467 research outputs found
Detecting and Denoising Gravitational Wave Signals from Binary Black Holes using Deep Learning
We present a convolutional neural network, designed in the auto-encoder
configuration that can detect and denoise astrophysical gravitational waves
from merging black hole binaries, orders of magnitude faster than the
conventional matched-filtering based detection that is currently employed at
advanced LIGO (aLIGO). The Neural-Net architecture is such that it learns from
the sparse representation of data in the time-frequency domain and constructs a
non-linear mapping function that maps this representation into two separate
masks for signal and noise, facilitating the separation of the two, from raw
data. This approach is the first of its kind to apply machine learning based
gravitational wave detection/denoising in the 2D representation of
gravitational wave data. We applied our formalism to the first gravitational
wave event detected, GW150914, successfully recovering the signal at all three
phases of coalescence at both detectors. This method is further tested on the
gravitational wave data from the second observing run () of aLIGO,
reproducing all binary black hole mergers detected in at both the aLIGO
detectors. The Neural-Net seems to have uncovered a pattern of 'ringing' after
the ringdown phase of the coalescence, which is not a feature that is present
in the conventional binary merger templates. This method can also interpolate
and extrapolate between modeled templates and explore gravitational waves that
are unmodeled and hence not present in the template bank of signals used in the
matched-filtering detection pipelines. Faster and efficient detection schemes,
such as this method, will be instrumental as ground based detectors reach their
design sensitivity, likely to result in several hundreds of potential
detections in a few months of observing runs.Comment: 15 pages, 11 figure
Evaluating Invariances in Document Layout Functions
With the development of variable-data-driven digital presses - where each document printed is potentially unique - there is a need for pre-press optimization to identify material that is invariant from document to document. In this way rasterisation can be confined solely to those areas which change between successive documents thereby alleviating a potential performance bottleneck.
Given a template document specified in terms of layout functions, where actual data is bound at the last possible moment before printing, we look at deriving and exploiting the invariant properties of layout functions from their formal specifications. We propose future work on generic extraction of invariance from such properties for certain classes of layout functions
Asymmetric Distribution of Extreme Values of Cubic -functions on the -line
We investigate the distribution of values of cubic Dirichlet -functions at
. Following ideas of Granville and Soundararajan for quadratic
-functions, we model the distribution of by the distribution of
random Euler products for certain family of random variables
attached to each prime. We obtain a description of the
proportion of that are larger or that are smaller than a given
bound, and yield more light into the Littlewood bounds. Unlike the quadratic
case, there is an asymmetry between lower and upper bounds for the cubic case,
and small values are less probable than large values.Comment: 56 page
Cognitive Organization, Perceptions of Parenting and Depression Symptoms in Early Adolescence
Despite its strong relation to depression and theorized development across childhood and adolescence, cognitive schema organization has not been explored in early adolescence, a sensitive developmental period for first depression onset. Schema organization is theorized to derive from childhood cognitive internalizations of caregiving relationships, such as critical parenting experiences (e.g., Young et al. in Schema therapy: a practitioner’s guide. Guilford Press, New York, 2003). Thus, the current investigation considers the organization of positive and negative schemas with youth’s perceptions of parental warmth and psychological control and self-reported emotional functioning. Participants were 198 boys and girls aged 9–14 years who completed the Psychological Distance Scaling Task, measures of perceptions of parenting behaviors, anxiety symptoms and depression symptoms. Consistent with hypotheses, higher depression, but not anxiety symptoms were associated with a loosely-interconnected positive schema organization and a tightly-interconnected negative schema organization. Parental responsiveness emerged as the strongest predictor of negative schema structure. Implications for cognitive-developmental theories of depression and early identification of depression risk are discussed
Detection of missense mutations by single-strand conformational polymorphism (SSCP) analysis in five dysfunctional variants of coagulation factor VII
Five unrelated subjects with dysfunctional coagulation factor VII (FVII) were studied In order to Identify missense mutations affecting function. Exons 2 to 8 and the Intron-exon Junctions of their FVIl genes were amplified from peripheral white blood cell DNA by PCR and screened by SSCP analysis. DNA fragments showing aberrant mobility were sequenced. The following mutations were Identified: In case 1 (FVII: C <1%, FVIl:Ag 18%) a heterozygous A to G transltion at nucleotlde 8915 In exon 6 results In the amlno acid substitution Lys-137 to Glu near the C-termlnus of the FVlla llght chaln; In case 2 (FVII: C 7%, FVll:Ag 47%) a heterozygous A to G transltion at nucleotide 7834 In exon 5 results in the substitution of Gin-100 by Arg in the second EGF-like domain; In case 3 (FVll:C 20%, FVIl:Ag 76%) a homozygous G to A transition at nucleotide position 6055 in exon 4 was detected resulting in substitution of Arg-79 by Gin in the first EGF-like domain; in case 5 (FVIl:C 10%, FVIl:Ag 52%) a heterozygous C to T transition at nucleotide position 6054 in exon 4 also results in the substitution of Arg79, but in this case it is replaced by Trp; case 4 (FVll:C <1%, FVIl:Ag 100%) was homozygous for a previously reported mutation (G to A) at nucleotide position 10715 in exon 8, substituting Gin for Arg at position 304 in the protease domain. Cases 1,2 and 5 evidently have additional undetected mutation
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Early polytherapy for benzodiazepine-refractory status epilepticus.
