As genes that confer increased risk for autism spectrum disorder (ASD) are identified, a crucial next step is to determine how these risk factors impact brain structure and function and contribute to ...disorder heterogeneity. With three converging lines of evidence, we show that a common, functional ASD risk variant in the Met Receptor Tyrosine Kinase (MET) gene is a potent modulator of key social brain circuitry in children and adolescents with and without ASD. MET risk genotype predicted atypical fMRI activation and deactivation patterns to social stimuli (i.e., emotional faces), as well as reduced functional and structural connectivity in temporo-parietal regions known to have high MET expression, particularly within the default mode network. Notably, these effects were more pronounced in individuals with ASD. These findings highlight how genetic stratification may reduce heterogeneity and help elucidate the biological basis of complex neuropsychiatric disorders such as ASD.
► The ASD-related risk MET promoter variant alters functional activity and connectivity ► The MET risk allele also disrupts the integrity of major white matter tracts ► Effects are more pronounced in MET-expressing regions and across individuals with ASD ► Findings provide mechanistic insights into gene-brain-behavior relationships in ASD
Rudie et al. show how an autism risk factor in the MET gene impacts multiple aspects of brain circuitry in children with and without autism. The study provides new insight into the neurobiological basis of the disorder.
We report microscopic calculations of the thermal conductivity, diffusion constant, and thermal diffusion constant for classical solutions of \( reversible reaction \) He in superfluid \( pound ...sterling \) He at temperatures \(T \lesssim 0.6\) K, where phonons are the dominant excitations of the \( pound sterling \) He. We focus on solutions with \( reversible reaction \) He concentrations \(\lesssim \) \(10-3}\) , for which the main scattering mechanisms are phonon-phonon scattering via 3-phonon Landau and Beliaev processes, which maintain the phonons in a drifting equilibrium distribution, and the slower process of \( reversible reaction \) He-phonon scattering, which is crucial for determining the \( reversible reaction \) He distribution function in transport. We use the fact that the relative changes in the energy and momentum of a \( reversible reaction \) He atom in a collision with a phonon are small to derive a Fokker-Planck equation for the \( reversible reaction \) He distribution function, which we show has an analytical solution in terms of Sonine polynomials. We also calculate the corrections to the Fokker-Planck results for the transport coefficients.
Electrospinning is a process that produces continuous polymer fibers with diameters in the sub-micron range through the action of an external electric field imposed on a polymer solution or melt. ...Non-woven textiles composed of electrospun fibers have a large specific surface area and small pore size compared to commercial textiles, making them excellent candidates for use in filtration and membrane applications. While the process of electrospinning has been known for over half a century, current understanding of the process and those parameters, which influence the properties of the fibers produced from it, is very limited. This work evaluates systematically the effects of 2 of the most important processing parameters: spinning voltage and solution concentration, on the morphology of the fibers formed. Findings indicate that spinning voltage is strongly correlated with the formation of bead defects in the fibers, and that current measurements may be used to signal the onset of the processing voltage at which the bead defect density increases substantially. Solution concentration has been found to most strongly affect fiber size, with fiber diameter increasing with increasing solution concentration according to a power law relationship. In addition, electrospinning from solutions of high concentration has been found to produce a bimodal distribution of fiber sizes, reminiscent of distributions observed in the similar droplet generation process of electrospray. Additionally, evidence is provided that electrostatic effects influence the macroscale morphology of electrospun textiles, and may result in the formation of heterogeneous or 3D structures. (Original abstract - amended)
