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1.
Moore MM Honma M Clements J Bolcsfoldi G Cifone M Delongchamp R Fellows M Gollapudi B Jenkinson P Kirby P Kirchner S Muster W Myhr B O'Donovan M Oliver J Omori T Ouldelhkim MC Pant K Preston R Riach C San R Stankowski LF Thakur A Wakuri S Yoshimura I;Mouse Lymphoma Assay Workgroup 《Mutation research》2003,540(2):127-140
The Mouse Lymphoma Assay (MLA) Workgroup of the International Workshop on Genotoxicity Tests (IWGT) met on June 28th and 29th, 2002, in Plymouth, England. This meeting of the MLA group was devoted to discussing the criteria for assay acceptance and appropriate approaches to data evaluation. Prior to the meeting, the group conducted an extensive analysis of data from both the microwell and soft agar versions of the assay. For the establishment of criteria for assay acceptance, 10 laboratories (6 using the microwell method and 4 using soft agar) provided data on their background mutant frequencies, plating efficiencies of the negative/vehicle control, cell suspension growth, and positive control mutant frequencies. Using the distribution curves generated from this data, the Workgroup reached consensus on the range of values that should be used to determine whether an individual experiment is acceptable. In order to establish appropriate approaches for data evaluation, the group used a number of statistical methods to evaluate approximately 400 experimental data sets from 10 laboratories entered into a database created for the earlier MLA Workshop held in New Orleans [Environ. Mol. Mutagen. 40 (2002) 292]. While the Workgroup could not, during this meeting, make a final recommendation for the evaluation of data, a general strategy was developed and the Workgroup members agreed to evaluate this new proposed approach using their own laboratory data. This evaluation should lead to a consensus global approach for data evaluation in the near future. 相似文献
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Follow-up testing of rodent carcinogens not positive in the standard genotoxicity testing battery: IWGT workgroup report 总被引:1,自引:0,他引:1
Kasper P Uno Y Mauthe R Asano N Douglas G Matthews E Moore M Mueller L Nakajima M Singer T Speit G;IWGT Workgroup 《Mutation research》2007,627(1):106-116
At the Plymouth Third International Workshop on Genotoxicity Testing in June 2002, a new expert group started a working process to provide guidance on a common strategy for genotoxicity testing beyond the current standard battery. The group identified amongst others "Follow-up testing of tumorigenic agents not positive in the standard genotoxicity test battery" as one subject for further consideration [L. Müller, D. Blakey, K.L. Dearfield, S. Galloway, P. Guzzie, M. Hayashi, P. Kasper, D. Kirkland, J.T. MacGregor, J.M. Parry, L. Schechtman, A. Smith, N. Tanaka, D. Tweats, H. Yamasaki, Strategy for genotoxicity testing and stratification of genotoxicity test results-report on initial activities of the IWGT Expert Group, Mutat. Res. 540 (2003) 177-181]. A workgroup devoted to this topic was formed and met on September 9-10, 2005, in San Francisco. This workgroup was devoted to the discussion of when it would be appropriate to conduct additional genetic toxicology studies, as well as what type of studies, if the initial standard battery of tests was negative, but tumor formation was observed in the rodent carcinogenicity assessment. The important role of the standard genetic toxicology testing to determine the mode of action (MOA) for carcinogenesis (genotoxic versus non-genotoxic) was discussed, but the limitations of the standard testing were also reviewed. The workgroup also acknowledged that the entire toxicological profile (e.g. structure-activity relationships, the nature of the tumor finding and metabolic profiles) of a compound needed to be taken into consideration before the conduct of any additional testing. As part of the meeting, case studies were discussed to understand the practical application of additional testing as well as to form a decision tree. Finally, suitable additional genetic toxicology assays to help determine the carcinogenic MOA or establish a weight of evidence (WOE) argument were discussed and formulated into a decision tree. 相似文献
3.
Analysis of HIV-1 pol sequences using Bayesian Networks: implications for drug resistance 总被引:2,自引:0,他引:2
Deforche K Silander T Camacho R Grossman Z Soares MA Van Laethem K Kantor R Moreau Y Vandamme AM;non-B Workgroup 《Bioinformatics (Oxford, England)》2006,22(24):2975-2979
Human Immunodeficiency Virus-1 (HIV-1) antiviral resistance is a major cause of antiviral therapy failure and compromises future treatment options. As a consequence, resistance testing is the standard of care. Because of the high degree of HIV-1 natural variation and complex interactions, the role of resistance mutations is in many cases insufficiently understood. We applied a probabilistic model, Bayesian networks, to analyze direct influences between protein residues and exposure to treatment in clinical HIV-1 protease sequences from diverse subtypes. We can determine the specific role of many resistance mutations against the protease inhibitor nelfinavir, and determine relationships between resistance mutations and polymorphisms. We can show for example that in addition to the well-known major mutations 90M and 30N for nelfinavir resistance, 88S should not be treated as 88D but instead considered as a major mutation and explain the subtype-dependent prevalence of the 30N resistance pathway. 相似文献
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5.
