Background & Aims Antidepressants are frequently prescribed to treat functional dyspepsia (FD), a common disorder characterized by upper abdominal symptoms, including discomfort or postprandial ...fullness. However, there is little evidence of the efficacy of these drugs in patients with FD. We performed a randomized, double-blind, placebo-controlled trial to evaluate the effects of antidepressant therapy on symptoms, gastric emptying (GE), and meal-induced satiety in patients with FD. Methods We performed a study at 8 North American sites of patients who met the Rome II criteria for FD and did not have depression or use antidepressants. Patients (n = 292; 44 ± 15 years old, 75% were female, 70% with dysmotility-like FD, and 30% with ulcer-like FD) were randomly assigned to groups given placebo, 50 mg amitriptyline, or 10 mg escitalopram for 10 weeks. The primary end point was adequate relief of FD symptoms for ≥5 weeks of the last 10 weeks (of 12). Secondary end points included GE time, maximum tolerated volume in Nutrient Drink Test, and FD-related quality of life. Results An adequate relief response was reported by 39 subjects given placebo (40%), 51 given amitriptyline (53%), and 37 given escitalopram (38%) ( P = .05, after treatment, adjusted for baseline balancing factors including all subjects). Subjects with ulcer-like FD given amitriptyline were >3-fold more likely to report adequate relief than those given placebo (odds ratio = 3.1; 95% confidence interval: 1.1−9.0). Neither amitriptyline nor escitalopram appeared to affect GE or meal-induced satiety after the 10-week period in any group. Subjects with delayed GE were less likely to report adequate relief than subjects with normal GE (odds ratio = 0.4; 95% confidence interval: 0.2−0.8). Both antidepressants improved overall quality of life. Conclusions Amitriptyline, but not escitalopram, appears to benefit some patients with FD, particularly those with ulcer-like (painful) FD. Patients with delayed GE do not respond to these drugs. ClinicalTrials.gov ID: NCT00248651.
Previous voxel-based and regions-of-interest (ROI)-based diffusion tensor imaging (DTI) studies have found above-normal mean diffusivity (MD) and below-normal fractional anisotropy (FA) in subjects ...with attention-deficit/hyperactivity disorder (ADHD). However, findings remain mixed, and few studies have examined the contribution of ADHD familial liability to white matter microstructure.
We used refined DTI tractography methods to examine MD, FA, axial diffusivity (AD), and radial diffusivity (RD) of the anterior thalamic radiation, cingulum, corticospinal tract, inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, forceps major, forceps minor, superior longitudinal fasciculus, and uncinate fasciculus in children and adolescents with ADHD (n = 56), unaffected siblings of ADHD probands (n = 31), and healthy controls (n = 17).
Subjects with ADHD showed significantly higher MD than controls in the anterior thalamic radiation, forceps minor, and superior longitudinal fasciculus. Unaffected siblings of subjects with ADHD displayed similar differences in MD as subjects with ADHD. Although none of the tested tracts showed a significant effect of FA, the tracts with elevated MD likewise displayed elevated AD both in subjects with ADHD and in unaffected siblings. Differences in RD between subjects with ADHD, unaffected siblings, and controls were not as widespread as differences in MD and AD.
Our findings suggest that disruptions in white matter microstructure occur in several large white matter pathways in association with ADHD and indicate a familial liability for the disorder. Furthermore, MD may reflect these abnormalities more sensitively than FA.
Sensory overresponsivity (SOR), an atypical negative reaction to sensory stimuli, is highly prevalent in autism spectrum disorder (ASD). Previous work has related SOR to increased brain response in ...sensory-limbic regions. This study investigated where these atypical responses fall in three fundamental stages of sensory processing: arousal (i.e., initial response), habituation (i.e., change in response over time), and generalization of response to novel stimuli. Different areas of atypical response would require distinct intervention approaches.
Functional MRI was used to examine these patterns of neural habituation to two sets of similar mildly aversive auditory and tactile stimuli in 42 high-functioning children and adolescents with ASD (21 with high levels of SOR and 21 with low levels of SOR) and 27 age-matched typically developing youths (ages 8-17). The relationship between SOR and change in amygdala-prefrontal functional connectivity across the sensory stimulation was also examined.
Across repeated sensory stimulation, high-SOR participants with ASD showed reduced ability to maintain habituation in the amygdala and relevant sensory cortices and to maintain inhibition of irrelevant sensory cortices. These results indicate that sensory habituation is a dynamic, time-varying process dependent on sustained regulation across time, which is a particular deficit in high-SOR participants with ASD. However, low-SOR participants with ASD also showed distinct, nontypical neural response patterns, including reduced responsiveness to novel but similar stimuli and increases in prefrontal-amygdala regulation across the sensory exposure.
