-Koch, A., Consortium, I., Smith, T.F., Anastopoulos, A.D., Garrett, M.E., Arias Vasquez, A., Franke, B., Oades, R.D., Sonuga-Barke, E., Asherson, P., Gill, M., Buitelaar, J.K., Sergeant, J.A., Kollins, S.H., Faraone, S.V., Ashley-Koch, A., and Consortium, I.

Abstract

Item does not contain fulltext, Low birth weight is associated with increased risk for Attention-Deficit/Hyperactivity Disorder (ADHD); however, the etiological underpinnings of this relationship remain unclear. This study investigated if genetic variants in angiogenic, dopaminergic, neurotrophic, kynurenine, and cytokine-related biological pathways moderate the relationship between birth weight and ADHD symptom severity. A total of 398 youth from two multi-site, family-based studies of ADHD were included in the analysis. The sample consisted of 360 ADHD probands, 21 affected siblings, and 17 unaffected siblings. A set of 164 SNPs from 31 candidate genes, representing five biological pathways, were included in our analyses. Birth weight and gestational age data were collected from a state birth registry, medical records, and parent report. Generalized Estimating Equations tested for main effects and interactions between individual SNPs and birth weight centile in predicting ADHD symptom severity. SNPs within neurotrophic (NTRK3) and cytokine genes (CNTFR) were associated with ADHD inattentive symptom severity. There was no main effect of birth weight centile on ADHD symptom severity. SNPs within angiogenic (NRP1 & NRP2), neurotrophic (NTRK1 & NTRK3), cytokine (IL16 & S100B), and kynurenine (CCBL1 & CCBL2) genes moderate the association between birth weight centile and ADHD symptom severity. The SNP main effects and SNP x birth weight centile interactions remained significant after adjusting for multiple testing. Genetic variability in angiogenic, neurotrophic, and inflammatory systems may moderate the association between restricted prenatal growth, a proxy for an adverse prenatal environment, and risk to develop ADHD. (c) 2014 Wiley Periodicals, Inc.

Published
2014

35. Predicting response to neoadjuvant therapy using tumor morphologic features on breast MRI

Author

Li, Wen, primary, Nadkarni, Rohan, additional, Newitt, David, additional, Onishi, Natsuko, additional, Gibbs, Jessica, additional, Wilmes, Lisa, additional, Joe, Bonnie, additional, Gennates, Efstathios, additional, Kornak, John, additional, Magbanua, Mark, additional, Veer, Laura van't, additional, LeStage, Barbara, additional, Consortium, I-SPY 2, additional, Esserman, Laura, additional, and Hylton, Nola, additional

