Prediction of proliferative diabetic retinopathy using machine learning in Latino and non-Hispanic black cohorts with routine blood and urine testing.

PURPOSE: The objective was to predict proliferative diabetic retinopathy (PDR) in non-Hispanic Black (NHB) and Latino (LA) patients by applying machine learning algorithms to routinely collected blood and urine laboratory results. METHODS: Electronic medical records of 1124 type 2 diabetes patients treated at the Bronxcare Hospital eye clinic between January and December 2019 were analysed. Data collected included demographic information (ethnicity, age and sex), blood (fasting glucose, haemoglobin A1C [HbA1c] high-density lipoprotein [HDL], low-density lipoprotein [LDL], serum creatinine and estimated glomerular filtration rate [eGFR]) and urine (albumin-to-creatinine ratio [ACR]) test results and the outcome measure of retinopathy status. The efficacy of different machine learning models was assessed and compared. SHapley Additive exPlanations (SHAP) analysis was employed to evaluate the contribution of each feature to the model's predictions. RESULTS: The balanced random forest model surpassed other models in predicting PDR for both NHB and LA cohorts, achieving an AUC (area under the curve) of 83%. Regarding sex, the model exhibited remarkable performance for the female LA demographic, with an AUC of 87%. The SHAP analysis revealed that PDR-related factors influenced NHB and LA patients differently, with more pronounced disparity between sexes. Furthermore, the optimal cut-off values for these factors showed variations based on sex and ethnicity. CONCLUSIONS: This study demonstrates the potential of machine learning in identifying individuals at higher risk for PDR by leveraging routine blood and urine test results. It allows clinicians to prioritise at-risk individuals for timely evaluations. Furthermore, the findings emphasise the importance of accounting for both ethnicity and sex when analysing risk factors for PDR in type 2 diabetes individuals.

Survey indicates addressing workplace environment, work-life balance, and flexibility are key to attracting and retaining veterinarians in academia.

OBJECTIVE: Referencing growing concerns over the recruitment and retention of faculty in academic veterinary medicine, the authors hypothesized that among surveyed veterinary residents and early-career faculty, work-life balance and workplace climate and culture are stronger motivators than financial considerations, regardless of demographic factors such as gender, race/ethnicity, and area of specialization. SAMPLE: 541 participants were included in data analysis. METHODS: A mixed methods approach was utilized, incorporating both quantitative data and qualitative, free-text responses to better understand veterinary career choices by contextualizing factors associated with academic medicine. RESULTS: Factors underpinning career-related decision-making were ranked by level of importance as (1) workplace environment/culture, (2) personal well-being/work-life balance, (3) salary and bonuses, (4) geographic location, (5) facilities and resources, (6) benefits, and (7) schedule flexibility. Desires for workload balance, schedule flexibility, support from leadership, and mentorship and collaboration were among the top themes of qualitative responses for both residents and early career faculty respondents. Factors influencing career decision-making for resident and early-career faculty are varied. Workplace environment, work-life balance, and schedule flexibility are areas that academic institutions can address and continue to improve and that are likely to positively impact entry into academia and the desire to stay. CLINICAL RELEVANCE: This study sought to understand factors related to career decision-making and interest in academic veterinary medicine among residents and early-career faculty. Understanding these factors can support efforts to recruit and retain faculty in academic veterinary medicine.

When can higher-order interactions produce stable coexistence?

Most ecological models are based on the assumption that species interact in pairs. Diverse communities, however, can have higher-order interactions, in which two or more species jointly impact the growth of a third species. A pitfall of the common pairwise approach is that it misses the higher-order interactions potentially responsible for maintaining natural diversity. Here, we explore the stability properties of systems where higher-order interactions guarantee that a specified set of abundances is a feasible equilibrium of the dynamics. Even these higher-order interactions which lead to equilibria do not necessarily produce stable coexistence. Instead, these systems are more likely to be stable when the pairwise interactions are weak or facilitative. Correlations between the pairwise and higher-order interactions, however, do permit robust coexistence even in diverse systems. Our work not only reveals the challenges in generating stable coexistence through higher-order interactions but also uncovers interaction patterns that can enable diversity.

Analytical Validation of Loss of Heterozygosity and Mutation Detection in Pancreatic Fine-Needle Aspirates by Capillary Electrophoresis and Sanger Sequencing.

