Template independent component analysis with spatial priors for accurate subject-level brain network estimation and inference.

Independent component analysis is commonly applied to functional magnetic resonance imaging (fMRI) data to extract independent components (ICs) representing functional brain networks. While ICA produces reliable group-level estimates, single-subject ICA often produces noisy results. Template ICA is a hierarchical ICA model using empirical population priors to produce more reliable subject-level estimates.

Spatial Bayesian GLM on the cortical surface produces reliable task activations in individuals and groups.

The general linear model (GLM) is a widely popular and convenient tool for estimating the functional brain response and identifying areas of significant activation during a task or stimulus. However, the classical GLM is based on a massive univariate approach that does not explicitly leverage the similarity of activation patterns among neighboring brain locations. As a result, it tends to produce noisy estimates and be underpowered to detect significant activations, particularly in individual subjects and small groups.

New Characterization Measures of Pore Shape and Connectivity Applied to Coatings used for Controlled Drug Release.

Pore geometry characterization-methods are important tools for understanding how pore structure influences properties such as transport through a porous material. Bottlenecks can have a large influence on transport and related properties. However, existing methods only catch certain types of bottleneck effects caused by variations in pore size.

A Bayesian General Linear Modeling Approach to Cortical Surface fMRI Data Analysis.

Cortical surface fMRI (cs-fMRI) has recently grown in popularity versus traditional volumetric fMRI. In addition to offering better whole-brain visualization, dimension reduction, removal of extraneous tissue types, and improved alignment of cortical areas across subjects, it is also more compatible with common assumptions of Bayesian spatial models. However, as no spatial Bayesian model has been proposed for cs-fMRI data, most analyses continue to employ the classical general linear model (GLM), a "massive univariate" approach.

3D high spatial resolution visualisation and quantification of interconnectivity in polymer films.

A porous network acts as transport paths for drugs through films for controlled drug release. The interconnectivity of the network strongly influences the transport properties. It is therefore important to quantify the interconnectivity and correlate it to transport properties for control and design of new films.

Inhibition of IRF5 cellular activity with cell-penetrating peptides that target homodimerization.

The transcription factor interferon regulatory factor 5 (IRF5) plays essential roles in pathogen-induced immunity downstream of Toll-, nucleotide-binding oligomerization domain-, and retinoic acid-inducible gene I-like receptors and is an autoimmune susceptibility gene. Normally, inactive in the cytoplasm, upon stimulation, IRF5 undergoes posttranslational modification(s), homodimerization, and nuclear translocation, where dimers mediate proinflammatory gene transcription. Here, we report the rational design of cell-penetrating peptides (CPPs) that disrupt IRF5 homodimerization.

Sleep Deprivation and Its Contribution to Mood and Performance Deterioration in College Athletes.

Sleep deprivation is very common among collegiate student athletes, resulting in impacts on mood, physiology, and performance. There are multifactorial contributions to sleep deprivation, but resulting alterations in sleep architecture explain impacts on learning, vigilance, mood, and athletic performance. Recognition of the physical impacts is key.

Postmortem examination (2016-2017) of weanling and older horses for the presence of select species of endoparasites: Gasterophilus spp., Anoplocephala spp. and Strongylus spp. in specific anatomical sites.

Parasite infections are more quantifiable postmortem than antemortem in horses. Thus a study was carried out examining dead horses for specific parasite species. Most of the weanling and older horses submitted to the University of Kentucky Veterinary Diagnostic Laboratory (UKVDL) for postmortem examination between November 22, 2016 and March 23, 2017 were examined for certain species of internal parasites.

Fatal bromethalin intoxication in 3 cats and 2 dogs with minimal or no histologic central nervous system spongiform change.

Use of the neurotoxic rodenticide bromethalin has steadily increased since 2011, resulting in an increased incidence of bromethalin intoxications in pets. Presumptive diagnosis of bromethalin toxicosis relies on history of possible rodenticide exposure coupled with compatible neurologic signs or sudden death, and postmortem examination findings that eliminate other causes of death. Diagnosis is confirmed by detecting the metabolite desmethylbromethalin (DMB) in tissues.

A three-dimensional statistical model for imaged microstructures of porous polymer films.

A thresholded Gaussian random field model is developed for the microstructure of porous materials. Defining the random field as a solution to stochastic partial differential equation allows for flexible modelling of nonstationarities in the material and facilitates computationally efficient methods for simulation and model fitting. A Markov Chain Monte Carlo algorithm is developed and used to fit the model to three-dimensional confocal laser scanning microscopy images.

Fast Bayesian whole-brain fMRI analysis with spatial 3D priors.

Spatial whole-brain Bayesian modeling of task-related functional magnetic resonance imaging (fMRI) is a great computational challenge. Most of the currently proposed methods therefore do inference in subregions of the brain separately or do approximate inference without comparison to the true posterior distribution. A popular such method, which is now the standard method for Bayesian single subject analysis in the SPM software, is introduced in Penny et al.

Fragment-Based Drug Design of Novel Pyranopyridones as Cell Active and Orally Bioavailable Tankyrase Inhibitors.

Tankyrase activity has been linked to the regulation of intracellular axin levels, which have been shown to be crucial for the Wnt pathway. Deregulated Wnt signaling is important for the genesis of many diseases including cancer. We describe herein the discovery and development of a new series of tankyrase inhibitors.

National Athletic Trainers' Association position statement: Preparticipation physical examinations and disqualifying conditions.

Objective: To present athletic trainers with recommendations for the content and administration of the preparticipation physical examination (PPE) as well as considerations for determining safe participation in sports and identifying disqualifying conditions.

Background: Preparticipation physical examinations have been used routinely for nearly 40 years. However, considerable debate exists as to their efficacy due to the lack of standardization in the process and the lack of conformity in the information that is gathered.