The results suggest that all children with autism have atypical brain responses to sensory stimuli, but whether they express atypical behavioral responses depends on top-down regulatory mechanisms. Results are discussed in terms of targeted intervention approaches.
Background Bullous pemphigoid (BP) has been associated with neurologic disorders. Objective We sought to analyze the association between BP and neurologic disorders. Methods We retrospectively ...identified residents of Olmsted County, Minnesota, with a first lifetime diagnosis of BP between January 1, 1960, and December 31, 2009. Three age- and sex-matched Olmsted County, Minnesota, residents without BP were selected as control subjects for each patient. We compared history of or development of neurologic disorders (dementia, Alzheimer disease, Parkinson disease, multiple sclerosis, cerebrovascular disease, and seizures) between groups using case-control and cohort designs. Results In all, 87 patients with BP were identified and matched to 261 control subjects. The odds of a previous diagnosis of any neurologic disorder or a history of dementia were significantly increased among cases compared with controls (odds ratio 6.85; 95% confidence interval CI 3.00-15.64; P < .001; and odds ratio 6.75; 95% CI 2.08-21.92; P = .002, respectively). Both Parkinson disease (hazard ratio 8.56; 95% CI 1.55-47.25; P = .01) and any type of neurologic disorder (hazard ratio 2.02; 95% CI 1.17-3.49; P = .01) were significantly more likely to develop during follow-up in patients with than without BP. Limitations Small geographic area and retrospective study design are limitations. Conclusion Findings confirmed an association of BP with neurologic disorders, especially dementia and Parkinson disease.
The rational design of complementary DNA sequences can be used to create nanostructures that self-assemble with nanometer precision. DNA nanostructures have been imaged by atomic force microscopy and ...electron microscopy. Small-angle X-ray scattering (SAXS) provides complementary structural information on the ensemble-averaged state of DNA nanostructures in solution. Here we demonstrate that SAXS can distinguish between different single-layer DNA origami tiles that look identical when immobilized on a mica surface and imaged with atomic force microscopy. We use SAXS to quantify the magnitude of global twist of DNA origami tiles with different crossover periodicities: these measurements highlight the extreme structural sensitivity of single-layer origami to the location of strand crossovers. We also use SAXS to quantify the distance between pairs of gold nanoparticles tethered to specific locations on a DNA origami tile and use this method to measure the overall dimensions and geometry of the DNA nanostructure in solution. Finally, we use indirect Fourier methods, which have long been used for the interpretation of SAXS data from biomolecules, to measure the distance between DNA helix pairs in a DNA origami nanotube. Together, these results provide important methodological advances in the use of SAXS to analyze DNA nanostructures in solution and insights into the structures of single-layer DNA origami.
Sex differences in white matter microstructure have been robustly demonstrated in the adult brain using both conventional and advanced diffusion‐weighted magnetic resonance imaging approaches. ...However, sex differences in white matter microstructure prior to adulthood remain poorly understood; previous developmental work focused on conventional microstructure metrics and yielded mixed results. Here, we rigorously characterized sex differences in white matter microstructure among over 6000 children from the Adolescent Brain Cognitive Development study who were between 9 and 10 years old. Microstructure was quantified using both the conventional model—diffusion tensor imaging (DTI)—and an advanced model, restriction spectrum imaging (RSI). DTI metrics included fractional anisotropy (FA) and mean, axial, and radial diffusivity (MD, AD, RD). RSI metrics included normalized isotropic, directional, and total intracellular diffusion (N0, ND, NT). We found significant and replicable sex differences in DTI or RSI microstructure metrics in every white matter region examined across the brain. Sex differences in FA were regionally specific. Across white matter regions, boys exhibited greater MD, AD, and RD than girls, on average. Girls displayed increased N0, ND, and NT compared to boys, on average, suggesting greater cell and neurite density in girls. Together, these robust and replicable findings provide an important foundation for understanding sex differences in health and disease.
We rigorously characterized developmental sex differences in white matter microstructure using both conventional (diffusion tensor imaging DTI) and advanced (restriction spectrum imaging RSI) diffusion‐weighted MRI models among over 6000 children from the Adolescent Brain Cognitive Development study who were between 9 and 10 years old. Significant, replicable, and robust sex differences in DTI or RSI microstructure metrics were observed in every white matter region examined across the brain. These robust and replicable findings provide an important foundation for understanding sex differences in health and disease.
