775 research outputs found

    Processor Allocation for Optimistic Parallelization of Irregular Programs

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    Optimistic parallelization is a promising approach for the parallelization of irregular algorithms: potentially interfering tasks are launched dynamically, and the runtime system detects conflicts between concurrent activities, aborting and rolling back conflicting tasks. However, parallelism in irregular algorithms is very complex. In a regular algorithm like dense matrix multiplication, the amount of parallelism can usually be expressed as a function of the problem size, so it is reasonably straightforward to determine how many processors should be allocated to execute a regular algorithm of a certain size (this is called the processor allocation problem). In contrast, parallelism in irregular algorithms can be a function of input parameters, and the amount of parallelism can vary dramatically during the execution of the irregular algorithm. Therefore, the processor allocation problem for irregular algorithms is very difficult. In this paper, we describe the first systematic strategy for addressing this problem. Our approach is based on a construct called the conflict graph, which (i) provides insight into the amount of parallelism that can be extracted from an irregular algorithm, and (ii) can be used to address the processor allocation problem for irregular algorithms. We show that this problem is related to a generalization of the unfriendly seating problem and, by extending Tur\'an's theorem, we obtain a worst-case class of problems for optimistic parallelization, which we use to derive a lower bound on the exploitable parallelism. Finally, using some theoretically derived properties and some experimental facts, we design a quick and stable control strategy for solving the processor allocation problem heuristically.Comment: 12 pages, 3 figures, extended version of SPAA 2011 brief announcemen

    Dense mapping of MYH9 localizes the strongest kidney disease associations to the region of introns 13 to 15

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    Admixture mapping recently identified MYH9 as a susceptibility gene for idiopathic focal segmental glomerulosclerosis (FSGS), HIV-associated nephropathy (HIVAN) and end-stage kidney disease attributed to hypertension (H-ESKD) in African Americans (AA). MYH9 encodes the heavy chain of non-muscle myosin IIA, a cellular motor involved in motility. A haplotype and its tagging SNPs spanning introns 12–23 were most strongly associated with kidney disease (OR 2–7; P < 10−8, recessive). To narrow the region of association and identify potential causal variation, we performed a dense-mapping study using 79 MYH9 SNPs in AA populations with FSGS, HIVAN and H-ESKD (typed for a subset of 46 SNPs), for a total of 2496 cases and controls. The strongest associations were for correlated SNPs rs5750250, rs2413396 and rs5750248 in introns 13, 14 and 15, a region of 5.6 kb. Rs5750250 showed OR 5.0, 8.0 and 2.8; P = 2 × 10−17, 2 × 10−10 and 3 × 10−22, respectively, for FSGS, HIVAN and H-ESKD; OR 5.7; P = 9 × 10−27 for combined FSGS and HIVAN, recessive. An independent association was observed for rs11912763 in intron 33. Neither the highly associated SNPs nor the results of resequencing MYH9 in 40 HIVAN or FSGS cases and controls revealed non-synonymous changes that could account for the disease associations. Rs2413396 and one of the highly associated SNPs in intron 23, rs4821480, are predicted splicing motif modifiers. Rs5750250 combined with rs11912763 had receiver operator characteristic (ROC) C statistics of 0.80, 0.73 and 0.65 for HIVAN, FSGS and H-ESKD, respectively, allowing prediction of genetic risk by typing two SNPs

    Resequencing and Analysis of Variation in the TCF7L2 Gene in African Americans Suggests That SNP rs7903146 Is the Causal Diabetes Susceptibility Variant

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    OBJECTIVE—Variation in the transcription factor 7-like 2 (TCF7L2) locus is associated with type 2 diabetes across multiple ethnicities. The aim of this study was to elucidate which variant in TCF7L2 confers diabetes susceptibility in African Americans. RESEARCH DESIGN AND METHODS—Through the evalua-tion of tagging single nucleotide polymorphisms (SNPs), type 2 diabetes susceptibility was limited to a 4.3-kb interval, which contains the YRI (African) linkage disequilibrium (LD) block containing rs7903146. To better define the relationship between type 2 diabetes risk and genetic variation we resequenced this 4.3-kb region in 96 African American DNAs. Thirty-three novel and 13 known SNPs were identified: 20 with minor allele frequencies (MAF).0.05 and 12 with MAF.0.10. These poly-morphisms and the previously identified DG10S478 microsatellite were evaluated in African American type 2 diabetic cases (n

    Selecting patients for randomized trials: a systematic approach based on risk group

