742 research outputs found
Interpretable Diabetic Retinopathy Diagnosis based on Biomarker Activation Map
Deep learning classifiers provide the most accurate means of automatically
diagnosing diabetic retinopathy (DR) based on optical coherence tomography
(OCT) and its angiography (OCTA). The power of these models is attributable in
part to the inclusion of hidden layers that provide the complexity required to
achieve a desired task. However, hidden layers also render algorithm outputs
difficult to interpret. Here we introduce a novel biomarker activation map
(BAM) framework based on generative adversarial learning that allows clinicians
to verify and understand classifiers decision-making. A data set including 456
macular scans were graded as non-referable or referable DR based on current
clinical standards. A DR classifier that was used to evaluate our BAM was first
trained based on this data set. The BAM generation framework was designed by
combing two U-shaped generators to provide meaningful interpretability to this
classifier. The main generator was trained to take referable scans as input and
produce an output that would be classified by the classifier as non-referable.
The BAM is then constructed as the difference image between the output and
input of the main generator. To ensure that the BAM only highlights
classifier-utilized biomarkers an assistant generator was trained to do the
opposite, producing scans that would be classified as referable by the
classifier from non-referable scans. The generated BAMs highlighted known
pathologic features including nonperfusion area and retinal fluid. A fully
interpretable classifier based on these highlights could help clinicians better
utilize and verify automated DR diagnosis.Comment: 12 pages, 8 figure
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Perimacular Atrophy Following Voretigene Neparvovec-Rzyl Treatment in the Setting of Previous Contralateral Eye Treatment With a Different Viral Vector
PurposeTo report on cases of unilateral perimacular atrophy after treatment with voretigene neparvovec-rzyl, in the setting of previous contralateral eye treatment with a different viral vector.DesignSingle-center, retrospective chart review.MethodsIn this case series, four patients between the ages of six and 11 years old with RPE65-related retinopathy were treated unilaterally with rAAV2-CB-hRPE65 as part of a gene augmentation clinical trial (NCT00749957). Six to 10 years later the contralateral eyes were treated with the Food and Drug Administration-approved drug, voretigene neparvovec-rzyl. Best-corrected visual acuity (BCVA), fundus photos, ocular coherence tomography, two-color dark-adapted perimetry, full field stimulus threshold testing (FST), and location of subretinal bleb and chorioretinal atrophy were evaluated.ResultsThree out of four patients showed unilateral perimacular atrophy after treatment with voretigene, ranging from five to 22 months after treatment. Areas of robust visual field improvement were followed by areas of chorioretinal atrophy. Despite perimacular changes, BCVA, FST, and subjective improvements in vision and nyctalopia were maintained. Perimacular atrophy was not observed in the first eye treated with the previous viral vector.ConclusionsWe observed areas of robust visual field improvement followed by perimacular atrophy in voretigene treated eyes, as compared to the initially treated contralateral eyes.Translational relevanceCaution is advised when using two different viral vectors between eyes in gene therapy. This may become an important issue in the future with increasing gene therapy clinical trials for inherited retinal dystrophies
A soluble model of evolution and extinction dynamics in a rugged fitness landscape
We consider a continuum version of a previously introduced and numerically
studied model of macroevolution (PRL 75, 2055, (1995)) in which agents evolve
by an optimization process in a rugged fitness landscape and die due to their
competitive interactions. We first formulate dynamical equations for the
fitness distribution and the survival probability. Secondly we analytically
derive the law which characterizes the life time distribution of
biological genera. Thirdly we discuss other dynamical properties of the model
such as the rate of extinction and conclude with a brief discussion.Comment: 6 pages LaTeX source with 2 figures. Submitted to PRL (Jan. 97
Neutral B-meson mixing from three-flavor lattice QCD: Determination of the SU(3)-breaking ratio \xi
We study SU(3)-breaking effects in the neutral B_d-\bar B_d and B_s-\bar B_s
systems with unquenched N_f=2+1 lattice QCD. We calculate the relevant matrix
