Abstract We used an operant delayed spatial alternation task to examine the role of rat dorsomedial prefrontal cortex (dmPFC) in spatial working memory. The task was designed to restrict movements ...during the delay period to minimize use of motor-mediating strategies. Inactivation of dmPFC (muscimol) resulted in increased errors and increased the temporal variability of responding. Animals did not show perseveration after errors (i.e., responding again at the erroneous location). Under control conditions, the time between spatial responses was greater and more variable before errors as compared to correct responses. These effects were eliminated when muscimol was infused into dmPFC. Trial outcome also affected movement and delay times in the next trial. This effect was diminished with muscimol in dmPFC. By contrast, when muscimol was infused in dorsal agranular insular cortex (AId)—a region that is strongly interconnected with dorsomedial prefrontal regions—there was no effect on delayed spatial alternation performance. These experiments confirm that dmPFC is necessary for successful delayed spatial alternation and establish that there is a relationship between response time variability and trial outcome that depends on dorsomedial prefrontal function.
Insulin resistance of adipose tissue is an important feature of obesity-related metabolic disease. However, assessment of lipolysis in humans requires labor-intensive and expensive methods, and there ...is limited validation of simplified measurement methods. We aimed to validate simplified methods for the quantification of adipose tissue insulin resistance against the assessment of insulin sensitivity of lipolysis suppression during hyperinsulinemic-euglycemic clamp studies.
We assessed the insulin-mediated suppression of lipolysis by tracer-dilution of 1,1,2,3,3-
H
glycerol during hyperinsulinemic-euglycemic clamp studies in 125 overweight or obese adults (85 men, 40 women; age 50±11 years; body mass index 38±7 kg m
). Seven indices of adipose tissue insulin resistance were validated against the reference measurement method.
Low-dose insulin infusion resulted in suppression of the glycerol rate of appearance ranging from 4% (most resistant) to 85% (most sensitive), indicating a good range of adipose tissue insulin sensitivity in the study population. The reference method correlated with (1) insulin-mediated suppression of plasma glycerol concentrations (r=0.960, P<0.001), (2) suppression of plasma non-esterified fatty acid (NEFA) concentrations (r=0.899, P<0.001), (3) the Adipose tissue Insulin Resistance (Adipo-IR) index (fasting plasma insulin-NEFA product; r=-0.526, P<0.001), (4) the fasting plasma insulin-glycerol product (r=-0.467, P<0.001), (5) the Adipose Tissue Insulin Resistance Index (fasting plasma insulin-basal lipolysis product; r=0.460, P<0.001), (6) the Quantitative Insulin Sensitivity Check Index (QUICKI)-NEFA index (r=0.621, P<0.001), and (7) the QUICKI-glycerol index (r=0.671, P<0.001). Bland-Altman plots showed no systematic errors for the suppression indices but proportional errors for all fasting indices. Receiver-operator characteristic curves confirmed that all indices were able to detect adipose tissue insulin resistance (area under the curve ⩾0.801, P<0.001).
Adipose tissue insulin sensitivity (that is, the antilipolytic action of insulin) can be reliably quantified in overweight and obese humans by simplified index methods. The sensitivity and specificity of the Adipo-IR index and the fasting plasma insulin-glycerol product, combined with their simplicity and acceptable agreement, suggest that these may be most useful in clinical practice.
The concept of adiabatic electronic potential-energy surfaces, defined by the Born–Oppenheimer approximation, is fundamental to our thinking about chemical processes. Recent computational as well as ...experimental studies have produced ample evidence that the so-called conical intersections of electronic energy surfaces, predicted by von Neumann and Wigner in 1929, are the rule rather than the exception in polyatomic molecules. It is nowadays increasingly recognized that conical intersections play a key mechanistic role in chemical reaction dynamics. This volume provides an up-to-date overview of the multi-faceted research on the role of conical intersections in photochemistry and photobiology, including basic theoretical concepts, novel computational strategies as well as innovative experiments. The contents and discussions will be of value to advanced students and researchers in photochemistry, molecular spectroscopy and related areas.
To examine the temporal evolution of spinal cord (SC) atrophy in multiple sclerosis (MS), and its association with clinical progression in a large MS cohort.
A total of 352 patients from two centres ...with MS (relapsing remitting MS (RRMS): 256, secondary progressive MS (SPMS): 73, primary progressive MS (PPMS): 23) were included. Clinical and MRI parameters were obtained at baseline, after 12 months and 24 months of follow-up. In addition to conventional brain and SC MRI parameters, the annualised percentage brain volume change and the annualised percentage upper cervical cord cross-sectional area change (aUCCA) were quantified. Main outcome measure was disease progression, defined by expanded disability status scale increase after 24 months.