Full Text
View/download PDF

36. Cherenkov Telescope Array : the World’s largest VHE gamma-ray observatory

Author

Roberta Zanin, H. Abdalla, H. Abe, S. Abe, A. Abusleme, F. Acero, A. Acharyya, V. Acin Portella, K. Ackley, R. Adam, C. Adams, S.S. Adhikari, I. Aguado Ruesga, I. Agudo, R. Aguilera, A. Aguirre Santaella, F. Aharonian, A. Alberdi, R. Alfaro, J. Alfaro, C. Alispach, R. Aloisio, R. Alves Batista, J.P. Amans, L. Amati, E. Amato, L. Ambrogi, G. Ambrosi, M. Ambrosio, R. Ammendola, J. Anderson, M. Anduze, E.O. Anguner, L.A. Antonelli, V. Antonuccio, P. Antoranz, R. Anutarawiramkul, J. Aragunde Gutierrez, C. Aramo, A. Araudo, M. Araya, A. Arbet Engels, C. Arcaro, V. Arendt, C. Armand, T. Armstrong, F. Arqueros, L. Arrabito, B. Arsioli, M. Artero, K. Asano, Y. Ascasibar, J. Aschersleben, M. Ashley, P. Attina, P. Aubert, C. B. Singh, D. Baack, A. Babic, M. Backes, V. Baena, S. Bajtlik, A. Baktash, C. Balazs, M. Balbo, O. Ballester, J. Ballet, B. Balmaverde, A. Bamba, R. Bandiera, A. Baquero Larriva, P. Barai, C. Barbier, V. Barbosa Martins, M. Barcelo, M. Barkov, M. Barnard, L. Baroncelli, U. Barres de Almeida, J.A. Barrio, D. Bastieri, P.I. Batista, I. Batkovic, C. Bauer, R. Bautista González, J. Baxter, U. Becciani, J. Becerra González, Y. Becherini, G. Beck, J. Becker Tjus, W. Bednarek, A. Belfiore, L. Bellizzi, R. Belmont, W. Benbow, D. Berge, E. Bernardini, M.I. Bernardos, K. Bernlöhr, A. Berti, M. Berton, B. Bertucci, V. Beshley, N. Bhatt, S. Bhattacharyya, W. Bhattacharyya, B. Y. Bi, G. Bicknell, N. Biederbeck, C. Bigongiari, A. Biland, R. Bird, E. Bissaldi, J. Biteau, M. Bitossi, O. Blanch, M. Blank, J. Blazek, J. Bobin, C. Boccato, F. Bocchino, C. Boehm, M. Bohacova, C. Boisson, J. Boix, J.P. Bolle, J. Bolmont, G. Bonanno, C. Bonavolontà, L. Bonneau Arbeletche, G. Bonnoli, P. Bordas, J. Borkowski, R. Bose, D. Bose, Z. Bosnjak, E. Bottacini, Markus Böttcher, M.T. Botticella, C. Boutonnet, F. Bouyjou, V. Bozhilov, E. Bozzo, L. Brahimi, C. Braiding, S. Brau Nogue, S. Breen, J. Bregeon, M. Breuhaus, A. Brill, W. Brisken, E. Brocato, A.M. Brown, K. Brügge, P. Brun, F. Brun, L. Brunetti, G. Brunetti, P. Bruno, A. Bruno, A. Bruzzese, N. Bucciantini, J. H. Buckley, R. Bühler, A. Bulgarelli, T. Bulik, M. Bünning, M. Bunse, M. Burton, A. Burtovoi, M. Buscemi, S. Buschjager, G. Busetto, J. Buss, K. Byrum, A. Caccianiga, F. Cadoux, A. Calanducci, C. Calderon, J. Calvo Tovar, R. A. Cameron, P. Campana, R. Canestrari, F. Cangemi, B. Cantlay, M. Capalbi, M. Capasso, M. Cappi, A. Caproni, R. Capuzzo Dolcetta, P. Caraveo, V. Cárdenas, L. Cardiel, M. Cardillo, C. Carlile, S. Caroff, R. Carosi, A. Carosi, E. Carquin, M. Carrere, J.M. Casandjian, S. Casanova, F. Cassol, F. Catalani, O. Catalano, D. Cauz, A. Ceccanti, C. Celestino Silva, K. Cerny, M. Cerruti, E. Chabanne, P. Chadwick, Y. Chai, P. Chambery, C. Champion, S. Chaty, A. Chen, K. Cheng, M. Chernyakova, G. Chiaro, A. Chiavassa, M. Chikawa, V.R. Chitnis, J. Chudoba, L. Chytka, S. Cikota, A. Circiello, P. Clark, M. Colak, E. Colombo, S. Colonges, A. Comastri, A. Compagnino, V. Conforti, E. Congiu, R. Coniglione, J. Conrad, F. Conte, J.L. Contreras, P. Coppi, R. Cornat, J. Coronado Blazquez, J. Cortina, A. Costa, H. Costantini, G. Cotter, B. Courty, S. Covino, S. Crestan, P. Cristofari, R. Crocker, J. Croston, K. Cubuk, O. Cuevas, X. Cui, G. Cusumano, S. Cutini, G. D'Amico, F. D'Ammando, P. D'Avanzo, P. Da Vela, M. Dadina, S. Dai, M. Dalchenko, M. Dall'Ora, M.K. Daniel, J. Dauguet, I. Davids, J. Davies, B. Dawson, A. De Angelis, A.E. de Araujo Carvalho, M. de Bony de Lavergne, G. De Cesare, F. de Frondat, I. de la Calle, E. de Gouveia Dal Pino, B. De Lotto, A. De Luca, D. De Martino, M. de Naurois, E. de Ona Wilhelmi, F. De Palma Persio, N. De Simone, V. de Souza Valle, E. Delagnes, G. Deleglise Reznicek, C. Delgado, A.G. Delgado Giler, J. Delgado Mengual Valle, Domenico Della Volpe, D. Depaoli, J. Devin, T. Di Girolamo, C. Di Giulio Pierro, L. Di Venere, C. Díaz, C. Dib, S. Diebold, S. Digel, A. Djannati Atai, J. Djuvsland, A. Dmytriiev, K. Docher, A. Domínguez, D. Dominis Prester, A. Donini, D. Dorner, M. Doro, Rita Cassia dos Anjos, J.L. Dournaux, T. Downes, G. Drake, H. Drass, D. Dravins, C. Duangchan, A. Duara, G. Dubus, L. Ducci, C. Duffy, D. Dumora, K. Dundas Mora, A. Durkalec, V.V. Dwarkadas, J. Ebr, C. Eckner, J. Eder, E. Edy, K. Egberts, S. Einecke, C. Eleftheriadis, D. Elsässer, G. Emery, D. Emmanoulopoulos, J.P. Ernenwein, M. Errando, P. Escarate, J. Escudero, C. Espinoza, S. Ettori, A. Eungwanichayapant, P. Evans, C. Evoli, M. Fairbairn, D. Falceta Goncalves, A. Falcone, V. Fallah Ramazanı, R. Falomo, K. Farakos, G. Fasola, A. Fattorini, Y. Favre, R. Fedora, E. Fedorova, K. Feijen, Q. Feng, G. Ferrand, G. Ferrara, O. Ferreira, M. Fesquet, E. Fiandrini, A. Fiasson, M. Filipovic, D. Fink, J.P. Finley, V. Fioretti, D.F.G. Fiorillo, M. Fiorini, S. Flis, H. Flores, L. Foffano, C. Fohr, M.V. Fonseca, L. Font, G. Fontaine, O. Fornieri, P. Fortin, L. Fortson, N. Fouque, B. Fraga, A. Franceschini, F.J. Franco, L. Freixas