70,089 Works

Self-Selecting Priority Queues with Burr Distributed Waiting Costs

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Service providers, in the presence of congestion and heterogeneity of customer waiting costs, often introduce a fee-based premier option using which the customers self-segment themselves. Examples of this practice are found in health care, amusement parks, government (consular services), and transportation. Using a single-server queuing system with customer waiting costs modeled as a Burr Distribution, we perform a detailed analysis to (i) determine the conditions (fees, cost structure, etc.) under which this strategy is profitable...

Dosing of Selective Serotonin Reuptake Inhibitors Among Children and Adults Before and After the FDA Black-Box Warning

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Prior research evaluated various effects of the antidepressant black-box warning on the risk of suicidality in children, but the dosing of antidepressants has not been considered. This study estimated, relative to the FDA warnings, whether the initial antidepressant dose prescribed decreased and the proportion augmenting dose on the second fill increased.

Relation between cannabis use and subcortical volumes in people at clinical high risk of psychosis

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Among people at genetic risk of schizophrenia, those who use cannabis show smaller thalamic and hippocampal volumes. We evaluated this relationship in people at clinical high risk (CHR) of psychosis. The Alcohol and Drug Use Scale was used to identify 132 CHR cannabis users, the majority of whom were non-dependent cannabis users, 387 CHR non-users, and 204 healthy control non-users, and all participants completed magnetic resonance imaging scans. Volumes of the thalamus, hippocampus and amygdala...

A randomized controlled trial of cognitive debiasing improves assessment and treatment selection for pediatric bipolar disorder.

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This study examined the efficacy of a new cognitive debiasing intervention in reducing decision-making errors in the assessment of pediatric bipolar disorder (PBD).

Traumatic brain injury in individuals at clinical high risk for psychosis

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Recent research suggests that a traumatic brain injury (TBI) can significantly increase the risk of later development of psychosis. However, it is unknown whether people at clinical high risk (CHR) of psychosis have experienced TBI at higher rates, compared to otherwise healthy individuals. This study evaluated the prevalence of mild TBI, whether it was related to past trauma and the relationship of mild TBI to later transition to psychosis.

Engineering extrinsic disorder to control protein activity in living cells

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Optogenetic and chemogenetic control of proteins has revealed otherwise inaccessible facets of signaling dynamics. Here we use light or ligand-sensitive domains to modulate the structural disorder of diverse proteins, thereby generating robust allosteric switches. Sensory domains were inserted into non-conserved, surface exposed loops that were tight and identified computationally as allosterically coupled to active sites. Allosteric switches introduced into motility signaling proteins (kinases, GTPases, guanine exchange factors) controlled conversion between conformations closely resembling natural active...

Latency reversal and viral clearance to cure HIV-1

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Research toward a cure for human immunodeficiency virus type 1 (HIV-1) infection has joined prevention and treatment efforts in the global public health agenda. A major approach to HIV eradication envisions antiretroviral suppression, paired with targeted therapies to enforce the expression of viral antigen from quiescent HIV-1 genomes, and immunotherapies to clear latent infection. These strategies are targeted to lead to viral eradication—a cure for AIDS. Paired testing of latency reversal and clearance strategies has...

A murine preclinical syngeneic transplantation model for breast cancer precision medicine

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We previously demonstrated that altered activity of lysophosphatidic acid in murine mammary glands promotes tumorigenesis. We have now established and characterized a heterogeneous collection of mouse-derived syngeneic transplants (MDSTs) as preclinical platforms for the assessment of personalized pharmacological therapies. Detailed molecular and phenotypic analyses revealed that MDSTs are the most heterogeneous group of genetically engineered mouse models (GEMMs) of breast cancer yet observed. Response of MDSTs to trametinib, a mitogen-activated protein kinase (MAPK) kinase inhibitor,...

