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BackgroundStandard protocols for adrenocorticotropic hormone (ACTH) stimulation testing (ACTHst) often involve intravenous (IV) injection of corticotropin. ACTH might be unintentionally injected into the perivascular (PV) space.ObjectiveTo compare stimulation test results after IV and PV injections of ACTH.AnimalsTwenty privately owned dogs were studied: 10 healthy and 10 with trilostane-treated naturally occurring hyperadrenocorticism (HAC).MethodsProspective study. Each of 20 dogs underwent 2 ACTHst not

BackgroundTrilostane medical treatment of naturally occurring hyperadrenocorticism (NOH) in dogs is common, as is use of the adrenocorticotropic hormone (ACTH) stimulation test (ACTHst) in monitoring response to treatment. There is uncertainty regarding when the ACTHst should be started relative to time of trilostane administration.ObjectiveTo compare ACTHst results in dogs being treated for NOH with trilostane when the test is begun 2 versus 4 hours after trilostane administration.AnimalsTwenty-one privately owned dogs with NOH, each treated with trilostane for at least 30 days.MethodsEach dog had 2 ACTHst completed, 1 started 2 hours and the other 4 hours after trilostane administration. The second test was started no sooner than 46 hours and no later than 74 hours after the first.ResultsFor all 21 dogs, the mean post-ACTH serum cortisol concentration from tests started 2 hours after trilostane administration (5.4 ± 3.7 μg/dL) was significantly lower (P = .03) as compared with results from the tests started 4 hours after administration (6.5 ± 4.5 μg/dL).ConclusionsResults of ACTHst started at different times yield significantly different results. Dogs with NOH, treated with trilostane, and monitored with ACTHst results should have all of their subsequent ACTHst tests begun at or about the same time after trilostane administration.

Objective: To validate the performance of a novel, integrated test for canine cancer screening that combines cell-free DNA quantification with next-generation sequencing (NGS) analysis., Sample: Retrospective data from a total of 1,947 cancer-diagnosed and presumably cancer-free dogs were used to validate test performance for the detection of 7 predefined cancer types (lymphoma, hemangiosarcoma, osteosarcoma, leukemia, histiocytic sarcoma, primary lung tumors, and urothelial carcinoma), using independent training and testing sets., Methods: Cell-free DNA quantification data from all samples were analyzed using a proprietary machine learning algorithm to determine a Cancer Probability Index (High, Moderate, or Low). High and Low Probability of Cancer were final result classifications. Moderate cases were additionally analyzed by NGS to arrive at a final classification of High Probability of Cancer (Cancer Signal Detected) or Low Probability of Cancer (Cancer Signal Not Detected)., Results: Of the 595 dogs in the testing set, 89% (n = 530) received a High or Low Probability result based on the machine learning algorithm; 11% (65) were Moderate Probability, and NGS results were used to assign a final classification. Overall, 87 of 122 dogs with the 7 predefined cancer types were classified as High Probability and 467 of 473 presumably cancer-free dogs were classified as Low Probability, corresponding to a sensitivity of 71.3% for the predefined cancer types at a specificity of 98.7%., Clinical Relevance: This integrated test offers a novel option to screen for cancer types that may be difficult to detect by physical examination at a dog's wellness visit.

Objective: The purpose of this study was to evaluate the performance of a next-generation sequencing-based liquid biopsy test for cancer monitoring in dogs., Samples: Pre- and postoperative blood samples were collected from dogs with confirmed cancer diagnoses originally enrolled in the CANcer Detection in Dogs (CANDiD) study. A subset of dogs also had longitudinal blood samples collected for recurrence monitoring., Methods: All cancer-diagnosed patients had a preoperative blood sample in which a cancer signal was detected and had at least 1 postoperative sample collected. Clinical data were used to assign a clinical disease status for each follow-up visit., Results: Following excisional surgery, in the absence of clinical residual disease at the postoperative visit, patients with Cancer Signal Detected results at that visit were 1.94 times as likely (95% CI, 1.21 to 3.12; P = .013) to have clinical recurrence within 6 months compared to patients with Cancer Signal Not Detected results. In the subset of patients with longitudinal liquid biopsy samples that had clinical recurrence documented during the study period, 82% (9/11; 95% CI, 48% to 97%) had Cancer Signal Detected in blood prior to or concomitant with clinical recurrence; in the 6 patients where molecular recurrence was detected prior to clinical recurrence, the median lead time was 168 days (range, 47 to 238)., Clinical Relevance: Next-generation sequencing-based liquid biopsy is a noninvasive tool that may offer utility as an adjunct to current standard-of-care clinical assessment for cancer monitoring; further studies are needed to confirm diagnostic accuracy in a larger population.

