688 research outputs found
Heavy-light mesons with staggered light quarks
We demonstrate the viability of improved staggered light quarks in studies of
heavy-light systems. Our method for constructing heavy-light operators exploits
the close relation between naive and staggered fermions. The new approach is
tested on quenched configurations using several staggered actionsn combined
with nonrelativistic heavy quarks. The B_s meson kinetic mass, the hyperfine
and 1P-1S splittings in B_s, and the decay constant f_{B_s} are calculated and
compared to previous quenched lattice studies. An important technical detail,
Bayesian curve-fitting, is discussed at length.Comment: 38 pages, figures included. v2: Entry in Table IX corrected and other
minor changes, version appearing in Phys. Rev.
Mechanical Mitral Valve Replacement: A Multicenter Study of Outcomes with Use of 15- to 17-mm Prostheses
Background: The aim of this study was to evaluate early and mid-term outcomes (mortality and prosthetic valve reintervention) after mitral valve replacement with 15- to 17-mm mechanical pr
Association between an AMH promoter polymorphism and serum AMH levels in PCOS patients
STUDY QUESTION: Do polymorphisms in the anti-MĂŒllerian hormone (AMH) promoter have an effect on AMH levels in patients with polycystic ovary syndrome (PCOS)? SUMMARY ANSWER: We have identified a novel AMH promoter polymorphism rs10406324 that is associated with lower serum AMH levels and is suggested to play a role in the mechanism of regulation of AMH gene expression in women. WHAT IS KNOWN ALREADY: Follicle number is positively correlated with serum AMH levels, reflected by elevated AMH levels in women with PCOS. In addition, it is suggested that AMH production per follicle is higher in women with PCOS than in normo-ovulatory women, implying an altered regulation of AMH in PCOS. STUDY DESIGN, SIZE, DURATION: A discovery cohort of 655 PCOS women of Northern European ancestry and both an internal and external validation PCOS cohort (nâ=â458 and nâ=â321, respectively) were included in this study. Summary-level data of an AMH genome-wide association study meta-analysis including 7049 normo-ovulatory women was included as a control cohort. A genetic approach was taken through association analysis and in silico analysis of the associated variants in the AMH promoter. In vitro analysis was performed to investigate the functional mechanisms. PARTICIPANTS/MATERIALS, SETTING, METHODS: All common two-allelic single-nucleotide polymorphisms (SNPs) in the region Chr19:2â245â353â2â250â827 bp (Build 37) were selected for the analysis. Linear regression analyses were performed to determine the association between SNPs in the AMH promoter region and serum AMH levels. For the in silico analysis, the webtools âHaploRegâ v4.1 for ENCODE prediction weight matrices and âatSNPâ were used. In vitro analysis was performed using KK1 cells, a mouse granulosa cell line and COV434 cells, a human granulosa tumor cell line. Cells were transfected with the reference or the variant human AMH promoter reporter construct together with several transcription factors (TFs). Dual-Glo(Âź) Luciferase Assay was performed to measure the luciferase activity. MAIN RESULTS AND THE ROLE OF CHANCE: Polymorphism rs10406324 was significantly associated with serum AMH levels in all three PCOS cohorts. Carriers of the minor allele G had significantly lower log-transformed serum AMH levels compared to non-carriers (Pâ=â8.58âĂâ10(â8), Pâ=â1.35âĂâ10(â3) and Pâ=â1.24âĂâ10(â3), respectively). This result was validated in a subsequent meta-analysis (Pâ=â3.24âĂâ10(â12)). Interestingly, rs10406324 was not associated with follicle count, nor with other clinical traits. Also, in normo-ovulatory women, the minor allele of this variant was associated with lower serum AMH levels (Pâ=â1.04âĂâ10(â5)). These findings suggest that polymorphism rs10406324 plays a role in the regulation of AMH expression, irrespective of clinical background. In silico analysis suggested a decreased binding affinity of the TFs steroidogenenic factor 1, estrogen-related receptor alpha and glucocorticoid receptor to the minor allele G variant, however in vitro analysis did not show a difference in promoter activity between the A and G allele. LIMITATIONS, REASONS FOR CAUTION: Functional analyses were performed in a mouse and a human granulosa cell line using an AMH promoter reporter construct. This may have limited assessment of the impact of the polymorphism on higher order chromatin structures. Human granulosa cells generated from induced pluripotent stem cells, combined with gene editing, may provide a method to elucidate the exact mechanism behind the decrease in serum AMH levels in carriers of the â210 G allele. We acknowledge that the lack of follicle number in the external validation and the control cohort is a limitation of the paper. Although we observed that the association between rs10406324 and AMH levels was independent of follicle number in our discovery and internal validation PCOS cohorts, we cannot fully rule out that the observed effects on serum AMH levels are, in part, caused by differences in follicle number. WIDER IMPLICATIONS OF THE FINDINGS: These results suggest that variations in serum AMH levels are not only caused by differences in follicle number but also by genetic factors. Therefore, the genetic context should be taken into consideration when assessing serum AMH levels in women. This may have clinical consequences when serum AMH levels are used as a marker for the polycystic ovarian morphology phenotype. STUDY FUNDING/COMPETING INTEREST(S): No external funding was used. J.S.E.L. has received consultancy fees from the following companies: Ferring, Roche Diagnostics and Ansh Labs and has received travel reimbursement from Ferring. J.A.V. has received royalties from AMH assays, paid to the institute/lab with no personal financial gain. The other authors declare no competing interests. TRIAL REGISTRATION NUMBER: N/A