Pancreatic cystic disease, including duct dilation, represents precursor states towards the development of pancreatic cancer, a form of malignancy with relatively low incidence but high mortality. While most of these cysts (>85%) are benign, the remainder can progress over time, leading to malignant transformation, invasion, and metastasis. Cytologic diagnosis is challenging, limited by the paucity or complete absence of cells representative of cystic lesions and fibrosis. Molecular analysis of fluids collected from endoscopic-guided fine-needle aspiration of pancreatic cysts and dilated duct lesions can be used to evaluate the risk of progression to malignancy. The basis for the enhanced diagnostic utility of molecular approaches is the ability to interrogate cell-free nucleic acid of the cyst/duct and/or extracellular fluid. The allelic imbalances at tumor suppressor loci and the selective oncogenic drivers are used clinically to help differentiate benign stable pancreatic cysts from those progressing toward high-grade dysplasia. Methods are discussed and used to determine the efficacy for diagnostic implementation. Here, we report the analytical validation of methods to detect causally associated molecular changes integral to the pathogenesis of pancreatic cancer from pancreatic cyst fluids.

Competition for time: Evidence for an overlooked, diversity-maintaining competitive mechanism.

Understanding how diversity is maintained in plant communities requires that we first understand the mechanisms of competition for limiting resources. In ecology, there is an underappreciated but fundamental distinction between systems in which the depletion of limiting resources reduces the growth rates of competitors and systems in which resource depletion reduces the time available for competitors to grow, a mechanism we call 'competition for time'. Importantly, modern community ecology and our framing of the coexistence problem are built on the implicit assumption that competition reduces the growth rate. However, recent theoretical work suggests competition for time may be the predominant competitive mechanism in a broad array of natural communities, a significant advance given that when species compete for time, diversity-maintaining trade-offs emerge organically. In this study, we first introduce competition for time conceptually using a simple model of interacting species. Then, we perform an experiment in a Mediterranean annual grassland to determine whether competition for time is an important competitive mechanism in a field system. Indeed, we find that species respond to increased competition through reductions in their lifespan rather than their rate of growth. In total, our study suggests competition for time may be overlooked as a mechanism of biodiversity maintenance.

Functional loss of tumor suppressor genes detected by loss of heterozygosity, but not driver mutations, predicts aggressive lymph node status in papillary thyroid carcinoma.

BACKGROUND: Recognizing aggressive tumor biology is essential to optimizing patient management for papillary thyroid carcinomas (PTC). Aggressive lymph node (ALN) status is one feature that influences decision-making. We evaluated genomic deletions in regions of tumor suppressor genes, detected by loss of heterozygosity (LOH) analysis, to understand causal alterations linked to thyroid cancer aggressiveness and to serve as a molecular diagnostic biomarker for ALN status. METHODS: We analyzed 105 primary PTC enriched for patients with ALN (64% with, 36% without). We also analyzed 39 positive lymph nodes (79% with, 21% without ALN). LOH was determined using a panel of 25 polymorphic microsatellite alleles targeting 10 genomic loci harboring common tumor suppressor genes. Additionally, ThyGeNEXT® and ThyraMIR® assays were performed. RESULTS: LOH was detected in 43/67 primary PTC from patients with ALN status, compared with only 5/38 primary PTC without ALN (minimal metastatic burden) (P=0.0000003). This is further supported by post hoc analyses of paired primary and metastatic samples. Paired samples from patients with ALN are more likely to harbor LOH, compared to the ALN negative group (P=0.0125). Additionally, 12/31 paired samples from patients with ALN demonstrated additional or different LOH loci in metastatic samples compared to the primary tumor samples. No association was seen between ALN and mutational, translocation, or microRNA data. CONCLUSIONS: LOH detected in primary PTC significantly predicts ALN status. Analysis of paired primary and metastatic samples from patients with / without ALN status further supports this relationship. The acquisition of LOH at additional loci is common in lymph nodes from patients with ALN status. SIMPLE SUMMARY: A subset of patients with papillary thyroid carcinoma (PTC) will develop recurrent disease. One known predictor of recurrence is the American Thyroid Association category "Aggressive Lymph Node" (ALN) disease, considering metastatic burden. Loss of heterozygosity (LOH) - chromosomal loss in regions of tumor suppressor genes - has yet to be investigated as a possible mechanism driving ALN status in PTC. The ability to predict ALN status prior to surgery can guide the extent of surgery and postoperative treatment options. We found that paired samples from patients with ALN are more likely to harbor LOH, compared to patients without ALN disease. 38% of patients with ALN demonstrated additional or different LOH loci in metastatic samples compared to the primary tumor samples. LOH complements current molecular analysis of thyroid cancer when searching for evidence of aggressive biology.