Coromina, L. Fresnillo, D. Fugazza, Y. Fujita, S. Fukami, Y. Fukazawa, D. Fulla, S. Funk, A. Furniss, S. Gabici, D. Gaggero, G. Galanti, P. Galdemard, Y. A. Gallant, D. Galloway, S. Gallozzi, V. Gammaldi, R. Garcia, L. E. García-Muñoz, E. Garcia Lopez, F. Gargano, C. Gargano, S. Garozzo, D. Gascon, T. Gasparetto, D. Gasparrini, H. Gasparyan, M. Gaug, N. Geffroy, A. Gent, S. Germani, A. Ghalumyan, A. Ghedina, G. Ghirlanda, F. Gianotti, S. Giarrusso, M. Giarrusso, G. Giavitto, B. Giebels, N. Giglietto, V. Gika, F. Gillardo, R. Gimenes, F. Giordano, E. Giro, M. Giroletti, Andrea Giuliani, M. Gjaja, J.F. Glicenstein, P. Gliwny, H. Goksu, P. Goldoni, J.L. Gomez, M.M. Gonzalez, Juan Manuel Gonzalez, K.S. Gothe, D. Gotz Coelho, T. Grabarczyk, R. Graciani, P. Grandi, G. Grasseau, D. Grasso, D. Green, J. Green, T. Greenshaw, P. Grespan, A. Grillo, M.H. Grondin, J. Grube, V. Guarino, B. Guest, O. Gueta, M. Günduz, S. Gunji, G. Gyuk, J. Hackfeld, D. Hadasch, L. Hagge, A. Hahn, J.E. Hajlaoui, A. Halim, P. Hamal, W. Hanlon, Y. Harada, M.J. Hardcastle, M. Harvey Collado, T. Haubold, A. Haupt, M. Havelka, K. Hayashi, M. Hayashida, H. He, L. Heckmann, M. Heller, F. Henault, Gilles Henri, G. Hermann, S. Hernández Cadena, J. Herrera Llorente, O. Hervet, J. Hinton, A. Hiramatsu, K. Hirotani, B. Hnatyk, R. Hnatyk, J.K. Hoang, D. H.H. Hoffmann, C. Hoischen, J. Holder, M. Holler, B. Hona, D. Horan, Dieter Horns, P. Horvath, J. Houles, M. Hrabovsky, D. Hrupec, Y. Huang, J.‑M. Huet, G. Hughes, G. Hull, T.B. Humensky, M. Hütten, M. Iarlori, J.M. Illa, R. Imazawa, T. Inada, F. Incardona, A. Ingallinera, S. Inoue, T. Inoue, Y. Inoue, F. Iocco, K. Ioka, M. Ionica, S. Iovenitti, A. Iriarte, K. Ishio, W. Ishizaki, Y. Iwamura, J. Jacquemier, M. Jacquemont, M. Jamrozy, P. Janecek, F. Jankowsky, A. JardinBlicq, C. Jarnot, P. Jean Martínez, L. Jocou, N. Jordana, M. Josselin, I. JungRichardt, F.J.P.A. Junqueira, C. Juramy Gilles, P. Kaaret, L.H.S. Kadowaki, M. Kagaya, R. Kankanyan, D. Kantzas, V. Karas, A. Karastergiou, S. Karkar, J. Kasperek, H. Katagiri, J. Kataoka, K. Katarzynski, S. Katsuda, N. Kawanaka, D. Kazanas, D. Kerszberg, B. Khélifi, M.C. Kherlakian, T.P. Kian, D.B. Kieda, T. Kihm, S. Kim, S. Kisaka, R. Kissmann, R. Kleijwegt, G. Kluge, W. Kluźniak, J. Knapp, A. Kobakhidze, Y. Kobayashi, B. Koch, J. Kocot, K. Kohri, N. Komin, A. Kong, K. Kosack, F. Krack, M. Krause, F. Krennrich, H. Kubo, V. N. Kudryavtsev, S. Kunwar, J. Kushida, P. Kushwaha, Barbera Parola, G. La Rosa, R. Lahmann, A. Lamastra, M. Landoni, D. Landriu, R.G. Lang, J. Lapington, P. Laporte, P. Lason, J. Lasuik, J. Lazendic Galloway, T. Le Flour, P. Le Sidaner, S. Leach, S.H. Lee, W.H. Lee, S. Lee Oliveira, A. Lemiere, M. Lemoine Goumard, J.P. Lenain, F. Leone, V. Leray, G. Leto, F. Leuschner, R. Lindemann, E. Lindfors, L. Linhoff, I. Liodakis, A. Lipniacka, M. Lobo, Thomas Lohse, S. Lombardi, A. Lopez, M. Lopez, R. Lopez Coto, F. Louis, M. Louys, F. Lucarelli, H. Ludwig Boudi, P.L. Luque Escamilla, M.C. Maccarone, E. Mach, A.J. Maciejewski, J. Mackey, P. Maeght, C. Maggio, G. Maier, P. Majumdar, M. Makariev, M. Mallamaci, R. Malta Nunes de Almeida, D. Malyshev, D. Mandat, G. Maneva, M. Manganaro, P. Manigot, K. Mannheim, N. Maragos, D. Marano, M. Marconi, A. Marcowith, M. Marculewicz, B. Marcun, J. Marin, N. Marinello, P. Marinos, S. Markoff, P. Marquez, G. Marsella, J. M. Martin, P. G. Martin, M. Martinez, G. Martinez, O. Martinez, H. Martinez Huerta, C. Marty, R. Marx, N. Masetti, P. Massimino, H. Matsumoto, N. Matthews, G. Maurin, W. Max Moerbeck, N. Maxted, M.N. Mazziotta, S.M. Mazzola, J.D. Mbarubucyeye, L. Mc Comb, I. McHardy, S. McKeague, S. McMuldroch, E. Medina, D. Medina Miranda, A. Melandri, C. Melioli, D. Melkumyan, S. Menchiari, S. Mereghetti, G. Merino Arevalo, E. Mestre, J.L. Meunier, T. Meures, S. Micanovic, M. Miceli, M. Michailidis, J. Michalowski, T. Miener, I. Mievre, J. D. Miller, T. Mineo, M. Minev, J.M. Miranda, A. Mitchell, T. Mizuno, B. A. Mode, R. Moderski, L. Mohrmann, E. Molinari, T. Montaruli, I. Monteiro, C. Moore, A. Moralejo, D. Morcuende Parrilla, E. Moretti, K. Mori, P. Moriarty, K. Morik, P. Morris, A. Morselli, K. Mosshammer, R. Mukherjee, J. Muller, C. Mundell, J. Mundet, T. Murach, A. Muraczewski, H. Muraishi, I. Musella, A. Musumarra, A. Nagai, S. Nagataki, T. Naito, T. Nakamori, K. Nakashima, K. Nakayama, N. Nakhjiri, G. Naletto, D. Naumann, L. Nava, M.A. Nawaz, H. Ndiyavala, D. Neise, L. Nellen, R. Nemmen, N. Neyroud, K. Ngernphat, T. Nguyen Trung, L. Nicastro, L. Nickel, J. Niemiec, D. Nieto, C. Nigro, M. Nikołajuk, D. Ninci, K. Noda, Y. Nogami, S. Nolan, R. P. Norris, D. Nosek, M. Nöthe, V. Novotny, S. Nozaki, F. Nunio, P. O'Brien, K. Obara, Y. Ohira, M. Ohishi, S. Ohm, T. Oka, N. Okazaki, A. Okumura, C. Oliver, G. Olivera, B. Olmi, M. Orienti, R. Orito, M. Orlandini, E. Orlando, J.P. Osborne, M. Ostrowski, N. Otte, E. Ovcharov, E. Owen, I. Oya, A. Ozieblo, M. Padovani, A. Pagliaro, A. Paizis, M. Palatiello, M. Palatka, E. Palazzi, J.