Age-related somatic genomic alterations in hematopoietic cell lines have been well characterized in humans; however, this phenomenon has not been well studied in other species. Next-generation sequencing-based liquid biopsy testing for cancer detection was recently developed for dogs and has been used to study the genomic profiles of blood samples from thousands of canine patients since 2021. In this study, 4870 client-owned dogs with and without a diagnosis or suspicion of cancer underwent liquid biopsy testing by this method. Copy number variants detected exclusively in genomic DNA derived from white blood cells (WBC gDNA-specific CNVs) were observed in 126 dogs (2.6%; 95% CI: 2.2-3.1); these copy number variants were absent from matched plasma cell-free DNA, and from tumor tissue in dogs with concurrent cancer. These findings were more common in older dogs and were persistent in WBC gDNA in over 70% of patients, with little to no change in the amplitude of the signal across longitudinal samples. Many of these alterations were observed at recurrent locations in the genome across subjects; the most common finding was a partial loss on CFA25, typically accompanied by a partial gain on the same chromosome. These early findings suggest that age-related somatic alterations may be present at an appreciable frequency in the general canine population. Further research is needed to determine the clinical significance of these findings.

Objective: To review ordering patterns, positivity rates, and outcome data for a subset of consecutive samples submitted for a commercially available, blood-based multicancer early-detection liquid biopsy test for dogs using next-generation sequencing at 1 laboratory., Sample: 1,500 consecutively submitted blood samples from client-owned dogs with and without clinical suspicion and/or history of cancer for prospective liquid biopsy testing between December 28, 2021, and June 28, 2022., Procedures: We performed a retrospective observational study, reviewing data from 1,500 consecutive clinical samples submitted for liquid biopsy testing. Outcome data were obtained via medical record review, direct communication with the referring clinic, and/or a patient outcome survey through October 16, 2022., Results: Sixty-four percent (910/1,419) of reportable samples were submitted for cancer screening, 26% (366/1,419) for aid in diagnosis, and 10% (143/1,419) for other indications. The positivity rate was 25.4% (93/366) in aid-in-diagnosis patients and 4.5% (41/910) in screening patients. Outcome data were available for 33% (465/1,401) of patients, and outcomes were classifiable for 428 patients. The relative observed sensitivity was 61.5% (67/109) and specificity was 97.5% (311/319). The positive predictive value was 75.0% (21/28) for screening patients and 97.7% (43/44) for aid-in-diagnosis patients, and the time to diagnostic resolution following a positive result was < 2 weeks in most cases., Clinical Relevance: Liquid biopsy using next-generation sequencing represents a novel tool for noninvasive detection of cancer in dogs. Real-world clinical performance meets or exceeds expectations established in the test's clinical validation study.