Predatory fish depletion and recovery potential on Caribbean reefs

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The natural, prehuman abundance of most large predators is unknown because of the lack of historical data and a limited understanding of the natural factors that control their populations. Determining the supportable predator biomass at a given location (that is, the predator carrying capacity) would help managers to optimize protection and would provide site-specific recovery goals. We assess the relationship between predatory reef fish biomass and several anthropogenic and environmental variables at 39 reefs across...

Integrating remote sensing with nutrient management plans to calculate nitrogen parameters for swine CAFOs at the sprayfield and sub-watershed scales

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No Abstract.

Evaluation of the selectivity and sensitivity of isoform- and mutation-specific RAS antibodies

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Researchers rely largely on antibodies to measure the abundance, activity, and localization of a protein, information that provides critical insight into both normal and pathological cellular functions. However, antibodies are not always reliable or universally valid for the methods in which they are used; in particular, the reliability of commercial antibodies against RAS is highly variable. Waters et al . rigorously assessed 22 commercially available RAS antibodies for their utility to detect the distinct RAS...

A genomic approach to therapeutic target validation identifies a glucose-lowering GLP1R variant protective for coronary heart disease

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Regulatory authorities have indicated that new drugs to treat type 2 diabetes (T2D) should not be associated with an unacceptable increase in cardiovascular risk. Human genetics may be able to inform development of antidiabetic therapies by predicting cardiovascular and other health endpoints. We therefore investigated the association of variants in 6 genes that encode drug targets for obesity or T2D with a range of metabolic traits in up to 11,806 individuals by targeted exome sequencing,...

Goethe's Social Philosophy: As Revealed in \"Campagne in Frankreich\" and \"Belagerung von Mainz\"

In this study originally published in 1955, Steer explores the importance of Goethe's family concept in two autobiographical works, "Campagne in Frankreich" and "Belagerung von Mainz". Through a close textual analysis, Steer argues that at the center of both pieces is Goethe's conception of the family as "Urform" of society.

Wilhelm Waiblinger in Italy

This study traces the importance of Italy as a source of literary inspiration in the work of the Swabian poet Wilhelm Waiblinger (1804-1830), who spent the last four years of his life, the most prolific of his career, living and traveling in Italy. Drawing on Waiblinger's poems, travel accounts, letters and diaries, Thompson compiles and analyzes Waiblinger's thoughts on and engagement with Italian art, literature, music, people and landscapes as well as the themes of...

Middle Ages—Reformation—Volkskunde: Festschrift for John G. Kunstmann

Twenty essays on medieval history, literature and language published in honor of John G. Kunstmann and his work on German literature in the Middle Ages. The contributors are Berthold Ullman, Urban Tigner Holmes, Edwin Zeydel, George Fenwick Jones, Wayland Hand, Robert Linker, John Keller, Carl Bayerschmidt, Helmut Motekat, Stuart Gallacher, John Fisher, Astrik Gabriel, James Engel, Eli Sobel, Lewis Spitz, Theodore Silverstein, Murray Cowie, Marian Cowie, Josef Ryan, Oscar Jones, and Fritjof Raven.

Goethe, the Lyrist: 100 Poems in New Translations Facing the Originals with a Biographical Introduction

In this volume originally published in 1955, Zeydel provides English translations of one hundred of Goethe's poems divided into nine periods. The biographical introduction traces Goethe's development as seen in his poems and an appendix gives information on musical settings to the poems.

Poems of Goethe: A Sequel to \"Goethe, the Lyrist\"

Following his previous translation of one hundred of Goethe's poems, in this volume Zeydel presents translations of a selection of Goethe's shorter poems, the majority of which were written in the last twenty years of his life. The translator gives careful attention to details of substance, form and style, and to the spirit of the original, reproducing the simplicity and naturalness of language so characteristic of Goethe. The original text in German appears on facing...