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    BACKGROUND: A key aspect of randomized trial design is the choice of risk group. Some trials include patients from the entire at-risk population, others accrue only patients deemed to be at increased risk. We present a simple statistical approach for choosing between these approaches. The method is easily adapted to determine which of several competing definitions of high risk is optimal. METHOD: We treat eligibility criteria for a trial, such as a smoking history, as a prediction rule associated with a certain sensitivity (the number of patients who have the event and who are classified as high risk divided by the total number patients who have an event) and specificity (the number of patients who do not have an event and who do not meet criteria for high risk divided by the total number of patients who do not have an event). We then derive simple formulae to determine the proportion of patients receiving intervention, and the proportion who experience an event, where either all patients or only those at high risk are treated. We assume that the relative risk associated with intervention is the same over all choices of risk group. The proportion of events and interventions are combined using a net benefit approach and net benefit compared between strategies. RESULTS: We applied our method to design a trial of adjuvant therapy after prostatectomy. We were able to demonstrate that treating a high risk group was superior to treating all patients; choose the optimal definition of high risk; test the robustness of our results by sensitivity analysis. Our results had a ready clinical interpretation that could immediately aid trial design. CONCLUSION: The choice of risk group in randomized trials is usually based on rather informal methods. Our simple method demonstrates that this decision can be informed by simple statistical analyses

    Use of tamoxifen and raloxifene for breast cancer chemoprevention in 2010

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    PURPOSE: Two selective estrogen receptor modulators (SERMs), tamoxifen and raloxifene, have been shown in randomized clinical trials to reduce the risk of developing primary invasive breast cancer (IBC) in high-risk women. In 1998, the U.S. Food and Drug Administration (FDA) used these studies as a basis for approving tamoxifen for primary breast chemoprevention in both premenopausal and postmenopausal women at high risk. In 2007, the FDA approved raloxifene for primary breast cancer chemoprevention for postmenopausal women. METHODS: Data from the year 2010 National Health Interview Survey (NHIS) were analyzed to estimate the prevalence of tamoxifen and raloxifene use for chemoprevention of primary breast cancers among U.S. women. RESULTS: Prevalence of use of chemopreventive agents for primary tumors was 20,598 (95% CI, 518–114,864) for U.S. women aged 35 to 79 for tamoxifen. Prevalence was 96,890 (95% CI, 41,277–192,391) for U.S. women aged 50 to79 for raloxifene. CONCLUSION: Use of tamoxifen and raloxifene for prevention of primary breast cancers continues to be low. In 2010, women reporting medication use for breast cancer chemoprevention were primarily using the more recently FDA-approved drug raloxifene. Multiple possible explanations for the low use exist, including lack of awareness and/or concern about side effects among primary care physicians and patients

    Problems with Time-Varying Extra Dimensions or "Cardassian Expansion" as Alternatives to Dark Energy

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    It has recently been proposed that the Universe might be accelerating as a consequence of extra dimensions with time varying size. We show that although these scenarios can lead to acceleration, they run into serious difficulty when taking into account limits on the time variation of the four dimensional Newton's constant. On the other hand, models of ``Cardassian'' expansion based on extra dimensions which have been constructed so far violate the weak energy condition for the bulk stress energy, for parameters that give an accelerating universe.Comment: 8 pages, minor changes. To appear in Physical Review

    The Masses of the Milky Way and Andromeda galaxies

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    We present a family of robust tracer mass estimators to compute the enclosed mass of galaxy haloes from samples of discrete positional and kinematical data of tracers, such as halo stars, globular clusters and dwarf satellites. The data may be projected positions, distances, line of sight velocities or proper motions. Forms of the estimator tailored for the Milky Way galaxy and for M31 are given. Monte Carlo simulations are used to quantify the uncertainty as a function of sample size. For the Milky Way, the satellite sample consists of 26 galaxies with line-of-sight velocities. We find that the mass of the Milky Way within 300 kpc is ~ 0.9 x 10^12 solar masses assuming velocity isotropy. However, the mass estimate is sensitive to the anisotropy and could plausibly lie between 0.7 - 3.4 x 10^12 solar masses. Incorporating the proper motions of 6 Milky Way satellites into the dataset, we find ~ 1.4 x 10^12 solar masses. The range here if plausible anisotropies are used is still broader, from 1.2 - 2.7 x 10^12 solar masses. For M31, there are 23 satellite galaxies with measured line-of-sight velocities, but only M33 and IC 10 have proper motions. We use the line of sight velocities and distances of the satellite galaxies to estimate the mass of M31 within 300 kpc as ~ 1.4 x 10^12 solar masses assuming isotropy. There is only a modest dependence on anisotropy, with the mass varying between 1.3 -1.6 x 10^12 solar masses. Given the uncertainties, we conclude that the satellite data by themselves yield no reliable insights into which of the two galaxies is actually the more massive.Comment: 15 pages, submitted to MNRA

    An Ovariectomy-Induced Rabbit Osteoporotic Model: A New Perspective

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    Study DesignExperimental Animal Model.PurposeThe aim of our study was to validate a pure bilateral ovariectomy (OVX) female New Zealand white rabbit model of postmenopausal osteoporosis utilizing animal-sparing in vivo techniques for evaluating bone mineral density (BMD). We also sought to demonstrate that bilateral OVX in female New Zealand white rabbits can produce diminished BMD in the spinal column and simulate osteoporosis, without the need for adjuvant chemotherapeutic agents (i.e., no additional glucocorticosteroids or other drugs were used for stimulating accelerated BMD loss), which can be assessed by in vivo BMD testing.Overview of LiteratureMultiple animal models of postmenopausal osteoporosis have been described. Rat ovariectomy models have been successful, but are limited by rats' inability to achieve true skeletal maturity and a slight morphology that limits surgical instrumentation. Rabbit models have been described which do not have these limitations, but previous models have relied on adjunctive steroid therapy to achieve osteoporosis and have required animal sacrifice for bone mineral density assessment.MethodsThirty-six skeletally mature female rabbits underwent bilateral OVX. BMD was measured using dual-energy X-ray absorptiometry on the metaphysis of the proximal tibia and distal femur, at baseline and 17 weeks postoperatively.ResultsMean BMD values were significantly reduced by 21.9% (p<0.05) in the proximal tibia and 11.9% (p<0.001) in the distal femur at 17 weeks.ConclusionsThis study is the first to demonstrate a significant bone loss within four months of pure OVX in rabbits using animal-sparing validation techniques. We believe that this OVX model is safe, reproducible, and can be employed to longitudinally evaluate the effect of anti-osteoporosis therapeutics and surgical interventions

    Risk Model-Based Lung Cancer Screening and Racial and Ethnic Disparities in the US

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    Importance The revised 2021 US Preventive Services Task Force (USPSTF) guidelines for lung cancer screening have been shown to reduce disparities in screening eligibility and performance between African American and White individuals vs the 2013 guidelines. However, potential disparities across other racial and ethnic groups in the US remain unknown. Risk model–based screening may reduce racial and ethnic disparities and improve screening performance, but neither validation of key risk prediction models nor their screening performance has been examined by race and ethnicity.Objective To validate and recalibrate the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial 2012 (PLCOm2012) model—a well-established risk prediction model based on a predominantly White population—across races and ethnicities in the US and evaluate racial and ethnic disparities and screening performance through risk-based screening using PLCOm2012 vs the USPSTF 2021 criteria.Design, Setting, and Participants In a population-based cohort design, the Multiethnic Cohort Study enrolled participants in 1993-1996, followed up through December 31, 2018. Data analysis was conducted from April 1, 2022, to May 19. 2023. A total of 105 261 adults with a smoking history were included.Exposures The 6-year lung cancer risk was calculated through recalibrated PLCOm2012 (ie, PLCOm2012-Update) and screening eligibility based on a 6-year risk threshold greater than or equal to 1.3%, yielding similar eligibility as the USPSTF 2021 guidelines.Outcomes Predictive accuracy, screening eligibility-incidence (E-I) ratio (ie, ratio of the number of eligible to incident cases), and screening performance (sensitivity, specificity, and number needed to screen to detect 1 lung cancer).Results Of 105 261 participants (60 011 [57.0%] men; mean [SD] age, 59.8 [8.7] years), consisting of 19 258 (18.3%) African American, 27 227 (25.9%) Japanese American, 21 383 (20.3%) Latino, 8368 (7.9%) Native Hawaiian/Other Pacific Islander, and 29 025 (27.6%) White individuals, 1464 (1.4%) developed lung cancer within 6 years from enrollment. The PLCOm2012-Update showed good predictive accuracy across races and ethnicities (area under the curve, 0.72-0.82). The USPSTF 2021 criteria yielded a large disparity among African American individuals, whose E-I ratio was 53% lower vs White individuals (E-I ratio: 9.5 vs 20.3; P &lt; .001). Under the risk-based screening (PLCOm2012-Update 6-year risk ≥1.3%), the disparity between African American and White individuals was substantially reduced (E-I ratio: 15.9 vs 18.4; P &lt; .001), with minimal disparities observed in persons of other minoritized groups, including Japanese American, Latino, and Native Hawaiian/Other Pacific Islander. Risk-based screening yielded superior overall and race and ethnicity–specific performance to the USPSTF 2021 criteria, with higher overall sensitivity (67.2% vs 57.7%) and lower number needed to screen (26 vs 30) at similar specificity (76.6%).Conclusions The findings of this cohort study suggest that risk-based lung cancer screening can reduce racial and ethnic disparities and improve screening performance across races and ethnicities vs the USPSTF 2021 criteria

    The contribution of microlensing surveys to the distance scale

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    In the early nineties several teams started large scale systematic surveys of the Magellanic Clouds and the Galactic Bulge to search for microlensing effects. As a by product, these groups have created enormous time-series databases of photometric measurements of stars with a temporal sampling duration and accuracy which are unprecedented. They provide the opportunity to test the accuracy of primary distance indicators, such as Cepheids, RRLyrae stars, the detached eclipsing binaries, or the luminosity of the red clump. We will review the contribution of the microlensing surveys to the understanding of the physics of the primary distance indicators, recent differential studies and direct distance determinations to the Magellanic Clouds and the Galactic Bulge.Comment: Invited review article to appear in: `Post-Hipparcos Cosmic Candles', A. Heck & F. Caputo (Eds), Kluwer Academic Publ., Dordrecht, in press. 21 pages; uses Kluwer's crckapb.sty LaTeX style file, enclose
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