The "Claw Sign" may aid in axial localization in cases of peripherally located canine glioma on MRI.

The "claw sign" is a radiographic sign studied in human imaging to determine if a mass arises from a solid structure or organ versus a close adjacent location, resulting in distortion of the outline of an organ. We investigated its utility in characterizing MRI axial localization of peripherally located intracranial glioma versus meningioma, due to their overlap in MRI appearance. This retrospective, secondary analysis, cross-sectional study aimed to report the sensitivity, specificity, and inter- and intraobserver variabilities using kappa statistics, hypothesizing that the claw sign will have strong inter- and intraobserver agreement (κ > 0.8). Dogs with a histologically confirmed diagnosis of peripherally located glioma or meningioma and available 3T MRI data were retrieved from medical record archives from 2009 to 2021. A total of 27 cases, 11 glioma and 16 meningioma, were included. The postcontrast T1-weighted images were provided to five blinded image evaluators in two separate randomized sessions separated by a 6-week wash out period. Prior to the first evaluation, evaluators were provided with a training video and set of training cases for the "claw sign," which were excluded from the study. Evaluators were asked to rate cases as "positive," "negative," or "indeterminate" for the "claw sign." The sensitivity and specificity for the "claw sign" for the first session were 85.5% and 80%, respectively. The interobserver agreement for identifying the "claw sign" was moderate (κ = 0.48), and the intraobserver agreement across the two sessions was substantial (κ = 0.72). These findings indicate the claw sign is supportive but not pathognomonic for intra-axial localization in cases of canine glioma on MRI.

Case report: Hemangioblastoma in the brainstem of a dog.

A 3-year-old castrated male, American Pit Bull Terrier presented to Texas A&M University due to a 3-week mixed cerebellar and general proprioceptive ataxia, circling, head tilt, and dull mentation. Neurologic examination revealed signs of vestibular and mesencephalic dysfunction. Postmortem examination revealed a 1.1 × 1 × 0.8-cm, soft, dark red, well-circumscribed, left-sided mass, extending from the crus cerebri of the midbrain caudally to the pons. Microscopically, the neoplasm was composed of a spindle-shaped interstitial population of cells interspersed between a prominent capillary network, consistent with the reticular pattern of hemangioblastoma. Interstitial cells had strong, diffuse, intracytoplasmic immunolabeling for neuron-specific enolase (NSE) and were variably positive for intracytoplasmic glial fibrillary acidic protein (GFAP). Vascular endothelial cells had strong diffuse, intracytoplasmic immunolabeling for von Willebrand factor (VWF) glycoprotein. To date, only six cases of hemangioblastoma have been reported in canines, five in the spinal cord, and one in the rostral cerebrum. Our case may represent the first canine hemangioblastoma localized to the brainstem.

Baseline characteristics in the Israel refraction, environment, and devices (iREAD) study.

The purpose of this study is to present baseline data from a longitudinal study assessing behavioral factors in three groups of boys in Israel with varying myopia prevalence. Ultra-Orthodox (N = 57), religious (N = 67), and secular (N = 44) Jewish boys (age 8.6 ± 1.4 years) underwent cycloplegic autorefraction and axial-length measurement. Time-outdoors and physical-activity were assessed objectively using an Actiwatch. Ocular history, educational factors, and near-work were assessed with a questionnaire. Group effects were tested and mixed effects logistic and linear regression were used to evaluate behaviors and their relationship to myopia. The prevalence of myopia (≤ - 0.50D) varied by group (ultra-Orthodox: 46%, religious: 25%, secular: 20%, P < 0.021). Refraction was more myopic in the ultra-Orthodox group (P = 0.001). Ultra-Orthodox boys learned to read at a younger age (P < 0.001), spent more hours in school (P < 0.001), spent less time using electronic devices (P < 0.001), and on weekdays, spent less time outdoors (P = 0.02). Increased hours in school (OR 1.70) and near-work (OR 1.22), increased the odds of myopia. Being ultra-Orthodox (P < 0.05) and increased near-work (P = 0.007) were associated with a more negative refraction. Several factors were associated with the prevalence and degree of myopia in young boys in Israel, including being ultra-Orthodox, learning to read at a younger age, and spending more hours in school.

Resident Perspective of the Virtual Diagnostic Radiology Residency Interview Process: A National Survey From the Association of Program Directors in Radiology.

