207 results on '"Conner, T."'
Search Results
52. PCN3 AN ANALYSIS OF OUTPATIENT SERVICE UTILIZATION FOR DELAYED NAUSEA AND VOMITING USING ELECTRONIC MEDICAL RECORDS
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Forsyth, M, primary, Conner, T, additional, Curtis, V, additional, and Johnsrud, M, additional
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- 2006
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53. PHP26 INTENSIVIST PRACTICE CHANGE IN GLUCOSE CONTROL FOR CRITICALLY ILL PATIENTS
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Conner, T, primary, Drosu, D, additional, Krstic, B, additional, Rankin, S, additional, Newby, C, additional, Rascati, KL, additional, Flesner, K, additional, and Weingarten, J, additional
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- 2003
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54. PHS85 - Determining Patient Satisfaction, Perception Of Value, And Monetary Worth Associated With Adherence Packaging And Pharmacy Services
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Pinto, S.L., Bechtol, R.A., Omerza, K., and Conner, T.
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- 2014
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55. POD5 EVALUATION OF A PALLIATIVE CARE TEAM ON RESOURCE UTILIZATION IN AN ACUTE CARE SETTING
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Conner, T, primary, Limerick, M, additional, and Rascati, K, additional
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- 2002
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56. Association of Prepartum Plasina Non-esterified Fatty Acid Concentration with Retained Placenta in Multiparous Holstein Cows
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Conner, T., primary, Herdt, T. H., additional, and Neuder, L., additional
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- 2001
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57. Genetic Transformation of Wheat Mediated by Agrobacterium tumefaciens
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Cheng, M., primary, Fry, J. E., additional, Pang, S., additional, Zhou, H., additional, Hironaka, C. M., additional, Duncan, D. R., additional, Conner, T. W., additional, and Wan, Y., additional
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- 1997
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58. A roadmap for boundary-scan test reuse.
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Wedge, G. and Conner, T.
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- 1996
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59. The effect of care setting on elder abuse: results from a Michigan survey.
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Page C, Conner T, Prokhorov A, Fang Y, and Post L
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This study compares abuse rates for elders age 60 and older in three care settings: nursing home, paid home care, and assisted living. The results are based on a 2005 random-digit dial survey of relatives of, or those responsible for, a peson in long-term care. Nursing homes have the highest rates of all types of abuse, although paid home care has a relatively high rate of verbal abuse and assisted living has an unexpected high rate of neglect. Even when adjusting for health conditions, care setting is a significant factor in both caretaking and neglect abuses. Moving from paid home care to nursing homes is shown to more than triple the odds of neglect. Furthermore, when computing abuse rates by care setting for persons with specified health conditions, nursing homes no longer have the highest abuse rates. [ABSTRACT FROM AUTHOR]
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- 2009
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60. The impact of mental health treatment intensity on the emotional and behavioral problems of youth in a residential treatment facility.
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Conner T and Koeske G
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This study focused on the growing number of juvenile delinquents who enter the juvenile justice system presenting severe mental health issues that often go undetected by juvenile justice professionals. The sample consisted of 163 court ordered juvenile delinquents at a residential treatment facility in northwestern Pennsylvania. The sample was required to complete two surveys in an attempt to measure presenting mental health symptoms, emotional, and behavioral problems while at the facility, mental health service intensity, and severity of prior delinquent behaviors. This study is intended to examine the impact treatment intensity had on the emotional and behavioral problems the delinquent experiences while at the facility controlling for presenting mental health issues and severity of prior delinquent activity. The results show a not significant relationship between treatment intensity and emotional problems while at the facility. However, greater service intensity was related to the amount of behavioral problems the youth experiences while at the facility. Severity of prior delinquent activity and presenting mental health issues are strong predictors of increased behavioral problems while at the facility, while high levels of mental health symptoms can predict elevated emotional problems. [ABSTRACT FROM AUTHOR]
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- 2005
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61. The two alpha-tubulin genes of Chlamydomonas reinhardi code for slightly different proteins
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Silflow, C D, Chisholm, R L, Conner, T W, and Ranum, L P
- Abstract
Full-length cDNA clones corresponding to the transcripts of the two alpha-tubulin genes in Chlamydomonas reinhardi were isolated. DNA sequence analysis of the cDNA clones and cloned gene fragments showed that each gene contains 1,356 base pairs of coding sequence, predicting alpha-tubulin products of 451 amino acids. Of the 27 nucleotide differences between the two genes, only two result in predicted amino acid differences between the two gene products. In the more divergent alpha 2 gene, a leucine replaces an arginine at amino acid 308, and a valine replaces a glycine at amino acid 366. The results predicted that two alpha-tubulin proteins with different net charges are produced as primary gene products. The predicted amino acid sequences are 86 and 70% homologous with alpha-tubulins from rat brain and Schizosaccharomyces pombe, respectively. Each gene had two intervening sequences, located at identical positions. Portions of an intervening sequence highly conserved between the two beta-tubulin genes are also found in the second intervening sequence of each of the alpha genes. These results, together with our earlier report of the beta-tubulin sequences in C. reinhardi, present a picture of the total complement of genetic information for tubulin in this organism.
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- 1985
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62. LETTERS.
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GUINKH, SOPHIA A., LEVIN, HARRY, SPECTORSKY, A. C., FISKE, HEIDI, BELONG, SAMUEL, PETROFF, ALEX, BLACKWELL, DEBORAH, MARQUIS, DEANIE, STEPHENS, NANCY, CONNER, T., BELLI, MELVIN M., UTRATA, CARL I., CLASSEN, HANS GEORGE, and WARD, DONALD
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LETTERS to the editor ,SOCIAL problems ,SCHOOL violence ,CRIME victims - Abstract
Several letters to the editor are presented in response to articles in previous issues including the recognition of author Vladimir Nabokov, the brutal incident at the People's Park and the unrest of campuses.
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- 1969
63. Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer
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Phelan, CM, Kuchenbaecker, KB, Tyrer, JP, Kar, SP, Lawrenson, K, Winham, SJ, Dennis, J, Pirie, A, Riggan, MJ, Chornokur, G, Earp, MA, Lyra, PC, Lee, JM, Coetzee, S, Beesley, J, McGuffog, L, Soucy, P, Dicks, E, Lee, A, Barrowdale, D, Lecarpentier, J, Leslie, G, Aalfs, CM, Aben, KKH, Adams, M, Adlard, J, Andrulis, IL, Anton-Culver, H, Antonenkova, N, AOCS Study Group, Aravantinos, G, Arnold, N, Arun, BK, Arver, B, Azzollini, J, Balmaña, J, Banerjee, SN, Barjhoux, L, Barkardottir, RB, Bean, Y, Beckmann, MW, Beeghly-Fadiel, A, Benitez, J, Bermisheva, M, Bernardini, MQ, Birrer, MJ, Bjorge, L, Black, A, Blankstein, K, Blok, MJ, Bodelon, C, Bogdanova, N, Bojesen, A, Bonanni, B, Borg, Å, Bradbury, AR, Brenton, JD, Brewer, C, Brinton, L, Broberg, P, Brooks-Wilson, A, Bruinsma, F, Brunet, J, Buecher, B, Butzow, R, Buys, SS, Caldes, T, Caligo, MA, Campbell, I, Cannioto, R, Carney, ME, Cescon, T, Chan, SB, Chang-Claude, J, Chanock, S, Chen, XQ, Chiew, Y-E, Chiquette, J, Chung, WK, Claes, KBM, Conner, T, Cook, LS, Cook, J, Cramer, DW, Cunningham, JM, D'Aloisio, AA, Daly, MB, Damiola, F, Damirovna, SD, Dansonka-Mieszkowska, A, Dao, F, Davidson, R, DeFazio, A, Delnatte, C, Doheny, KF, Diez, O, Ding, YC, Doherty, JA, Domchek, SM, Dorfling, CM, Dörk, T, Dossus, L, Duran, M, Dürst, M, Dworniczak, B, Eccles, D, Edwards, T, Eeles, R, Eilber, U, Ejlertsen, B, Ekici, AB, Ellis, S, Elvira, M, EMBRACE Study, Eng, KH, Engel, C, Evans, DG, Fasching, PA, Ferguson, S, Ferrer, SF, Flanagan, JM, Fogarty, ZC, Fortner, RT, Fostira, F, Foulkes, WD, Fountzilas, G, Fridley, BL, Friebel, TM, Friedman, E, Frost, D, Ganz, PA, Garber, J, García, MJ, Garcia-Barberan, V, Gehrig, A, GEMO Study Collaborators, Gentry-Maharaj, A, Gerdes, A-M, Giles, GG, Glasspool, R, Glendon, G, Godwin, AK, Goldgar, DE, Goranova, T, Gore, M, Greene, MH, Gronwald, J, Gruber, S, Hahnen, E, Haiman, CA, Håkansson, N, Hamann, U, Hansen, TVO, Harrington, PA, Harris, HR, Hauke, J, HEBON