UCCA was lower in SPMS and PPMS compared with RRMS for all time points. aUCCA over 24 months was highest in patients with SPMS (-2.2% per year) and was significantly higher in patients with disease progression (-2.3% per year) than in stable patients (-1.2% per year; p=0.003), while annualised percentage brain volume change did not differ between subtypes (RRMS: -0.42% per year; SPMS -0.6% per year; PPMS: -0.46% per year) nor between progressive and stable patients (p=0.055). Baseline UCCA and aUCCA over 24 months were found to be relevant contributors of expanded disability status scale at month-24, while baseline UCCA as well as number of SC segments involved by lesions at baseline but not aUCCA were relevant contributors of disease progression.
SC MRI parameters including baseline UCCA and SC lesions were significant MRI predictors of disease progression. Progressive 24-month upper SC atrophy occurred in all MS subtypes, and was faster in patients exhibiting disease progression at month-24.
Abstract This study stratifies complication risk in primary total joint arthroplasty (TJA) based on body mass index (BMI). Demographics, co-morbidities, perioperative variables, and complications ...were reviewed for 22,808 patients. Chi-squared, one-way ANOVA, univariate and multivariable regression analysis were performed. Increasing BMI led to an increase ( P < 0.05) in combined complications, acute kidney injury (AKI), cardiac arrest (CA), reintubation, reoperation, and superficial infection (SI). Univariate analysis for BMI > 40 revealed an increase in combined complications (15.21-vs-17.40%), AKI (1.93-vs-3.87%), CA (0.22-vs-0.57%), reintubation (0.47-vs-0.95%), reoperation (2.36-vs-3.37%), and SI (0.82-vs-1.65%). Multivariable regression showed BMI > 40 as an independent predictor for combined complications (OR = 1.18), AKI (OR = 1.79), CA (OR = 3.94), reintubation (OR = 2.56), reoperation (OR = 1.44), and SI (OR = 2.11). Morbid obesity confers increased risk for complications in TJA.
•We propose an anisotropic multi-stream segmentation CNN design exploiting multi-planar information for prostate segmentation•Usage of sagittal and coronal volumes in addition to axial ones improves ...segmentation accuracy•Significant quality improvement was observed at apex and base prostate region
Background and Objective: Accurate and reliable segmentation of the prostate gland in MR images can support the clinical assessment of prostate cancer, as well as the planning and monitoring of focal and loco-regional therapeutic interventions. Despite the availability of multi-planar MR scans due to standardized protocols, the majority of segmentation approaches presented in the literature consider the axial scans only. In this work, we investigate whether a neural network processing anisotropic multi-planar images could work in the context of a semantic segmentation task, and if so, how this additional information would improve the segmentation quality. Methods: We propose an anisotropic 3D multi-stream CNN architecture, which processes additional scan directions to produce a high-resolution isotropic prostate segmentation. We investigate two variants of our architecture, which work on two (dual-plane) and three (triple-plane) image orientations, respectively. The influence of additional information used by these models is evaluated by comparing them with a single-plane baseline processing only axial images. To realize a fair comparison, we employ a hyperparameter optimization strategy to select optimal configurations for the individual approaches. Results: Training and evaluation on two datasets spanning multiple sites show statistical significant improvement over the plain axial segmentation (p<0.05 on the Dice similarity coefficient). The improvement can be observed especially at the base (0.898 single-plane vs. 0.906 triple-plane) and apex (0.888 single-plane vs. 0.901 dual-plane). Conclusion: This study indicates that models employing two or three scan directions are superior to plain axial segmentation. The knowledge of precise boundaries of the prostate is crucial for the conservation of risk structures. Thus, the proposed models have the potential to improve the outcome of prostate cancer diagnosis and therapies.
Behavioral flexibility, which allows organisms to adapt their actions in response to environmental changes, is impaired in a number of neuropsychiatric conditions, including obsessive-compulsive ...disorder and addiction. Studies in human subjects and monkeys have reported correlations between individual differences in dopamine D2-type receptor (D2R) levels in the caudate nucleus and performance in a discrimination reversal task, in which established contingent relationships between abstract stimuli and rewards (or punishments) are reversed. Global genetic deletion of the D2R in mice disrupts reversal performance, indicating a likely causal role for this receptor in supporting flexible behaviors. To directly examine the specific role of caudate D2-type receptors in reversal performance, the D2/3/4R agonist quinpirole was infused via chronic indwelling cannulae into the medial caudate of male and female marmoset monkeys performing a touchscreen-based serial discrimination reversal task. Given prior evidence for dose-dependent effects of quinpirole and other dopaminergic drugs, a full dose-response curve was established. Individually, marmosets displayed marked differences in behavioral sensitivity to specific doses of intra-caudate quinpirole. Collectively, they exhibited a behaviorally specific bi-phasic deficit in reversal learning, being consistently impaired at both relatively low and high doses of quinpirole. However, intermediate doses of intra-caudate quinpirole produced significant improvement in reversal performance. These data support previous human and monkey neuroimaging studies by providing causal evidence of a U-shaped function describing how dopamine modulates cognitive flexibility in the primate striatum.
