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Sökning: WFRF:(Leske M Cristina)

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1.
  • Gusev, Alexander, et al. (författare)
  • Atlas of prostate cancer heritability in European and African-American men pinpoints tissue-specific regulation
  • 2016
  • Ingår i: Nature communications. - 2041-1723. ; 7, s. 10979
  • Tidskriftsartikel (refereegranskat)abstract
    • Although genome-wide association studies have identified over 100 risk loci that explain ∼33% of familial risk for prostate cancer (PrCa), their functional effects on risk remain largely unknown. Here we use genotype data from 59,089 men of European and African American ancestries combined with cell-type-specific epigenetic data to build a genomic atlas of single-nucleotide polymorphism (SNP) heritability in PrCa. We find significant differences in heritability between variants in prostate-relevant epigenetic marks defined in normal versus tumour tissue as well as between tissue and cell lines. The majority of SNP heritability lies in regions marked by H3k27 acetylation in prostate adenoc7arcinoma cell line (LNCaP) or by DNaseI hypersensitive sites in cancer cell lines. We find a high degree of similarity between European and African American ancestries suggesting a similar genetic architecture from common variation underlying PrCa risk. Our findings showcase the power of integrating functional annotation with genetic data to understand the genetic basis of PrCa.
2.
  • Broman, Aimee Teo, et al. (författare)
  • Estimating the rate of progressive visual field damage in those with open-angle glaucoma, from cross-sectional data
  • 2008
  • Ingår i: Investigative Ophthalmology & Visual Science. - ASSOC RESEARCH VISION OPHTHALMOLOGY INC. - 1552-5783. ; 49:1, s. 66-76
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE. To estimate the rate of visual field progression in open-angle glaucoma (OAG) subjects, by using data from population-based cross-sectional studies. METHODS. Subjects with OAG were identified in nine surveys of randomly sampled populations using standard criteria for glaucomatous optic neuropathy. Subjects were of European, African, Chinese, and Hispanic ethnicity. The measure of OAG damage was the mean deviation (MD) of an automated visual field test (Humphrey Field Analyzer; Carl Zeiss Meditec, Inc., Dublin, CA). The rate of progression was the mean of all subjects' damage in the worse eye divided by an average time since onset. Time since onset was estimated from age-specific prevalence rates. RESULTS. A total of 1066 subjects with OAG contributed visual field data. The mean worsening in decibels per year was: European-derived, -1.12; Hispanic, -1.26; African-derived, -1.33; and Chinese -1.56 (difference among ethnicities, P = 0.16). The mean duration of disease was lowest among Chinese persons at 10.5 years (95% CI: 8.8-12.6) and was highest in African-derived subjects at 15.4 years (95% CI: 14.6-15.9). The progression rate was not consistently related to age or gender. By combining disease duration and progression rate, the model predicted that 15% or fewer of the worse eyes would reach the end of the field damage scale in the patient's lifetime. CONCLUSIONS. The estimates of typical worsening per year in the worse eye among subjects with OAG suggested slightly more rapid progression than in some clinic-based studies. The rate did not differ significantly by ethnicity or gender, but was worse in those with known, treated OAG and in pseudophakic subjects.
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4.
  • Bengtsson, Boel, et al. (författare)
  • Disc Hemorrhages and Treatment in the Early Manifest Glaucoma Trial.