Study, Hein, A, Henderson, A, Hildebrandt, MAT, Hillemanns, P, Hodgson, S, Høgdall, CK, Høgdall, E, Hogervorst, FBL, Holland, H, Hooning, MJ, Hosking, K, Huang, R-Y, Hulick, PJ, Hung, J, Hunter, DJ, Huntsman, DG, Huzarski, T, Imyanitov, EN, Isaacs, C, Iversen, ES, Izatt, L, Izquierdo, A, Jakubowska, A, James, P, Janavicius, R, Jernetz, M, Jensen, A, Jensen, UB, John, EM, Johnatty, S, Jones, ME, Kannisto, P, Karlan, BY, Karnezis, A, Kast, K, KConFab Investigators, Kennedy, CJ, Khusnutdinova, E, Kiemeney, LA, Kiiski, JI, Kim, S-W, Kjaer, SK, Köbel, M, Kopperud, RK, Kruse, TA, Kupryjanczyk, J, Kwong, A, Laitman, Y, Lambrechts, D, Larrañaga, N, Larson, MC, Lazaro, C, Le, ND, Le Marchand, L, Lee, JW, Lele, SB, Leminen, A, Leroux, D, Lester, J, Lesueur, F, Levine, DA, Liang, D, Liebrich, C, Lilyquist, J, Lipworth, L, Lissowska, J, Lu, KH, Lubinński, J, Luccarini, C, Lundvall, L, Mai, PL, Mendoza-Fandiño, G, Manoukian, S, Massuger, LFAG, May, T, Mazoyer, S, McAlpine, JN, McGuire, V, McLaughlin, McNeish, I, Meijers-Heijboer, H, Meindl, A, Menon, U, Mensenkamp, AR, Merritt, MA, Milne, RL, Mitchell, G, Modugno, F, Moes-Sosnowska, J, Moffitt, M, Montagna, M, Moysich, KB, Mulligan, AM, Musinsky, J, Nathanson, KL, Nedergaard, L, Ness, RB, Neuhausen, SL, Nevanlinna, H, Niederacher, D, Nussbaum, RL, Odunsi, K, Olah, E, Olopade, OI, Olsson, H, Olswold, C, O'Malley, DM, Ong, K-R, Onland-Moret, NC, OPAL Study Group, Orr, N, Orsulic, S, Osorio, A, Palli, D, Papi, L, Park-Simon, T-W, Paul, J, Pearce, CL, Pedersen, IS, Peeters, PHM, Peissel, B, Peixoto, A, Pejovic, T, Pelttari, LM, Permuth, JB, Peterlongo, P, Pezzani, L, Pfeiler, G, Phillips, K-A, Piedmonte, M, Pike, MC, Piskorz, AM, Poblete, Pocza, T, Poole, EM, Poppe, B, Porteous, ME, Prieur, F, Prokofyeva, D, Pugh, E, Pujana, MA, Pujol, P, Radice, P, Rantala, J, Rappaport-Fuerhauser, C, Rennert, G, Rhiem, K, Rice, P, Richardson, A, Robson, M, Rodriguez, GC, Rodríguez-Antona, C, Romm, J, Rookus, MA, Rossing, MA, Rothstein, JH, Rudolph, A, Runnebaum, IB, Salvesen, HB, Sandler, DP, Schoemaker, MJ, Senter, L, Setiawan, VW, Severi, G, Sharma, P, Shelford, T, Siddiqui, N, Side, LE, Sieh, W, Singer, CF, Sobol, H, Song, H, Southey, MC, Spurdle, AB, Stadler, Z, Steinemann, D, Stoppa-Lyonnet, D, Sucheston-Campbell, LE, Sukiennicki, G, Sutphen, R, Sutter, C, Swerdlow, AJ, Szabo, CI, Szafron, L, Tan, YY, Taylor, JA, Tea, M-K, Teixeira, MR, Teo, S-H, Terry, KL, Thompson, PJ, Thomsen, LCV, Thull, DL, Tihomirova, L, Tinker, AV, Tischkowitz, M, Tognazzo, S, Toland, AE, Tone, A, Trabert, B, Travis, RC, Trichopoulou, A, Tung, N, Tworoger, SS, Van Altena, AM, Van Den Berg, D, Van Der Hout, AH, Van Der Luijt, RB, Van Heetvelde, M, Van Nieuwenhuysen, E, Van Rensburg, EJ, Vanderstichele, A, Varon-Mateeva, R, Vega, A, Edwards, DV, Vergote, I, Vierkant, RA, Vijai, J, Vratimos, A, Walker, L, Walsh, C, Wand, D, Wang-Gohrke, S, Wappenschmidt, B, Webb, PM, Weinberg, CR, Weitzel, JN, Wentzensen, N, Whittemore, AS, Wijnen, JT, Wilkens, LR, Wolk, A, Woo, M, Wu, X, Wu, AH, Yang, H, Yannoukakos, D, Ziogas, A, Zorn, KK, Narod, SA, Easton, DF, Amos, CI, Schildkraut, JM, Ramus, SJ, Ottini, L, Goodman, MT, Park, SK, Kelemen, LE, Risch, HA, Thomassen, M, Offit, K, Simard, J, Schmutzler, RK, Hazelett, D, Monteiro, AN, Couch, FJ, Berchuck, A, Chenevix-Trench, G, Goode, EL, Sellers, TA, Gayther, SA, Antoniou, AC, and Pharoah, PDP
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ovarian cancer ,endocrine system diseases ,genome-wide association studies ,epidemiology ,female genital diseases and pregnancy complications ,3. Good health - Abstract
To identify common alleles associated with different histotypes of epithelial ovarian cancer (EOC), we pooled data from multiple genome-wide genotyping projects totaling 25,509 EOC cases and 40,941 controls. We identified nine new susceptibility loci for different EOC histotypes: six for serous EOC histotypes (3q28, 4q32.3, 8q21.11, 10q24.33, 18q11.2 and 22q12.1), two for mucinous EOC (3q22.3 and 9q31.1) and one for endometrioid EOC (5q12.3). We then performed meta-analysis on the results for high-grade serous ovarian cancer with the results from analysis of 31,448 $\textit{BRCA1}$ and $\textit{BRCA2}$ mutation carriers, including 3,887 mutation carriers with EOC. This identified three additional susceptibility loci at 2q13, 8q24.1 and 12q24.31. Integrated analyses of genes and regulatory biofeatures at each locus predicted candidate susceptibility genes, including OBFC1, a new candidate susceptibility gene for low-grade and borderline serous EOC.
64. The jekyll and hyde of our drinking: Event specific drinking, intervention, and prevention
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Riordan, B. C., Flett, J. A. M., Lam, T., Conner, T. S., and Damian Scarf
65. DIABETES MELLITUS AND VASCULAR DISEASE: POSSIBLE ROLE OF HYDROXYACIDS IN ITS GENESIS
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Stuart, M, primary, Graeber, J, additional, Setty, Y, additional, Walenga, R, additional, Conner, T, additional, and Glaser, B, additional
- Published
- 1984
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66. Articulation in the teaching of bookkeeping and accounting--Abstract
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Jones, Conner T., primary
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- 1926
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67. The Two-Year High School Commercial Course
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Conner T. Jones
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Medical education ,Psychology ,Education ,Course (navigation) - Published
- 1916
68. Eliminating the Old-Age Bugbear
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Conner T. Jones
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Pediatrics ,medicine.medical_specialty ,medicine ,Education - Published
- 1916
69. PHS85 Determining Patient Satisfaction, Perception Of Value, And Monetary Worth Associated With Adherence Packaging And Pharmacy Services
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Pinto, S.L., Bechtol, R.A., Omerza, K., and Conner, T.
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70. Three Public Gardens Share Their Sustainable Practices.
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Conner, T. C.
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- 2011
71. Outcomes after Angiography with Sodium Bicarbonate and Acetylcysteine.
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Weisbord, S. D., Gallagher, M., Jneid, H., Garcia, S., Cass, A., Thwin, S.-S., Conner, T. A., Chertow, G. M., Bhatt, D. L., Shunk, K., Parikh, C. R., McFalls, E. O., Brophy, M., Ferguson, R., Wu, H., Androsenko, M., Myles, J., Kaufman, J., Palevsky, P. M., and Weisbord, Steven D
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- *
SODIUM bicarbonate , *ACETYLCYSTEINE , *KIDNEY injuries , *PREVENTIVE medicine , *ANGIOGRAPHY , *ACUTE kidney failure prevention , *TREATMENT of chronic kidney failure , *HALOTHERAPY , *ACUTE kidney failure , *COMPARATIVE studies , *CREATININE , *FLUID therapy , *HEMODIALYSIS , *INTRAVENOUS therapy , *RESEARCH methodology , *MEDICAL cooperation , *ORAL drug administration , *RESEARCH , *EVALUATION research , *RANDOMIZED controlled trials , *TREATMENT effectiveness , *CONTRAST media , *BLIND experiment , *THERAPEUTICS - Abstract
Background: Intravenous sodium bicarbonate and oral acetylcysteine are widely used to prevent acute kidney injury and associated adverse outcomes after angiography without definitive evidence of their efficacy.Methods: Using a 2-by-2 factorial design, we randomly assigned 5177 patients at high risk for renal complications who were scheduled for angiography to receive intravenous 1.26% sodium bicarbonate or intravenous 0.9% sodium chloride and 5 days of oral acetylcysteine or oral placebo; of these patients, 4993 were included in the modified intention-to-treat analysis. The primary end point was a composite of death, the need for dialysis, or a persistent increase of at least 50% from baseline in the serum creatinine level at 90 days. Contrast-associated acute kidney injury was a secondary end point.Results: The sponsor stopped the trial after a prespecified interim analysis. There was no interaction between sodium bicarbonate and acetylcysteine with respect to the primary end point (P=0.33). The primary end point occurred in 110 of 2511 patients (4.4%) in the sodium bicarbonate group as compared with 116 of 2482 (4.7%) in the sodium chloride group (odds ratio, 0.93; 95% confidence interval [CI], 0.72 to 1.22; P=0.62) and in 114 of 2495 patients (4.6%) in the acetylcysteine group as compared with 112 of 2498 (4.5%) in the placebo group (odds ratio, 1.02; 95% CI, 0.78 to 1.33; P=0.88). There were no significant between-group differences in the rates of contrast-associated acute kidney injury.Conclusions: Among patients at high risk for renal complications who were undergoing angiography, there was no benefit of intravenous sodium bicarbonate over intravenous sodium chloride or of oral acetylcysteine over placebo for the prevention of death, need for dialysis, or persistent decline in kidney function at 90 days or for the prevention of contrast-associated acute kidney injury. (Funded by the U.S. Department of Veterans Affairs Office of Research and Development and the National Health and Medical Research Council of Australia; PRESERVE ClinicalTrials.gov number, NCT01467466 .). [ABSTRACT FROM AUTHOR]- Published
- 2018
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72. Pre- and post-flasking factors affecting establishment of Cordyline 'Purple Tower' from tissue culture
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Thomas, Michael B., Friend, Adam P., Conner, G., and Conner, T.