‑L. Panazol, D. Paneque, S. Panny, Francesca Romana Pantaleo, M. Panter, M. Paolillo, A. Papitto, A. Paravac, J.M. Paredes, G. Pareschi, N. Parmiggiani, R.D. Parsons, P. Paśko, S. R. Patel, B. Patricelli, L. Pavletic, S. Pavy, A. Peer, M. Pecimotika, M.G. Pellegriti, P. Peñil Del Campo, A. Pepato, S. Perard, C. Perennes, M. Peresano, A. Perez Aguilera, J. Perez Romero, M.A. Perez Torres, M. Persic, P. O. Petrucci, O. Petruk, B. Peyaud, K. Pfrang, E. Pian, P. Piatteli, E. Pietropaolo, R. Pillera, D. Pimentel, F. Pintore, C. Pio Garcia, G. Pirola, F. Piron, S. Pita, M. Pohl, V. Poireau, A. Pollo, M. Polo, C. Pongkitivanichkul, J. Porthault, J. Powell, D. Pozo, R.R. Prado, E. Prandini, J. Prast, K. Pressard, G. Principe, N. Produit, D. Prokhorov, H. Prokoph, H. Przybilski, E. Pueschel, G. Pühlhofer, I. Puljak, M.L. Pumo, M. Punch, F. Queiroz, J. Quinn, A. Quirrenbach, P.J. Rajda, R. Rando, S. Razzaque, S. Recchia, P. Reichherzer, O. Reimer, A. Reisenegger, Q. Remy, M. Renaud, T. Reposeur, B. Reville, J.M. Reymond, J. Reynolds, D. Ribeiro, M. Ribo, G. Richards, J. Rico, F. Rieger, L. Riitano, M. Riquelme, D. Riquelme, S. Rivoire, V. Rizi, E. Roache, M. Roche, J. Rodriguez, G. Rodriguez Fernandez, J.C. Rodriguez Ramirez, J.J. Rodriguez Vazquez, G. Rojas, P. Romano, G. Romeo Lobato, C. Romoli, M. Roncadelli, J. Rosado, A. Rosales de Leon, G. Rowell, A. Rugliancich, J.E. Ruiz del Mazo, C. Rulten, C. Russell, F. Russo Hatlen, S. Safi Harb, L. Saha, V. Sahakian, S. Sailer, T. Saito, N. Sakaki, S. Sakurai, G. Salina, H. Salzmann, D. Sanchez, H. Sandaker, A. Sandoval, P. Sangiorgi, M. Sanguillon, H. Sano, M. Santander, A. Santangelo, R. Santos Lima, A. Sanuy, L. Sapozhnikov, T. Saric, S. Sarkar, H. Sasaki, N. Sasaki, Y. Sato, F.G. Saturni, M. Sawada, J. Schaefer, A. Scherer, J. Scherpenberg, P. Schipani, B. Schleicher, J. Schmoll, M. Schneider, H. Schoorlemmer, P. Schovanek, F. Schussler, B. Schwab, U. Schwanke, J. Schwarz, E. Sciacca, S. Scuderi, M. Seglar Arroyo, I. Seitenzahl, D. Semikoz, O. Sergijenko, J.E. Serna Franco, Karol Seweryn, V. Sguera, A. Shalchi, R.Y. Shang, P. Sharma, L. Sidoli, J. Sieiro, H. Siejkowski, A. Sillanpaa, B.B. Singh, K.K. Singh, A. Sinha, C. Siqueira, J. Sitarek, P. Sizun, V. Sliusar, D. Sobczynska, R.W. Sobrinho, H. Sol, G. Sottile, H. Spackman, S. Spencer, G. Spengler, D. Spiga, W. Springer, A. Stamerra, S. Stanic, R. Starling, Ł. Stawarz, Stanislav Stefanik, C. Stegmann, A. Steiner, S. Steinmassl, C. Stella, R. Sternberger, M. Sterzel, C. Stevens, B. Stevenson, T. Stolarczyk, G. Stratta, U. Straumann, J. Striskovic, M. Strzys, R. Stuik, M. Suchenek, Y. Sunada, Tiina Suomijarvi, T. Suric, H. Suzuki, P. Swierk, T. Szepieniec, K. Tachihara, G. Tagliaferri, H. Tajima, N. Tajima, D. Tak, H. Takahashi, M. Takahashi, J. Takata, R. Takeishi, T. Tam, M. Tanaka, T. Tanaka, S. Tanaka, M. Tavani, F. Tavecchio, T. Tavernier, A. Russ Taylor, L.A. Tejedor, P. Temnikov, K. Terauchi, J.C. Terrazas, R. Terrier, T. Terzic, M. Teshima, D. Thibaut, F. Thocquenne, W. Tian, L. Tibaldo, A. Tiengo, M. Tluczykont, C.J. Todero Peixoto, K. Toma, L. Tomankova, J. Tomastik, M. Tornikoski, D.F. Torres, E. Torresi, G. Tosti, L. Tosti, N. Tothill, F. Toussenel, G. Tovmassian, C. Trichard, M. Trifoglio, A. Trois, S. Truzzi, A. Tsiahina, B. Turk, A. Tutone, Y. Uchiyama, P. Utayarat, L. Vaclavek, M. Vacula, V. Vagelli, F. Vagnetti, J.A. Valdivia, M. Valentino, A. Valio, B. Vallage, P. Vallania Quispe, A.M. van den Berg, W. van Driel, C. van Eldik, C. van Rensburg, Brian van Soelen, J. Vandenbroucke, G. Vasileiadis, V. Vassiliev, M. Vazquez Acosta, M. Vecchi, A. Vega, J. Veh, P. Veitch, C. Venter, S. Ventura, S. Vercellone, V. Verguilov, G. Verna, S. Vernetto, V. Verzi, G.P. Vettolani, C. Veyssiere, I. Viale, A. Viana, N. Viaux, J. Vignatti, C.F. Vigorito, J. Villanueva, V. Vitale, V. Vittorini, V. Vodeb, N. Vogel, V. Voisin, S. Vorobiov, M. Vrastil, T. Vuillaume, S.J. Wagner, P. Wagner, K. Wakazono, S.P. Wakely, M. Ward, D. Warren, J. Watson, M. Wechakama, P. Wegner, A. Weinstein, C. Weniger, F. Werner, H. Wetteskind, M. L. White, A. Wierzcholska, S. Wiesand, R. Wijers, M. Wilkinson, M. Will, J. Williams, T. J. Williamson, A. Wolter, Y.W. Wong, M. Wood, T. Yamamoto, H. Yamamoto, Y. Yamane, R. Yamazaki, S. Yanagita, L. Yang, S. Yoo, T. Yoshida, T. Yoshikoshi, P. Yu, A. Yusafzai, Michael Zacharias, B. Zaldivar, L. Zampieri, R. Zanin, R. Zanmar Sanchez, D. Zaric, M. Zavrtanik, D. Zavrtanik, Andrzej Zdziarski, A. Zech, H. Zechlin, A. Zenin, A. Zerwekh, K. Ziętara, A. Zink, J. Ziolkowski, M. Zivec, A. Zmija, Współautorami artykułu są członkowie CTA Observatory, CTA Consortium i LST Collaboration w liczbie 1139, Astronomy, Research unit Nuclear & Hadron Physics, and Research unit Astroparticle Physics