Yutao Liu Melanie E. Garrett Michelle F. Dennis Kimberly T. Green VA Mid-Atlantic MIRECC Registry Workgroup Allison E. Ashley-Koch Michael A. Hauser Jean C. Beckham Nathan A. Kimbrel 《PloS one》2015,10(3)
Objective
To examine the association between the 5-HTTLPR polymorphism of the serotonin transporter (SLC6A4) gene, combat exposure, and posttraumatic stress disorder (PTSD) diagnosis and among two samples of combat-exposed veterans.Method
The first sample included 550 non-Hispanic Black (NHB) combat-exposed veterans. The second sample included 555 non-Hispanic White (NHW) combat-exposed veterans. Participants were genotyped for the 5-HTTLPR/rs25531 variants of the SLC6A4 gene. A structured clinical interview was used to diagnose PTSD. Combat and civilian trauma exposure were assessed with validated self-report instruments. Logistic regression was used to test for main effects of 5-HTTLPR on PTSD diagnosis as well as gene x environment (GxE) interactions after adjusting for sex, ancestry proportion scores, civilian trauma exposure, and combat exposure.Results
Within the NHB sample, a significant additive effect was observed for 5-HTTLPR (OR = 1.502, p = .0025), such that the odds of having a current diagnosis of PTSD increased by 1.502 for each additional S’ allele. No evidence for an association between 5-HTTLPR and PTSD was observed in the NHW sample. In addition, no evidence for combat x 5-HTTLPR effects were observed in either sample.Conclusion
The present study suggests that there may be an association between 5-HTTLPR genotype and PTSD diagnosis among NHB veterans; however, no evidence for the hypothesized 5-HTTLPR x combat interaction was found. 相似文献6.
Moore MM Honma M Clements J Bolcsfoldi G Burlinson B Cifone M Clarke J Clay P Doppalapudi R Fellows M Gollapudi B Hou S Jenkinson P Muster W Pant K Kidd DA Lorge E Lloyd M Myhr B O'Donovan M Riach C Stankowski LF Thakur AK Van Goethem F;Mouse Lymphoma Assay Workgroup IWGT 《Mutation research》2007,627(1):36-40
The Mouse Lymphoma Assay (MLA) Workgroup of the International Workshop on Genotoxicity Testing (IWGT), comprised of experts from Japan, Europe and the United States, met on September 9, 2005, in San Francisco, CA, USA. This meeting of the MLA Workgroup was devoted to reaching a consensus on issues involved with 24-h treatment. Recommendations were made concerning the acceptable values for the negative/solvent control (mutant frequency, cloning efficiency and suspension growth) and the criteria to define an acceptable positive control response. Consensus was also reached concerning the use of the global evaluation factor (GEF) and appropriate statistical trend analysis to define positive and negative responses for the 24-h treatment. The Workgroup agreed to continue their support of the International Committee on Harmonization (ICH) recommendation that the MLA assay should include a 24-h treatment (without S-9) in those situations where the short treatment (3-4 h) gives negative results. 相似文献
7.
Improving access and systems of care for evidence‐based childhood obesity treatment: Conference key findings and next steps
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H. Irene Hall Lorena Espinoza Nanette Benbow Yunyin W. Hu for the Urban Areas HIV Surveillance Workgroup 《PloS one》2010,5(9)
Background
While the U.S. HIV epidemic continues to be primarily concentrated in urban area, local epidemiologic profiles may differ and require different approaches in prevention and treatment efforts. We describe the epidemiology of HIV in large urban areas with the highest HIV burden.Methods/Principal Findings
We used data from national HIV surveillance for 12 metropolitan statistical areas (MSAs) to determine disparities in HIV diagnoses and prevalence and changes over time. Overall, 0.3% to 1% of the MSA populations were living with HIV at the end of 2007. In each MSA, prevalence was >1% among blacks; prevalence was >2% in Miami, New York, and Baltimore. Among Hispanics, prevalence was >1% in New York and Philadelphia. The relative percentage differences in 2007 HIV diagnosis rates, compared to whites, ranged from 239 (San Francisco) to 1239 (Baltimore) for blacks and from 15 (Miami) to 413 (Philadelphia) for Hispanics. The epidemic remains concentrated, with more than 50% of HIV diagnoses in 2007 attributed to male-to-male sexual contact in 7 of the 12 MSAs; heterosexual transmission surpassed or equaled male-to-male sexual transmission in Baltimore, Philadelphia, and Washington, DC. Yet in several MSAs, including Baltimore and Washington, DC, AIDS diagnoses increased among men-who-have sex with men in recent years.Conclusions/Significance
These data are useful to identify local drivers of the epidemic and to tailor public health efforts for treatment and prevention services for people living with HIV. 相似文献10.
Brenda Y. Hernandez Marc T. Goodman Charles F. Lynch Wendy Cozen Elizabeth R. Unger Martin Steinau Trevor Thompson Maria Sibug Saber Sean F. Altekruse Christopher Lyu Mona Saraiya The HPV Typing of Cancer Workgroup 《PloS one》2014,9(12)