RATIONALE AND OBJECTIVES: The purpose of this study was to assess differences in first-year radiology resident perception of the match process and early satisfaction with residency programs between those who matched in 2020 versus 2021, the first virtual application cycle after the start of the COVID-19 pandemic. MATERIALS AND METHODS: A 33-question survey was distributed to first-year diagnostic radiology residents at programs throughout the United States through the Association of Program Directors in Radiology. Responses were collected in June of 2022 from residents who matched in 2020 and in July of 2022 from residents who matched in 2021. Questions were designed to assess applicant demographics, outcomes and attitudes towards the interview process. Comparison was made between the two cohorts. RESULTS: Of the 2231 matched residents in the 2020 and 2021 match years, 108 residents (4.8%) received, responded, and met inclusion criteria for the survey. Forty-three of 46 (92.5%) respondents that matched in 2020 interviewed in-person compared to one of 60 (1.7%) that matched in 2021 (p < 0.0001). There was no difference in satisfaction of match results, current training programs, work culture, satisfaction with facilities, and depiction of residency structure. Applicants from the 2021 cohort were more likely to express concerns about interview hoarding, having enough time to ask questions on interview days, and ability to accurately present themselves in interviews but were more likely to favor virtual interviews for future cycles. CONCLUSION: The virtual interview process is perceived neutrally or positively by most early diagnostic radiology residents and produced similar satisfactory results compared to applicants that interviewed in person. Attention should be given to concerns of those who matched virtually if the virtual interview process is to be continued.

Does deterministic coexistence theory matter in a finite world?

Contemporary studies of species coexistence are underpinned by deterministic models that assume that competing species have continuous (i.e., noninteger) densities, live in infinitely large landscapes, and coexist over infinite time horizons. By contrast, in nature, species are composed of discrete individuals subject to demographic stochasticity and occur in habitats of finite size where extinctions occur in finite time. One consequence of these discrepancies is that metrics of species' coexistence derived from deterministic theory may be unreliable predictors of the duration of species coexistence in nature. These coexistence metrics include invasion growth rates and niche and fitness differences, which are now commonly applied in theoretical and empirical studies of species coexistence. In this study, we tested the efficacy of deterministic coexistence metrics on the duration of species coexistence in a finite world. We introduce new theoretical and computational methods to estimate coexistence times in stochastic counterparts of classic deterministic models of competition. Importantly, we parameterized this model using experimental field data for 90 pairwise combinations of 18 species of annual plants, allowing us to derive biologically informed estimates of coexistence times for a natural system. Strikingly, we found that for species expected to deterministically coexist, community sizes containing only 10 individuals had predicted coexistence times of more than 1000 years. We also found that invasion growth rates explained 60% of the variation in intrinsic coexistence times, reinforcing their general usefulness in studies of coexistence. However, only by integrating information on both invasion growth rates and species' equilibrium population sizes could most (>99%) of the variation in species coexistence times be explained. This integration was achieved with demographically uncoupled single-species models solely determined by the invasion growth rates and equilibrium population sizes. Moreover, because of a complex relationship between niche overlap/fitness differences and equilibrium population sizes, increasing niche overlap and increasing fitness differences did not always result in decreasing coexistence times, as deterministic theory would predict. Nevertheless, our results tend to support the informed use of deterministic theory for understanding the duration of species' coexistence while highlighting the need to incorporate information on species' equilibrium population sizes in addition to invasion growth rates.

Can veterinary medicine improve diversity in post-graduate training programs? Current state of academic veterinary medicine and recommendations on best practices.

The American Association of Veterinary Clinicians (AAVC) convened a Diversity, Equity, and Inclusivity working group in March 2021 to address the limited diversity (including but not limited to ethnic, racial, and cultural diversity) in clinical post-DVM graduate training programs and academic faculty. Concurrent with a working group formation, the AAVC developed a strategic plan. The central mission of the AAVC is to develop, support, and connect academic leaders to fuel the future of the veterinary medical profession. House officers and their training programs are central to all goals outlined in the strategic plan. Amongst other strategic goals, the working group identified best practices for intern and resident recruitment and selection. We report herein from the current health profession literature ways to identify and recruit talented, diverse candidates especially those with non-traditional (atypical) preparation and experience. We also provide recommendations on best practices for intern and resident selection. This document highlights holistic approaches, some of which are incrementally being incorporated into the Veterinary Intern Resident Matching Program application, that emphasize diversity as a selection criteria for intern and resident selection an important step towards building a more resilient and inclusive workforce. These include expanding candidate assessment beyond grades and class rank into a more standardized method for screening candidates that includes consideration of life experiences and talents outside of veterinary medicine.

