Variants of uncertain significance represent a massive challenge to medical genetics. Multiplexed functional assays, in which the functional effects of thousands of genomic variants are assessed ...simultaneously, are increasingly generating data that can be used as additional evidence for or against variant pathogenicity. Such assays have the potential to resolve variants of uncertain significance, thereby increasing the clinical utility of genomic testing. Existing standards from the American College of Medical Genetics and Genomics (ACMG)/Association for Molecular Pathology (AMP) and new guidelines from the Clinical Genome Resource (ClinGen) establish the role of functional data in variant interpretation, but do not address the specific challenges or advantages of using functional data derived from multiplexed assays. Here, we build on these existing guidelines to provide recommendations to experimentalists for the production and reporting of multiplexed functional data and to clinicians for the evaluation and use of such data. By following these recommendations, experimentalists can produce transparent, complete, and well-validated datasets that are primed for clinical uptake. Our recommendations to clinicians and diagnostic labs on how to evaluate the quality of multiplexed functional datasets, and how different datasets could be incorporated into the ACMG/AMP variant-interpretation framework, will hopefully clarify whether and how such data should be used. The recommendations that we provide are designed to enhance the quality and utility of multiplexed functional data, and to promote their judicious use.
•Developing accelerator driven subcritical fission to destroy transuranics in SNF.•The core is a vessel containing a molten mixture of NaCl and transuranic chlorides.•Molecular dynamics used to ...calculate the thermophysical properties of the salt.•Density and molecular structure for actinide salts reported here.•The neutronics of ADS fission in molten salt are presented.
We report a design for accelerator-driven subcritical fission in a molten salt core (ADSMS) that utilizes a fuel salt composed of NaCl and transuranic (TRU) chlorides. The ADSMS core is designed for fast neutronics (28% of neutrons >1MeV) to optimize TRU destruction. The choice of a NaCl-based salt offers benefits for corrosion, operating temperature, and actinide solubility as compared with LiF-based fuel salts. A molecular dynamics (MD) code has been used to estimate properties of the molten salt system which are important for ADSMS design but have never been measured experimentally. Results from the MD studies are reported. Experimental measurements of fuel salt properties and studies of corrosion and radiation damage on candidate metals for the core vessel are anticipated.
Background
There is increasing evidence indicating oral factor Xa inhibitors can be used for secondary prevention of venous thromboembolism. Studies are needed to compare oral factor Xa inhibitors, ...low molecular weight heparins, and warfarin in the oncology population. The purpose of this study is to evaluate the recurrent venous thromboembolism incidence in oncology patients utilizing oral Xa inhibitors, low molecular weight heparins, or warfarin.
Methods
Using retrospectively collected data, we compared the recurrent venous thromboembolism incidence in oncology patients taking rivaroxaban/apixaban, enoxaparin, or warfarin with at least three months of follow-up. Patients were included if they had an active cancer, venous thromboembolism, and taking warfarin, enoxaparin, or rivaroxaban/apixaban. The primary endpoint was the first episode of recurrent venous thromboembolism at three months. Secondary endpoints included recurrent venous thromboembolism after six months, major bleeding, and mortality.
Results
Of 127 venous thromboembolism patients, 48 received rivaroxaban or apixaban, 23 received enoxaparin, and 56 received warfarin. The three most common cancer diagnoses were lung (21%), colorectal (14%), and breast (14%). There was no difference in venous thromboembolism recurrence at three months between the rivaroxaban/apixaban (0%), warfarin (3.6%), and the enoxaparin cohorts (4.4%) (p = 0.8319). Major bleeding at three months was only seen in one patient in the enoxaparin arm (4.2%). Mortality at three months was 0%, 3.6%, and 17.4% in the rivaroxaban/apixaban, warfarin, and enoxaparin cohorts, respectively.
Conclusion
The results of this retrospective study suggest that oral factor Xa inhibitors are potential options for cancer patients with venous thromboembolism. However, randomized, controlled trials are needed to confirm these results.
Exclusive photoproduction of Formula omitted mesons is studied using the H1 detector at the ep collider HERA. A sample of about 900,000 events is used to measure single- and double-differential cross ...sections for the reaction Formula omitted. Reactions where the proton stays intact ( Formula omitted) are statistically separated from those where the proton dissociates to a low-mass hadronic system ( Formula omitted). The double-differential cross sections are measured as a function of the invariant mass Formula omitted of the decay pions and the squared 4-momentum transfer t at the proton vertex. The measurements are presented in various bins of the photon-proton collision energy Formula omitted. The phase space restrictions are Formula omitted, Formula omitted, and Formula omitted. Cross section measurements are presented for both elastic and proton-dissociative scattering. The observed cross section dependencies are described by analytic functions. Parametrising the Formula omitted dependence with resonant and non-resonant contributions added at the amplitude level leads to a measurement of the Formula omitted meson mass and width at Formula omitted and Formula omitted, respectively. The model is used to extract the Formula omitted contribution to the Formula omitted cross sections and measure it as a function of t and Formula omitted. In a Regge asymptotic limit in which one Regge trajectory Formula omitted dominates, the intercept Formula omitted and the slope Formula omitted of the t dependence are extracted for the case Formula omitted.
The first measurement of lepton-jet momentum imbalance and azimuthal correlation in lepton-proton scattering at high momentum transfer is presented. These data, taken with the H1 detector at HERA, ...are corrected for detector effects using an unbinned machine learning algorithm (multifold), which considers eight observables simultaneously in this first application. The unfolded cross sections are compared with calculations performed within the context of collinear or transverse-momentum-dependent factorization in quantum chromodynamics as well as Monte Carlo event generators.
Charged particle multiplicity distributions in positron-proton deep inelastic scattering at a centre-of-mass energy
s
=
319
GeV are measured. The data are collected with the H1 detector at HERA ...corresponding to an integrated luminosity of 136 pb
-
1
. Charged particle multiplicities are measured as a function of photon virtuality
Q
2
, inelasticity
y
and pseudorapidity
η
in the laboratory and the hadronic centre-of-mass frames. Predictions from different Monte Carlo models are compared to the data. The first and second moments of the multiplicity distributions are determined and the KNO scaling behaviour is investigated. The multiplicity distributions as a function of
Q
2
and the Bjorken variable
x
bj
are converted to the hadron entropy
S
hadron
, and predictions from a quantum entanglement model are tested.
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