ABSTRACT
Large galaxy samples from multiobject integral field spectroscopic (IFS) surveys now allow for a statistical analysis of the z ∼ 0 galaxy population using resolved kinematic measurements. ...However, the improvement in number statistics comes at a cost, with multiobject IFS survey more severely impacted by the effect of seeing and lower signal-to-noise ratio. We present an analysis of ∼1800 galaxies from the SAMI Galaxy Survey taking into account these effects. We investigate the spread and overlap in the kinematic distributions of the spin parameter proxy $\lambda _{R_{\rm {e}}}$ as a function of stellar mass and ellipticity εe. For SAMI data, the distributions of galaxies identified as regular and non-regular rotators with kinemetry show considerable overlap in the $\lambda _{R_{\rm {e}}}$–εe diagram. In contrast, visually classified galaxies (obvious and non-obvious rotators) are better separated in $\lambda _{R_{\rm {e}}}$ space, with less overlap of both distributions. Then, we use a Bayesian mixture model to analyse the observed $\lambda _{R_{\rm {e}}}$–log (M⋆/M⊙) distribution. By allowing the mixture probability to vary as a function of mass, we investigate whether the data are best fit with a single kinematic distribution or with two. Below log (M⋆/M⊙) ∼ 10.5, a single beta distribution is sufficient to fit the complete $\lambda _{R_{\rm {e}}}$ distribution, whereas a second beta distribution is required above log (M⋆/M⊙) ∼ 10.5 to account for a population of low-$\lambda _{R_{\rm {e}}}$ galaxies. While the Bayesian mixture model presents the cleanest separation of the two kinematic populations, we find the unique information provided by visual classification of galaxy kinematic maps should not be disregarded in future studies. Applied to mock-observations from different cosmological simulations, the mixture model also predicts bimodal $\lambda _{R_{\rm {e}}}$ distributions, albeit with different positions of the $\lambda _{R_{\rm {e}}}$ peaks. Our analysis validates the conclusions from previous, smaller IFS surveys, but also demonstrates the importance of using selection criteria for identifying different kinematic classes that are dictated by the quality and resolution of the observed or simulated data.
Objective
The aim of this study was to investigate the mediating role of child brain structure in the relationship between prenatal gestational diabetes mellitus (GDM) exposure and child adiposity.
...Methods
This was a cross‐sectional study of 9– to 10‐year‐old participants and siblings across the US. Data were obtained from the baseline assessment of the Adolescent Brain Cognitive Development (ABCD) Study®. Brain structure was evaluated by magnetic resonance imaging. GDM exposure was self‐reported, and discordance for GDM exposure within biological siblings was identified. Mixed effects and mediation models were used to examine associations among prenatal GDM exposure, brain structure, and adiposity markers with sociodemographic covariates.
Results
The sample included 8521 children (7% GDM‐exposed), among whom there were 28 sibling pairs discordant for GDM exposure. Across the entire study sample, prenatal exposure to GDM was associated with lower global and regional cortical gray matter volume (GMV) in the bilateral rostral middle frontal gyrus and superior temporal gyrus. GDM‐exposed siblings also demonstrated lower global cortical GMV than unexposed siblings. Global cortical GMV partially mediated the associations between prenatal GDM exposure and child adiposity markers.
Conclusions
The results identify brain markers of prenatal GDM exposure and suggest that low cortical GMV may explain increased obesity risk for offspring prenatally exposed to GDM.
Global cortical gray matter volume mediating the associations between maternal diabetes exposure and child adiposity
CcNav: Understanding Compiler Optimizations in Binary Code Devkota, Sabin; Aschwanden, Pascal; Kunen, Adam ...
IEEE transactions on visualization and computer graphics,
02/2021, Letnik:
27, Številka:
2
Journal Article, Conference Proceeding
Recenzirano
Odprti dostop
Program developers spend significant time on optimizing and tuning programs. During this iterative process, they apply optimizations, analyze the resulting code, and modify the compilation until they ...are satisfied. Understanding what the compiler did with the code is crucial to this process but is very time-consuming and labor-intensive. Users need to navigate through thousands of lines of binary code and correlate it to source code concepts to understand the results of the compilation and to identify optimizations. We present a design study in collaboration with program developers and performance analysts. Our collaborators work with various artifacts related to the program such as binary code, source code, control flow graphs, and call graphs. Through interviews, feedback, and pair-analytics sessions, we analyzed their tasks and workflow. Based on this task analysis and through a human-centric design process, we designed a visual analytics system Compilation Navigator (CcNav) to aid exploration of the effects of compiler optimizations on the program. CcNav provides a streamlined workflow and a unified context that integrates disparate artifacts. CcNav supports consistent interactions across all the artifacts making it easy to correlate binary code with source code concepts. CcNav enables users to navigate and filter large binary code to identify and summarize optimizations such as inlining, vectorization, loop unrolling, and code hoisting. We evaluate CcNav through guided sessions and semi-structured interviews. We reflect on our design process, particularly the immersive elements, and on the transferability of design studies through our experience with a previous design study on program analysis.
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