The goal of cancer screening is to detect disease at an early stage when treatment may be more effective. Cancer screening in dogs has relied upon annual physical examinations and routine laboratory tests, which are largely inadequate for detecting preclinical disease. With the introduction of non-invasive liquid biopsy cancer detection methods, the discussion is shifting from how to screen dogs for cancer to when to screen dogs for cancer. To address this question, we analyzed data from 3,452 cancer-diagnosed dogs to determine the age at which dogs of certain breeds and weights are typically diagnosed with cancer. In our study population, the median age at cancer diagnosis was 8.8 years, with males diagnosed at younger ages than females, and neutered dogs diagnosed at significantly later ages than intact dogs. Overall, weight was inversely correlated with age at cancer diagnosis, and purebred dogs were diagnosed at significantly younger ages than mixed-breed dogs. For breeds represented by ≥10 dogs, a breed-based median age at diagnosis was calculated. A weight-based linear regression model was developed to predict the median age at diagnosis for breeds represented by ≤10 dogs and for mixed-breed dogs. Our findings, combined with findings from previous studies which established a long duration of the preclinical phase of cancer development in dogs, suggest that it might be reasonable to consider annual cancer screening starting 2 years prior to the median age at cancer diagnosis for dogs of similar breed or weight. This logic would support a general recommendation to start cancer screening for all dogs at the age of 7, and as early as age 4 for breeds with a lower median age at cancer diagnosis, in order to increase the likelihood of early detection and treatment., Competing Interests: All authors are employed by and hold vested or unvested equity in PetDx. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Rafalko et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Guidelines-driven screening protocols for early cancer detection in dogs are lacking, and cancer often is detected at advanced stages., Hypothesis/objectives: To examine how cancer typically is detected in dogs and whether the addition of a next-generation sequencing-based "liquid biopsy" test to a wellness visit has the potential to enhance cancer detection., Animals: Client-owned dogs with definitive cancer diagnoses enrolled in a clinical validation study for a novel blood-based multicancer early detection test., Methods: Retrospective medical record review was performed to establish the history and presenting complaint that ultimately led to a definitive cancer diagnosis. Blood samples were subjected to DNA extraction, library preparation, and next-generation sequencing. Sequencing data were analyzed using an internally developed bioinformatics pipeline to detect genomic alterations associated with the presence of cancer., Results: In an unselected cohort of 359 cancer-diagnosed dogs, 4% of cases were detected during a wellness visit, 8% were detected incidentally, and 88% were detected after the owner reported clinical signs suggestive of cancer. Liquid biopsy detected disease in 54.7% (95% confidence interval [CI], 49.5%-59.8%) of patients, including 32% of dogs with early-stage cancer, 48% of preclinical dogs, and 84% of dogs with advanced-stage disease., Conclusions/clinical Importance: Most cases of cancer were diagnosed after the onset of clinical signs; only 4% of dogs had cancer detected using the current standard of care (i.e., wellness visit). Liquid biopsy has the potential to increase detection of cancer when added to a dog's wellness visit., (© 2023 PetDx, Inc and The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Overcoming the challenges of patterning luminescent materials will unlock additive and more sustainable paths for the manufacturing of next-generation on-chip photonic devices. Electrohydrodynamic (EHD) inkjet printing is a promising method for deterministically placing emitters on these photonic devices. However, the use of this technique to pattern luminescent lead halide perovskite nanocrystals (NCs), notable for their defect tolerance and impressive optical and spin coherence properties, for integration with optoelectronic devices remains unexplored. In this work, we additively deposit nanoscale CsPbBr 3 NC features on photonic structures via EHD inkjet printing. We perform transmission electron microscopy of EHD inkjet printed NCs to demonstrate that the NCs' structural integrity is maintained throughout the printing process. Finally, NCs are deposited with sub-micrometer control on an array of parallel silicon nitride nanophotonic cavities and demonstrate cavity-emitter coupling via photoluminescence spectroscopy. These results demonstrate EHD inkjet printing as a scalable, precise method to pattern luminescent nanomaterials for photonic applications.

Rationale and Objectives: The use of natural language processing (NLP) in radiology provides an opportunity to assist clinicians with phenotyping patients. However, the performance and generalizability of NLP across healthcare systems is uncertain. We assessed the performance within and generalizability across four healthcare systems of different NLP representational methods, coupled with elastic-net logistic regression to classify lower back pain-related findings from lumbar spine imaging reports., Materials and Methods: We used a dataset of 871 X-ray and magnetic resonance imaging reports sampled from a prospective study across four healthcare systems between October 2013 and September 2016. We annotated each report for 26 findings potentially related to lower back pain. Our framework applied four different NLP methods to convert text into feature sets (representations). For each representation, our framework used an elastic-net logistic regression model for each finding (i.e., 26 binary or "one-vs.-rest" classification models). For performance evaluation, we split data into training (80%, 697/871) and testing (20%, 174/871). In the training set, we used cross validation to identify the optimal hyperparameter value and then retrained on the full training set. We then assessed performance based on area under the curve (AUC) for the test set. We repeated this process 25 times with each repeat using a different random train/test split of the data, so that we could estimate 95% confidence intervals, and assess significant difference in performance between representations. For generalizability evaluation, we trained models on data from three healthcare systems with cross validation and then tested on the fourth. We repeated this process for each system, then calculated mean and standard deviation (SD) of AUC across the systems., Results: For individual representations, n-grams had the best average performance across all 26 findings (AUC: 0.960). For generalizability, document embeddings had the most consistent average performance across systems (SD: 0.010). Out of these 26 findings, we considered eight as potentially clinically important (any stenosis, central stenosis, lateral stenosis, foraminal stenosis, disc extrusion, nerve root displacement compression, endplate edema, and listhesis grade 2) since they have a relatively greater association with a history of lower back pain compared to the remaining 18 classes. We found a similar pattern for these eight in which n-grams and document embeddings had the best average performance (AUC: 0.954) and generalizability (SD: 0.007), respectively., Conclusion: Based on performance assessment, we found that n-grams is the preferred method if classifier development and deployment occur at the same system. However, for deployment at multiple systems outside of the development system, or potentially if physician behavior changes within a system, one should consider document embeddings since embeddings appear to have the most consistent performance across systems., (Copyright © 2021 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