Magnetic fields pervade the interstellar medium (ISM), but are difficult to detect and characterize. The new generation of low-frequency radio telescopes, such as the Low Frequency Array (LOFAR: a ...Square Kilometre Array-low pathfinder), provides advancements in our capability of probing Galactic magnetism through low-frequency polarimetry. Maps of diffuse polarized radio emission and the associated Faraday rotation can be used to infer properties of, and trace structure in, the magnetic fields in the ISM. However, to date very little of the sky has been probed at high angular and Faraday depth resolution. We observed a 5° by 5° region centred on the nearby galaxy IC 342 (ℓ = 138.2°,b = + 10.6°) using the LOFAR high-band antennae in the frequency range 115–178 MHz. We imaged this region at 4′.5x3′.8 resolution and performed Faraday tomography to detect foreground Galactic polarized synchrotron emission separated by Faraday depth (different amounts of Faraday rotation). Our Faraday depth cube shows a rich polarized structure, with up to 30 K of polarized emission at 150 MHz. We clearly detect two polarized features that extend over most of the field, but are clearly separated in Faraday depth. Simulations of the behaviour of the depolarization of Faraday-thick structures at such low frequencies show that such structures would be too strongly depolarized to explain the observations. These structures are therefore rejected as the source of the observed polarized features. Only Faraday thin structures will not be strongly depolarized at low frequencies; producing such structures requires localized variations in the ratio of synchrotron emissivity to Faraday depth per unit distance. Such variations can arise from several physical phenomena, such as a transition between regions of ionized and (mostly) neutral gas. We conclude that the observed polarized emission is Faraday thin, and propose that the emission originates from two mostly neutral clouds in the local ISM. Using maps of the local ISM to estimate distances to these clouds, we have modelled the Faraday rotation for this line of sight and estimated that the strength of the line of sight component of magnetic field of the local ISM for this direction varies between −0.86 and+0.12 μG (where positive is towards the Earth). We propose that this may be a useful method for mapping magnetic fields within the local ISM in all directions towards nearby neutral clouds.
Growth implant efficacy may be affected when administered to nutritionally stressed calves, whereas the procedure may alter health or the humoral immune response to respiratory vaccination. The study ...objective was to determine the effect of different administration times (d 0, 14, or 28) of a growth implant containing 200 mg progesterone and 20 mg estradiol benzoate on health, performance, and metabolic and immunologic variables in high-risk, newly received beef calves used in a 120-d receiving/grazing stocker system. Crossbred bull and steer calves ( = 203) were weighed (initial BW = 203 ± 2.7 kg), stratified by castrate status on arrival, and randomly assigned to experimental treatments consisting of 1) negative control (no growth implant administered), 2) growth implant administered on d 0, 3) growth implant administered on d 14, and 4) growth implant administered on d 28. There were no differences ( ≥ 0.16) in BW or ADG during the 42-d receiving period. However, ADG during the subsequent grazing period and overall was greater ( ≤ 0.01) for implanted calves versus the negative control. Growth implant timing did not affect the rate of clinical bovine respiratory disease morbidity ( = 0.52; 94% morbidity overall) or bovine viral diarrhea virus type 1a antibody titer concentration ( = 0.61). Indicative of an overall negative energy balance on arrival, NEFA decreased sharply subsequent to d 0 (day effect, < 0.001), but was not affected ( = 0.47) by the timing of growth implantation. Blood urea N concentrations increased transiently (day effect, < 0.001); however, no treatment effect was observed ( = 0.72). Therefore, under conditions of this study, the timing of growth implant administration did not affect growth implant efficacy, health, or metabolic or immunologic variables in newly received, high-risk beef stocker calves. Overall, our observations suggest that there is not a clear benefit to delaying growth implantation and that a growth implant does not affect health or vaccine response in newly received beef calves.
