Effect of Dutasteride on the Risk of Prostate Cancer Andriole, Gerald L; Bostwick, David G; Brawley, Otis W ...
New England journal of medicine/The New England journal of medicine,
04/2010, Volume:
362, Issue:
13
Journal Article
Peer reviewed
Open access
Dutasteride, an inhibitor of 5α-reductase in the prostate, was tested in a large, randomized trial to determine its ability to prevent prostate cancer. Over the 4 years of the trial, dutasteride, as ...compared with placebo, reduced the relative risk of biopsy-detected prostate cancer by 23%. The reduction was limited mainly to tumors with Gleason scores of 5 or 6; by year 4, there were 12 tumors with Gleason scores of 8 to 10 in the dutasteride group but only 1 in the placebo group.
Dutasteride, an inhibitor of 5α-reductase in the prostate, reduced the relative risk of biopsy-detected prostate cancer by 23%; however, the reduction was limited mainly to tumors with Gleason scores of 5 or 6.
The 5α-reductase inhibitors that are used to treat benign prostatic hyperplasia block the conversion of testosterone to dihydrotestosterone and may reduce the risk of prostate cancer.
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The results of the Prostate Cancer Prevention Trial showed that finasteride, as compared with placebo, reduced the risk of prostate cancer by 25%, but among the tumors that were detected, there was a 27% increase in the number of those that had Gleason scores of 7 to 10.
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(The Gleason score is the sum of the two most common histologic patterns or grades in a prostate tumor, each of which is graded on a . . .
A single-particle soot photometer (SP2) was flown on a NASA WB-57F high-altitude research aircraft in November 2004 from Houston, Texas. The SP2 uses laser-induced incandescence to detect individual ...black carbon (BC) particles in an air sample in the mass range of approx.3-300 fg (approx.0.15-0.7 microns volume equivalent diameter). Scattered light is used to size the remaining non-BC aerosols in the range of approx.0.17-0.7 microns diameter. We present profiles of both aerosol types from the boundary layer to the lower stratosphere from two midlatitude flights. Results for total aerosol amounts in the size range detected by the SP2 are in good agreement with typical particle spectrometer measurements in the same region. All ambient incandescing particles were identified as BC because their incandescence properties matched those of laboratory-generated BC aerosol. Approximately 40% of these BC particles showed evidence of internal mixing (e.g., coating). Throughout profiles between 5 and 18.7 km, BC particles were less than a few percent of total aerosol number, and black carbon aerosol (BCA) mass mixing ratio showed a constant gradient with altitude above 5 km. SP2 data was compared to results from the ECHAM4/MADE and LmDzT-INCA global aerosol models. The comparison will help resolve the important systematic differences in model aerosol processes that determine BCA loadings. Further intercomparisons of models and measurements as presented here will improve the accuracy of the radiative forcing contribution from BCA.
Empirically supported psychological treatments have been developed for a range of psychiatric disorders but there is evidence that patients are not receiving them in routine clinical care. ...Furthermore, even when patients do receive these treatments there is evidence that they are often not well delivered. The aim of this paper is to identify the barriers to the dissemination of evidence-based psychological treatments and then propose ways of overcoming them, hence potentially bridging the gap between research findings and clinical practice.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Here, absolute cross sections for the addition of s- and d-wave neutrons to 14C and 14N have been determined simultaneously via the (d,p) reaction at 10 MeV/u. The difference between the neutron and ...proton separation energies, ΔS, is around -20 MeV for the 14C+n system and +8 MeV for 14N+n. The population of the 1s1/2 and 0d5/2 orbitals for both systems is reduced by a factor of approximately 0.5 compared with the independent single-particle model, or about 0.6 when compared with the shell model. This finding strongly contrasts with results deduced from intermediate-energy knockout reactions between similar nuclei on targets of 9Be and 12C. The simultaneous technique used removes many systematic uncertainties.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UL, UM
We report the result of a blinded search for weakly interacting massive particles (WIMPs) using the majority of the SuperCDMS Soudan data set. With an exposure of 1690 kg d, a single candidate event ...is observed, consistent with expected backgrounds. This analysis (combined with previous Ge results) sets an upper limit on the spin-independent WIMP-nucleon cross section of 1.4×10^{-44} (1.0×10^{-44}) cm^{2} at 46 GeV/c^{2}. These results set the strongest limits for WIMP-germanium-nucleus interactions for masses >12 GeV/c^{2}.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UL, UM
Colorectal cancer (CRC) is the most common gastrointestinal malignancy in the U.S.A. and approximately 50% of patients develop metastatic disease (mCRC). Despite our understanding of long non-coding ...RNAs (lncRNAs) in primary colon cancer, their role in mCRC and treatment resistance remains poorly characterized. Therefore, through transcriptome sequencing of normal, primary, and distant mCRC tissues we find 148 differentially expressed RNAs Associated with Metastasis (RAMS). We prioritize RAMS11 due to its association with poor disease-free survival and promotion of aggressive phenotypes in vitro and in vivo. A FDA-approved drug high-throughput viability assay shows that elevated RAMS11 expression increases resistance to topoisomerase inhibitors. Subsequent experiments demonstrate RAMS11-dependent recruitment of Chromobox protein 4 (CBX4) transcriptionally activates Topoisomerase II alpha (TOP2α). Overall, recent clinical trials using topoisomerase inhibitors coupled with our findings of RAMS11-dependent regulation of TOP2α supports the potential use of RAMS11 as a biomarker and therapeutic target for mCRC.