  • 2008
  • Ingår i: Ophthalmology. - Elsevier. - 1549-4713. ; Aug 7, s. 2044-2048
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: To evaluate the effect of intraocular pressure (IOP)-reducing treatment on the development of disc hemorrhages in patients with glaucoma. DESIGN: Prospective cohort study of patients in the Early Manifest Glaucoma Trial, followed up to 11 years (median = 8 years). PARTICIPANTS: Patients with newly detected glaucoma randomized to argon laser trabeculoplasty plus betaxolol (n = 129) or no initial treatment (n = 126), followed with tonometry, perimetry, and ophthalmoscopy every 3 months, and fundus photography every 6 months. METHODS: Logistic regression expressed as odds ratios (OR) and 95% confidence intervals (CIs), analysis of variance, and Cox time-dependent models, expressed as hazard ratios (HRs) and CIs. MAIN OUTCOME MEASURES: Presence (yes/no) and frequency of disc hemorrhages. RESULTS: Disc hemorrhages were identified in approximately 55% of all patients, whether by ophthalmoscopy or review of photographs. In analyses including data up to the time of progression, disc hemorrhages were equally common among treated and control patients: 51.2% versus 45.2%, respectively (P = 0.34), based on ophthalmoscopy, and 50.4% versus 44.4%, respectively (P = 0.34), based on photographs. Gender was the only factor related to the presence of disc hemorrhages detected by both ophthalmoscopy (OR = 0.48; CI, 0.26-0.88; P = 0.022) and photographs (OR = 0.64; CI, 0.38-1.09; P = 0.099) for male patients. The frequency of disc hemorrhages over time did not differ between treated and control patients: 8.4% versus 8.5%, respectively (P = 0.93), based on ophthalmoscopy, and 12.4% versus 11.2%, respectively (P = 0.36), based on photographs. Disc hemorrhages were significantly associated with time to progression (HR = 1.02; CI, 1.01-1.04), and there was no evidence of interaction between treatment group and disc hemorrhages. CONCLUSIONS: IOP-reducing treatment was unrelated to the presence or frequency of disc hemorrhages. The results may suggest that disc hemorrhages cannot be considered an indication of insufficient IOP-lowering treatment, and that glaucoma progression in eyes with disc hemorrhages cannot be totally halted by IOP reduction. The results also suggest that disc hemorrhages do not occur in all patients with glaucoma. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.
5.
  • Heijl, Anders, et al. (författare)
  • A Comparison of Visual Field Progression Criteria of 3 Major Glaucoma Trials in Early Manifest Glaucoma Trial Patients.
  • 2008
  • Ingår i: Ophthalmology. - Elsevier. - 1549-4713. ; 115, s. 1557-1565
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: Three major glaucoma trials, all using the same Humphrey visual field tests, specified different criteria to define visual field progression. This article compares the performance of these criteria with a reference standard of unanimous classifications by 3 independent glaucoma experts. DESIGN: Longitudinal, comparative study of diagnostic criteria. PARTICIPANTS AND CONTROLS: Two hundred forty-five patients with manifest glaucoma in the Early Manifest Glaucoma Trial (EMGT). METHODS: Visual field series of 1 eye of each of 245 EMGT patients were classified by 3 independent glaucoma specialists as definitely progressing, definitely nonprogressing, or neither. Field series that were classified in the first 2 categories by all 3 experts met the reference standards for the progressing and nonprogressing groups and were analyzed according to the progression criteria of the Advanced Glaucoma Intervention Study (AGIS), the Collaborative Initial Glaucoma Treatment Study (CIGTS), and the EMGT. Sensitivity, specificity, time to progression, and sustainability were calculated. MAIN OUTCOME MEASURES: Progression, nonprogression, sensitivity, specificity, time to progression, and sustainability. RESULTS: Seventy-seven field series were definitely progressing, and 95 series were definitely nonprogressing. Among progressing eyes, 45 (58%) of 77 were identified using AGIS criteria, 58 (75%) of 77 were identified with CIGTS criteria, and 74 (96%) of 77 were identified with EMGT criteria; all comparisons of sensitivities were significant, simultaneous (P<0.001), and pairwise (P<0.01). The specificity for EMGT criteria was 89%, lower (P<0.05) than that of AGIS (98%) and CIGTS (99%) criteria. Median time to progression was considerably shorter with EMGT criteria (33 months; 95% confidence interval [CI], 30-36 months) than with AGIS (66 months; 95% CI, 57-78 months) and CIGTS (55 months; 95% CI, 48-66 months) criteria. Sustainability increased with time after progression; it averaged 79%, 84%, and 81%, respectively, for AGIS, CIGTS, and EMGT criteria during the first year after the first progression and 95%, 100%, and 93% during the fourth year after progression. CONCLUSIONS: The EMGT criteria identified progression earlier and more often than AGIS and CIGTS criteria. Specificity was good for all criteria but was better with AGIS and CIGTS than with EMGT criteria. Sustainability was high for all 3 sets of criteria and best for CIGTS criteria and increased with time after progression.
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6.
  • Heijl, Anders, et al. (författare)
  • Cataract epidemiology
  • 2007
  • Ingår i: Ophthalmology. - Elsevier. - 1549-4713. ; 114:1, s. 201-201
  • Tidskriftsartikel (refereegranskat)
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7.
  • Heijl, Anders, et al. (författare)
  • Intraocular pressure reduction with a fixed treatment protocol in the Early Manifest Glaucoma Trial.