Design and synthesis of 2-N-substituted indazolone derivatives as non-carboxylic acid glycogen synthase activators.

Glycogen synthase (GS) catalyzes the transfer of glucose residues from UDP-glucose to a glycogen polymer chain, a critical step for glucose storage. Patients with type 2 diabetes normally exhibit low glycogen levels and decreased muscle glucose uptake is the major defect in whole body glucose disposal. Therefore, activating GS may provide a potential approach for the treatment of type 2 diabetes.

Discovery and optimization of 2-phenyloxazole derivatives as diacylglycerol acyltransferase-1 inhibitors.

In a discovery effort to find safe and effective DGAT-1 inhibitors, we have identified 2-phenyloxazole 4-carboxamide 1 as a conformationally constrained analog of a hydrazide hit, which was previously identified from high-throughput screening. Further optimization of this series has led to chemically more stable 2-phenyloxazole-based DGAT-1 inhibitor 25 with improved solubility, cell-based activity, and pharmacokinetic properties. Compound 25 also demonstrated in vivo efficacy in a diet-induced obesity (DIO) rat model.

Discovery of 1-arylcarbonyl-6,7-dimethoxyisoquinoline derivatives as glutamine fructose-6-phosphate amidotransferase (GFAT) inhibitors.

Through high throughput screening and subsequent hit identification and optimization, we synthesized a series of 1-arylcarbonyl-6,7-dimethoxyisoquinoline derivatives as the first reported potent and reversible GFAT inhibitors. SAR studies of this class of compounds indicated significant impact on GFAT inhibition potency by substitutions on the A-ring and C-ring. The ketone group was found to be necessary for high potency.

Discovery of orally active carboxylic acid derivatives of 2-phenyl-5-trifluoromethyloxazole-4-carboxamide as potent diacylglycerol acyltransferase-1 inhibitors for the potential treatment of obesity and diabetes.

Diacylglycerol acyltransferase-1 (DGAT-1) is the enzyme that catalyzes the final and committed step of triglyceride formation, namely, the acylation of diacylglycerol with acyl coenzyme A. DGAT-1 deficient mice demonstrate resistance to weight gain on high fat diet, improved insulin sensitivity, and reduced liver triglyceride content. Inhibition of DGAT-1 thus represents a potential novel approach for the treatment of obesity, dyslipidemia, and metabolic syndrome.

Dual bronchodilatory and pulmonary anti-inflammatory activity of RO5024118, a novel agonist at vasoactive intestinal peptide VPAC2 receptors.

Background And Purpose: Vasoactive intestinal peptide is expressed in the respiratory tract and induces its effects via its receptors, VPAC(1) and VPAC(2). RO5024118 is a selective VPAC(2) receptor agonist derived via chemical modification of an earlier VPAC(2) agonist, RO0251553. In the present studies, we characterized the pharmacological activity of RO5024118.

The application of osteopathic treatments to pediatric sports injuries.

The application of manual techniques to pediatric athletic injuries has been considered alternative medicine. There are many injuries that are associated with loss of normal motion. Altered biomechanics can be readily identified and treated using manual methods.

Prevalence of latent, neuropathogenic equine herpesvirus-1 in the Thoroughbred broodmare population of central Kentucky.

Reason For Performing Study: An emerging problem of equine herpesvirus-1 (EHV-1) infection in horses in the USA is a high-mortality myeloencephalopathy that commonly occurs where large numbers of horses are stabled. EHV-1 isolates recovered from recent neurological outbreaks represent a mutant virus strain that possesses enhanced neuropathogenicity. A central question of EHV-1 myeloencephalopathy is the latency carriage rate for these mutants of EHV-1 in USA horse populations.

Equine multinodular pulmonary fibrosis: a newly recognized herpesvirus-associated fibrotic lung disease.

Pulmonary fibrosis and interstitial lung disease are poorly understood in horses; the causes of such conditions are rarely identified. Equine herpesvirus 5 (EHV-5) is a gamma-herpesvirus of horses that has not been associated with disease in horses. Pathologic and virologic findings from 24 horses with progressive nodular fibrotic lung disease associated with EHV-5 infection are described and compared with 23 age-matched control animals.

Accidental intra-auricular artery injection of ceftiofur in two beef steers.

Two beef steers accidentally injected into a branch of the auricular artery with an oil-based formulation of ceftiofur died within 5 minutes of injection. Notable pathologic findings included distention and obstruction of cerebral and cerebellar arteries by a whitish tan material and hemorrhages within meningeal spaces, the choroid plexus, cerebrum, and cerebellum. Lipid material was identified within cerebral blood vessels in frozen sections stained with oil red O.

Three equine cases of mixed hepatoblastoma with teratoid features.

Hepatoblastoma was diagnosed in 3 Thoroughbreds at the University of Kentucky Livestock Disease Diagnostic Center (LDDC) since 1997. Case #1 involved a fetus with a well-demarcated, multilobulated, solitary mass that extended from the left liver lobe. Case #2 was observed in a neonate with a primary hepatic mass and multiple metastases in the skin, brain, meninges, and stylohyoid bone.

Classification of Actinobacillus spp isolates from horses involved in mare reproductive loss syndrome.

Objective: To identify Actinobacillus spp isolates recovered from fetuses and pericardial fluid from horses affected with mare reproductive loss syndrome (MRLS) and determine whether these bacterial species are the same as those isolated from clinically normal horses.

Sample Population: Isolates of actinobacilli recovered from 18 horses with pericarditis and 109 fetuses aborted by mares affected by MRLS. Procedures-Actinobacillus spp isolates were identified to the level of species or subspecies by use of conventional phenotypic tests and biochemical and enzyme test kits.