Appraisal, Agency and Atypicality: Evidence from Manufactured Homes
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73056/1/j.1540-6229.2005.00128.x.pd
Characteristics of patients in platform C19, a COVID-19 research database combining primary care electronic health record and patient reported information
Background
Data to better understand and manage the COVID-19 pandemic is urgently needed. However, there are gaps in information stored within even the best routinely-collected electronic health records (EHR) including test results, remote consultations for suspected COVID-19, shielding, physical activity, mental health, and undiagnosed or untested COVID-19 patients. Observational and Pragmatic Research Institute (OPRI) Singapore and Optimum Patient Care (OPC) UK established Platform C19, a research database combining EHR data and bespoke patient questionnaire. We describe the demographics, clinical characteristics, patient behavior, and impact of the COVID-19 pandemic using data within Platform C19.
Methods
EHR data from Platform C19 were extracted from 14 practices across UK participating in the OPC COVID-19 Quality Improvement program on a continuous, monthly basis. Starting 7th August 2020, consenting patients aged 18â85 years were invited in waves to fill an online questionnaire. Descriptive statistics were summarized using all data available up to 22nd January 2021.
Findings
From 129,978 invitees, 31,033 responded. Respondents were predominantly female (59.6%), white (93.5%), and current or ex-smokers (52.6%). Testing for COVID-19 was received by 23.8% of respondents, of which 7.9% received positive results. COVID-19 symptoms lasted â„4 weeks in 19.5% of COVID-19 positive respondents. Up to 39% respondents reported a negative impact on questions regarding their mental health. Most (67%-76%) respondents with asthma, Chronic Obstructive Pulmonary Disease (COPD), diabetes, heart, or kidney disease reported no change in the condition of their diseases.
Interpretation
Platform C19 will enable research on key questions relating to COVID-19 pandemic not possible using EHR data alone
Detecting Endometrial Cancer by Blood Spectroscopy: A Diagnostic Cross-Sectional Study
Endometrial cancer is the sixth most common cancer in women, with a rising incidence worldwide. Current approaches for the diagnosis and screening of endometrial cancer are invasive, expensive or of moderate diagnostic accuracy, limiting their clinical utility. There is a need for cost-effective and minimally invasive approaches to facilitate the early detection and timely management of endometrial cancer. We analysed blood plasma samples in a cross-sectional diagnostic accuracy study of women with endometrial cancer (n = 342), its precursor lesion atypical hyperplasia (n = 68) and healthy controls (n = 242, total n = 652) using attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy and machine learning algorithms. We show that blood-based infrared spectroscopy has the potential to detect endometrial cancer with 87% sensitivity and 78% specificity. Its accuracy is highest for Type I endometrial cancer, the most common subtype, and for atypical hyperplasia, with sensitivities of 91% and 100%, and specificities of 81% and 88%, respectively. Our large-cohort study shows that a simple blood test could enable the early detection of endometrial cancer of all stages in symptomatic women and provide the basis of a screening tool in high-risk groups. Such a test has the potential not only to differentially diagnose endometrial cancer but also to detect its precursor lesion atypical hyperplasiaâthe early recognition of which may allow fertility sparing management and cancer prevention
Metal enrichment processes
There are many processes that can transport gas from the galaxies to their
environment and enrich the environment in this way with metals. These metal
enrichment processes have a large influence on the evolution of both the
galaxies and their environment. Various processes can contribute to the gas
transfer: ram-pressure stripping, galactic winds, AGN outflows, galaxy-galaxy
interactions and others. We review their observational evidence, corresponding
simulations, their efficiencies, and their time scales as far as they are known
to date. It seems that all processes can contribute to the enrichment. There is
not a single process that always dominates the enrichment, because the
efficiencies of the processes vary strongly with galaxy and environmental
properties.Comment: 18 pages, 8 figures, accepted for publication in Space Science
Reviews, special issue "Clusters of galaxies: beyond the thermal view",
Editor J.S. Kaastra, Chapter 17; work done by an international team at the
International Space Science Institute (ISSI), Bern, organised by J.S.
