Objective: Responsible gambling (RG) tools that include play management software, self-limit features, and self-exclusion are relatively common offerings on major online gambling platforms. However, ...how online gaming and daily fantasy sports (DFS) players use such tools is less clear. The goals of this article were to understand how players use self-exclusion at a major DFS platform and to identify DFS activity-related predictors of self-exclusion. Method: During November 2015, DraftKings, a major DFS provider, rolled out a self-exclusion feature that allows players to self-exclude from the platform for a specified amount of time, up to 5 years. We used player records from DraftKings, examining play patterns and self-exclusion across 3+ years of data. Results: We found that less than 0.5% of subscribers in our sample self-excluded during the study period and almost one third of those who self-excluded did so more than once. In general, self-excluders engaged with a greater variety of contests and sports and entered contests with higher entry fees than those who did not self-exclude. Repeat self-excluders selected shorter initial self-exclusion terms and also engaged with a greater variety of game types and sports than one-time self-excluders. However, self-excluders did not engage in riskier contests or experience higher percent losses. Conclusion: Our findings have implications for our understanding of RG feature use among DFS subscribers and markers of risk for experiencing problems with DFS and gambling more generally.
Public Health Significance Statement
This study found that while self-exclusion from a daily fantasy sports (DFS) platform was a rare behavior, those who self-excluded displayed distinguishable patterns of activity prior to self-exclusion. These findings contribute to a body of literature identifying potential risk factors for experiencing problems with DFS play and gambling.
Transcriptomics data have been integrated with genome-wide association studies (GWASs) to help understand disease/trait molecular mechanisms. The utility of metabolomics, integrated with ...transcriptomics and disease GWASs, to understand molecular mechanisms for metabolite levels or diseases has not been thoroughly evaluated. We performed probabilistic transcriptome-wide association and locus-level colocalization analyses to integrate transcriptomics results for 49 tissues in 706 individuals from the GTEx project, metabolomics results for 1,391 plasma metabolites in 6,136 Finnish men from the METSIM study, and GWAS results for 2,861 disease traits in 260,405 Finnish individuals from the FinnGen study. We found that genetic variants that regulate metabolite levels were more likely to influence gene expression and disease risk compared to the ones that do not. Integrating transcriptomics with metabolomics results prioritized 397 genes for 521 metabolites, including 496 previously identified gene-metabolite pairs with strong functional connections and suggested 33.3% of such gene-metabolite pairs shared the same causal variants with genetic associations of gene expression. Integrating transcriptomics and metabolomics individually with FinnGen GWAS results identified 1,597 genes for 790 disease traits. Integrating transcriptomics and metabolomics jointly with FinnGen GWAS results helped pinpoint metabolic pathways from genes to diseases. We identified putative causal effects of UGT1A1/UGT1A4 expression on gallbladder disorders through regulating plasma (E,E)-bilirubin levels, of SLC22A5 expression on nasal polyps and plasma carnitine levels through distinct pathways, and of LIPC expression on age-related macular degeneration through glycerophospholipid metabolic pathways. Our study highlights the power of integrating multiple sets of molecular traits and GWAS results to deepen understanding of disease pathophysiology.
Display omitted
We integrated transcriptomics data for 49 human tissues, metabolomics data for 1,391 metabolites, and genome-wide association studies for 2,861 diseases. We identified 397 genes for 521 metabolites and 1,597 genes for 790 diseases. The results help understand the metabolic pathways underlying disease genetic associations.
The male genital tract (MGT) is a viral sanctuary and likely HIV reservoir; understanding MGT pharmacokinetics (PK) of antiretrovirals (ARVs) used for curative strategies is critical to eradication ...and cure. Tenofovir alafenamide (TAF) is a tenofovir (TFV) formulation designed to maximize efficacy/minimize toxicity with unknown MGT PK.
HIV-positive and HIV-negative men receiving TFV-based regimens provided six paired blood plasma (BP) and semen samples. Extracellular (TFV, TAF, emtricitabine FTC) drug concentrations in BP and seminal plasma (SP), and intracellular metabolite (IM) and endogenous nucleotide (EN) concentrations were measured in peripheral blood mononuclear cells (PBMCs) and seminal mononuclear cells (SMCs). Exposure ratios for SP:BP, SMC:PBMC and IM:EN were calculated from PK parameters generated by noncompartmental analysis. HIV viral load was measured in BP and SP.