elements on the MILC collaboration's gauge configurations with asqtad-improved
staggered sea quarks. For the valence light-quarks (u, d, and s) we use the
asqtad action, while for b quarks we use the Fermilab action. We obtain
\xi=f_{B_s}\sqrt{B_{B_s}}/f_{B_d}\sqrt{B_{B_d}}=1.268+-0.063. We also present
results for the ratio of bag parameters B_{B_s}/B_{B_d} and the ratio of CKM
matrix elements |V_{td}|/|V_{ts}|. Although we focus on the calculation of \xi,
the strategy and techniques described here will be employed in future extended
studies of the B mixing parameters \Delta M_{d,s} and \Delta\Gamma_{d,s} in the
Standard Model and beyond.Comment: 36 pages, 7 figure
form factors with 2+1 flavors
Using the MILC 2+1 flavor asqtad quark action ensembles, we are calculating
the form factors and for the semileptonic decay. A total of six ensembles with lattice spacing from
to 0.06 fm are being used. At the coarsest and finest lattice
spacings, the light quark mass is one-tenth the strange quark mass
. At the intermediate lattice spacing, the ratio ranges from
0.05 to 0.2. The valence quark is treated using the Sheikholeslami-Wohlert
Wilson-clover action with the Fermilab interpretation. The other valence quarks
use the asqtad action. When combined with (future) measurements from the LHCb
and Belle II experiments, these calculations will provide an alternate
determination of the CKM matrix element .Comment: 8 pages, 6 figures, to appear in the Proceedings of Lattice 2017,
June 18-24, Granada, Spai
Update of from the form factor at zero recoil with three-flavor lattice QCD
We compute the zero-recoil form factor for the semileptonic decay
(and modes related by isospin and charge
conjugation) using lattice QCD with three flavors of sea quarks. We use an
improved staggered action for the light valence and sea quarks (the MILC
\asqtad\ configurations), and the Fermilab action for the heavy quarks. Our
calculations incorporate higher statistics, finer lattice spacings, and lighter
quark masses than our 2008 work. As a byproduct of tuning the new data set, we
obtain the and hyperfine splittings with few-MeV accuracy. For the
zero-recoil form factor, we obtain , where the
first error is statistical and the second is the sum in quadrature of all
systematic errors. With the latest HFAG average of experimental results and a
cautious treatment of QED effects, we find . The
QCD error is now commensurate with the experimental error.Comment: 53 pages, 12 figures; expanded discussion of correlator fits, typos
corrected, conforms to version published in PR
Origins of the Greenland shark (Somniosus microcephalus): Impacts of ice-olation and introgression
Herein, we use genetic data from 277 sleeper sharks to perform coalescent-based modeling to test the hypothesis of early Quaternary emergence of the Greenland shark (Somniosus microcephalus) from ancestral sleeper sharks in the Canadian Arctic-Subarctic region. Our results show that morphologically cryptic somniosids S. microcephalus and Somniosus pacificus can be genetically distinguished using combined mitochondrial and nuclear DNA markers. Our data confirm the presence of genetically admixed individuals in the Canadian Arctic and sub-Arctic, and temperate Eastern Atlantic regions, suggesting introgressive hybridization upon secondary contact following the initial species divergence. Conservative substitution rates fitted to an Isolation with Migration (IM) model indicate a likely species divergence time of 2.34 Ma, using the mitochondrial sequence DNA, which in conjunction with the geographic distribution of admixtures and Pacific signatures likely indicates speciation associated with processes other than the closing of the Isthmus of Panama. This time span coincides with further planetary cooling in the early Quaternary period followed by the onset of oscillating glacial-interglacial cycles. We propose that the initial S. microcephalus–S. pacificus split, and subsequent hybridization events, were likely associated with the onset of Pleistocene glacial oscillations, whereby fluctuating sea levels constrained connectivity among Arctic oceanic basins, Arctic marginal seas, and the North Atlantic Ocean. Our data demonstrates support for the evolutionary consequences of oscillatory vicariance via transient oceanic isolation with subsequent secondary contact associated with fluctuating sea levels throughout the Quaternary period—which may serve as a model for the origins of Arctic marine fauna on a broad taxonomic scale
Hypertension in Pregnancy Is a Risk Factor for Microalbuminuria Later in Life
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/99687/1/jch12116.pd
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