Intricacies of Human-AI Interaction in Dynamic Decision-Making for Precision Oncology: A Case Study in Response-Adaptive Radiotherapy.

Background: Adaptive treatment strategies that can dynamically react to individual cancer progression can provide effective personalized care. Longitudinal multi-omics information, paired with an artificially intelligent clinical decision support system (AI-CDSS) can assist clinicians in determining optimal therapeutic options and treatment adaptations. However, AI-CDSS is not perfectly accurate, as such, clinicians' over/under reliance on AI may lead to unintended consequences, ultimately failing to develop optimal strategies. To investigate such collaborative decision-making process, we conducted a Human-AI interaction case study on response-adaptive radiotherapy (RT). Methods: We designed and conducted a two-phase study for two disease sites and two treatment modalities-adaptive RT for non-small cell lung cancer (NSCLC) and adaptive stereotactic body RT for hepatocellular carcinoma (HCC)-in which clinicians were asked to consider mid-treatment modification of the dose per fraction for a number of retrospective cancer patients without AI-support (Unassisted Phase) and with AI-assistance (AI-assisted Phase). The AI-CDSS graphically presented trade-offs in tumor control and the likelihood of toxicity to organs at risk, provided an optimal recommendation, and associated model uncertainties. In addition, we asked for clinicians' decision confidence level and trust level in individual AI recommendations and encouraged them to provide written remarks. We enrolled 13 evaluators (radiation oncology physicians and residents) from two medical institutions located in two different states, out of which, 4 evaluators volunteered in both NSCLC and HCC studies, resulting in a total of 17 completed evaluations (9 NSCLC, and 8 HCC). To limit the evaluation time to under an hour, we selected 8 treated patients for NSCLC and 9 for HCC, resulting in a total of 144 sets of evaluations (72 from NSCLC and 72 from HCC). Evaluation for each patient consisted of 8 required inputs and 2 optional remarks, resulting in up to a total of 1440 data points. Results: AI-assistance did not homogeneously influence all experts and clinical decisions. From NSCLC cohort, 41 (57%) decisions and from HCC cohort, 34 (47%) decisions were adjusted after AI assistance. Two evaluations (12%) from the NSCLC cohort had zero decision adjustments, while the remaining 15 (88%) evaluations resulted in at least two decision adjustments. Decision adjustment level positively correlated with dissimilarity in decision-making with AI [NSCLC: ρ = 0.53 ( p < 0.001); HCC: ρ = 0.60 ( p < 0.001)] indicating that evaluators adjusted their decision closer towards AI recommendation. Agreement with AI-recommendation positively correlated with AI Trust Level [NSCLC: ρ = 0.59 ( p < 0.001); HCC: ρ = 0.7 ( p < 0.001)] indicating that evaluators followed AI's recommendation if they agreed with that recommendation. The correlation between decision confidence changes and decision adjustment level showed an opposite trend [NSCLC: ρ = -0.24 ( p = 0.045), HCC: ρ = 0.28 ( p = 0.017)] reflecting the difference in behavior due to underlying differences in disease type and treatment modality. Decision confidence positively correlated with the closeness of decisions to the standard of care (NSCLC: 2 Gy/fx; HCC: 10 Gy/fx) indicating that evaluators were generally more confident in prescribing dose fractionations more similar to those used in standard clinical practice. Inter-evaluator agreement increased with AI-assistance indicating that AI-assistance can decrease inter-physician variability. The majority of decisions were adjusted to achieve higher tumor control in NSCLC and lower normal tissue complications in HCC. Analysis of evaluators' remarks indicated concerns for organs at risk and RT outcome estimates as important decision-making factors. Conclusions: Human-AI interaction depends on the complex interrelationship between expert's prior knowledge and preferences, patient's state, disease site, treatment modality, model transparency, and AI's learned behavior and biases. The collaborative decision-making process can be summarized as follows: (i) some clinicians may not believe in an AI system, completely disregarding its recommendation, (ii) some clinicians may believe in the AI system but will critically analyze its recommendations on a case-by-case basis; (iii) when a clinician finds that the AI recommendation indicates the possibility for better outcomes they will adjust their decisions accordingly; and (iv) When a clinician finds that the AI recommendation indicate a worse possible outcome they will disregard it and seek their own alternative approach.