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- 2001
73. Advancing healthcare practice and education via data sharing: demonstrating the utility of open data by training an artificial intelligence model to assess cardiopulmonary resuscitation skills.
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Constable MD, Zhang FX, Conner T, Monk D, Rajsic J, Ford C, Park LJ, Platt A, Porteous D, Grierson L, and Shum HPH
- Abstract
Health professional education stands to gain substantially from collective efforts toward building video databases of skill performances in both real and simulated settings. An accessible resource of videos that demonstrate an array of performances - both good and bad-provides an opportunity for interdisciplinary research collaborations that can advance our understanding of movement that reflects technical expertise, support educational tool development, and facilitate assessment practices. In this paper we raise important ethical and legal considerations when building and sharing health professions education data. Collective data sharing may produce new knowledge and tools to support healthcare professional education. We demonstrate the utility of a data-sharing culture by providing and leveraging a database of cardio-pulmonary resuscitation (CPR) performances that vary in quality. The CPR skills performance database (collected for the purpose of this research, hosted at UK Data Service's ReShare Repository) contains videos from 40 participants recorded from 6 different angles, allowing for 3D reconstruction for movement analysis. The video footage is accompanied by quality ratings from 2 experts, participants' self-reported confidence and frequency of performing CPR, and the demographics of the participants. From this data, we present an Automatic Clinical Assessment tool for Basic Life Support that uses pose estimation to determine the spatial location of the participant's movements during CPR and a deep learning network that assesses the performance quality., (© 2024. Crown.)
- Published
- 2024
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74. Sex-specific effects of injury and beta-adrenergic activation on metabolic and inflammatory mediators in a murine model of post-traumatic osteoarthritis.
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Komaravolu RK, Mehta-D'souza P, Conner T, Allen M, Lumry J, Batushansky A, Pezant NP, Montgomery CG, and Griffin TM
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- Animals, Female, Male, Mice, Disease Models, Animal, Sex Factors, Synovial Membrane metabolism, Adipose Tissue metabolism, Inflammation Mediators metabolism, Receptors, Adrenergic, beta metabolism, Injections, Intra-Articular, Knee Injuries complications, Knee Injuries metabolism, Osteoarthritis, Knee metabolism, Osteoarthritis, Knee etiology, Cartilage, Articular metabolism, Cartilage, Articular drug effects, Cartilage, Articular pathology, Mice, Inbred C57BL, Isoproterenol pharmacology, Adrenergic beta-Agonists pharmacology
- Abstract
Objective: Metabolic processes are intricately linked to the resolution of innate inflammation and tissue repair, two critical steps for treating post-traumatic osteoarthritis (PTOA). Based on lipolytic and immunoregulatory actions of norepinephrine, we hypothesized that intra-articular β-adrenergic receptor (βAR) stimulation would suppress PTOA-associated inflammation in the infrapatellar fat pad (IFP) and synovium., Design: We used the βAR agonist isoproterenol to perturb intra-articular metabolism 3.5 weeks after applying a non-invasive single-load compression injury to knees of 12-week-old male and female mice. We examined the acute effects of intra-articular isoproterenol treatment relative to saline on IFP histology, multiplex gene expression of synovium-IFP tissue, synovial fluid metabolomics, and mechanical allodynia., Results: Injured knees developed PTOA pathology characterized by heterotopic ossification, articular cartilage loss, and IFP atrophy and fibrosis. Isoproterenol suppressed the upregulation of pro-fibrotic genes and downregulated the expression of adipose genes and pro-inflammatory genes (Adam17, Cd14, Icam1, Csf1r, and Casp1) in injured joints of female (but not male) mice. Analysis of published single-cell RNA-seq data identified elevated catecholamine-associated gene expression in resident-like synovial-IFP macrophages after injury. Injury substantially altered synovial fluid metabolites by increasing amino acids, peptides, sphingolipids, phospholipids, bile acids, and dicarboxylic acids, but these changes were not appreciably altered by isoproterenol. Intra-articular injection of either isoproterenol or saline increased mechanical allodynia in female mice, whereas neither substance affected male mice., Conclusions: Acute βAR activation altered synovial-IFP transcription in a sex and injury-dependent manner, suggesting that women with PTOA may be more sensitive than men to treatments targeting sympathetic neural signaling pathways., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2024
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75. Factors influencing the willingness to pay a price premium for red meat with potential to improve consumer wellness in Australia and the United States of America.
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Zhang R, Kallas Z, Conner TS, Loeffen MPF, Lee M, Day L, Farouk MM, and Realini CE
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- Humans, Australia, United States, Male, Female, Adult, Middle Aged, Surveys and Questionnaires, Young Adult, Adolescent, Animals, Aged, Exercise, Consumer Behavior, Red Meat economics
- Abstract
This study determined consumers' attitudes towards physical and mental wellness related to red meat consumption and their willingness to pay (WTP) more for the meat. In 2019, two online surveys of red meat eaters were conducted in the USA (n = 1000) and Australia (n = 523) using commercial platforms. Results showed that over 90% of respondents indicated interest in purchasing red meat to improve their wellness status. Additionally, about 85% indicated their WTP more for red meat for its wellness benefits, with Americans indicating stronger willingness than Australian respondents. The potential of meat consumption to improve overall wellness among red meat eaters was a dominant factor influencing consumers' WTP more. Other factors that increased WTP included frequency of meat consumption, physical exercise, sleep quality, number of children in a household, partnership status, and economic position. Outcomes from this study highlight a unique opportunity for the meat industry to position meat on its qualities that include wellness improvement if backed up with robust scientific evidence., Competing Interests: Declaration of competing interest The authors declare no conflict of interest associated with this submission., (Copyright © 2023. Published by Elsevier Ltd.)
- Published
- 2024
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76. Use of digital health technologies in periprocedural pediatric cardiac ablation.
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Miller N, Catherall D, Pompa AG, Roelle L, Conner T, Orr WB, and Avari Silva JN
- Abstract
Competing Interests: JNAS has the following disclosures: Kardia 6 lead devices supplied by AliveCor to our group to carry out the study. No other disclosures.
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- 2024
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77. Imaging mass cytometry reveals tissue-specific cellular immune phenotypes in the mouse knee following ACL injury.
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South SM, Marlin MC, Mehta-D'souza P, Stephens T, Conner T, Burt KG, Guthridge JM, Scanzello CR, and Griffin TM
- Abstract
Objective: To develop an imaging mass cytometry method for identifying complex cell phenotypes, inter-cellular interactions, and population changes in the synovium and infrapatellar fat pad (IFP) of the mouse knee following a non-invasive compression injury., Design: Fifteen male C57BL/6 mice were fed a high-fat diet for 8 weeks prior to random assignment to sham, 0.88 mm, or 1.7 mm knee compression displacement at 24 weeks of age. 2-weeks after loading, limbs were prepared for histologic and imaging mass cytometry analysis, focusing on myeloid immune cell populations in the synovium and IFP., Results: 1.7 mm compression caused anterior cruciate ligament (ACL) rupture, development of post-traumatic osteoarthritis, and a 2- to 3-fold increase in cellularity of synovium and IFP tissues compared to sham or 0.88 mm compression. Imaging mass cytometry identified 11 myeloid cell subpopulations in synovium and 7 in IFP, of which approximately half were elevated 2 weeks after ACL injury in association with the vasculature. Notably, two monocyte/macrophage subpopulations and an MHC II
hi population were elevated 2-weeks post-injury in the synovium but not IFP. Vascular and immune cell interactions were particularly diverse in the synovium, incorporating 8 unique combinations of 5 myeloid cell populations, including a monocyte/macrophage population, an MHC IIhi population, and 3 different undefined F4/80+ myeloid populations., Conclusions: Developing an imaging mass cytometry method for the mouse enabled us to identify a diverse array of synovial and IFP vascular-associated myeloid cell subpopulations. These subpopulations were differentially elevated in synovial and IFP tissues 2-weeks post injury, providing new details on tissue-specific immune regulation., Competing Interests: CRS and TMG have filed provisional patent applications #63/479,605 and #63/484,099 entitled, “COMPOSITIONS AND METHODS FOR TREATING OSTEOARTHRITIS USING A CD14 INHIBITOR”.- Published
- 2023
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78. What the Evidence Does (and Does Not) Show for the Centers for Disease Control and Prevention Child Development Milestones: An Illustrative Example Using Expressive Vocabulary.
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Roberts MY, Sone BJ, Jones MK, Standley M, Conner T, Lee ED, Norton ES, Roman J, Speights M, Young R, and Weisleder A
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- Child, Humans, Language Development, Communication, Child Development, Vocabulary
- Abstract
Purpose: Child development milestones are a critical tool for pediatricians and caregivers to use for developmental surveillance. Following review and selection by a panel of subject matter experts, the Centers for Disease Control and Prevention (CDC) published a revised list of milestones across multiple domains of development. Using expressive vocabulary, a key indicator of language development, as an illustrative example, the purpose of this brief review is to evaluate the evidence used to establish the CDC developmental milestones and determine whether the samples used to establish these milestones are representative of U.S. children., Method: Authors reviewed the methods and evidence cited to determine the CDC milestones. First, authors identified each language/communication milestone that measured expressive vocabulary as number of words, followed by review of the sources cited in support of each extracted milestone. Then, data related to both milestones and sample characteristics were extracted and compiled as well as compared with data from a validated parent report measure of expressive vocabulary, the MacArthur-Bates Communication Development Inventories., Results: Results indicated that evidence was conflicting, misaligned, or missing for the selected CDC expressive vocabulary milestones. This review also indicated that the samples used to determine the selected CDC expressive vocabulary milestones are not representative of U.S. children., Conclusion: The striking paucity of evidence supporting the new CDC milestones for expressive vocabulary illustrates the critical need for future research in this area to establish more accurate milestones for U.S. children, with a focus on culturally inclusive large-scale data.