  • 2011
  • Ingår i: Acta Ophthalmologica. - Wiley-Blackwell. - 1755-3768. ; 89, s. 749-754
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: To evaluate: (i) the relationship between intraocular pressure (IOP) reduction attained with a fixed treatment protocol and the untreated IOP level; (ii) the consistency of IOP reduction over time; and (iii) whether there is a threshold pretreatment IOP level below which IOP reduction might be less effective. Results are based on 128 patients with glaucoma with field defects, who were randomized to the treatment arm of the Early Manifest Glaucoma Trial (EMGT). Methods: The EMGT fixed treatment protocol consisted of 360 degrees laser trabeculoplasty and topical betaxolol eye drops B.I.D. Treatment was unchanged as long as progression did not occur. Analyses assessed the initial IOP reduction after 3 months and also the mean reduction based on all follow-up values; IOP changes over time were evaluated with linear regression analysis. Factors influencing initial and mean IOP reduction were also explored using linear models. Results: Mean age at baseline was 68 years, and untreated baseline IOP ranged from 13 to 30.5 mmHg. On average, eyes with higher baseline IOP experienced larger pressure reductions than eyes with lower baseline IOP, whether expressed in mmHg or as percentages. Each mmHg of higher baseline IOP was associated with approximately 0.6 mmHg larger IOP reduction. IOP changed little over time, with 66% of patients changing less than 0.5 mmHg/year, and only 13% (17/128) changing >1.0 mmHg/year. The treatment protocol did not achieve any average IOP reduction in eyes with baseline pressures </= 15 mmHg. Factors related to more IOP reduction at 3 months were higher baseline IOP and positive refractive error, while higher baseline IOP and male gender (more reduction) and cardiovascular disease history (less reduction) were associated with mean IOP on treatment. Conclusion: With a fixed treatment protocol, the IOP reduction achieved depended very strongly on baseline untreated IOP levels. There seemed to be a lower threshold around 15 mmHg, where therapy did not result in any reduction of IOP. Our results suggest that when effects of IOP-lowering treatment are reported, whether expressed in mmHg or as a percentage of untreated pressure levels, the baseline IOP levels should be specified as well.
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9.
  • Heijl, Anders, et al. (författare)
  • Natural History of Open-Angle Glaucoma.
  • 2009
  • Ingår i: Ophthalmology. - Elsevier. - 1549-4713. ; 116, s. 2271-2276
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: This article, based on the Early Manifest Glaucoma Trial (EMGT), provides prospective natural history data on progression of glaucomatous field defects in 3 of the most common glaucoma types. DESIGN: Cohort of EMGT patients randomized to the untreated control group and followed up to the time of progression, when treatment could be initiated. PARTICIPANTS: We evaluated 118 control patients: 46 with high-tension glaucoma (HTG), 57 with normal-tension glaucoma (NTG), and 15 with pseudoexfoliation glaucoma (PEXG). METHODS: Visual fields were tested every 3 months with the Humphrey 30-2 Full Threshold test program. MAIN OUTCOME MEASURES: Linear regression analyses of the perimetric mean deviation (MD) values were performed, and the rate of progression was defined as the regression coefficient in decibels per year. Percentages of progressed eyes and time to progression were determined using EMGT event-based predetermined progression criteria derived from Glaucoma Change Probability Maps. RESULTS: The median and interquartile rates of visual function loss were -0.40 (1.05) dB/year overall and -0.46 (1.61) in HTG, -0.22 (0.65) in NTG, and -1.13 (6.13) in PEXG. Thus, interpatient variability was large. Mean rates were considerably higher than medians: -1.08 dB/year overall, -1.31 in HTG, -0.36 in NTG, and -3.13 in PEXG. Differences in median visual function progression rates among groups were statistically significant (NTG vs. HTG, P = 0.003; PEXG vs. non-PEXG, P<0.001). Progression was considerably and significantly faster in older than in younger patients (P = 0.002). By 6 years, 68% of patients had progressed overall, 74% of those with HTG, 56% of those with NTG, and 93% of those with PEXG (P = 0.012). Median time to progression also differed considerably among groups: 19.5 months in PEXG, 44.8 months in HTG, and particularly 61.1 months in NTG (P<0.0001). CONCLUSIONS: In this 6-year follow-up study, the median untreated rate of progression corresponded to advancing from normal visual function to blindness in approximately 70 years, whereas on the basis of the mean rate, visual function would show the same deterioration in approximately 25 years. Large differences existed among patients and different glaucoma types, with PEXG progressing considerably faster than HTG, and NTG progressing at the lowest rate. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.
10.
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