Subjects
Physics, Observatory, Gamma ray, Astronomy
Abstract

Very-high Energy (VHE) gamma-ray astroparticle physics is a relatively young field, and observations over the past decade have surprisingly revealed almost two hundred VHE emitters which appear to act as cosmic particle accelerators. These sources are an important component of the Universe, influencing the evolution of stars and galaxies. At the same time, they also act as a probe of physics in the most extreme environments known - such as in supernova explosions, and around or after the merging of black holes and neutron stars. However, the existing experiments have provided exciting glimpses, but often falling short of supplying the full answer. A deeper understanding of the TeV sky requires a significant improvement in sensitivity at TeV energies, a wider energy coverage from tens of GeV to hundreds of TeV and a much better angular and energy resolution with respect to the currently running facilities. The next generation gamma-ray observatory, the Cherenkov Telescope Array Observatory (CTAO), is the answer to this need. In this talk I will present this upcoming observatory from its design to the construction, and its potential science exploitation. CTAO will allow the entire astronomical community to explore a new discovery space that will likely lead to paradigm-changing breakthroughs. In particular, CTA has an unprecedented sensitivity to short (sub-minute) timescale phenomena, placing it as a key instrument in the future of multi-messenger and multi-wavelength time domain astronomy. I will conclude the talk presenting the first scientific results obtained by the LST-1, the prototype of one CTAO telescope type - the Large-Sized Telescope, that is currently under commission., PoS: Proceedings of Science, 395, ISSN:1824-8039, Proceedings of 37th International Cosmic Ray Conference (ICRC2021)

Published
2022

37. Prevalence and co-occurrence of symptoms of mental and substance use disorders among people with HIV age 40 and older in low- and middle-income countries: a cross-sectional study.

Author

Parcesepe AM, Stockton M, Bernard C, Kanguya T, Kwobah EK, Lopez A, Murenzi G, Ross J, Minga A, Maruri F, Tlali M, Goodrich S, Perazzo H, Musabyimana F, Nimkar S, Lancaster K, and Consortium I

Subjects
Humans, Female, Male, Prevalence, Cross-Sectional Studies, Adult, Middle Aged, Aged, Comorbidity, Substance-Related Disorders epidemiology, HIV Infections epidemiology, HIV Infections drug therapy, HIV Infections complications, HIV Infections psychology, Mental Disorders epidemiology, Developing Countries statistics & numerical data
Abstract

