1,748 research outputs found

    Decision-Making as a Latent Construct and its Measurement Invariance in a Large Sample of Adolescent Cannabis Users

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    OBJECTIVE: Relative to the vast literature that employs measures of decision-making (DM), rigorous examination of their psychometric properties is sparse. This study aimed to determine whether three measures of DM assess the same construct, and to measure invariance of this construct across relevant covariates. METHOD: Participants were 372 adolescents at risk of escalation in cannabis use. DM was assessed via four indices from the Cups Task, Game of Dice Task (GDT), and Iowa Gambling Task (IGT). We used confirmatory factor analysis to assess unidimensionality of the DM construct, and moderated nonlinear factor analysis (MNLFA) to examine its measurement invariance. RESULTS: The unidimensional model of DM demonstrated good fit. MNLFA results revealed that sex influenced mean DM scores, such that boys had lower risk-taking behaviors. There was evidence of differential item functioning (DIF), such that IQ and age moderated the IGT intercept and GDT factor loading, respectively. Significant effects were retained in the final model, which produced participant-specific DM factor scores. These scores showed moderate stability over time. CONCLUSIONS: Indices from three DM tasks loaded significantly onto a single factor, suggesting that these DM tasks assess a single underlying construct. We suggest that this construct represents the ability to make optimal choices that maximize rewards in the presence of risk. Our final DM factor accounts for DIF caused by covariates, making it comparable across adolescents with different characteristics. (JINS, 2019, 25, 661-667)

    Obesity-Induced Colorectal Cancer Is Driven by Caloric Silencing of the Guanylin-GUCY2C Paracrine Signaling Axis.

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    Obesity is a well-known risk factor for colorectal cancer but precisely how it influences risks of malignancy remains unclear. During colon cancer development in humans or animals, attenuation of the colonic cell surface receptor guanylyl cyclase C (GUCY2C) that occurs due to loss of its paracrine hormone ligand guanylin contributes universally to malignant progression. In this study, we explored a link between obesity and GUCY2C silencing in colorectal cancer. Using genetically engineered mice on different diets, we found that diet-induced obesity caused a loss of guanylin expression in the colon with subsequent GUCY2C silencing, epithelial dysfunction, and tumorigenesis. Mechanistic investigations revealed that obesity reversibly silenced guanylin expression through calorie-dependent induction of endoplasmic reticulum stress and the unfolded protein response in intestinal epithelial cells. In transgenic mice, enforcing specific expression of guanylin in intestinal epithelial cells restored GUCY2C signaling, eliminating intestinal tumors associated with a high calorie diet. Our findings show how caloric suppression of the guanylin-GUCY2C signaling axis links obesity to negation of a universal tumor suppressor pathway in colorectal cancer, suggesting an opportunity to prevent colorectal cancer in obese patients through hormone replacement with the FDA-approved oral GUCY2C ligand linaclotide

    Hand problems among endourologists.

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    BACKGROUND AND PURPOSE: Endourology has evolved rapidly for the management of both benign and malignant disease of the upper urinary tract. Limited data exist, however, on the occupational hazards posed by complex endourologic procedures. The aim of this study was to determine the prevalence and possible causes of hand problems among endourologists who routinely perform flexible ureteroscopy compared with controls. MATERIALS AND METHODS: An online computer survey targeted members of the Endourological Society and psychiatrists in academic and community settings. A total of 600 endourologists and 578 psychiatrists were contacted by e-mail. Invited physicians were queried regarding their practice settings and symptoms of hand pain, neuropathy, and/or discomfort. RESULTS: Survey responses were obtained from 122 (20.3%) endourologists and 74 (12.8%) psychiatrists. Of endourologists, 61% were in an academic setting and 70% devoted their practice to endourology. Endourologists were in practice for a mean 13 years, performing 4.5 ureteroscopic cases per week with a mean operative time of 50 minutes. Hand/wrist problems were reported by 39 (32%) endourologists compared with 14 (19%) psychiatrists (P=0.0486, relative risk [RR]=1.69). Surgeons who preferred counterintuitive ureteroscope deflection were significantly more likely to have problems (56%) compared with intuitive users (27%) (RR 2.07, P=0.0139) or those with no preference (26%) (RR 2.15, P=0.0451). Overall, most respondents (85%) with hand/wrist problems needed either medical or surgical intervention. CONCLUSIONS: Hand and wrist problems are very common among endourologists. Future studies are needed to develop more ergonomic platforms and thereby reduce the endourologist\u27s exposure to these occupational hazards