Sixteen HIV-positive (n=8, TDF/FTC; n=8, TAF/FTC) and eight HIV-negative (TDF/FTC) men provided samples. Median TFV SP:BP ratios differed between TDF and TAF (1.5 versus 7.4), due to lower TFV BP concentrations with TAF coupled with TFV SP concentrations similar to TDF.
BP ratios were approximately 3. SMC concentrations of IMs and ENs were a fraction of PBMC concentrations (1-22%), though IM:EN ratios exceed a suggested protective threshold.
TAF SP PK was unexpected. IM SMC concentrations were low relative to PBMC, as were EN concentrations, suggesting differences in cell phenotype and lineage in the MGT; these differences in phenotype and pharmacology may have an impact on selecting and dosing ARVs used in cure strategies.
Glycogen synthase kinase‐3 α/β is involved in dysregulation of neuronal tau protein in Alzheimer's disease (AD). There is an unmet clinical need for a blood‐brain barrier (BBB) permeable positron ...emission tomography (PET) probe for imaging of GSK‐3α/β in the brain to understand the pathogenesis of AD. Herein, we synthesized two PET probes, 18FF‐CNBI and 18FF‐CNPIFE, and evaluated their BBB permeability and affinity towards GSK‐3α/β. 19FF‐CNPIFE showed higher in‐vitro binding towards GSK‐3α/β (IC50=19.4±2.5 nM; n=3, for GSK‐3α, IC50=19.4±3.8 nM; n=3, for GSK‐3β) compared to 19FF‐CNBI (IC50=107.6±26.0 nM; n=4, for GSK‐3α, IC50=105.3±18.2 nM; n=3, for GSK‐3β). 18FF‐CNPIFE showed 9.5‐fold higher brain uptake than 18FF‐CNBI, in normal FVB/NJ mice, which was increased by additional 1.5‐fold on co‐administration of 19FF‐CNPIFE with respect to 18FF‐CNBI. Overall, 18FF‐CNPIFE is a promising PET probe for GSK‐3α/β imaging and warrants further evaluation in an AD mouse model.
This study presents comparative uptake of two positron emission tomography (PET) probes 18FF‐CNBI and 18FF‐CNPIFE for imaging of the Glycogen Synthase Kinase‐3α/β in normal FVB/NJ mouse brain. Developed PET probes showed nanomolar affinity towards GSK‐3α/β. The PET probe 18FF‐CNPIFE showed order of magnitude higher brain uptake than 18FF‐CNBI in FVB/NJ mouse.
Aberrant insulin signaling has been considered one of the risk factors for the development of Alzheimer’s disease (AD) and has drawn considerable attention from the research community to further ...study its role in AD pathophysiology. Herein, we describe the development of an insulin-based novel positron emission tomography (PET) probe, 68GaGa-NOTA-insulin, to noninvasively study the role of insulin in AD. The developed PET probe 68GaGa-NOTA-insulin showed a significantly higher uptake (0.396 ± 0.055 SUV) in the AD mouse brain compared to the normal (0.140 ± 0.027 SUV) mouse brain at 5 min post injection and also showed a similar trend at 10, 15, and 20 min post injection. In addition, 68GaGa-NOTA-insulin was found to have a differential uptake in various brain regions at 30 min post injection. Among the brain regions, the cortex, thalamus, brain stem, and cerebellum showed a significantly higher standard uptake value (SUV) of 68GaGa-NOTA-insulin in AD mice as compared to normal mice. The inhibition of the insulin receptor (IR) with an insulin receptor antagonist peptide (S961) in normal mice showed a similar brain uptake profile of 68GaGa-NOTA-insulin as it was observed in the AD case, suggesting nonfunctional IR in AD and the presence of an alternative insulin uptake route in the absence of a functional IR. The Gjedde–Patlak graphical analysis was also performed to predict the input rate of 68GaGa-NOTA-insulin into the brain using MicroPET imaging data and supported the in vivo results. The 68GaGa-NOTA-insulin PET probe was successfully synthesized and evaluated in a mouse model of AD in comparison with 18FAV1451 and 11CPIB to noninvasively study the role of insulin in AD pathophysiology.
Objective
To describe the versatility of the axial pattern flap based on the cutaneous perforating branch of the angularis oris artery for reconstruction of large facial defects in dogs, including ...complications and clinical outcomes.
Study Design
Retrospective clinical case series.
Animals
Client‐owned dogs (n = 8).
Methods
Facial flaps (n = 9) based at the commissure of the lip with a caudodorsal orientation were utilized, with established anatomical borders. Flaps were elevated deep to the panniculus carnosus in a caudal to rostral direction, preserving the angularis oris artery, its cutaneous perforator, and surrounding cutaneous vasculature. Flaps were rotated dorsally or ventrally to cover the defect. Primary closure of the donor site was by direct apposition in all cases.