Las Cumbres Observatory Global Telescope Network Brown, T. M.; Baliber, N.; Bianco, F. B. ...
Publications of the Astronomical Society of the Pacific,
09/2013, Letnik:
125, Številka:
931
Journal Article
Recenzirano
Odprti dostop
Las Cumbres Observatory Global Telescope (LCOGT) is a young organization dedicated to time-domain observations at optical and (potentially) near-IR wavelengths. To this end, LCOGT is constructing a ...worldwide network of telescopes, including the two 2 m Faulkes telescopes, as many as 17 × 1 m telescopes, and as many as 23 × 40 cm telescopes. These telescopes initially will be outfitted for imaging and (excepting the 40 cm telescopes) spectroscopy at wavelengths between the atmospheric UV cutoff and the roughly 1-μm limit of silicon detectors. Since the first of LCOGT's 1 m telescopes are now being deployed, we lay out here LCOGT's scientific goals and the requirements that these goals place on network architecture and performance, we summarize the network's present and projected level of development, and we describe our expected schedule for completing it. In the bulk of the paper, we describe in detail the technical approaches that we have adopted to attain desired performance. In particular, we discuss our choices for the number and location of network sites, for the number and sizes of telescopes, for the specifications of the first generation of instruments, for the software that will schedule and control the network's telescopes and reduce and archive its data, and for the structure of the scientific and educational programs for which the network will provide observations.
To determine whether spinal cord atrophy differs among disease subtypes in multiple sclerosis (MS) and whether it offers diagnostic and clinical correlative information beyond that provided by other ...magnetic resonance (MR) imaging markers.
The institutional review board approved the study; all subjects gave written informed consent. Upper cervical cord cross-sectional area (UCCA), brain and spinal cord lesion loads, and brain atrophy were measured in 440 patients with MS (311 with relapsing-remitting RR MS, 92 with secondary-progressive SP MS, and 37 with primary-progressive PP MS) studied in two centers. Disability was scored with the Expanded Disability Status Scale (EDSS), the timed 25-foot walk test (TWT), and the nine-hole peg test. UCCA was compared between groups with the Mann-Whitney U test. Correlations were assessed with the Spearman ρ test. Multivariate associations between UCCA and clinical and other MR imaging parameters, including number of hypointense brain lesions on T1-weighted MR images, presence of diffuse abnormalities, and number of involved segments in the spinal cord, were assessed by using multiple linear regression, adjusted for study center site.
The UCCA in patients with SP MS (median, 79 mm(2); interquartile range, 72.4-84.9 mm(2)) and PP MS (median, 77.3 mm(2); interquartile range, 69-82.5 mm(2)) was significantly smaller (P < .001) than that in patients with RR MS (median, 84 mm(2); interquartile range, 78.7-89.3 mm(2)). UCCA was inversely correlated with EDSS score, TWT, and nine-hole peg test findings (ρ ≤ -0.29, P < .001 for all comparisons). UCCA, number of hypointense brain lesions on T1-weighted MR images, presence of diffuse abnormalities, and number of involved segments in the spinal cord were found to be significant explanatory factors for clinical disability (R(2) = 0.564). The UCCA and the number of hypointense brain lesions on T1-weighted images were the strongest MR imaging parameters for explaining physical disability, as measured with the EDSS.
Spinal cord abnormalities have a strong effect on clinical disability in MS. MR imaging-derived UCCA was found to be the most significant spinal cord parameter for explaining EDSS score.
Summary
Obesogenic environments are thought to underlie the increased obesity prevalence observed in youth during the past decades. Understanding the environmental factors that are associated with ...physical activity (PA) in youth is needed to better inform the development of effective intervention strategies attempting to halt the obesity epidemic. We conducted a systematic semi‐quantitative review of 150 studies on environmental correlates of youth PA published in the past 25 years. The ANalysis Grid for Environments Linked to Obesity (ANGELO) framework was used to classify the environmental correlates studied. Most studies retrieved used cross‐sectional designs and subjective measures of environmental factors and PA. Variables of the home and school environments were especially associated with children’s PA. Most consistent positive correlates of PA were father’s PA, time spent outdoors and school PA‐related policies (in children), and support from significant others, mother’s education level, family income, and non‐vocational school attendance (in adolescents). Low crime incidence (in adolescents) was characteristic of the neighbourhood environment associated with higher PA. Convincing evidence of an important role for many other environmental factors was, however, not found. Further research should aim at longitudinal and intervention studies, and use more objective measures of PA and its potential (environmental) determinants.
PDF