Abstract
The study objective was to determine if acute or chronic water restriction affected haptoglobin (Hp) and serum and mucosal antibody concentration in beef calves after parenteral or ...intranasal vaccination. A total of 60 crossbred beef steer (n = 28) and heifer (n = 32) calves were used. Animals were previously unvaccinated and confirmed seronegative for antibodies against infectious bovine rhinotracheitis virus (IBRV), bovine viral diarrhea virus (BVDV), and parainfluenza-3 virus (PI3V) from sera collected at weaning (d -28; 183 days of age). On d -7, calves within sex were assigned randomly to 1 of 6 treatments arranged in a 3 × 2 factorial. Water restriction treatments (Factor A) were applied at the origin ranch via 3 different models: A1) Control, no water restriction except during transport to the feedlot (CON), A2) Acute, consisting of 48 h water restriction prior to transport to the feedlot (ACU), or A3) Chronic, consisting of alternating 24 h periods of water access and restriction, over a 7-d period prior to transport to the feedlot (CHR). Upon feedlot arrival (d 0), 2 respiratory vaccine treatments were applied (Factor B): B1) parenteral administration of a pentavalent modified-live virus (MLV) respiratory vaccine (2 mL s.c. in the neck; EX), or B2) intranasal administration of a trivalent MLV respiratory vaccine (1 mL/naris; IN). Sera was collected weekly from d 0 to 56 for antibody titer analyses, and d -7, -5, -3, -1, 0, 1, 3, 5, 7 and 14 to determine Hp concentration. Nasal swabs were collected on d 0, 3, 7, 14, 21, 28, 35, 42, 49 and 56 to determine presence of bovine respiratory syncytial virus (BRSV)-specific mucosal antibodies. Data were analyzed using Proc Mixed with repeated measures. Overall, haptoglobin was increased on d -7, decreased before feedlot transport on d -1, and increased after arrival (day effect; P < 0.001). An A × B × day interaction (P = 0.004) existed for Hp such that CON-EX and ACU-IN were greatest on d 5 (P ≤ 0.04). The BRSV (P ≤ 0.002) and IBRV (P ≤ 0.04) antibody titer was greater for IN vs. EX from d 14 to 56 and d 21 to 35, respectively. The EX treatment had increased BRSV-specific mucosal antibodies on d 3 and 7 (P ≤ 0.03); however, these were greater for IN from d 35 to 56 (P ≤ 0.05). In this study, water restriction did not clearly alter Hp or antibody responses to parenteral or intranasal vaccination but BRSV and IBRV antibody was increased for IN vs. EX.
Objectives: Implementation of the International Statistical Classification of Disease and Related Health Problems, 10th Revision (ICD-10) coding system presents challenges for using administrative ...data. Recognizing this, we conducted a multistep process to develop ICD-10 coding algorithms to define Charlson and Elixhauser comorbidities in administrative data and assess the performance of the resulting algorithms. Methods: ICD-10 coding algorithms were developed by "translation" of the ICD-9-CM codes constituting Deyo's (for Charlson comorbidities) and Elixhauser's coding algorithms and by physicians' assessment of the face-validity of selected ICD-10 codes. The process of carefully developing ICD-10 algorithms also produced modified and enhanced ICD-9-CM coding algorithms for the Charlson and Elixhauser comorbidities. We then used data on in-patients aged 18 years and older in ICD-9-CM and ICD-10 administrative hospital discharge data from a Canadian health region to assess the comorbidity frequencies and mortality prediction achieved by the original ICD-9-CM algorithms, the enhanced ICD-9-CM algorithms, and the new ICD-10 coding algorithms. Results: Among 56,585 patients in the ICD-9-CM data and 58,805 patients in the ICD-10 data, frequencies of the 17 Charlson comorbidities and the 30 Elixhauser comorbidities remained generally similar across algorithms. The new ICD-10 and enhanced ICD-9-CM coding algorithms either matched or outperformed the original Deyo and Elixhauser ICD-9-CM coding algorithms in predicting in-hospital mortality. The C-statistic was 0.842 for Deyo's ICD-9-CM coding algorithm, 0.860 for the ICD-10 coding algorithm, and 0.859 for the enhanced ICD-9-CM coding algorithm, 0.868 for the original Elixhauser ICD-9-CM coding algorithm, 0.870 for the ICD-10 coding algorithm and 0.878 for the enhanced ICD-9-CM coding algorithm. Conclusions: These newly developed ICD-10 and ICD-9-CM comorbidity coding algorithms produce similar estimates of comorbidity prevalence in administrative data, and may outperform existing ICD-9-CM coding algorithms.
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