Introduction: Due to the increased effectiveness of and access to antiretroviral therapy (ART), people with HIV (PWH) are living longer. As a result, the population of older PWH has increased. Mental and substance use disorders (MSDs) are common and frequently co-occurring among PWH and are associated with poor HIV care outcomes. Research into the prevalence and co-occurrence of MSDs among ageing PWH remains limited, particularly in low- and middle-income countries (LMICs)., Methods: We analysed data collected between 2020 and 2022 from the International epidemiology Databases to Evaluate AIDS (IeDEA) Sentinel Research Network cohort of PWH aged 40 years or older on ART at 11 HIV clinics in Brazil, Côte d'Ivoire, India, Kenya, Mexico, Uganda, Rwanda, Togo, Vietnam, Zambia and Zimbabwe. We estimated the prevalence and co-occurrence of unhealthy alcohol use (AUDIT-C ≥3 for women, ≥4 for men), unhealthy drug use (ASSIST >3 for cannabis, cocaine, amphetamines, inhalants, sedatives, hallucinogens and/or opioids), and moderate to severe symptoms of depression (PHQ-9 ≥10), anxiety (GAD-7 ≥10) and post-traumatic stress disorder (PTSD) (PCL-5 ≥33). Psychiatric multimorbidity was defined as having symptoms of two or more disorders assessed. Log binomial models assessed the association between socio-demographic and HIV care characteristics and symptoms of anxiety, depression, PTSD or unhealthy substance use., Results: Of 2821 participants, the prevalence of unhealthy alcohol and drug use was 21% and 5%, respectively. The prevalence of moderate to severe symptoms of depression, anxiety and PTSD was 14%, 9% and 6%, respectively. Overall, the prevalence of psychiatric multimorbidity was 11%. Among those with symptoms of at least one mental health or substance use outcome assessed (n = 1036), the prevalence of psychiatric multimorbidity was 31%. In binomial models, the prevalence of symptoms of depression and anxiety was higher, while the prevalence of unhealthy alcohol and drug use was lower among women than men., Conclusions: Unhealthy alcohol use and symptoms of depression were most commonly reported, among this cohort of PWH aged 40 or older across 11 LMICs. Integration of MSD screening and treatment into HIV care should be prioritized. The effectiveness and implementation of transdiagnostic or multi-focus mental health treatment approaches in HIV care settings should be examined., (© 2024 The Author(s). Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of International AIDS Society.)

Published
2024
Full Text
View/download PDF

38. Behavioural and neurodevelopmental characteristics of SYNGAP1.

Author

Bednarczuk N, Housby H, Lee IO, Consortium I, Skuse D, and Wolstencroft J

Subjects
Humans, Female, Male, Child, Adolescent, Child, Preschool, Developmental Disabilities genetics, Developmental Disabilities etiology, United Kingdom, Neurodevelopmental Disorders genetics, Cohort Studies, Phenotype, Epilepsy genetics, Seizures genetics, ras GTPase-Activating Proteins genetics, Intellectual Disability genetics, Intellectual Disability etiology
Abstract

Background: SYNGAP1 variants are associated with varying degrees of intellectual disability (ID), developmental delay (DD), epilepsy, autism, and behavioural difficulties. These features may also be observed in other monogenic conditions. There is a need to systematically compare the characteristics of SYNGAP1 with other monogenic causes of ID and DD to identify features unique to the SYNAGP1 phenotype. We aimed to contrast the neurodevelopmental and behavioural phenotype of children with SYNGAP1-related ID (SYNGAP1-ID) to children with other monogenic conditions and a matched degree of ID., Methods: Participants were identified from the IMAGINE-ID study, a UK-based, national cohort study of neuropsychiatric risk in children with ID of known genetic origin. Thirteen children with SYNGAP1 variants (age 4-16 years; 85% female) were matched (2:1) with 26 controls with other monogenic causes of ID for chronological and mental age, sex, socio-economic deprivation, adaptive behaviour, and physical health difficulties. Caregivers completed the Development and Wellbeing Assessment (DAWBA) and physical health questionnaires., Results: Our results demonstrate that seizures affected children with SYNGAP1-ID (84.6%) more frequently than the ID-comparison group (7.6%; p =  < 0.001). Fine-motor development was disproportionally impaired in SYNGAP1-ID, with 92.3% of children experiencing difficulties compared to 50% of ID-comparisons(p = 0.03). Gross motor and social development did not differ between the two groups. Children with SYNGAP1-ID were more likely to be non-verbal (61.5%) than ID-comparisons (23.1%; p = 0.01). Those children able to speak, spoke their first words at the same age as the ID-comparison group (mean = 3.25 years), yet achieved lower language competency (p = 0.04). Children with SYNGAP1-ID compared to the ID-comparison group were not more likely to meet criteria for autism (SYNGAP1-ID = 46.2%; ID-comparison = 30.7%; p = .35), attention-deficit hyperactivity disorder (15.4%;15.4%; p = 1), generalised anxiety (7.7%;15.4%; p = .49) or oppositional defiant disorder (7.7%;0%; p = .15)., Conclusion: For the first time, we demonstrate that SYNGAP1-ID is associated with fine motor and language difficulties beyond those experienced by children with other genetic causes of DD and ID. Targeted occupational and speech and language therapies should be incorporated early into SYNGAP1-ID management., (© 2024. The Author(s).)

Published
2024
Full Text
View/download PDF

39. Reliability of Morphological and PCR Methods for the Official Diagnosis of Aethina tumida (Coleoptera: Nitidulidae): A European Inter-Laboratory Comparison.