- Published
- 2023
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79. Educators' perceptions of their experiences of transnational education in nursing: A grounded theory study.
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Straughair C, Allan J, Conner T, Morgan D, and Machin A
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- Humans, Grounded Theory, Curriculum, Delivery of Health Care, Faculty, Nursing, Education, Nursing, Baccalaureate, Students, Nursing, Education, Nursing
- Abstract
Aim: The study aim was to explore educators' perceptions of their experiences of participating in transnational education in nursing., Background: In an increasingly globalised world, involvement with the delivery of transnational education has become commonplace across the international higher education sector. In recent years, transnational education within the academic discipline of nursing has developed at pace, evolving in response to a global need to invest in nurse education, address nursing shortages and strengthen nursing leadership. However, despite acknowledgement that transnational education is a complex activity that needs to be more fully understood, research specifically exploring transnational education in nursing is scarce, as previous studies predominantly focus on other academic disciplines. The study addresses this knowledge gap, advancing understanding of transnational education in the context of nursing., Design: The study was positioned within the interpretivist paradigm and underpinned by a constructivist grounded theory methodological design, acknowledging the prior knowledge and experience of the research team in relation to phenomenon under investigation., Methods: Ethical approval was obtained before the study commenced, ensuring adherence to key ethical principles. The study was conducted during May to August 2020, in a university in the North of England that provides undergraduate and postgraduate nurse education in the United Kingdom and transnational context. Participants were recruited via e mail and invited to complete a brief questionnaire, informing a preliminary theoretical sampling strategy. Ten educators with experience of transnational education across a diverse range of international locations participated in individual, semi-structured, online interviews that were recorded and transcribed verbatim. Data were analysed using initial and focused coding, constant comparison, theoretical memos and diagrams., Findings: The findings uncovered three overarching data categories, each of which were crucial to supporting effective transnational education in nursing. Prepare- involved developing an understanding of the context of healthcare and education, being supported and collaborating with transnational partners. Perform- involved recognising language and cultural influences, adapting to the environment and implementing responsive educational pedagogies. Progress- involved recognition of personal development at individual level and valuing the benefits at organisational level., Conclusions: Although transnational education in nursing can be challenging and complex, it can offer worthwhile advantages for all stakeholders. However, effective transnational education in nursing is dependent on strategies which prepare educators appropriately and enable them to perform effectively, thereby promoting successful outcomes at individual, organisational and transnational partner level and facilitating advancement in future potential collaborative activity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2023
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80. Do Kinesio tapes increase the skin exposure to pathogenic bacteria?
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Oesterle ME, Conner T, Bunch M, Fleming A, Johnson P, and Bialonska D
- Subjects
- Humans, Skin microbiology, Anti-Bacterial Agents pharmacology, Staphylococcus epidermidis, Staphylococcus aureus, Athletic Tape
- Abstract
Background: Kinesio tapes (KTs) are tapes used in physical therapy and athletics. We sought to evaluate if wearing KTs for extended periods of time increases exposure to antibiotic resistant opportunistic pathogens and/or effects normal human skin bacteria., Methods: The study consisted of 10 volunteers wearing 9 KTs on their arms for 5 consecutive days. Microorganisms were isolated from fragments collected on the second and fifth day then analyzed. Bacteria were identified using the BIOLOG system. Resistance to selected antibiotics was performed using E-Test. The effect of KTs on the growth of Staphylococcus aureus, Staphylococcus epidermidis, and Micrococcus luteus was evaluated in a diffusion-based assay., Results: We found that KTs accumulated environmental bacteria. Among 22 species 8 were opportunistic pathogens, and all of them exhibited resistance to at least one antibiotic. None of the tapes produced inhibition zones against S. aureus. One tape, Leukotape P, caused growth inhibition in non-pathogenic S. epidermidis and M. luteus. The adhesive material of the tapes inhibited the growth of all tested bacteria., Conclusions: These results indicate that KTs may increase the exposure to antibiotic resistant pathogens which can accumulate from the environment. Further, extended exposure could lead to changes in normal skin microbiota, potentially contributing to increased risks of skin infections., (Copyright © 2022 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)
- Published
- 2023
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81. Expanding telehealth through technology: Use of digital health technologies during pediatric electrophysiology telehealth visits.
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Roelle L, Ocasio J, Littell L, Fredman E, Miller N, Conner T, Van Hare G, and Avari Silva JN
- Published
- 2022
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82. Durability of Antibody Response and Frequency of SARS-CoV-2 Infection 6 Months after COVID-19 Vaccination in Healthcare Workers.
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Laing ED, Weiss CD, Samuels EC, Coggins SA, Wang W, Wang R, Vassell R, Sterling SL, Tso MS, Conner T, Goguet E, Moser M, Jackson-Thompson BM, Illinik L, Davies J, Ortega O, Parmelee E, Hollis-Perry M, Maiolatesi SE, Wang G, Ramsey KF, Reyes AE, Alcorta Y, Wong MA, Lindrose AR, Duplessis CA, Tribble DR, Malloy AMW, Burgess TH, Pollett SD, Olsen CH, Broder CC, and Mitre E
- Subjects
- Antibodies, Viral, Antibody Formation, COVID-19 Vaccines, Health Personnel, Humans, SARS-CoV-2, Vaccination, COVID-19 epidemiology, COVID-19 prevention & control
- Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies decay but persist 6 months postvaccination; lower levels of neutralizing titers persist against Delta than wild-type virus. Of 227 vaccinated healthcare workers tested, only 2 experienced outpatient symptomatic breakthrough infections, despite 59/227 exhibiting serologic evidence of SARS-CoV-2 infection, defined as presence of nucleocapsid protein antibodies.
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- 2022
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83. A Modern Flexitarian Dietary Intervention Incorporating Web-Based Nutrition Education in Healthy Young Adults: Protocol for a Randomized Controlled Trial.
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Braakhuis A, Gillies N, Worthington A, Knowles S, Conner T, Roy R, Pham T, Bermingham E, and Cameron-Smith D
- Abstract
Background: The trend of flexitarian eating patterns is on the rise, with young adults among the biggest adopters claiming health and environmental reasons to reduce red meat intake. Nutrient-dense meat and animal products are often the lynchpin of these diets, even when consumed only occasionally and in moderate amounts. Red meat provides forms and concentrations of essential proteins, lipids, and micronutrients that are scarce in exclusively vegetarian regimens., Objective: The aim of this study is to consider the effects of moderate consumption of lean red meat as part of an otherwise vegetarian balanced diet and its impact on biomarkers of sustained health and well-being., Methods: A cohort of healthy, young (20-34 years old, n=80) male and female participants will take part in a 2-arm, parallel randomized controlled trial (RCT) for a duration of 12 weeks, with a 3-month posttrial follow-up. The trial will commence with a 2-week assessment period followed by allocation to the intervention arms. The intervention will include the consumption of red meat or meat alternatives 3 times per week for 10 weeks. Blood samples of the participants will be collected to measure changes in erythrocyte fatty acid distribution, circulating amino acids, neurotransmitters, markers of mineral status, and inflammatory markers. Questionnaires to assess well-being and mental health will be undertaken every 2 weeks. Body composition, physical function, and blood parameters will be assessed at allocation (t
0 ), week 5 into the intervention (t5 ), and post intervention (t10 )., Results: The protocol has been developed using the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) checklist and the outcomes will be reported in accordance with the CONSORT (Consolidated Standards of Reporting Trials) guidelines. The trial was approved by the New Zealand Ministry of Health's Health and Disability Ethics Committees (protocol 20/STH/157). The results of this study will be communicated via publication., Conclusions: To our knowledge, this is the first RCT investigating the overarching health consequences of consuming pasture-fed red meat or no meat as part of a healthy diet., Trial Registration: ClinicalTrials.gov NCT04869163; https://clinicaltrials.gov/ct2/show/NCT04869163., International Registered Report Identifier (irrid): PRR1-10.2196/30909., (©Andrea Braakhuis, Nicola Gillies, Anna Worthington, Scott Knowles, Tamlin Conner, Rajshri Roy, Toan Pham, Emma Bermingham, David Cameron-Smith. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 21.12.2021.)- Published
- 2021
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84. Prevalence of Congenital Heart Disease in an Isolated Single Umbilical Artery Is Low at a Tertiary Referral Center.
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Tai C, Conner T, Pevyandi S, and Moon-Grady AJ
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- Female, Humans, Pregnancy, Prevalence, Retrospective Studies, Tertiary Care Centers, Ultrasonography, Prenatal, Umbilical Arteries diagnostic imaging, Heart Defects, Congenital diagnostic imaging, Heart Defects, Congenital epidemiology, Single Umbilical Artery
- Published
- 2021
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85. Genetic Polymorphisms on OPRM1, DRD2, DRD4 , and COMT in Young Adults: Lack of Association With Alcohol Consumption.