The transition from single seizures to status epilepticus (SE) is associated with malaptive trafficking of synaptic gamma-aminobutyric acid (GABAA) and glutamate receptors. The receptor trafficking hypothesis proposes that these changes are key events in the development of pharmacoresistance to antiepileptic drugs (AEDs) during SE, and that blocking their expression will help control drug-refractory SE (RSE). We tested this hypothesis in a model of SE induced by very high-dose lithium and pilocarpine (RSE), and in a model of SE induced by sc soman. Both models are refractory to benzodiazepines when treated 40 min after seizure onset. Our treatments aimed to correct the loss of inhibition because of SE-associated internalization of synaptic GABAA receptors (GABAAR), using an allosteric GABAAR modulator, sometimes supplemented by an AED acting at a nonbenzodiazepine site. At the same time, we reduced excitation because of increased synaptic localization of NMDA and AMPA (?-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and N-methyl-D-aspartate) receptors (NMDAR, AMPAR (?-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor, N-methyl-D-aspartate receptors)) with an NMDAR channel blocker, since AMPAR changes are NMDAR-dependent. Treatment of RSE with combinations of the GABAAR allosteric modulators midazolam or diazepam and the NMDAR antagonists dizocilpine or ketamine terminated RSE unresponsive to high-dose monotherapy. It also reduced RSE-associated neuronal injury, spatial memory deficits, and the occurrence of spontaneous recurrent seizures (SRS), tested several weeks after SE. Treatment of soman-induced SE also reduced seizures, behavioral deficits, and epileptogenesis. Addition of an AED further improved seizure outcome in both models. Three-dimensional isobolograms demonstrated positive cooperativity between midazolam, ketamine, and valproate, without any interaction between the toxicity of these drugs, so that the therapeutic index was increased by combination therapy. The midazolam-ketamine-valproate combination based on the receptor trafficking hypothesis was far more effective in stopping RSE than the midazolam-fosphenytoin-valproate combination inspired from clinical guidelines for the treatment of SE. Furthermore, sequential administration of midazolam, ketamine, and valproate was far less effective than simultaneous treatment with the same drugs at the same dose. These data suggest that treatment of RSE should be based at least in part on its pathophysiology. The search for a better treatment should focus on the cause of pharmacoresistance, which is loss of synaptic GABAAR and gain of synaptic glutamate receptors. Both need to be treated. Monotherapy addresses only half the problem. Improved pharmacokinetics will not help pharmacoresistance because of loss of receptors. Waiting for one drug to fail before giving the second drugs gives pharmacoresistance time to develop. Future clinical trials should consider treating both the failure of inhibition and the runaway excitation which characterize RSE, and should include an early polytherapy arm. This article is part of the Special Issue "Proceedings of the 7th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures"
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Rational polytherapy in the treatment of cholinergic seizures.
The initiation and maintenance phases of cholinergic status epilepticus (SE) are associated with maladaptive trafficking of synaptic GABAA and glutamate receptors. The resulting pharmacoresistance reflects a decrease in synaptic GABAA receptors and increase in NMDA and AMPA receptors, which tilt the balance between inhibition and excitation in favor of the latter. If these changes are important to the pathophysiology of SE, both should be treated, and blocking their consequences should have therapeutic potential. We used a model of benzodiazepine-refractory SE (RSE) (Tetz et al., 2006) and a model of soman-induced SE to test this hypothesis. Treatment of RSE with combinations of the GABAAR agonists midazolam or diazepam and the NMDAR antagonists MK-801 or ketamine terminated RSE unresponsive to high-dose monotherapy with benzodiazepines, ketamine or other antiepileptic drugs (AEDs). It also reduced RSE-associated neuronal injury, spatial memory deficits and the occurrence of spontaneous recurrent seizures (SRS), tested several weeks after SE. Treatment of sc soman-induced SE similarly showed much greater reduction of EEG power by a combination of midazolam with ketamine, compared to midazolam monotherapy. When treating late (40 min after seizure onset), there may not be enough synaptic GABAAR left to be able to restore inhibition with maximal GABAAR stimulation, and further benefit is derived from the addition of an AED which increases inhibition or reduces excitation by a non-GABAergic mechanism. The midazolam-ketamine-valproate combination is effective in terminating RSE. 3-D isobolograms demonstrate positive cooperativity between midazolam, ketamine and valproate, without any interaction between the toxicity of these drugs, so that the therapeutic index is increased by combination therapy between GABAAR agonist, NMDAR antagonist and selective AEDs. We compared this drug combination based on the receptor trafficking hypothesis to treatments based on clinical practice. The midazolam-ketamine-valproate combination is far more effective in stopping RSE than the midazolam-fosphenytoin-valproate combination inspired from clinical guidelines. Furthermore, sequential administration of midazolam, ketamine and valproate is far less effective than simultaneous treatment with the same drugs at the same dose. These data suggest that we should re-evaluate our traditional treatment of RSE, and that treatment should be based on pathophysiology. The search for a better drug has to deal with the fact that most monotherapy leaves half the problem untreated. The search for a better benzodiazepine should acknowledge the main cause of pharmacoresistance, which is loss of synaptic GABAAR. Future clinical trials should consider treating both the failure of inhibition and the runaway excitation which characterize RSE, and should include an early polytherapy arm
Crude incidence in two-phase designs in the presence of competing risks.