Author

Franco S, Cougoule N, Tison A, Del Cont A, Gastaldi C, Consortium I, and Duquesne V

Abstract

The Small Hive Beetle ( Aethina tumida Murray, 1867) is an invasive scavenger of honeybees. Originally endemic in sub-Saharan Africa, it is regulated internationally in order to preserve the areas still free from this species. To ensure the reliability of official diagnoses in case of introduction, an inter-laboratory comparison was organised on the identification of A. tumida by morphology and real-time PCR. Twenty-two National Reference Laboratories in Europe participated in the study and analysed 12 samples with adult coleopterans and insect larvae. The performance of the laboratories was evaluated in terms of sensitivity and specificity. Sensitivity was satisfactory for all the participants and both types of methods, thus fully meeting the diagnostic challenge of confirming all truly positive cases as positive. Two participants encountered specificity problems. For one, the anomaly was minor whereas, for the other, the issues concerned a larger number of results, especially real-time PCR, which probably were related to inexperience with this technique. The comparison demonstrated the reliability of official diagnosis, including the entire analytical process of A. tumida identification: from the first step of the analysis to the expression of opinions. The performed diagnostic tools, in parallel with field surveillance, are essential to managing A. tumida introduction.

Published
2021
Full Text
View/download PDF

40. ICTV Virus Taxonomy Profile: Caulimoviridae .

Author

Teycheney PY, Geering ADW, Dasgupta I, Hull R, Kreuze JF, Lockhart B, Muller E, Olszewski N, Pappu H, Pooggin MM, Richert-Pöggeler KR, Schoelz JE, Seal S, Stavolone L, Umber M, and Report Consortium I

Subjects
Genome, Viral, Plants virology, Virus Replication, Caulimoviridae classification, Caulimoviridae physiology, Caulimoviridae ultrastructure
Abstract

Caulimoviridae is a family of non-enveloped reverse-transcribing plant viruses with non-covalently closed circular dsDNA genomes of 7.1-9.8 kbp in the order Ortervirales . They infect a wide range of monocots and dicots. Some viruses cause economically important diseases of tropical and subtropical crops. Transmission occurs through insect vectors (aphids, mealybugs, leafhoppers, lace bugs) and grafting. Activation of infectious endogenous viral elements occurs in Musa balbisiana , Petunia hybrida and Nicotiana edwardsonii . However, most endogenous caulimovirids are not infectious. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Caulimoviridae, which is available at ictv.global/report/caulimoviridae.

Published
2020
Full Text
View/download PDF

41. ICTV Virus Taxonomy Profile: Finnlakeviridae .

Author

Mäntynen S, Laanto E, Sundberg LR, Poranen MM, Oksanen HM, and Report Consortium I

Subjects
Bacteriolysis, DNA, Single-Stranded genetics, DNA, Viral genetics, Genome, Viral, Virion chemistry, Virion ultrastructure, Virus Replication, Bacteriophages classification, Bacteriophages genetics, Bacteriophages physiology, Bacteriophages ultrastructure, DNA Viruses classification, DNA Viruses genetics, DNA Viruses physiology, DNA Viruses ultrastructure, Flavobacterium virology
Abstract

Finnlakeviridae is a family of icosahedral, internal membrane-containing bacterial viruses with circular, single-stranded DNA genomes. The family includes the genus, Finnlakevirus , with the species, Flavobacterium virus FLiP . Flavobacterium phage FLiP was isolated with its Gram-negative host bacterium from a boreal freshwater habitat in Central Finland in 2010. It is the first described single-stranded DNA virus with an internal membrane and shares minimal sequence similarity with other known viruses. The virion organization (pseudo T =21 dextro ) and major capsid protein fold (double-β-barrel) resemble those of Pseudoalteromonas phage PM2 (family Corticoviridae ), which has a double-stranded DNA genome. A similar major capsid protein fold is also found in other double-stranded DNA viruses in the kingdom Bamfordvirae . This is a summary of the International Committee on Taxonomy of Viruses (ICTV) report on the family Finnlakeviridae , which is available at ictv.global/report/finnlakeviridae.

Published
2020
Full Text
View/download PDF

42. ICTV Virus Taxonomy Profile: Alphaflexiviridae .

Author

Kreuze JF, Vaira AM, Menzel W, Candresse T, Zavriev SK, Hammond J, Hyun Ryu K, and Report Consortium I

Subjects
Flexiviridae ultrastructure, Gene Expression Regulation, Viral, Genome, Viral, Host Specificity, Phylogeny, Virion ultrastructure, Virus Replication, Flexiviridae classification, Flexiviridae physiology
Abstract

The family Alphaflexiviridae includes viruses with flexuous filamentous virions that are 470-800 nm in length and 12-13 nm in diameter. Alphaflexiviruses have a single-stranded, positive-sense RNA genome of 5.5-9 kb. They infect plants and plant-infecting fungi. They share a distinct lineage of alphavirus-like replication proteins that is unusual in lacking any recognized protease domain. With a single exception, cell-to-cell and long-distance movement is facilitated by triple gene block proteins in plant-infecting genera. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Alphaflexiviridae, which is available at www.ictv.global/report/alphaflexiviridae.

Published
2020
Full Text
View/download PDF

43. ICTV Virus Taxonomy Profile: Closteroviridae .

Author

Fuchs M, Bar-Joseph M, Candresse T, Maree HJ, Martelli GP, Melzer MJ, Menzel W, Minafra A, Sabanadzovic S, and Report Consortium I

Subjects
Closteroviridae metabolism, Closteroviridae ultrastructure, Genome, Viral, Phylogeny, Virion genetics, Virion ultrastructure, Virus Replication, Closteroviridae genetics
Abstract

Viruses in the family Closteroviridae have a mono-, bi- or tripartite positive-sense RNA genome of 13-19 kb, and non-enveloped, filamentous particles 650-2200 nm long and 12 nm in diameter. They infect plants, mainly dicots, many of which are fruit crops. This is a summary of the ICTV Report on the family Closteroviridae , which is available at ictv.global/report/closteroviridae.

Published
2020
Full Text
View/download PDF

44. ushr: Understanding suppression of HIV in R.