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Chung P, Logge WB, Riordan BC, Haber PS, Merriman ME, Phipps-Green A, Topless RK, Merriman TR, Conner T, and Morley KC
- Abstract
Background: Risk behaviors for young adults such as alcohol use are associated with increased risk of morbidity and mortality. Patterns of risk behavior may be genetically determined and vary between genders. Previous studies in both young adults and heavy drinking adult samples have demonstrated that some genotypes, such as OPRM1 A118G, COMT Val158Met and DRD2 Taq1A and DRD4 C52IT, may predict addictive behaviors including alcohol consumption and impulsivity, although results have been mixed. Methods: This study aimed to investigate the predictive relationship of these four single nucleotide polymorphisms (SNPs) prospectively on student patterns of drinking using a micro-longitudinal daily diary design in a sample of 628 young adults ages 18-25 of predominantly of European ethnicity. Linear mixed models were used to examine the effect of SNPs on the number of drinks per drinking session with gender as a moderating variable. Results: There were no main effects for genotype on alcohol consumption, nor for gender × genotype for any of the SNPs. There was a trend for an effect of the DRD2 Taq1A on the number of drinks per drinking day and for the interaction of gender and DRD2 Taq1A on the number of drinks per drinking day. Conclusion: These findings suggest that the DRD2 Taq1A , OPRM1 A118G, DRD4 C521T, or COMT Val158Met polymorphisms, are not associated with alcohol consumption in young adults, although there may be a relationship between DRD2 Taq1A and alcohol consumption in young adult males., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Chung, Logge, Riordan, Haber, Merriman, Phipps-Green, Topless, Merriman, Conner and Morley.)
- Published
- 2020
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86. Patient safety from executive hospital management to wards: A qualitative study identifying factors influencing implementation.
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Conner T, Unsworth J, and Machin A
- Subjects
- Focus Groups methods, Humans, Organization and Administration standards, Organization and Administration statistics & numerical data, Patient Safety statistics & numerical data, Patients' Rooms organization & administration, Patients' Rooms standards, Patients' Rooms statistics & numerical data, Program Evaluation methods, Qualitative Research, Safety Management statistics & numerical data, State Medicine organization & administration, State Medicine statistics & numerical data, Patient Safety standards, Safety Management standards
- Abstract
Aim: To examine the journey of safety initiatives from executive hospital management to ward., Background: Hospital management teams are often responsible for identifying safety priorities and ensuring delivery of these., Method: Naturalistic study design within a large NHS Hospital Trust. Using semi-structured interviews, focus groups and secondary data analysis, the study examines the implementation of safety initiatives., Results: While hospital management developed five safety initiatives, only one of these (falls prevention) was actually seen to permeate all layers of the organisation. Other initiatives stopped one layer down. Both middle management and ward staff added to the list of initiatives developed, resulting in 16 priorities. A range of positive and negative influences to successful implementation are identified., Conclusions: Safety initiatives need positive reinforcement at all levels to be addressed appropriately. The research suggests that a model related to improvement science may prove useful in ensuring that priorities are addressed., Implications for Nursing Management: Care should be taken to ensure that safety initiatives are successfully implemented at all levels within an organisation. Identifying priorities with staff and sharing values and priorities are a key approach to leading such initiatives., (© 2020 John Wiley & Sons Ltd.)
- Published
- 2020
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87. Symmetric Age Association of Retinal Degeneration in Patients with CLN2-Associated Batten Disease.
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Kovacs KD, Patel S, Orlin A, Kim K, Van Everen S, Conner T, Sondhi D, Kaminsky SM, D'Amico DJ, Crystal RG, and Kiss S
- Subjects
- Aminopeptidases metabolism, Child, Preschool, DNA Mutational Analysis, Dipeptidyl-Peptidases and Tripeptidyl-Peptidases metabolism, Fluorescein Angiography, Fundus Oculi, Humans, Infant, Macular Degeneration diagnosis, Neuronal Ceroid-Lipofuscinoses complications, Neuronal Ceroid-Lipofuscinoses diagnosis, Retrospective Studies, Serine Proteases metabolism, Tomography, Optical Coherence methods, Tripeptidyl-Peptidase 1, Aminopeptidases genetics, DNA genetics, Dipeptidyl-Peptidases and Tripeptidyl-Peptidases genetics, Macular Degeneration etiology, Mutation, Neuronal Ceroid-Lipofuscinoses genetics, Retina pathology, Serine Proteases genetics, Visual Acuity
- Abstract
Purpose: Mutations in the CLN2 gene lead to a neurodegenerative and blinding lysosomal storage disorder: late infantile neuronal ceroid lipofucinosis, also known as "CLN2 disease." The purpose of the current study was to characterize the evolution of CLN2-associated retinal manifestations using the Weill Cornell Batten Scale (WCBS) and the age association of the retinal degeneration using central subfield thickness (CST) measurements and then correlate these findings with fundus photography and OCT to determine a critical period for retinal intervention., Design: Retrospective, single-center cohort., Participants: Eighty-four eyes of 42 treatment-naïve patients with CLN2 disease., Methods: Clinical records, fundus photographs, and OCT imaging for patients with CLN2 disease collected during examinations under anesthesia were reviewed. Imaging was categorized per WCBS criteria by 3 masked graders., Main Outcome Measures: CLN2-associated retinopathy assessed using WCBS scores, fundus photographs, and OCT imaging, correlated with patient age., Results: Eighty-four eyes of 42 patients had baseline fundus photographs, with baseline OCT in 31 eyes of 16 patients. Fundus photographs were obtained serially for 26 eyes of 13 patients, and serial OCT scans were obtained in 10 eyes of 5 patients. At baseline, bilateral WCBS scores were highly correlated for OCT and fundus photographs (r = 0.96 and 0.82, respectively). Central subfield thickness was negatively correlated with left and right eye WCBS OCT scores (r = -0.92 and -0.83, respectively; P < 0.001) and fundus photograph scores (r = -0.80 and -0.83, respectively; P < 0.001). OCT thickness was symmetrical between each eye. Baseline OCT data with age fit using a sigmoid function demonstrated a period of accelerated loss between 48 and 72 months of age., Conclusions: Retinal degeneration associated with CLN2 disease manifests as a progressive, symmetrical decline, which appears to accelerate during a critical period at 48 to 72 months of age, suggesting intervention with retina-specific CLN2 gene therapy should occur ideally before or as early as possible within this critical period. The WCBS is a valuable tool and is highly correlated with the extent of retinal degeneration observed in OCT or fundus photographs; by using the fellow eye as a control, this grading scale can be used to monitor the effect of CLN2 gene therapy in future trials., (Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)
- Published
- 2020
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88. An online survey of burden of illness in families with mucopolysaccharidosis type II children in the United States.
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Conner T, Cook F, Fernandez V, and Rangel-Miller V
- Published
- 2019
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89. Observed data quality concerns involving low-cost air sensors.
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Clements AL, Reece S, Conner T, and Williams R
- Abstract
Competing Interests: Conflicts of interest None.
- Published
- 2019
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90. Global citizens.
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Porteous D, Morgan D, Solomon J, Platt A, Allan J, Shao CHJ, and Conner T
- Subjects
- Global Health, Humans, Learning, United Kingdom, Education, Nursing organization & administration, International Educational Exchange, Students, Nursing psychology
- Abstract
Nurses and nursing students from the UK and overseas are learning in each other's countries.
- Published
- 2019
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91. An online survey on burden of illness among families with post-stem cell transplant mucopolysaccharidosis type I children in the United States.
- Author
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Conner T, Cook F, Fernandez V, Rascati K, and Rangel-Miller V
- Subjects
- Adolescent, Child, Child, Preschool, Cost of Illness, Female, Humans, Internet, Male, Stem Cell Transplantation economics, Surveys and Questionnaires, United States, Mucopolysaccharidosis I economics
- Abstract
Background: Severe mucopolysaccharidosis type I (also known as Hurler syndrome) is a rare devasting recessive genetic disease caused by the deficiency of an enzyme. Hematopoietic stem cell transplant is the standard of care in the United States, usually conducted before the child is 3 years of age, but little is known about the continued medical and educational needs of the child after transplant. A greater understanding of the burden of illness on the primary caregiver is also needed. Therefore, this online survey sought to gather information on the burden of severe MPS I in the United States at least 1 year after transplant., Results: Thirty-two respondents reported that children with severe MPS I have significant medical and educational needs after transplant. Healthcare resource use was frequent, especially in the outpatient setting specifically for bone, cardiac, and vision complications that were not relieved by HSCT. Twenty-five percent of the children had been hospitalized at least once in the last year and two had been hospitalized twice. The most common reasons for overnight hospitalizations included orthopedic surgeries and respiratory infections. Among children ages 5 and older, only 3 of 28 (11%) were able to attend school with no special support. While caregivers were generally satisfied with the healthcare services their child receives, 69% of working caregivers reported negative impact on their ability to conduct work tasks, and 54% of caregivers did not work so that they could care for the child., Conclusions: Results suggest that severe MPS I children continue to require medical care and special support for education. Future research on the burden of illness on families affected by severe MPS I is needed to better understand total cost of care, and to identify therapies and interventions that reduce burden of illness. Future studies that compare cost of and access to health care in different countries may provide a more global view of the burden of MPS I.
- Published
- 2019
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92. The Brief Case: Misidentification of Brucella melitensis as Ochrobactrum anthropi by Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS).
- Author
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Poonawala H, Marrs Conner T, and Peaper DR
- Subjects
- Anti-Bacterial Agents therapeutic use, Antibodies, Bacterial blood, Brucella melitensis genetics, Brucella melitensis immunology, Brucellosis drug therapy, Child, Gram-Negative Bacterial Infections microbiology, Humans, Male, Ochrobactrum anthropi genetics, Polymerase Chain Reaction, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Splenomegaly diagnostic imaging, Travel-Related Illness, Treatment Outcome, Brucella melitensis isolation & purification, Brucellosis diagnosis, Diagnostic Errors, Ochrobactrum anthropi isolation & purification
- Published
- 2018
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93. Closing the Brief Case: Misidentification of Brucella melitensis as Ochrobactrum anthropi by Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS).
- Author
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Poonawala H, Marrs Conner T, and Peaper DR
- Subjects
- Polymerase Chain Reaction, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Brucella melitensis, Ochrobactrum anthropi genetics
- Published
- 2018
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94. Prostate-specific antigen velocity in a prospective prostate cancer screening study of men with genetic predisposition.