    Higgs-Boson Mass Limits and Precise Measurements beyond the Standard Model

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    The triviality and vacuum stability bounds on the Higgs-boson mass (\mh) were revisited in presence of weakly-coupled new interactions parameterized in a model-independent way by effective operators of dimension 6. The constraints from precision tests of the Standard Model were taken into account. It was shown that for the scale of new physics in the region \Lambda \simeq 2 \div 50 \tev the Standard Model triviality upper bound remains unmodified whereas it is natural to expect that the lower bound derived from the requirement of vacuum stability is substantially modified depending on the scale \La and strength of coefficients of effective operators. A natural generalization of the standard triviality condition leads also to a substantial reduction of the allowed region in the (\Lambda,\mh) space.Comment: 18 pages 3 eps figures. The discussion in the appendix was modified slightly and some typographical errors were correcte

    Comparison of two ancient DNA extraction protocols for skeletal remains from tropical environments

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    Objectives The tropics harbor a large part of the world\u27s biodiversity and have a long history of human habitation. However, paleogenomics research in these climates has been constrained so far by poor ancient DNA yields. Here we compare the performance of two DNA extraction methods on ancient samples of teeth and petrous portions excavated from tropical and semi‐tropical sites in Tanzania, Mexico, and Puerto Rico (N = 12). Materials and Methods All samples were extracted twice, built into double‐stranded sequencing libraries, and shotgun sequenced on the Illumina HiSeq 2500. The first extraction protocol, Method D, was previously designed for recovery of ultrashort DNA fragments from skeletal remains. The second, Method H, modifies the first by adding an initial EDTA wash and an extended digestion and decalcification step. Results No significant difference was found in overall ancient DNA yields or post‐mortem damage patterns recovered from samples extracted with either method, irrespective of tissue type. However, Method H samples had higher endogenous content and more mapped reads after quality‐filtering, but also higher clonality. In contrast, samples extracted with Method D had shorter average DNA fragments. Discussion Both methods successfully recovered endogenous ancient DNA. But, since surviving DNA in ancient or historic remains from tropical contexts is extremely fragmented, our results suggest that Method D is the optimal choice for working with samples from warm and humid environments. Additional optimization of extraction conditions and further testing of Method H with different types of samples may allow for improvement of this protocol in the future

    A Universal Phase Diagram for PMN-xPT and PZN-xPT

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    The phase diagram of the Pb(Mg1/3Nb2/3)O3 and PbTiO3 solid solution (PMN-xPT) indicates a rhombohedral ground state for x < 0.32. X-ray powder measurements by Dkhil et al. show a rhombohedrally split (222) Bragg peak for PMN-10%PT at 80 K. Remarkably, neutron data taken on a single crystal of the same compound with comparable q-resolution reveal a single resolution-limited (111) peak down to 50 K, and thus no rhombohedral distortion. Our results suggest that the structure of the outer layer of these relaxors differs from that of the bulk, which is nearly cubic, as observed in PZN by Xu et al.Comment: Replaced Fig. 3 with better versio

    Coarse Graining of Data via Inhomogeneous Diffusion Condensation

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    Big data often has emergent structure that exists at multiple levels of abstraction, which are useful for characterizing complex interactions and dynamics of the observations. Here, we consider multiple levels of abstraction via a multiresolution geometry of data points at different granularities. To construct this geometry we define a time-inhomogeneous diffusion process that effectively condenses data points together to uncover nested groupings at larger and larger granularities. This inhomogeneous process creates a deep cascade of intrinsic low pass filters on the data affinity graph that are applied in sequence to gradually eliminate local variability while adjusting the learned data geometry to increasingly coarser resolutions. We provide visualizations to exhibit our method as a continuously-hierarchical clustering with directions of eliminated variation highlighted at each step. The utility of our algorithm is demonstrated via neuronal data condensation, where the constructed multiresolution data geometry uncovers the organization, grouping, and connectivity between neurons.Comment: 14 pages, 7 figure