BackgroundIn many studies, some information might not be available for the whole cohort, some covariates, or even the outcome, might be ascertained in selected subsamples. These studies are part of a broad category termed two-phase studies. Common examples include the nested case-control and the case-cohort designs. For two-phase studies, appropriate weighted survival estimates have been derived; however, no estimator of cumulative incidence accounting for competing events has been proposed. This is relevant in the presence of multiple types of events, where estimation of event type specific quantities are needed for evaluating outcome.MethodsWe develop a non parametric estimator of the cumulative incidence function of events accounting for possible competing events. It handles a general sampling design by weights derived from the sampling probabilities. The variance is derived from the influence function of the subdistribution hazard.ResultsThe proposed method shows good performance in simulations. It is applied to estimate the crude incidence of relapse in childhood acute lymphoblastic leukemia in groups defined by a genotype not available for everyone in a cohort of nearly 2000 patients, where death due to toxicity acted as a competing event. In a second example the aim was to estimate engagement in care of a cohort of HIV patients in resource limited setting, where for some patients the outcome itself was missing due to lost to follow-up. A sampling based approach was used to identify outcome in a subsample of lost patients and to obtain a valid estimate of connection to care.ConclusionsA valid estimator for cumulative incidence of events accounting for competing risks under a general sampling design from an infinite target population is derived
Are the patterns of cytomegalovirus viral load seen after solid organ transplantation affected by circadian rhythm?
Background:
Cytomegalovirus (CMV) is an important opportunistic pathogen after transplantation. Some virological variation in transplant recipients is explained by donor and recipient CMV serostatus, but not all. Circadian variability of herpesviruses has been described, so we investigated the effect of time of day of transplantation on posttransplant CMV viremia.
Methods:
We performed a retrospective analysis of 1517 patients receiving liver or kidney allografts at a single center from 2002 to 2018. All patients were given preemptive therapy with CMV viremia monitoring after transplantation. Circulatory arrest and reperfusion time of donor organ were categorized into 4 periods. Patients were divided into serostatus groups based on previous CMV infection in donor and recipient. CMV viremia parameters were compared between time categories for each group. Factor analysis of mixed data was used to interrogate this complex data set.
Results:
Live-donor transplant recipients were less likely to develop viremia than recipients of deceased-donor organs (48% vs 61%; P < .001). After controlling for this, there was no evidence of time of day of transplantation affecting CMV parameters in any serostatus group, by logistic regression or factor analysis of mixed data.
Discussion:
We found no evidence for a circadian effect of transplantation on CMV viremia, but these novel results warrant confirmation by other centers
Using built environment characteristics to predict walking for exercise
Background: Environments conducive to walking may help people avoid sedentary lifestyles and associated diseases. Recent studies developed walkability models combining several built environment characteristics to optimally predict walking. Developing and testing such models with the same data could lead to overestimating one's ability to predict walking in an independent sample
of the population. More accurate estimates of model fit can be obtained by splitting a single study population into training and validation sets (holdout approach) or through developing and
evaluating models in different populations. We used these two approaches to test whether built
environment characteristics near the home predict walking for exercise. Study participants lived in western Washington State and were adult members of a health maintenance organization. The physical activity data used in this study were collected by telephone interview and were selected for their relevance to cardiovascular disease. In order to limit confounding by prior health conditions, the sample was restricted to participants in good self-reported health and without a
documented history of cardiovascular disease.
Results: For 1,608 participants meeting the inclusion criteria, the mean age was 64 years, 90 percent were white, 37 percent had a college degree, and 62 percent of participants reported that they walked for exercise. Single built environment characteristics, such as residential density or connectivity, did not significantly predict walking for exercise. Regression models using multiple built environment characteristics to predict walking were not successful at predicting walking for
exercise in an independent population sample. In the validation set, none of the logistic models had a C-statistic confidence interval excluding the null value of 0.5, and none of the linear models
explained more than one percent of the variance in time spent walking for exercise. We did not detect significant differences in walking for exercise among census areas or postal codes, which
were used as proxies for neighborhoods.
Conclusion: None of the built environment characteristics significantly predicted walking for exercise, nor did combinations of these characteristics predict walking for exercise when tested
using a holdout approach. These results reflect a lack of neighborhood-level variation in walking for exercise for the population studied.University of Washington Royalty Research fund award; by contracts R01-HL043201, R01-HL068639, and T32-HL07902 from the National Heart, Lung, and Blood Institute; and by grant R01-AG09556 from the National Institute on Aging
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