- Author
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Mikropoulos C, Hutten Selkirk CG, Saya S, Bancroft E, Vertosick E, Dadaev T, Brendler C, Page E, Dias A, Evans DG, Rothwell J, Maehle L, Axcrona K, Richardson K, Eccles D, Jensen T, Osther PJ, van Asperen CJ, Vasen H, Kiemeney LA, Ringelberg J, Cybulski C, Wokolorczyk D, Hart R, Glover W, Lam J, Taylor L, Salinas M, Feliubadaló L, Oldenburg R, Cremers R, Verhaegh G, van Zelst-Stams WA, Oosterwijk JC, Cook J, Rosario DJ, Buys SS, Conner T, Domchek S, Powers J, Ausems MGEM, Teixeira MR, Maia S, Izatt L, Schmutzler R, Rhiem K, Foulkes WD, Boshari T, Davidson R, Ruijs M, Helderman-van den Enden ATJM, Andrews L, Walker L, Snape K, Henderson A, Jobson I, Lindeman GJ, Liljegren A, Harris M, Adank MA, Kirk J, Taylor A, Susman R, Chen-Shtoyerman R, Pachter N, Spigelman A, Side L, Zgajnar J, Mora J, Brewer C, Gadea N, Brady AF, Gallagher D, van Os T, Donaldson A, Stefansdottir V, Barwell J, James PA, Murphy D, Friedman E, Nicolai N, Greenhalgh L, Obeid E, Murthy V, Copakova L, McGrath J, Teo SH, Strom S, Kast K, Leongamornlert DA, Chamberlain A, Pope J, Newlin AC, Aaronson N, Ardern-Jones A, Bangma C, Castro E, Dearnaley D, Eyfjord J, Falconer A, Foster CS, Gronberg H, Hamdy FC, Johannsson O, Khoo V, Lubinski J, Grindedal EM, McKinley J, Shackleton K, Mitra AV, Moynihan C, Rennert G, Suri M, Tricker K, Moss S, Kote-Jarai Z, Vickers A, Lilja H, Helfand BT, and Eeles RA
- Abstract
This corrects the article DOI: 10.1038/bjc.2017.429.
- Published
- 2018
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95. Identification of ten variants associated with risk of estrogen-receptor-negative breast cancer.
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Milne RL, Kuchenbaecker KB, Michailidou K, Beesley J, Kar S, Lindström S, Hui S, Lemaçon A, Soucy P, Dennis J, Jiang X, Rostamianfar A, Finucane H, Bolla MK, McGuffog L, Wang Q, Aalfs CM, Adams M, Adlard J, Agata S, Ahmed S, Ahsan H, Aittomäki K, Al-Ejeh F, Allen J, Ambrosone CB, Amos CI, Andrulis IL, Anton-Culver H, Antonenkova NN, Arndt V, Arnold N, Aronson KJ, Auber B, Auer PL, Ausems MGEM, Azzollini J, Bacot F, Balmaña J, Barile M, Barjhoux L, Barkardottir RB, Barrdahl M, Barnes D, Barrowdale D, Baynes C, Beckmann MW, Benitez J, Bermisheva M, Bernstein L, Bignon YJ, Blazer KR, Blok MJ, Blomqvist C, Blot W, Bobolis K, Boeckx B, Bogdanova NV, Bojesen A, Bojesen SE, Bonanni B, Børresen-Dale AL, Bozsik A, Bradbury AR, Brand JS, Brauch H, Brenner H, Bressac-de Paillerets B, Brewer C, Brinton L, Broberg P, Brooks-Wilson A, Brunet J, Brüning T, Burwinkel B, Buys SS, Byun J, Cai Q, Caldés T, Caligo MA, Campbell I, Canzian F, Caron O, Carracedo A, Carter BD, Castelao JE, Castera L, Caux-Moncoutier V, Chan SB, Chang-Claude J, Chanock SJ, Chen X, Cheng TD, Chiquette J, Christiansen H, Claes KBM, Clarke CL, Conner T, Conroy DM, Cook J, Cordina-Duverger E, Cornelissen S, Coupier I, Cox A, Cox DG, Cross SS, Cuk K, Cunningham JM, Czene K, Daly MB, Damiola F, Darabi H, Davidson R, De Leeneer K, Devilee P, Dicks E, Diez O, Ding YC, Ditsch N, Doheny KF, Domchek SM, Dorfling CM, Dörk T, Dos-Santos-Silva I, Dubois S, Dugué PA, Dumont M, Dunning AM, Durcan L, Dwek M, Dworniczak B, Eccles D, Eeles R, Ehrencrona H, Eilber U, Ejlertsen B, Ekici AB, Eliassen AH, Engel C, Eriksson M, Fachal L, Faivre L, Fasching PA, Faust U, Figueroa J, Flesch-Janys D, Fletcher O, Flyger H, Foulkes WD, Friedman E, Fritschi L, Frost D, Gabrielson M, Gaddam P, Gammon MD, Ganz PA, Gapstur SM, Garber J, Garcia-Barberan V, García-Sáenz JA, Gaudet MM, Gauthier-Villars M, Gehrig A, Georgoulias V, Gerdes AM, Giles GG, Glendon G, Godwin AK, Goldberg MS, Goldgar DE, González-Neira A, Goodfellow P, Greene MH, Alnæs GIG, Grip M, Gronwald J, Grundy A, Gschwantler-Kaulich D, Guénel P, Guo Q, Haeberle L, Hahnen E, Haiman CA, Håkansson N, Hallberg E, Hamann U, Hamel N, Hankinson S, Hansen TVO, Harrington P, Hart SN, Hartikainen JM, Healey CS, Hein A, Helbig S, Henderson A, Heyworth J, Hicks B, Hillemanns P, Hodgson S, Hogervorst FB, Hollestelle A, Hooning MJ, Hoover B, Hopper JL, Hu C, Huang G, Hulick PJ, Humphreys K, Hunter DJ, Imyanitov EN, Isaacs C, Iwasaki M, Izatt L, Jakubowska A, James P, Janavicius R, Janni W, Jensen UB, John EM, Johnson N, Jones K, Jones M, Jukkola-Vuorinen A, Kaaks R, Kabisch M, Kaczmarek K, Kang D, Kast K, Keeman R, Kerin MJ, Kets CM, Keupers M, Khan S, Khusnutdinova E, Kiiski JI, Kim SW, Knight JA, Konstantopoulou I, Kosma VM, Kristensen VN, Kruse TA, Kwong A, Lænkholm AV, Laitman Y, Lalloo F, Lambrechts D, Landsman K, Lasset C, Lazaro C, Le Marchand L, Lecarpentier J, Lee A, Lee E, Lee JW, Lee MH, Lejbkowicz F, Lesueur F, Li J, Lilyquist J, Lincoln A, Lindblom A, Lissowska J, Lo WY, Loibl S, Long J, Loud JT, Lubinski J, Luccarini C, Lush M, MacInnis RJ, Maishman T, Makalic E, Kostovska IM, Malone KE, Manoukian S, Manson JE, Margolin S, Martens JWM, Martinez ME, Matsuo K, Mavroudis D, Mazoyer S, McLean C, Meijers-Heijboer H, Menéndez P, Meyer J, Miao H, Miller A, Miller N, Mitchell G, Montagna M, Muir K, Mulligan AM, Mulot C, Nadesan S, Nathanson KL, Neuhausen SL, Nevanlinna H, Nevelsteen I, Niederacher D, Nielsen SF, Nordestgaard BG, Norman A, Nussbaum RL, Olah E, Olopade OI, Olson JE, Olswold C, Ong KR, Oosterwijk JC, Orr N, Osorio A, Pankratz VS, Papi L, Park-Simon TW, Paulsson-Karlsson Y, Lloyd R, Pedersen IS, Peissel B, Peixoto A, Perez JIA, Peterlongo P, Peto J, Pfeiler G, Phelan CM, Pinchev M, Plaseska-Karanfilska D, Poppe B, Porteous ME, Prentice R, Presneau N, Prokofieva D, Pugh E, Pujana MA, Pylkäs K, Rack B, Radice P, Rahman N, Rantala J, Rappaport-Fuerhauser C, Rennert G, Rennert HS, Rhenius V, Rhiem K, Richardson A, Rodriguez GC, Romero A, Romm J, Rookus MA, Rudolph A, Ruediger T, Saloustros E, Sanders J, Sandler DP, Sangrajrang S, Sawyer EJ, Schmidt DF, Schoemaker MJ, Schumacher F, Schürmann P, Schwentner L, Scott C, Scott RJ, Seal S, Senter L, Seynaeve C, Shah M, Sharma P, Shen CY, Sheng X, Shimelis H, Shrubsole MJ, Shu XO, Side LE, Singer CF, Sohn C, Southey MC, Spinelli JJ, Spurdle AB, Stegmaier C, Stoppa-Lyonnet D, Sukiennicki G, Surowy H, Sutter C, Swerdlow A, Szabo CI, Tamimi RM, Tan YY, Taylor JA, Tejada MI, Tengström M, Teo SH, Terry MB, Tessier DC, Teulé A, Thöne K, Thull DL, Tibiletti MG, Tihomirova L, Tischkowitz M, Toland AE, Tollenaar RAEM, Tomlinson I, Tong L, Torres D, Tranchant M, Truong T, Tucker K, Tung N, Tyrer J, Ulmer HU, Vachon C, van Asperen CJ, Van Den Berg D, van den Ouweland AMW, van Rensburg EJ, Varesco L, Varon-Mateeva R, Vega A, Viel A, Vijai J, Vincent D, Vollenweider J, Walker L, Wang Z, Wang-Gohrke S, Wappenschmidt B, Weinberg CR, Weitzel JN, Wendt C, Wesseling J, Whittemore AS, Wijnen JT, Willett W, Winqvist R, Wolk A, Wu AH, Xia L, Yang XR, Yannoukakos D, Zaffaroni D, Zheng W, Zhu B, Ziogas A, Ziv E, Zorn KK, Gago-Dominguez M, Mannermaa A, Olsson H, Teixeira MR, Stone J, Offit K, Ottini L, Park SK, Thomassen M, Hall P, Meindl A, Schmutzler RK, Droit A, Bader GD, Pharoah PDP, Couch FJ, Easton DF, Kraft P, Chenevix-Trench G, García-Closas M, Schmidt MK, Antoniou AC, and Simard J
- Subjects
- Breast Neoplasms ethnology, Breast Neoplasms metabolism, Female, Genetic Predisposition to Disease ethnology, Genome-Wide Association Study methods, Heterozygote, Humans, Receptors, Estrogen metabolism, Risk Factors, White People genetics, BRCA1 Protein genetics, Breast Neoplasms genetics, Genetic Predisposition to Disease genetics, Mutation, Polymorphism, Single Nucleotide
- Abstract
Most common breast cancer susceptibility variants have been identified through genome-wide association studies (GWAS) of predominantly estrogen receptor (ER)-positive disease. We conducted a GWAS using 21,468 ER-negative cases and 100,594 controls combined with 18,908 BRCA1 mutation carriers (9,414 with breast cancer), all of European origin. We identified independent associations at P < 5 × 10
-8 with ten variants at nine new loci. At P < 0.05, we replicated associations with 10 of 11 variants previously reported in ER-negative disease or BRCA1 mutation carrier GWAS and observed consistent associations with ER-negative disease for 105 susceptibility variants identified by other studies. These 125 variants explain approximately 16% of the familial risk of this breast cancer subtype. There was high genetic correlation (0.72) between risk of ER-negative breast cancer and breast cancer risk for BRCA1 mutation carriers. These findings may lead to improved risk prediction and inform further fine-mapping and functional work to better understand the biological basis of ER-negative breast cancer.- Published
- 2017
- Full Text
- View/download PDF
96. Rationale and design of the Drug-Eluting Stents vs Bare-Metal Stents in Saphenous Vein Graft Angioplasty (DIVA) Trial.