Author

Morris SE, Dziobek-Garrett L, Yates AJ, and Collaboration With The Epiical Consortium I

Subjects
HIV isolation & purification, Humans, Models, Biological, Viral Load, Anti-HIV Agents therapeutic use, HIV Infections drug therapy, HIV Infections virology, Software
Abstract

Background: HIV/AIDS is responsible for the deaths of one million people every year. Although mathematical modeling has provided many insights into the dynamics of HIV infection, there is still a lack of accessible tools for researchers unfamiliar with modeling techniques to apply them to their own clinical data., Results: Here we present ushr, a free and open-source R package that models the decline of HIV during antiretroviral treatment (ART) using a popular mathematical framework. ushr can be applied to longitudinal data of viral load measurements, and provides processing tools to prepare it for computational analysis. By mathematically fitting the data, important biological parameters can then be estimated, including the lifespans of short and long-lived infected cells, and the time to reach viral suppression below a defined detection threshold. The package also provides visualization and summary tools for fast assessment of model results., Conclusions: ushr enables researchers without a strong mathematical or computational background to model the dynamics of HIV using longitudinal clinical data. Increasing accessibility to such methods may facilitate quantitative analysis across a broader range of independent studies, so that greater insights on HIV infection and treatment dynamics may be gained.

Published
2020
Full Text
View/download PDF

45. Predicting dropout in adolescents receiving therapy for depression.

Author

O'Keeffe S, Martin P, Goodyer IM, Wilkinson P, Consortium I, and Midgley N

Subjects
Adolescent, Child, Cognitive Behavioral Therapy methods, Female, Humans, Male, Psychoanalytic Therapy methods, Psychotherapy, Brief methods, Adolescent Behavior psychology, Depression therapy, Depressive Disorder therapy, Outcome and Process Assessment, Health Care, Patient Dropouts psychology, Psychotherapy methods, Therapeutic Alliance
Abstract

Objective: Therapy dropout is a common occurrence, especially in adolescence. This study investigated whether dropout could be predicted from a range of child, family, and treatment factors in a sample of adolescents receiving therapy for depression., Method: This study draws on data from 406 participants of the IMPACT study, a randomized controlled trial, investigating three types of therapy in the treatment of adolescent depression. Logistic regression was used to estimate the effects of predictors on the odds of dropout., Results: Few pre-treatment predictors of dropout were found, with the only significant predictors being older age, antisocial behaviour, and lower scores of verbal intelligence. Missed sessions and poorer therapeutic alliance early in treatment also predicted dropout. Most child and family factors investigated were not significantly associated with dropout., Conclusions: There may be little about depressed adolescents' presentation prior to therapy starting that indicates their risk of dropout. However, within-treatment factors indicated that warning signs of dropout may be identifiable during the initial phase of therapy. Identifying and targeting early treatment indicators of dropout may provide possibilities for improving engagement. Clinical and methodological significance of this article: In the literature, a great deal of attention has been paid to child and family factors that predict therapy dropout, yet in this study, few pre-treatment characteristics were predictive of dropout. However, findings revealed possible warning signs of dropout in the early part of treatment, as poor therapeutic alliance and missed sessions were both found to be predictive of dropout. These findings call for therapists to be aware of such warning signs and clinical guidelines for managing cases at risk of dropout are warranted.

Published
2018
Full Text
View/download PDF

46. Gene-set and multivariate genome-wide association analysis of oppositional defiant behavior subtypes in attention-deficit/hyperactivity disorder.

Author

Aebi M, van Donkelaar MM, Poelmans G, Buitelaar JK, Sonuga-Barke EJ, Stringaris A, Consortium I, Faraone SV, Franke B, Steinhausen HC, and van Hulzen KJ

Subjects
Adolescent, Aggression psychology, Attention Deficit Disorder with Hyperactivity psychology, Child, Female, Genetic Association Studies methods, Genome-Wide Association Study, Humans, Male, Parenting psychology, Parents, Polymorphism, Single Nucleotide genetics, Attention Deficit Disorder with Hyperactivity genetics, Attention Deficit and Disruptive Behavior Disorders genetics, Attention Deficit and Disruptive Behavior Disorders psychology
Abstract

Oppositional defiant disorder (ODD) is a frequent psychiatric disorder seen in children and adolescents with attention-deficit-hyperactivity disorder (ADHD). ODD is also a common antecedent to both affective disorders and aggressive behaviors. Although the heritability of ODD has been estimated to be around 0.60, there has been little research into the molecular genetics of ODD. The present study examined the association of irritable and defiant/vindictive dimensions and categorical subtypes of ODD (based on latent class analyses) with previously described specific polymorphisms (DRD4 exon3 VNTR, 5-HTTLPR, and seven OXTR SNPs) as well as with dopamine, serotonin, and oxytocin genes and pathways in a clinical sample of children and adolescents with ADHD. In addition, we performed a multivariate genome-wide association study (GWAS) of the aforementioned ODD dimensions and subtypes. Apart from adjusting the analyses for age and sex, we controlled for "parental ability to cope with disruptive behavior." None of the hypothesis-driven analyses revealed a significant association with ODD dimensions and subtypes. Inadequate parenting behavior was significantly associated with all ODD dimensions and subtypes, most strongly with defiant/vindictive behaviors. In addition, the GWAS did not result in genome-wide significant findings but bioinformatics and literature analyses revealed that the proteins encoded by 28 of the 53 top-ranked genes functionally interact in a molecular landscape centered around Beta-catenin signaling and involved in the regulation of neurite outgrowth. Our findings provide new insights into the molecular basis of ODD and inform future genetic studies of oppositional behavior. © 2015 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by Wiley Periodicals, Inc., (© 2015 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by Wiley Periodicals, Inc.)

Published
2016
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results