This tutorial review presents our perspective on designing organic molecules for the functionalization of inorganic nanomaterial surfaces, through the model of an "anchor-functionality" paradigm. This "anchor-functionality" paradigm is a streamlined design strategy developed from a comprehensive range of materials ( e.g. , lead halide perovskites, II-VI semiconductors, III-V semiconductors, metal oxides, diamonds, carbon dots, silicon, etc. ) and applications ( e.g. , light-emitting diodes, photovoltaics, lasers, photonic cavities, photocatalysis, fluorescence imaging, photo dynamic therapy, drug delivery, etc. ). The structure of this organic interface modifier comprises two key components: anchor groups binding to inorganic surfaces and functional groups that optimize their performance in specific applications. To help readers better understand and utilize this approach, the roles of different anchor groups and different functional groups are discussed and explained through their interactions with inorganic materials and external environments.

Carrier spins in semiconductor nanocrystals are promising candidates for quantum information processing. Using a combination of time-resolved Faraday rotation and photoluminescence spectroscopies, we demonstrate optical spin polarization and coherent spin precession in colloidal CsPbBr 3 nanocrystals that persists up to room temperature. By suppressing the influence of inhomogeneous hyperfine fields with a small applied magnetic field, we demonstrate inhomogeneous hole transverse spin-dephasing times ( T 2 * ) that approach the nanocrystal photoluminescence lifetime, such that nearly all emitted photons derive from coherent hole spins. Thermally activated LO phonons drive additional spin dephasing at elevated temperatures, but coherent spin precession is still observed at room temperature. These data reveal several major distinctions between spins in nanocrystalline and bulk CsPbBr 3 and open the door for using metal-halide perovskite nanocrystals in spin-based quantum technologies.

A 3-year-old male castrated domestic shorthair cat was presented with an acute history of lethargy and decreased appetite. Pertinent physical examination abnormalities included palpable irregularity of the right kidney and pain on palpation of the left kidney. Ultrasonographic imaging of the abdomen revealed gas present at the corticomedullary junction of the left kidney, consistent with emphysematous pyelonephritis, as well as emphysematous cystitis. While quantitative urine culture via pyelocentesis yielded a negative culture, a sample via cystocentesis was positive for Escherichia coli and emphysematous changes were presumed most likely secondary to an ascending infection. The purpose of this report is to describe the temporary management of ureteral obstruction secondary to emphysematous pyelonephritis using a ureteral stent in a cat., (© The Author(s) 2015.)

Background: Two commercially available forms of synthetic ACTH are used to diagnose and monitor hyper- and hypoadrenocorticism in dogs., Objective: To compare the biologic activity of the liquid and lyophilized forms of cosyntropin., Animals: Eighteen privately owned healthy dogs were included., Methods: Dogs were assigned to one of 2 groups of 9 dogs each. Group 1 dogs were tested with the lyophilized product first and the liquid solution 30-60 days later. The Group 2 dogs were tested with the liquid solution first and the lyophilized drug 30-60 days later. For the ACTH stimulation tests, serum samples were collected before and 1 hour after IM administration of 0.25 mg reconstituted lyophilized product or 1 hour after IV administration of 0.25 mg of liquid solution. Cortisol concentrations of all serum samples were measured by use of a commercial cortisol radioimmunoassay., Results: Serum cortisol concentrations before and after ACTH stimulation did not differ significantly between groups (P = .57). In addition, no individual dog had as much as a 20% difference in serum cortisol concentrations after administration of either ACTH formulation., Conclusions and Clinical Importance: Given the lack of significant differences of the ACTH stimulation test results, the lyophilized and liquid solution products can be used interchangeably., (Copyright © 2012 by the American College of Veterinary Internal Medicine.)