Developmental Changes in Sleep Spindle Characteristics and Sigma Power across Early Childhood

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Sleep spindles, a prominent feature of the non-rapid eye movement (NREM) sleep electroencephalogram (EEG), are linked to cognitive abilities. Early childhood is a time of rapid cognitive and neurophysiological maturation; however, little is known about developmental changes in sleep spindles. In this study, we longitudinally examined trajectories of multiple sleep spindle characteristics (i.e., spindle duration, frequency, integrated spindle amplitude, and density) and power in the sigma frequency range (10–16 Hz) across ages 2, 3, and...

Scalable joint segmentation and registration framework for infant brain images

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The first year of life is the most dynamic and perhaps the most critical phase of postnatal brain development. The ability to accurately measure structure changes is critical in early brain development study, which highly relies on the performances of image segmentation and registration techniques. However, either infant image segmentation or registration, if deployed independently, encounters much more challenges than segmentation/registration of adult brains due to dynamic appearance change with rapid brain development. In fact,...

CSF Volumetric Analysis for Quantification of Cerebral Edema After Hemispheric Infarction

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Malignant cerebral edema (CED) complicates at least 20 % of large hemispheric infarcts (LHI) and may result in neurological deterioration or death. Midline shift (MLS) is a standard but crude measure of edema severity. We propose that volumetric analysis of shifts in cerebrospinal fluid (CSF) over time provides a reliable means of quantifying the spectrum of edema severity after LHI.

A multi-centre evaluation of eleven clinically feasible brain PET/MRI attenuation correction techniques using a large cohort of patients

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AIM: To accurately quantify the radioactivity concentration measured by PET, emission data need to be corrected for photon attenuation; however, the MRI signal cannot easily be converted into attenuation values, making attenuation correction (AC) in PET/MRI challenging. In order to further improve the current vendor-implemented MR-AC methods for absolute quantification, a number of prototype methods have been proposed in the literature. These can be categorized into three types: template/atlas-based, segmentation-based, and reconstruction-based. These proposed methods...

Failure to retreat: Blunted sensitivity to negative feedback supports risky behavior in adolescents

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Decision-making processes rarely occur in isolation. Rather, representations are updated constantly based on feedback to past decisions and actions. However, previous research has focused on the reaction to feedback receipt itself, instead of examining how feedback information is integrated into future decisions. In the current study, we examined differential neural sensitivity during risk decisions following positive versus negative feedback in a risk-taking context, and how this differential sensitivity is linked to adolescent risk behavior. Fifty-eight...

Genome-wide association analysis of secondary imaging phenotypes from the Alzheimer's disease neuroimaging initiative study

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The aim of this paper is to systematically evaluate a biased sampling issue associated with genome-wide association analysis (GWAS) of imaging phenotypes for most imaging genetic studies, including the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Specifically, the original sampling scheme of these imaging genetic studies is primarily the retrospective case-control design, whereas most existing statistical analyses of these studies ignore such sampling scheme by directly correlating imaging phenotypes (called the secondary traits) with genotype. Although it...

Abstinence-Only-Until-Marriage: An Updated Review of U.S. Policies and Programs and Their Impact

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Adolescence is marked by the emergence of human sexuality, sexual identity and the initiation of intimate relations; within this context, abstinence from sexual intercourse can be a healthy choice. However, programs that promote abstinence-only-until-marriage (AOUM) or sexual risk avoidance (SRA), are scientifically and ethically problematic and—as such—have been widely rejected by medical and public health professionals. Although abstinence is theoretically effective, in actual practice, intentions to abstain from sexual activity often fail. Given a rising...

How should we screen for depression following a natural disaster? An ROC approach to post-disaster screening in adolescents and adults

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The present study’s aim was to provide the foundation for an efficient, empirically based protocol for depression screening following a natural disaster. Utilizing a Receiver Operating Characteristic (ROC) analytic approach, the study tested a) what specific disaster-related stressors (i.e., property damage, loss of basic services) and individual-related constructs (i.e., PTSD symptoms, trauma history, social support) conveyed the greatest risk for post-natural disaster depression, b) specific cutoff scores across these measures, and c) whether the significance...

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