    Infectious Complications of Ventricular Assist Device Use in Children in the US: Data from the Pediatric Interagency Registry for Mechanical Circulatory Support (Pedimacs)

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    Background Infections are frequent in pediatric ventricular assist device (VAD) patients. In this study we aimed to describe infections in durable VAD patients reported to Pedimacs. Methods Durable VAD data from the Pedimacs registry (September 19, 2012 to December 31, 2015) were analyzed. Infections were described with standard descriptive statistics, Kaplan–Meier analysis and competing outcomes analysis. Results There were 248 implants in 222 patients, with a mean age and a median follow-up of 11 ± 6.4 years and 2.4 patient-months (<1 day to 2.6 years), respectively. Device types were pulsatile flow (PF) in 91 (41%) patients and continuous flow (CF) in 131 (59%) patients. PF patients were younger (4 ± 4 vs 14 ± 4 years; p < 0.0001) and were more likely to have congenital heart disease (25% vs 12%; p = 0.03), prior surgery (53% vs 26%; p < 0.0001) and prior extracorporeal membrane oxygenation (24% vs 7%; p = 0.0003). Infection accounted for 17% (96 of 564) of the reported adverse events (AEs). A non-device infection was most common (51%), followed by sepsis (24%), external pump component infection (20%) and internal pump component infection (5%). Most infections were bacterial (73%) and required intravenous therapy only (77%). The risk of infection in the constant phase was higher in patients with a history of prior infection and in patients with a history of a non-infectious major AEs. Survival was lower after infection only in CF patients (p = 0.008). Conclusions Infection was the most common AE after pediatric VAD implantation. Non-device infections were most common. The best predictor of a future infection was a past infection. CF patients have higher risk of death after an infection

    Selective Serotonin Reuptake Inhibitors and Associated Bleeding Risks: A Narrative and Clinical Review.

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    Major Depressive Disorder (MDD) is a major cause of disability worldwide and is associated with serious lasting impairment. A leading hypothesis of the pathophysiology of MDD is the monoamine deficiency hypothesis which suggests that depression is caused by depletion of serotonin, norepinephrine, or dopamine in the central nervous system. Serotonin is the most widely studied neurotransmitter in the pathophysiology of depression, with studies showing that reduced central serotonin synthesis leads to depressive symptoms in individuals at risk for depression. Selective Serotonin Reuptake Inhibitors (SSRI) inhibit serotonin reuptake and subsequently increase the amount of serotonin available in synapses. Common side effects of SSRIs include increased suicidality of patients under the age of 25, sexual dysfunction, anxiety, dizziness, weight gain, gastrointestinal distress, and headache. Other side effects include prolonging the QT interval, coagulopathy, and the risk of serotonin syndrome, as well as SSRI discontinuation syndrome. Sites of increased bleeding related to SSRI use have been reported to occur in the upper gastrointestinal tract, as well as intracranially. Based on the current literature, three studies have found that SSRIs are not associated with increased bleeding and/or increased perioperative risk, while others have demonstrated that SSRIs are associated with an increased risk in perioperative use. The inhibition of serotonin reuptake can affect platelet aggregation since platelets also express the serotonin transporter. SSRIs can result in decreased storage of serotonin in platelet dense granules. Increased serotonin can also increase gastric acid secretion, which increases the risk for ulceration. SSRIs in combination with NSAIDs also show a significantly increased risk of upper GI bleeding. Some studies show an increased bleeding risk from 30% to 70% when taking a combination of vitamin K antagonists and SSRIs in hospitalized patients. Related to the high prevalence of conditions that are treated with SSRIs, the bleeding risk associated with this class of medication merits further study
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