Humans in the loop: Community science and machine learning synergies for overcoming herbarium digitization bottlenecks.

Premise: Among the slowest steps in the digitization of natural history collections is converting imaged labels into digital text. We present here a working solution to overcome this long-recognized efficiency bottleneck that leverages synergies between community science efforts and machine learning approaches. Methods: We present two new semi-automated services. The first detects and classifies typewritten, handwritten, or mixed labels from herbarium sheets. The second uses a workflow tuned for specimen labels to label text using optical character recognition (OCR). The label finder and classifier was built via humans-in-the-loop processes that utilize the community science Notes from Nature platform to develop training and validation data sets to feed into a machine learning pipeline. Results: Our results showcase a >93% success rate for finding and classifying main labels. The OCR pipeline optimizes pre-processing, multiple OCR engines, and post-processing steps, including an alignment approach borrowed from molecular systematics. This pipeline yields >4-fold reductions in errors compared to off-the-shelf open-source solutions. The OCR workflow also allows human validation using a custom Notes from Nature tool. Discussion: Our work showcases a usable set of tools for herbarium digitization including a custom-built web application that is freely accessible. Further work to better integrate these services into existing toolkits can support broad community use.

Pneumonitis After Chemoradiotherapy and Adjuvant Durvalumab in Stage III Non-Small Cell Lung Cancer.

PURPOSE: Adjuvant durvalumab after definitive chemoradiotherapy (CRT) for unresectable stage III non-small cell lung cancer (NSCLC) is well-tolerated in clinical trials. However, pneumonitis rates outside of clinical trials remain poorly defined with CRT followed by durvalumab. We aimed to describe the influence of durvalumab on pneumonitis rates among a large cohort of patients with stage III NSCLC. METHODS AND MATERIALS: We studied patients with stage III NSCLC in the national Veterans Health Administration from 2015 to 2021 who received concurrent CRT alone or with adjuvant durvalumab. We defined pneumonitis as worsening respiratory symptoms with radiographic changes within 2 years of CRT and graded events according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03. We used Cox regression to analyze risk factors for pneumonitis and the effect of postbaseline pneumonitis on overall survival. RESULTS: Among 1994 patients (989 CRT alone, 1005 CRT followed by adjuvant durvalumab), the 2-year incidence of grade 2 or higher pneumonitis was 13.9% for CRT alone versus 22.1% for CRT plus durvalumab (unadjusted P < .001). On multivariable analysis, durvalumab was associated with higher risk of grade 2 pneumonitis (hazard ratio, 1.45; 95% CI, 1.09-1.93; P = .012) but not grade 3 to 5 pneumonitis (P = .2). Grade 3 pneumonitis conferred worse overall survival (hazard ratio, 2.51; 95% CI, 2.06-3.05; P < .001) but grade 2 pneumonitis did not (P = .4). CONCLUSIONS: Adjuvant durvalumab use was associated with increased risk of low-grade but not higher-grade pneumonitis. Reassuringly, low-grade pneumonitis did not increase mortality risk. We observed increased rates of high-grade pneumonitis relative to clinical trials; the reasons for this require further study.

Random mutagenesis of Phaeodactylum tricornutum using ultraviolet, chemical, and X-radiation demonstrates the need for temporal analysis of phenotype stability.

We investigated two non-ionising mutagens in the form of ultraviolet radiation (UV) and ethyl methanosulfonate (EMS) and an ionising mutagen (X-ray) as methods to increase fucoxanthin content in the model diatom Phaeodactylum tricornutum. We implemented an ultra-high throughput method using fluorescence-activated cell sorting (FACS) and live culture spectral deconvolution for isolation and screening of potential pigment mutants, and assessed phenotype stability by measuring pigment content over 6 months using high-performance liquid chromatography (HPLC) to investigate the viability of long-term mutants. Both UV and EMS resulted in significantly higher fucoxanthin within the 6 month period after treatment, likely as a result of phenotype instability. A maximum fucoxanthin content of 135 ± 10% wild-type found in the EMS strain, a 35% increase. We found mutants generated using all methods underwent reversion to the wild-type phenotype within a 6 month time period. X-ray treatments produced a consistently unstable phenotype even at the maximum treatment of 1000 Grays, while a UV mutant and an EMS mutant reverted to wild-type after 4 months and 6 months, respectively, despite showing previously higher fucoxanthin than wild-type. This work provides new insights into key areas of microalgal biotechnology, by (i) demonstrating the use of an ionising mutagen (X-ray) on a biotechnologically relevant microalga, and by (ii) introducing temporal analysis of mutants which has substantial implications for strain creation and utility for industrial applications.

Dietary counselling plus omega-3 supplementation in the treatment of generalized anxiety disorder: protocol for a randomized wait-list controlled pilot trial (the "EASe-GAD Trial").

BACKGROUND: Anxiety disorders are prevalent and disabling conditions involving excessive worry and tension. Generalized anxiety disorder (GAD), the most common anxiety disorder, affects 5% of individuals from high-income countries and many individuals report that treatment options are not accessible, effective, or tolerable. Clinical evidence suggests that nutrition interventions, based on the Mediterranean diet and supplementation of omega-3 fatty acids, can significantly improve symptoms of depression; however, the effect of nutrition interventions on anxiety symptoms has not been studied in a clinical population. The primary objective of the present study is to assess the feasibility and acceptability of a dietary counselling and omega-3 fatty acid supplementation intervention delivered to adult women with GAD. The secondary objectives include assessing changes in anxiety symptom severity, assessing changes in quality of life, assessing changes in biomarkers, and evaluating the components of the program. METHODS: This study is a randomized, wait-list controlled pilot trial delivering a 12-week, dietary counselling intervention and omega-3 supplementation to 50 adult women with GAD. Participants will complete seven individual counselling sessions which include education, personalized recommendations, mindful eating techniques, motivational interviewing, and goal setting. They will be provided with recipes, instructional videos, and food items. The intervention is designed based on the Social Cognitive Theory and previous research that has been done by the author team to identify dietary constituents with the most evidence to support their use in the treatment of anxiety disorders. Questionnaires and blood work will be completed at baseline, after the waiting period (for those in the waitlist group), and after the intervention. DISCUSSION: Results from this study will lay the foundation for future large-scale studies in this area and may provide preliminary evidence of the role of diet counselling and omega-3 supplementation in the management of GAD. Research on the role of nutrition in psychiatric care has been identified as a priority by a number of international organizations. The present trial directly addresses the call for the research that is most needed to advance the field. TRIAL REGISTRATION: This protocol was registered at ClinicalTrials.gov on October 10, 2022; NCT05573672 . Trial sponsor: The Canadian College of Naturopathic Medicine, 1255 Sheppard Ave E, Toronto, ON M2K 1E2, 416-498-1255. Steering committee: Composed of MA, LL, KC, IvdW, SM, UN, AJ. The committee meets monthly to oversee the trial. Protocol identifier: CCNM_EASe-GADCT_2201v4.

Senolytic and senomorphic secondary metabolites as therapeutic agents in Drosophila melanogaster models of Parkinson's disease.

Drosophila melanogaster is a valuable model organism for a wide range of biological exploration. The well-known advantages of D. melanogaster include its relatively simple biology, the ease with which it is genetically modified, the relatively low financial and time costs associated with their short gestation and life cycles, and the large number of offspring they produce per generation. D. melanogaster has facilitated the discovery of many significant insights into the pathology of Parkinson's disease (PD) and has served as an excellent preclinical model of PD-related therapeutic discovery. In this review, we provide an overview of the major D. melanogaster models of PD, each of which provide unique insights into PD-relevant pathology and therapeutic targets. These models are discussed in the context of their past, current, and future potential use for studying the utility of secondary metabolites as therapeutic agents in PD. Over the last decade, senolytics have garnered an exponential interest in their ability to mitigate a broad spectrum of diseases, including PD. Therefore, an emphasis is placed on the senolytic and senomorphic properties of secondary metabolites. It is expected that D. melanogaster will continue to be critical in the effort to understand and improve treatment of PD, including their involvement in translational studies focused on secondary metabolites.

Cannabis Use in Patients Seen in an Academic Radiation Oncology Department.