We have fit the far-ultraviolet (FUV) to sub-millimeter (850 μm) spectral energy distributions (SEDs) of the 61 galaxies from the Key Insights on Nearby Galaxies: A Far-Infrared Survey with Herschel ...(KINGFISH). The fitting has been performed using three models: the Code for Investigating GALaxy Evolution (CIGALE), the GRAphite-SILicate approach (GRASIL), and the Multiwavelength Analysis of Galaxy PHYSical properties (MAGPHYS). We have analyzed the results of the three codes in terms of the SED shapes, and by comparing the derived quantities with simple “recipes” for stellar mass (Mstar), star-formation rate (SFR), dust mass (Mdust), and monochromatic luminosities. Although the algorithms rely on different assumptions for star-formation history, dust attenuation and dust reprocessing, they all well approximate the observed SEDs and are in generally good agreement for the associated quantities. However, the three codes show very different behavior in the mid-infrared regime: in the 5–10 μm region dominated by PAH emission, and also between 25 and 70 μm where there are no observational constraints for the KINGFISH sample. We find that different algorithms give discordant SFR estimates for galaxies with low specific SFR, and that the standard recipes for calculating FUV absorption overestimate the extinction compared to the SED-fitting results. Results also suggest that assuming a “standard” constant stellar mass-to-light ratio overestimates Mstar relative to the SED fitting, and we provide new SED-based formulations for estimating Mstar from WISE W1 (3.4 μm) luminosities and colors. From a principal component analysis of Mstar, SFR, Mdust, and O/H, we reproduce previous scaling relations among Mstar, SFR, and O/H, and find that Mdust can be predicted to within ∼0.3 dex using only Mstar and SFR.
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FMFMET, NUK, UL, UM, UPUK
Human immunodeficiency virus-1 (HIV-1) infection disrupts the intestinal immune system, leading to microbial translocation and systemic immune activation. We investigated the impact of HIV-1 ...infection on the intestinal microbiome and its association with mucosal T-cell and dendritic cell (DC) frequency and activation, as well as with levels of systemic T-cell activation, inflammation, and microbial translocation. Bacterial 16S ribosomal DNA sequencing was performed on colon biopsies and fecal samples from subjects with chronic, untreated HIV-1 infection and uninfected control subjects. Colon biopsies of HIV-1-infected subjects had increased abundances of Proteobacteria and decreased abundances of Firmicutes compared with uninfected donors. Furthermore at the genus level, a significant increase in Prevotella and decrease in Bacteroides was observed in HIV-1-infected subjects, indicating a disruption in the Bacteroidetes bacterial community structure. This HIV-1-associated increase in Prevotella abundance was associated with increased numbers of activated colonic T cells and myeloid DCs. Principal coordinates analysis demonstrated an HIV-1-related change in the microbiome that was associated with increased mucosal cellular immune activation, microbial translocation, and blood T-cell activation. These observations suggest that an important relationship exists between altered mucosal bacterial communities and intestinal inflammation during chronic HIV-1 infection.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Population viability is driven by individual survival, which in turn depends on individuals balancing energy budgets. As carnivores may function close to maximum sustained power outputs, decreased ...food availability or increased activity may render some populations energetically vulnerable. Prey theft may compromise energetic budgets of mesopredators, such as cheetahs and wild dogs, which are susceptible to competition from larger carnivores. We show that daily energy expenditure (DEE) of cheetahs was similar to size-based predictions and positively related to distance traveled. Theft at 25% only requires cheetahs to hunt for an extra 1.1 hour per day, increasing DEE by just 12%. Therefore, not all mesopredators are energetically constrained by direct competition. Other factors that increase DEE, such as those that increase travel, may be more important for population viability.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
The tortuosity of the track taken by an animal searching for food profoundly affects search efficiency, which should be optimised to maximise net energy gain. Models examining this generally describe ...movement as a series of straight steps interspaced by turns, and implicitly assume no turn costs. We used both empirical‐ and modelling‐based approaches to show that the energetic costs for turns in both terrestrial and aerial locomotion are substantial, which calls into question the value of conventional movement models such as correlated random walk or Lévy walk for assessing optimum path types. We show how, because straight‐line travel is energetically most efficient, search strategies should favour constrained turn angles, with uninformed foragers continuing in straight lines unless the potential benefits of turning offset the cost.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK