University of British Columbia

About: University of British Columbia is a education organization based out in Vancouver, British Columbia, Canada. It is known for research contribution in the topics: Population & Health care. The organization has 89939 authors who have published 209679 publications receiving 9226862 citations. The organization is also known as: UBC & The University of British Columbia.

Integrative analysis of 111 reference human epigenomes

Abstract: The reference human genome sequence set the stage for studies of genetic variation and its association with human disease, but epigenomic studies lack a similar reference. To address this need, the NIH Roadmap Epigenomics Consortium generated the largest collection so far of human epigenomes for primary cells and tissues. Here we describe the integrative analysis of 111 reference human epigenomes generated as part of the programme, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression. We establish global maps of regulatory elements, define regulatory modules of coordinated activity, and their likely activators and repressors. We show that disease- and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease. Our results demonstrate the central role of epigenomic information for understanding gene regulation, cellular differentiation and human disease.

First year Wilkinson Microwave Anisotropy Probe (WMAP) observations: Preliminary maps and basic results

Abstract: We present full sky microwave maps in five frequency bands (23 to 94 GHz) from the WMAP first year sky survey. Calibration errors are less than 0.5% and the low systematic error level is well specified. The cosmic microwave background (CMB) is separated from the foregrounds using multifrequency data. The sky maps are consistent with the 7 in. full-width at half-maximum (FWHM) Cosmic Background Explorer (COBE) maps. We report more precise, but consistent, dipole and quadrupole values. The CMB anisotropy obeys Gaussian statistics with -58 less than f(sub NL) less than 134 (95% CL). The 2 less than or = l less than or = 900 anisotropy power spectrum is cosmic variance limited for l less than 354 with a signal-to-noise ratio greater than 1 per mode to l = 658. The temperature-polarization cross-power spectrum reveals both acoustic features and a large angle correlation from reionization. The optical depth of reionization is tau = 0.17 +/- 0.04, which implies a reionization epoch of t(sub r) = 180(sup +220, sub -80) Myr (95% CL) after the Big Bang at a redshift of z(sub r) = 20(sup +10, sub -9) (95% CL) for a range of ionization scenarios. This early reionization is incompatible with the presence of a significant warm dark matter density. A best-fit cosmological model to the CMB and other measures of large scale structure works remarkably well with only a few parameters. The age of the best-fit universe is t(sub 0) = 13.7 +/- 0.2 Gyr old. Decoupling was t(sub dec) = 379(sup +8, sub -7)kyr after the Big Bang at a redshift of z(sub dec) = 1089 +/- 1. The thickness of the decoupling surface was Delta(sub z(sub dec)) = 195 +/- 2. The matter density of the universe is Omega(sub m)h(sup 2) = 0.135(sup +0.008, sub -0.009) the baryon density is Omega(sub b)h(sup 2) = 0.0224 +/- 0.0009, and the total mass-energy of the universe is Omega(sub tot) = 1.02 +/- 0.02. There is progressively less fluctuation power on smaller scales, from WMAP to fine scale CMB measurements to galaxies and finally to the Ly-alpha forest. This is accounted for with a running spectral index, significant at the approx. 2(sigma) level. The spectral index of scalar fluctuations is fit as n(sub s) = 0.93 +/-0.03 at wavenumber k(sub o) = 0.05/Mpc ((sub eff) approx. = 700), with a slope of dn(sub s)/d I(sub nk) = -0.031(sup + 0.016, sub -0.018) in the best-fit model.

Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer

Abstract: background Trastuzumab, a recombinant monoclonal antibody against HER2, has clinical activity in advanced breast cancer that overexpresses HER2. We investigated its efficacy and safety after excision of early-stage breast cancer and completion of chemotherapy. methods This international, multicenter, randomized trial compared one or two years of trastuzumab given every three weeks with observation in patients with HER2-positive and either node-negative or node-positive breast cancer who had completed locoregional therapy and at least four cycles of neoadjuvant or adjuvant chemotherapy. results Data were available for 1694 women randomly assigned to two years of treatment with trastuzumab, 1694 women assigned to one year of trastuzumab, and 1693 women assigned to observation. We report here the results only of treatment with trastuzumab for one year or observation. At the first planned interim analysis (median follow-up of one year), 347 events (recurrence of breast cancer, contralateral breast cancer, second nonbreast malignant disease, or death) were observed: 127 events in the trastuzumab group and 220 in the observation group. The unadjusted hazard ratio for an event in the trastuzumab group, as compared with the observation group, was 0.54 (95 percent confidence interval, 0.43 to 0.67; P<0.0001 by the log-rank test, crossing the interim analysis boundary), representing an absolute benefit in terms of disease-free survival at two years of 8.4 percentage points. Overall survival in the two groups was not significantly different (29 deaths with trastuzumab vs. 37 with observation). Severe cardiotoxicity developed in 0.5 percent of the women who were treated with trastuzumab. conclusions One year of treatment with trastuzumab after adjuvant chemotherapy significantly improves disease-free survival among women with HER2-positive breast cancer. (clinicaltrials.gov number, NCT 00045032.)