PURPOSE: Cannabis use rates are increasing in the United States. Patients with cancer use cannabis for many reasons, even without high-quality supporting data. This study sought to characterize cannabis use among patients seen in radiation oncology in a state that has legalized adult nonmedical use cannabis and to identify key cannabis-related educational topics. METHODS AND MATERIALS: Cannabis history was documented by providers using a structured template at patient visits in an academic radiation oncology practice October 2020 to November 2021. Cannabis use data, including recency/frequency of use, reason, and mode of administration, were summarized, and logistic regression was used to explore associations between patient and disease characteristics and recent cannabis use. A multivariable model employed stepwise variable selection using the Akaike Information Criterion. RESULTS: Of 3143 patients total, 91 (2.9%) declined to answer cannabis use questions, and 343 (10.9%) endorsed recent use (≤1 month ago), 235 (7.5%) noted nonrecent use (>1 month ago), and 2474 (78.7%) denied history of cannabis use. In multivariable analyses, those ≥50 years old (odds ratio [OR], 0.409; 95% confidence interval [CI], 0.294-0.568; P < .001) or with history of prior courses of radiation (OR, 0.748; 95% CI, 0.572-0.979; P = .034) were less likely, and those with a mental health diagnosis not related to substance use (OR, 1.533; 95% CI, 1.171-2.005; P = .002) or who smoked tobacco (OR, 3.003; 95% CI, 2.098-4.299; P < .001) were more likely to endorse recent cannabis use. Patients reported pain, insomnia, and anxiety as the most common reasons for use. Smoking was the most common mode of administration. CONCLUSIONS: Patients are willing to discuss cannabis use with providers and reported recent cannabis use for a variety of reasons. Younger patients new to oncologic care and those with a history of mental illness or tobacco smoking may benefit most from discussions about cannabis given higher rates of cannabis use in these groups.

Neuroglial Senescence, α-Synucleinopathy, and the Therapeutic Potential of Senolytics in Parkinson's Disease.

Parkinson's disease (PD) is the most common movement disorder and the second most prevalent neurodegenerative disease after Alzheimer's disease. Despite decades of research, there is still no cure for PD and the complicated intricacies of the pathology are still being worked out. Much of the research on PD has focused on neurons, since the disease is characterized by neurodegeneration. However, neuroglia has become recognized as key players in the health and disease of the central nervous system. This review provides a current perspective on the interactive roles that α-synuclein and neuroglial senescence have in PD. The self-amplifying and cyclical nature of oxidative stress, neuroinflammation, α-synucleinopathy, neuroglial senescence, neuroglial chronic activation and neurodegeneration will be discussed. Finally, the compelling role that senolytics could play as a therapeutic avenue for PD is explored and encouraged.

Novel Genetic Signatures Associated With Sporadic Amyotrophic Lateral Sclerosis.

Amyotrophic Lateral Sclerosis (ALS) is a complex polygenetic neurodegenerative disorder. Establishing a diagnosis for ALS is a challenging and lengthy process. By the time a diagnosis is made, the lifespan prognosis is only about two to 5 years. Genetic testing can be critical in assessing a patient's risk for ALS, provided they have one of the known familial genes. However, the vast majority of ALS cases are sporadic and have no known associated genetic signatures. Our analysis of the whole genome sequencing data from ALS patients and healthy controls from the Answer ALS Consortium has uncovered twenty-three novel mutations in twenty-two protein-coding genes associated with sporadic ALS cases. The results show the majority of patients with the sporadic form of ALS have at least one or more mutation(s) in the 22 genes we have identified with probabilities of developing ALS ranging from 25-99%, depending on the number of mutations a patient has among the identified genes. Moreover, we have identified a subset of the ALS cohort that has >17 mutations in the 22 identified. In this case, a patient with this mutation profile has a 99% chance of developing ALS and could be classified as being at high risk for the disease. These genetic biomarkers can be used as an early ALS disease diagnostic tool with a rapid and non-invasive technique.

Deep Convolutional Neural Networks With Ensemble Learning and Generative Adversarial Networks for Alzheimer's Disease Image Data Classification.

Recent advancements in deep learning (DL) have made possible new methodologies for analyzing massive datasets with intriguing implications in healthcare. Convolutional neural networks (CNN), which have proven to be successful supervised algorithms for classifying imaging data, are of particular interest in the neuroscience community for their utility in the classification of Alzheimer's disease (AD). AD is the leading cause of dementia in the aging population. There remains a critical unmet need for early detection of AD pathogenesis based on non-invasive neuroimaging techniques, such as magnetic resonance imaging (MRI) and positron emission tomography (PET). In this comprehensive review, we explore potential interdisciplinary approaches for early detection and provide insight into recent advances on AD classification using 3D CNN architectures for multi-modal PET/MRI data. We also consider the application of generative adversarial networks (GANs) to overcome pitfalls associated with limited data. Finally, we discuss increasing the robustness of CNNs by combining them with ensemble learning (EL).

Mechanistic Investigation of Site-specific DNA Methylating Agents Targeting Breast Cancer Cells.

We previously described the development of a DNA-alkylating compound that showed selective toxicity in breast cancer cells. This compound contained an estrogen receptor α (ERα)-binding ligand and a DNA-binding/methylating component that could selectively methylate the N3-position of adenines at adenine-thymine rich regions of DNA. Herein, we describe mechanistic investigations that demonstrate that this class of compounds facilitate the translocation of the ERα-compound complex to the nucleus and induce the expression of ERα target genes. We confirm that the compounds show selective toxicity in ERα-expressing cells, induce ERα localization in the nucleus, and verify the essential role of ERα in modulating the toxicity. Minor alterations in the compound structure significantly affects the DNA binding ability, which correlates to the DNA-methylating ability. These studies demonstrate the utility of DNA-alkylating compounds to accomplish targeted inhibition of the growth of specific cancer cells; an approach that may overcome shortcomings of currently used chemotherapy agents.

Comparative Study Highlights the Potential of Spectral Deconvolution for Fucoxanthin Screening in Live Phaeodactylum tricornutum Cultures.

Microalgal biotechnology shows considerable promise as a sustainable contributor to a broad range of industrial avenues. The field is however limited by processing methods that have commonly hindered the progress of high throughput screening, and consequently development of improved microalgal strains. We tested various microplate reader and flow cytometer methods for monitoring the commercially relevant pigment fucoxanthin in the marine diatom Phaeodactylum tricornutum. Based on accuracy and flexibility, we chose one described previously to adapt to live culture samples using a microplate reader and achieved a high correlation to HPLC (R2 = 0.849), effectively removing the need for solvent extraction. This was achieved by using new absorbance spectra inputs, reducing the detectable pigment library and changing pathlength values for the spectral deconvolution method in microplate reader format. Adaptation to 384-well microplates and removal of the need to equalize cultures by density further increased the screening rate. This work is of primary interest to projects requiring detection of biological pigments, and could theoretically be extended to other organisms and pigments of interest, improving the viability of microalgae biotechnology as a contributor to sustainable industry.

Putative Otobius megnini-associated clinical signs in horses in South Africa (2012-2018).

Otobius megnini has been associated with certain clinical conditions in horses in both California and Mexico. A number of cases similar to those described previously have been identified by the author in South Africa. This case report summarises these cases to demonstrate that the clinical condition occurs readily in South Africa and may be increasing in occurrence. The disease has minimal coverage in the literature making it more likely that a veterinarian, unfamiliar with the disease, will miss the diagnosis. The author would like to make veterinarians aware of this as a potential differential diagnosis. This study is a retrospective review of clinical data. Clinical records of patients with similar clinical signs and treatment were reviewed and grouped together as relevant cases for this case report. Ten cases of O. megnini associated neuromuscular dysfunction are reported, suggesting a link between the occurrence of the tick and the clinical condition. Clinical signs include third eyelid prolapse, localised muscle fasciculations, elevated heart rate and limb stamping. Serum chemistry changes commonly show increased aspartate aminotransferase and creatine kinase enzymes activities. The occurrence of the ticks within South Africa and the increasing number of cases presented demonstrate the need for more investigation into the pathophysiology of this condition.

Upregulation of Alzheimer's Disease Amyloid-ß Protein Precursor in Astrocytes Both in vitro and in vivo.

BACKGROUND: The amyloid cascade hypothesis of Alzheimer's disease (AD) posits that amyloid-ß (Aß) protein accumulation underlies the pathogenesis of the disease by leading to the formation of amyloid plaques, a pathologic hallmark of AD. Aß is a proteolytic product of amyloid-ß protein precursor (AßPP; APP), which is expressed in both neurons and astrocytes. Although considerable evidence shows that astrocytes may play critical roles in the pathogenesis of AD, the longitudinal changes of amyloid plaques in relationship to AßPP expression in astrocytes and cellular consequences are largely unknown. OBJECTIVE: Here, we aimed to investigate astrocyte-related pathological changes of Aß and AßPP using immunohistochemistry and biochemical studies in both animal and cell models. METHODS/RESULTS: We utilized 5XFAD transgenic mice and found age-dependent upregulation of AßPP in astrocytes demonstrated with astrocytic reactive properties, which followed appearance of amyloid plaques in the brain. We also observed that AßPP proteins presented well-defined punctate immuno reactivity in young animals, whereas AßPP staining showed disrupted structures surrounding amyloid plaques in older mice. Moreover, we utilized astrocyte cell models and showed that pretreatment of Aß42 resulted in downstream astrocyte autonomous changes, including up regulation in AßPP and BACE1 levels, as well as prolonged amyloidogenesis that could be reduced by pharmacological inhibition of BACE1. CONCLUSION: Collectively, our results show that age-dependent AßPP up regulation in astrocytes is a key feature in AD, which will not only provide novel insights for understanding AD progression, but also may offer new therapeutic strategies for treating AD.

Assessing Human Airway Epithelial Progenitor Cells for Cystic Fibrosis Cell Therapy.

Cystic fibrosis (CF) is caused by loss-of-function mutations in the CFTR (CF transmembrane regulator) gene. Pharmacologic therapies directed at CFTR have been developed but are not effective for mutations that result in little or no mRNA or protein expression. Cell therapy is a potential mutation-agnostic approach to treatment. One strategy is to harvest human bronchial epithelial cells (HBECs) for gene addition or genetic correction, followed by expansion and engraftment. This approach will require cells to grow extensively while retaining their ability to reconstitute CFTR activity. We hypothesized that conditionally reprogrammed cell (CRC) technology, namely growth in the presence of irradiated feeder cells and a Rho kinase inhibitor, would enable expansion while maintaining cell capacity to express functional CFTR. Our goal was to compare expression of the basal cell marker NGFR (nerve growth factor receptor) and three-dimensional bronchosphere colony-forming efficiency (CFE) in early- and later-passage HBECs grown using nonproprietary bronchial epithelial growth medium or the CRC method. Cell number and CFTR activity were determined in a competitive repopulation assay employing chimeric air-liquid interface cultures. HBECs expanded using the CRC method expressed the highest NGFR levels, had the greatest 3D colony-forming efficiency at later passage, generated greater cell numbers in chimeric cultures, and most effectively reconstituted CFTR activity. In our study, the HBEC air-liquid interface model, an informative testing platform proven vital for the development of other CF therapies, illustrated that cells grown by CRC technology or equivalent methods may be useful for cell therapy of CF.

Endoscopic recurrent laryngeal neuropathy grade prevalence in a sample of thoroughbred yearlings at public auction in South Africa (2013-2019).

Endoscopy of thoroughbred (TB) yearlings at public auctions is common in South Africa. Laryngeal function (LF) is a common concern of buyers of young TBs. Cancellation of sale because of LF abnormalities is a concern for both the vendor and the buyer, with recurrent laryngeal neuropathy (RLN) being a common cause of sale cancellation. The aim of this descriptive study was to determine the prevalence of RLN at South African premier TB yearling sales. This study was designed as a retrospective descriptive analysis of upper respiratory tract (URT) endoscopic examinations to determine RLN grade, performed at two premier TB yearling sales in South Africa. Results of buyer-requested endoscopic examination from 2013 to 2019 were included. Results from the yearling sales were analysed for prevalence of RLN grade (using Rakestraw's 4-point system) and compared to similar previously published studies. For analysis of effects of gender on RLN grading, horses were grouped and Fisher's exact test was used to determine if there was a relationship between gender and grade. For comparison of the effects of age on grade, and sales year on grade, a Kruskal-Wallis test was conducted. A value of p 0.05 was considered significant. A total of 858 horses were examined out of 4149 offered for sale; there were 57.58% colts and 42.42% fillies (mean age of 18.1 months). The annual percentage for grade 1 was 84.04% ± 9.98%, for grade 2: 14.49% ± 10.69%, for grade 3: 0.71% ± 0.57% and for grade 4: 0.76% ± 0.94%. There were no other significant findings. The exclusive nature of the sale and the increasing proclivity for pre-sale scoping may have skewed the results. This study shows that RLN grade incidences in TB yearlings at public auctions in South Africa are as follows: grade 1: 84.04%, grade 2: 14.49%, grade 3: 0.71% and grade 4: 0.76%. The results were similar to that of an adult population of horses examined in South Africa in a previous study.

Metabolic Tumor Volume Response Assessment Using (11)C-Methionine Positron Emission Tomography Identifies Glioblastoma Tumor Subregions That Predict Progression Better Than Baseline or Anatomic Magnetic Resonance Imaging Alone.

PURPOSE: To evaluate whether response assessment of newly diagnosed glioblastoma at 3 months using 11C-methionine-positron emission tomography (MET-PET) is better associated with patient outcome compared with baseline MET-PET or anatomic magnetic resonance imaging alone. METHODS AND MATERIALS: Patients included were participants in a phase I/II trial of dose-escalated chemoradiation based on anatomic magnetic resonance imaging. Automated segmentation of metabolic tumor volume (MTV) was performed at a threshold of 1.5 times mean cerebellar uptake. Progression-free (PFS) and overall survival were estimated with the Kaplan-Meier method and compared with log-rank tests. Multivariate analysis for PFS and overall survival was performed using Cox proportional hazards, and spatial overlap between imaging and recurrence volumes were analyzed. RESULTS: Among 37 patients, 15 had gross total resection, of whom 10 (67%) had residual MTV, 16 subtotal resection, and 6 biopsy alone. Median radiation therapy dose was 75 Gy (range, 66-81). Median baseline T1 Gd-enhanced tumor volume (GTV-Gd) was 38.0 cm3 (range, 8.0-81.5). Median pre-CRT MTV was 4.9 cm3 (range, 0-43.8). Among 25 patients with 3-month MET-PET, MTV was only 2.4 cm3 (range, 0.004-18.0) in patients with uptake. Patients with MTV = 0 cm3 at 3 months had superior PFS (18.2 vs 10.1 months, P = .03). On multivariate analysis, larger 3-month MTV (hazard ratio [HR] 2.4, 95% confidence interval [CI], 1.4-4.3, P = .03), persistent MET-PET subvolume (overlap of pre-CRT and 3 month MTV; HR 2.0, 95% CI, 1.2-3.4, P = .06), and increase in MTV (HR 1.8, 95% CI, 1.1-3.1, P = .09) were the only imaging factors significant for worse PFS. GTV-Gd at recurrence encompassed 97% of the persistent MET-PET subvolume (interquartile range 72%-100%), versus 71% (interquartile range 39%-93%) of baseline MTV, 54% of baseline GTV-Gd (18%-87%), and 78% of 3-month MTV (47%-95%). CONCLUSIONS: The majority of patients with apparent gross total resection of glioblastoma have measurable postoperative MTV. Total and persisting MTV 3 months post-CRT were significant predictors of PFS, and persistent MET-PET subvolume was the strongest predictor for localizing tumor recurrence.

Ultrasonographic findings post laryngoplasty in the horse.

Laryngoplasty is commonly used to treat laryngeal hemiplegia in Thoroughbred racehorses. Evaluation of the success of the laryngoplasty is traditionally determined using endoscopy. Laryngeal ultrasonography and normal ultrasonographic appearance have been reported in the standing horse, but post-laryngoplasty and ventriculectomy ultrasonographic evaluation has limited literature coverage. A prospective case series of 10 Thoroughbred racehorses with left laryngeal hemiplegia was examined ultrasonographically and endoscopically prior to 3-10 days, 30-50 days, and 6-12 months after laryngoplasty and ventriculectomy. Anatomical structures and Plica vocalis movements were described and measurements and gradings analyzed by repeated means analysis of variance (P < .05). Postsurgical ultrasonographic visualization of Ventriculus laryngis entrances was possible. The distance between Plica vocalis in exhalation was significantly larger than that during inhalation (P < .05). Pre- and postsurgical caudal Basihyoideum and rostral Cartilago thyroidea depth was significantly different in some instances (P < .05). No significant differences in the Muscularis cricoarytenoideus lateralis measurements were found. Complications in the extra-luminal structures were found in seven horses including soft tissue swelling, seroma, and hematoma. A luminal Plica vocalis abscess and Plica vocalis granuloma were also detected ultrasonographically. Ultrasonography can be used to evaluate the post-laryngoplasty horse for assessing the success of the procedure, monitoring healing, and detecting complications.