Objective: To evaluate accuracy of 6 portable blood glucose meters (PBGMs) by comparing results of these meters with results obtained with a reference chemistry analyzer., Design: Evaluation study., Animals: 49 dogs (158 blood samples). Procedures-Venous blood samples were tested with the 6 PBGMs, and results were compared with results of a commercially available analyzer that used a reference method based on the hexokinase reaction., Results: Plasma glucose concentrations obtained with the reference analyzer ranged from 41 to 639 mg/dL. There were significant correlations between blood glucose concentrations obtained with the 6 PBGMs and plasma glucose concentrations obtained with the reference analyzer (r > or = 0.96). However, for all 6 PBGMs, results differed from results for the reference analyzer, with the difference increasing as plasma glucose concentration increased. Significant differences in bias were found among meters. For 142 samples classified as hypoglycemic, euglycemic, or hyperglycemic on the basis of results of the reference analyzer, the percentage of samples that were misclassified on the basis of results of the PBGMs ranged from 2.1% to 38.7%., Conclusions and Clinical Relevance: Results of the present study suggested that there were substantial differences in the accuracy of currently available PBGMs when used to determine blood glucose concentration in dogs.

Objective: To compare effects of isoflurane and propofol on the cystometrogram and urethral pressure profile (UPP) in healthy female cats., Animals: 6 healthy female cats., Procedures: Cats were anesthetized, and a consistent plane of anesthesia was maintained with low and high doses of isoflurane and propofol. A 6-F double-lumen urinary catheter was placed aseptically in the urethra for cystometrogram and UPP measurements. Threshold pressure and volume were recorded for cystometrograms. Maximum urethral pressure for smooth and skeletal muscle portions of the urethra, maximum urethral closure pressure, and functional profile length were measured during each UPP measurement. Heart rate and respiratory rate were recorded., Results: Cats anesthetized with the low dose of propofol had consistent detrusor reflexes, compared with results for the other anesthetics. Mean +/- SD threshold pressure, volume per unit of body weight, and compliance were 75.7 +/- 16.3 cm H2O, 8.3 +/- 3.2 mL/kg, and 0.5 +/- 0.4 mL/cm H2O, respectively, for low-dose propofol. Anesthesia with either dose of propofol caused a significantly higher percentage change in heart rate during the cystometrogram, compared with results for anesthesia with isoflurane. Maximal urethral pressure in the area corresponding to skeletal muscle and the maximum urethral closure pressure were significantly higher for the low dose of propofol, compared with results for the high dose of propofol., Conclusions and Clinical Relevance: The low-dose propofol regimen was the easiest to titrate and maintain and yielded diagnostic-quality detrusor reflexes in all 6 cats. Anesthetic depth should be titrated appropriately when performing urodynamic procedures.

Objective: As healthcare practice transitions from paper-based to computer-based records, there is increasing need to determine an effective electronic format for clinical narratives. Our research focuses on utilizing a cognitive science methodology to guide the conversion of medical texts to a more structured, user-customized presentation in the electronic medical record (EMR)., Design: We studied the use of discharge summaries by psychiatrists with varying expertise-experts, intermediates, and novices. Experts were given two hypothetical emergency care scenarios with narrative discharge summaries and asked to verbalize their clinical assessment. Based on the results, the narratives were presented in a more structured form. Intermediate and novice subjects received a narrative and a structured discharge summary, and were asked to verbalize their assessments of each., Measurements: A qualitative comparison of the interview transcripts of all subjects was done by analysis of recall and inference made with respect to level of expertise., Results: For intermediate and novice subjects, recall was greater with the structured form than with the narrative. Novices were also able to make more inferences (not always accurate) from the structured form than with the narrative. Errors occurred in assessments using the narrative form but not the structured form., Conclusions: Our cognitive methods to study discharge summary use enabled us to extract a conceptual representation of clinical narratives from end-users. This method allowed us to identify clinically relevant information that can be used to structure medical text for the EMR and potentially improve recall and reduce errors.