- Author
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Brilakis ES, Banerjee S, Edson R, Shunk K, Goldman S, Holmes DR Jr, Bhatt DL, Rao SV, Smith MW, Sather M, Colling C, Kar B, Nielsen L, Conner T, Wagner T, Rangan BV, Ventura B, Lu Y, Holodniy M, and Shih MC
- Subjects
- Aged, Clinical Protocols, Coronary Artery Bypass mortality, Coronary Artery Disease mortality, Female, Graft Occlusion, Vascular diagnostic imaging, Graft Occlusion, Vascular mortality, Graft Occlusion, Vascular physiopathology, Humans, Male, Middle Aged, Percutaneous Coronary Intervention adverse effects, Percutaneous Coronary Intervention mortality, Platelet Aggregation Inhibitors administration & dosage, Prospective Studies, Prosthesis Design, Research Design, Risk Factors, Saphenous Vein diagnostic imaging, Saphenous Vein physiopathology, Time Factors, Treatment Outcome, United States, United States Department of Veterans Affairs, Vascular Patency, Coronary Artery Bypass adverse effects, Coronary Artery Disease surgery, Drug-Eluting Stents, Graft Occlusion, Vascular therapy, Metals, Percutaneous Coronary Intervention instrumentation, Saphenous Vein transplantation, Stents
- Abstract
VA Cooperative Studies Program #571 (DIVA) was designed to evaluate the efficacy of drug-eluting stents (DES) for reducing aortocoronary saphenous vein bypass graft (SVG) failure when compared with bare-metal stents (BMS) in participants undergoing stenting of de novo SVG lesions. Participants undergoing clinically indicated stenting of de novo SVG lesions were randomized in a 1:1 ratio to DES or BMS. Randomization was stratified by presence/absence of diabetes mellitus and the number of target SVG lesions (1 vs ≥2) within each participating site. At sites that did not routinely administer 12-months of dual antiplatelet therapy after SVG stenting participants without acute coronary syndromes received 1 month of open-label clopidogrel, followed by 11 months of clopidogrel for those assigned to DES and 11 months of placebo for those assigned to BMS. The primary endpoint was the 12-month incidence of target-vessel failure (defined as the composite of cardiac death, target-vessel myocardial infarction, or target-vessel revascularization). Secondary endpoints included the incidence of other clinical endpoints and the incremental cost-effectiveness of DES relative to BMS. Due to lower-than-anticipated target-vessel failure rates, target enrollment was increased from 519 to 762. The study had randomized 599 participants when recruitment ended in December 2015. The DIVA trial will provide clarity on the appropriate stent type for de novo SVG lesions., (© 2017 Wiley Periodicals, Inc.)
- Published
- 2017
- Full Text
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97. Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer.
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Phelan CM, Kuchenbaecker KB, Tyrer JP, Kar SP, Lawrenson K, Winham SJ, Dennis J, Pirie A, Riggan MJ, Chornokur G, Earp MA, Lyra PC Jr, Lee JM, Coetzee S, Beesley J, McGuffog L, Soucy P, Dicks E, Lee A, Barrowdale D, Lecarpentier J, Leslie G, Aalfs CM, Aben KKH, Adams M, Adlard J, Andrulis IL, Anton-Culver H, Antonenkova N, Aravantinos G, Arnold N, Arun BK, Arver B, Azzollini J, Balmaña J, Banerjee SN, Barjhoux L, Barkardottir RB, Bean Y, Beckmann MW, Beeghly-Fadiel A, Benitez J, Bermisheva M, Bernardini MQ, Birrer MJ, Bjorge L, Black A, Blankstein K, Blok MJ, Bodelon C, Bogdanova N, Bojesen A, Bonanni B, Borg Å, Bradbury AR, Brenton JD, Brewer C, Brinton L, Broberg P, Brooks-Wilson A, Bruinsma F, Brunet J, Buecher B, Butzow R, Buys SS, Caldes T, Caligo MA, Campbell I, Cannioto R, Carney ME, Cescon T, Chan SB, Chang-Claude J, Chanock S, Chen XQ, Chiew YE, Chiquette J, Chung WK, Claes KBM, Conner T, Cook LS, Cook J, Cramer DW, Cunningham JM, D'Aloisio AA, Daly MB, Damiola F, Damirovna SD, Dansonka-Mieszkowska A, Dao F, Davidson R, DeFazio A, Delnatte C, Doheny KF, Diez O, Ding YC, Doherty JA, Domchek SM, Dorfling CM, Dörk T, Dossus L, Duran M, Dürst M, Dworniczak B, Eccles D, Edwards T, Eeles R, Eilber U, Ejlertsen B, Ekici AB, Ellis S, Elvira M, Eng KH, Engel C, Evans DG, Fasching PA, Ferguson S, Ferrer SF, Flanagan JM, Fogarty ZC, Fortner RT, Fostira F, Foulkes WD, Fountzilas G, Fridley BL, Friebel TM, Friedman E, Frost D, Ganz PA, Garber J, García MJ, Garcia-Barberan V, Gehrig A, Gentry-Maharaj A, Gerdes AM, Giles GG, Glasspool R, Glendon G, Godwin AK, Goldgar DE, Goranova T, Gore M, Greene MH, Gronwald J, Gruber S, Hahnen E, Haiman CA, Håkansson N, Hamann U, Hansen TVO, Harrington PA, Harris HR, Hauke J, Hein A, Henderson A, Hildebrandt MAT, Hillemanns P, Hodgson S, Høgdall CK, Høgdall E, Hogervorst FBL, Holland H, Hooning MJ, Hosking K, Huang RY, Hulick PJ, Hung J, Hunter DJ, Huntsman DG, Huzarski T, Imyanitov EN, Isaacs C, Iversen ES, Izatt L, Izquierdo A, Jakubowska A, James P, Janavicius R, Jernetz M, Jensen A, Jensen UB, John EM, Johnatty S, Jones ME, Kannisto P, Karlan BY, Karnezis A, Kast K, Kennedy CJ, Khusnutdinova E, Kiemeney LA, Kiiski JI, Kim SW, Kjaer SK, Köbel M, Kopperud RK, Kruse TA, Kupryjanczyk J, Kwong A, Laitman Y, Lambrechts D, Larrañaga N, Larson MC, Lazaro C, Le ND, Le Marchand L, Lee JW, Lele SB, Leminen A, Leroux D, Lester J, Lesueur F, Levine DA, Liang D, Liebrich C, Lilyquist J, Lipworth L, Lissowska J, Lu KH, Lubinński J, Luccarini C, Lundvall L, Mai PL, Mendoza-Fandiño G, Manoukian S, Massuger LFAG, May T, Mazoyer S, McAlpine JN, McGuire V, McLaughlin JR, McNeish I, Meijers-Heijboer H, Meindl A, Menon U, Mensenkamp AR, Merritt MA, Milne RL, Mitchell G, Modugno F, Moes-Sosnowska J, Moffitt M, Montagna M, Moysich KB, Mulligan AM, Musinsky J, Nathanson KL, Nedergaard L, Ness RB, Neuhausen SL, Nevanlinna H, Niederacher D, Nussbaum RL, Odunsi K, Olah E, Olopade OI, Olsson H, Olswold C, O'Malley DM, Ong KR, Onland-Moret NC, Orr N, Orsulic S, Osorio A, Palli D, Papi L, Park-Simon TW, Paul J, Pearce CL, Pedersen IS, Peeters PHM, Peissel B, Peixoto A, Pejovic T, Pelttari LM, Permuth JB, Peterlongo P, Pezzani L, Pfeiler G, Phillips KA, Piedmonte M, Pike MC, Piskorz AM, Poblete SR, Pocza T, Poole EM, Poppe B, Porteous ME, Prieur F, Prokofyeva D, Pugh E, Pujana MA, Pujol P, Radice P, Rantala J, Rappaport-Fuerhauser C, Rennert G, Rhiem K, Rice P, Richardson A, Robson M, Rodriguez GC, Rodríguez-Antona C, Romm J, Rookus MA, Rossing MA, Rothstein JH, Rudolph A, Runnebaum IB, Salvesen HB, Sandler DP, Schoemaker MJ, Senter L, Setiawan VW, Severi G, Sharma P, Shelford T, Siddiqui N, Side LE, Sieh W, Singer CF, Sobol H, Song H, Southey MC, Spurdle AB, Stadler Z, Steinemann D, Stoppa-Lyonnet D, Sucheston-Campbell LE, Sukiennicki G, Sutphen R, Sutter C, Swerdlow AJ, Szabo CI, Szafron L, Tan YY, Taylor JA, Tea MK, Teixeira MR, Teo SH, Terry KL, Thompson PJ, Thomsen LCV, Thull DL, Tihomirova L, Tinker AV, Tischkowitz M, Tognazzo S, Toland AE, Tone A, Trabert B, Travis RC, Trichopoulou A, Tung N, Tworoger SS, van Altena AM, Van Den Berg D, van der Hout AH, van der Luijt RB, Van Heetvelde M, Van Nieuwenhuysen E, van Rensburg EJ, Vanderstichele A, Varon-Mateeva R, Vega A, Edwards DV, Vergote I, Vierkant RA, Vijai J, Vratimos A, Walker L, Walsh C, Wand D, Wang-Gohrke S, Wappenschmidt B, Webb PM, Weinberg CR, Weitzel JN, Wentzensen N, Whittemore AS, Wijnen JT, Wilkens LR, Wolk A, Woo M, Wu X, Wu AH, Yang H, Yannoukakos D, Ziogas A, Zorn KK, Narod SA, Easton DF, Amos CI, Schildkraut JM, Ramus SJ, Ottini L, Goodman MT, Park SK, Kelemen LE, Risch HA, Thomassen M, Offit K, Simard J, Schmutzler RK, Hazelett D, Monteiro AN, Couch FJ, Berchuck A, Chenevix-Trench G, Goode EL, Sellers TA, Gayther SA, Antoniou AC, and Pharoah PDP
- Subjects
- Alleles, BRCA1 Protein genetics, BRCA2 Protein genetics, Carcinoma, Ovarian Epithelial, Female, Genome-Wide Association Study, Genotype, Humans, Meta-Analysis as Topic, Mutation, Neoplasms, Glandular and Epithelial pathology, Ovarian Neoplasms pathology, Polymorphism, Single Nucleotide, Risk Factors, Telomere-Binding Proteins genetics, Genetic Loci genetics, Genetic Predisposition to Disease genetics, Neoplasms, Glandular and Epithelial genetics, Ovarian Neoplasms genetics