Results
Angularis oris axial pattern flaps were most commonly used to close large defects of the nasomaxillary area rostral to the eyes (6 dogs), followed by orbital (2) and intermandibular (1) defects. Defects occurred because of tumor resection (6 dogs), trauma (2), and a chronic, non‐healing wounding (1). All flaps healed with acceptable functional and cosmetic outcomes without major complications. Followup ranged from 10 days to 16 months. Minor postoperative complications included flap edema (8 dogs), partial incisional dehiscence (3), distal tip necrosis (2), and oroantral fistula recurrence (1).
Conclusion
Angularis oris axial pattern flaps provided hirsute, full‐thickness skin coverage of a variety of large facial defects with minor complications, and should be considered when restructuring large defects of the rostral face or chin.
Elevated blood pressure is a highly prevalent condition that is etiologically related to coronary heart disease and stroke, two of the leading causes of morbidity and mortality throughout the world. ...Excess salt (sodium chloride) intake is a major determinant of elevated blood pressure. In this article, we discuss the scientific rationale for population-wide salt reduction, the types and strength of available evidence, policy-making on dietary salt intake in the United States and other countries, and the role and impact of key stakeholders. We highlight a number of lessons learned, many of which are germane to policy development in other domains.
Daily fantasy sports (DFS), a rapidly growing industry, allows players to create fantasy teams of real-life players and potentially win cash prizes, derived from entry fees. Some stakeholders have ...expressed concern that DFS’s accelerated nature and other features might promote excessive play and related harm. We conducted the first descriptive summary of actual DFS play using records from a cohort of subscribers to a dominant operator, DraftKings. Participants (N = 10,385) initially entered paid National Football League (NFL) contests. Across all participants, players entered a median of two contests per entry day and typically submitted a single entry for each contest they entered. Players paid a median of $87 in entry fees throughout the 2014 NFL season and experienced an overall median net loss of $30.7. However, we identified heavily involved sub-groups of players based on number of contests entered, total entry fees, and net loss. These top 1% groups were less likely to restrict themselves to NFL games, exhibited greater time involvement, but also won a greater percentage of the contests they entered than typical players. Our observations of typical and heavily involved players tend to mirror those generated in previous Internet sports gambling research.
Each winter, populations of striped bass (Morone saxatilis) migrate north from the coastal mid-Atlantic region of the US to the coastal waters of New England. During this migration, striped bass ...spend significant time in estuaries and saltmarshes, presumably to forage. However, the extent to which saltmarsh productivity supports striped bass remains unresolved. We used a three-isotope Bayesian mixing model to determine the relative contribution of three primary producers C4 saltmarsh cordgrass (Spartina spp.), phytoplankton, and benthic diatoms to striped bass tissue. Phytoplankton (51 % contribution) and Spartina-denved sources (44 % contribution) are the primary sources of production to striped bass, while benthic diatoms made a relatively small contribution (5 %). Our results highlight the importance of saltmarshes to striped bass by showing that primary producers unique to saltmarsh ecosystems support a large proportion of striped bass production.
Historical trauma has contributed to the reality that addiction disproportionately affects tribal communities, including American Indian youth. We sought to understand American Indian youths' own ...experiences and perceptions of the environments to which they return after completing residential treatment for substance use disorder. We recruited three cohorts of American Indian residents of a substance use disorder treatment facility (N = 40). These residents completed a survey that measured risk and protective factors, as well as actual risk behaviors, including drug use, gambling, and violence. Participants were at risk not only for substance use disorders, but for other negative outcomes, and had elevated scores on several community, family, and school risk factors, including perceived availability of drugs, community disorganization, family history of antisocial behavior, favorable parental attitudes toward drug use, academic failure, and low school commitment. At the same time, they were exposed to community-level and family protective factors, and they engaged in many tribal cultural activities. When compared to a national sample of American Indian students of similar age, youth in our sample scored similarly on protective factors, including indicators of community, family, and school opportunities and rewards for prosocial involvement, as well as family attachment, suggesting potential resources and strengths for supporting recovery.
PDF
![Comparison of [18F]F‐CNBI a...](http://api.summon.serialssolutions.com/2.0.0/image/issn/XR4PS5YY4K/1434-193X/small "Comparison of [18F]F‐CNBI and [18F]F‐CNPIFE as Positron Emission Tomography Probes for Noninvasive Imaging of Glycogen Synthase Kinase‐3 in Normal Mice")