Kaastra, A.M. Bykov, S. Schindler & J.A.M. Bleeke
An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics
For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types
The last reconnection of the Marmara Sea (Turkey) to the World Ocean : A paleoceanographic and paleoclimatic perspective
Author Posting. © Elsevier B.V., 2008. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Marine Geology 255 (2008): 64-82, doi:10.1016/j.margeo.2008.07.005.During the late glacial, marine isotope Stage 2, the Marmara Sea transformed into a
brackish lake as global sea level fell below the sill in the Dardanelles Strait. A record of the
basinâs reconnection to the global ocean is preserved in its sediments permitting the extraction of
the paleoceanographic and paleoclimatic history of the region. The goal of this study is to
develop a high-resolution record of the lacustrine to marine transition of Marmara Sea in order to
reconstruct regional and global climatic events at 24 a millennial scale. For this purpose, we mapped
the paleoshorelines of Marmara Sea along the northern, eastern, and southern shelves at
Ăekmece, Prince Islands, and Imrali, using data from multibeam bathymetry, high-resolution
subbottom profiling (chirp) and ten sediment cores. Detailed sedimentologic, biostratigraphic
(foraminifers, mollusk, diatoms), X-ray fluorescence geochemical scanning, and oxygen and
carbon stable isotope analyses correlated to a calibrated radiocarbon chronology provided
evidence for cold and dry conditions prior to 15 ka BP, warm conditions of the Bolling-Allerod
from ~15 to 13 ka BP, a rapid marine incursion at 12 ka BP, still stand of Marmara Sea and
sediment reworking of the paleoshorelines during the Younger Dryas at ~11.5 to 10.5 ka BP, and
development of strong stratification and influx of nutrients as Black Sea waters spilled into
Marmara Sea at 9.2 ka BP. Stable environmental conditions developed in Marmara Sea after 6.0
ka BP as sea-level reached its present shoreline and the basin floors filled with sediments
achieving their present configuration.Support for the analyses was
from NSF-OCE-0222139; OCE-9807266 and PSC-CUNY 69138-00 38
Origins of the Ambient Solar Wind: Implications for Space Weather
The Sun's outer atmosphere is heated to temperatures of millions of degrees,
and solar plasma flows out into interplanetary space at supersonic speeds. This
paper reviews our current understanding of these interrelated problems: coronal
heating and the acceleration of the ambient solar wind. We also discuss where
the community stands in its ability to forecast how variations in the solar
wind (i.e., fast and slow wind streams) impact the Earth. Although the last few
decades have seen significant progress in observations and modeling, we still
do not have a complete understanding of the relevant physical processes, nor do
we have a quantitatively precise census of which coronal structures contribute
to specific types of solar wind. Fast streams are known to be connected to the
central regions of large coronal holes. Slow streams, however, appear to come
from a wide range of sources, including streamers, pseudostreamers, coronal
loops, active regions, and coronal hole boundaries. Complicating our
understanding even more is the fact that processes such as turbulence,
stream-stream interactions, and Coulomb collisions can make it difficult to
unambiguously map a parcel measured at 1 AU back down to its coronal source. We
also review recent progress -- in theoretical modeling, observational data
analysis, and forecasting techniques that sit at the interface between data and
theory -- that gives us hope that the above problems are indeed solvable.Comment: Accepted for publication in Space Science Reviews. Special issue
connected with a 2016 ISSI workshop on "The Scientific Foundations of Space
Weather." 44 pages, 9 figure
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