- Abstract
To identify common alleles associated with different histotypes of epithelial ovarian cancer (EOC), we pooled data from multiple genome-wide genotyping projects totaling 25,509 EOC cases and 40,941 controls. We identified nine new susceptibility loci for different EOC histotypes: six for serous EOC histotypes (3q28, 4q32.3, 8q21.11, 10q24.33, 18q11.2 and 22q12.1), two for mucinous EOC (3q22.3 and 9q31.1) and one for endometrioid EOC (5q12.3). We then performed meta-analysis on the results for high-grade serous ovarian cancer with the results from analysis of 31,448 BRCA1 and BRCA2 mutation carriers, including 3,887 mutation carriers with EOC. This identified three additional susceptibility loci at 2q13, 8q24.1 and 12q24.31. Integrated analyses of genes and regulatory biofeatures at each locus predicted candidate susceptibility genes, including OBFC1, a new candidate susceptibility gene for low-grade and borderline serous EOC.
- Published
- 2017
- Full Text
- View/download PDF
98. The Relationship Between Dietary Acculturation and Type 2 Diabetes Risk Among Asian Indians in the U.S.
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Venkatesh S, Conner T, Song WO, Olson BH, and Weatherspoon LJ
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- Adult, Aged, Aged, 80 and over, Body Weights and Measures, Cross-Sectional Studies, Female, Health Behavior, Humans, India ethnology, Life Style, Male, Middle Aged, Risk Factors, Socioeconomic Factors, United States epidemiology, Young Adult, Acculturation, Asian statistics & numerical data, Diabetes Mellitus, Type 2 ethnology, Diet ethnology, Emigrants and Immigrants statistics & numerical data
- Abstract
Asian Indians have a high prevalence of type 2 diabetes in the U.S. (17.4-29 %). This study examined the relationship between dietary acculturation of Asian Indians in the U.S. and their future risk for type 2 diabetes. A validated Asian Indian Dietary Acculturation Measure (AIDAM) and the Finnish Diabetes Risk Score (FINDRISC) were completed by 153 Asian Indians in the U.S. via a cross-sectional web-survey. Correlations and relative risk ratios were used to examine the association between AIDAM and FINDRISC. A significantly larger proportion of Non-Indian Oriented participants (44.7 %) had higher FINDRISC scores (scores 7-26) compared to the Asian Indian Oriented group (27.9 %) (p = .024), and also had increased relative predictive risk for type 2 diabetes (relative risk ratio = 1.6). A positive association between dietary acculturation and diabetes risk was evident in our sample, which highlights the importance of assessing dietary acculturation in non-native groups when investigating type 2 diabetes risk factors.
- Published
- 2017
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- View/download PDF
99. Integrative analyses reveal signaling pathways underlying familial breast cancer susceptibility.
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Piccolo SR, Hoffman LM, Conner T, Shrestha G, Cohen AL, Marks JR, Neumayer LA, Agarwal CA, Beckerle MC, Andrulis IL, Spira AE, Moos PJ, Buys SS, Johnson WE, and Bild AH
- Subjects
- Aged, Breast Neoplasms genetics, Breast Neoplasms pathology, Cell Adhesion, Cohort Studies, Female, Gene Expression Profiling, Genetic Variation, Humans, Leukocytes, Mononuclear metabolism, Middle Aged, Breast Neoplasms metabolism, Genetic Predisposition to Disease, Signal Transduction
- Abstract
The signaling events that drive familial breast cancer (FBC) risk remain poorly understood. While the majority of genomic studies have focused on genetic risk variants, known risk variants account for at most 30% of FBC cases. Considering that multiple genes may influence FBC risk, we hypothesized that a pathway-based strategy examining different data types from multiple tissues could elucidate the biological basis for FBC. In this study, we performed integrated analyses of gene expression and exome-sequencing data from peripheral blood mononuclear cells and showed that cell adhesion pathways are significantly and consistently dysregulated in women who develop FBC. The dysregulation of cell adhesion pathways in high-risk women was also identified by pathway-based profiling applied to normal breast tissue data from two independent cohorts. The results of our genomic analyses were validated in normal primary mammary epithelial cells from high-risk and control women, using cell-based functional assays, drug-response assays, fluorescence microscopy, and Western blotting assays. Both genomic and cell-based experiments indicate that cell-cell and cell-extracellular matrix adhesion processes seem to be disrupted in non-malignant cells of women at high risk for FBC and suggest a potential role for these processes in FBC development., (© 2016 The Authors. Published under the terms of the CC BY 4.0 license.)
- Published
- 2016
- Full Text
- View/download PDF
100. Gene-expression patterns in peripheral blood classify familial breast cancer susceptibility.
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Piccolo SR, Andrulis IL, Cohen AL, Conner T, Moos PJ, Spira AE, Buys SS, Johnson WE, and Bild AH
- Subjects
- Adult, Breast Neoplasms blood, Breast Neoplasms genetics, Breast Neoplasms therapy, Case-Control Studies, Cohort Studies, Computational Biology, Female, Humans, Middle Aged, Mutation, Pedigree, Support Vector Machine, Genetic Predisposition to Disease genetics, Leukocytes, Mononuclear metabolism, Transcriptome
- Abstract
Background: Women with a family history of breast cancer face considerable uncertainty about whether to pursue standard screening, intensive screening, or prophylactic surgery. Accurate and individualized risk-estimation approaches may help these women make more informed decisions. Although highly penetrant genetic variants have been associated with familial breast cancer (FBC) risk, many individuals do not carry these variants, and many carriers never develop breast cancer. Common risk variants have a relatively modest effect on risk and show limited potential for predicting FBC development. As an alternative, we hypothesized that additional genomic data types, such as gene-expression levels, which can reflect genetic and epigenetic variation, could contribute to classifying a person's risk status. Specifically, we aimed to identify common patterns in gene-expression levels across individuals who develop FBC., Methods: We profiled peripheral blood mononuclear cells from women with a family history of breast cancer (with or without a germline BRCA1/2 variant) and from controls. We used the support vector machines algorithm to differentiate between patients who developed FBC and those who did not. Our study used two independent datasets, a training set of 124 women from Utah (USA) and an external validation (test) set from Ontario (Canada) of 73 women (197 total). We controlled for expression variation associated with clinical, demographic, and treatment variables as well as lymphocyte markers., Results: Our multigene biomarker provided accurate, individual-level estimates of FBC occurrence for the Utah cohort (AUC = 0.76 [0.67-84]) . Even at their lower confidence bounds, these accuracy estimates meet or exceed estimates from alternative approaches. Our Ontario cohort resulted in similarly high levels of accuracy (AUC = 0.73 [0.59-0.86]), thus providing external validation of our findings. Individuals deemed to have "high" risk by our model would have an estimated 2.4 times greater odds of developing familial breast cancer than individuals deemed to have "low" risk., Conclusions: Together, these findings suggest that gene-expression levels in peripheral blood cells reflect genomic variation associated with breast cancer risk and that such data have potential to be used as a non-invasive biomarker for familial breast cancer risk.
- Published
- 2015
- Full Text
- View/download PDF
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