Small rainfall changes drive substantial changes in plant coexistence.

Although precipitation patterns have long been known to shape plant distributions1, the effect of changing climate on the interactions of species and therefore community composition is far less understood2,3. Here, we explored how changes in precipitation alter competitive dynamics via direct effects on individual species, as well as by the changing strength of competitive interactions between species, using an annual grassland community in California. We grew plants under ambient and reduced precipitation in the field to parameterize a competition model4 with which we quantified the stabilizing niche and fitness differences that determine species coexistence in each rainfall regime. We show that reduced precipitation had little direct effect on species grown alone, but it qualitatively shifted predicted competitive outcomes for 10 of 15 species pairs. In addition, species pairs that were functionally more similar were less likely to experience altered outcomes, indicating that functionally diverse communities may be most threatened by changing interactions. Our results highlight how important it is to account for changes to species interactions when predicting species and community response to global change.

Temporal and sequence-related variability in diffusion-weighted imaging of presumed cerebrovascular accidents in the dog brain.

Diffusion-weighted MRI (DWI) is often used to guide clinical interpretation of intraparenchymal brain lesions when there is suspicion for a cerebrovascular accident (CVA). Despite widespread evidence that imaging and patient parameters can influence diffusion-weighted measurements, such as apparent diffusion coefficient (ADC), there is little published data on such measurements for naturally occurring CVA in clinical cases in dogs. We describe a series of 22 presumed and confirmed spontaneous canine CVA with known time of clinical onset imaged on a single 3T magnet between 2011 and 2021. Median ADC values of < 1.0x10-3 mm2/s were seen in normal control tissues as well as within CVAs. Absolute and relative ADC values in CVAs were well-correlated (R2 = 0.82). Absolute ADC values < 1.0x10-3 mm2/s prevailed within ischemic CVAs, though there were exceptions, including some lesions of < 5 days age. Some lesions showed reduced absolute but not relative ADC values when compared to matched normal contralateral tissue. CVAs with large hemorrhagic components did not show restricted diffusion. Variation in the DWI sequence used impacted the ADC values obtained. Failure to identify a region of ADC < 1.0x10-3 mm2/s should not exclude CVA from the differential list when clinical suspicion is high.

Coexistence in diverse communities with higher-order interactions.

A central assumption in most ecological models is that the interactions in a community operate only between pairs of species. However, two species may interactively affect the growth of a focal species. Although interactions among three or more species, called higher-order interactions, have the potential to modify our theoretical understanding of coexistence, ecologists lack clear expectations for how these interactions shape community structure. Here we analytically predict and numerically confirm how the variability and strength of higher-order interactions affect species coexistence. We found that as higher-order interaction strengths became more variable across species, fewer species could coexist, echoing the behavior of pairwise models. If interspecific higher-order interactions became too harmful relative to self-regulation, coexistence in diverse communities was destabilized, but coexistence was also lost when these interactions were too weak and mutualistic higher-order effects became prevalent. This behavior depended on the functional form of the interactions as the destabilizing effects of the mutualistic higher-order interactions were ameliorated when their strength saturated with species' densities. Last, we showed that more species-rich communities structured by higher-order interactions lose species more readily than their species-poor counterparts, generalizing classic results for community stability. Our work provides needed theoretical expectations for how higher-order interactions impact species coexistence in diverse communities.

Relationship between Uveal Inflammation and Viral Detection in 30 Cats with Feline Infectious Peritonitis.

Feline infectious peritonitis (FIP) virus is the most common infectious cause of uveitis in cats. Confirmatory diagnosis is usually only reached at postmortem examination. The relationship between the histologic inflammatory pattern, which depends on the stage of the disease, and the likelihood of detection of the viral antigen and/or RNA has not been investigated. We hypothesized that viral detection rate by either immunohistochemistry, in situ hybridization or RT-qPCR is dependent upon the predominant type of uveal inflammatory response (i.e., pyogranulomatous vs. plasmacytic). Thus, the aims of this study were to evaluate cases of FIP-induced uveitis, localize the viral antigen and RNA, and assess the relationship between the inflammatory pattern (macrophage- vs. plasma cell-rich) and the likelihood of detecting the FIP antigen and/or RNA. We evaluated 30 cats with FIP-induced uveitis. The viral antigen and/or RNA were detected within uveal macrophages in 11/30 cases, of which 8 tested positive by RT-qPCR. Correlation analysis determined a weak to moderate but significant negative correlation between the degree of plasmacytic uveal inflammation and the likelihood of detecting the FIP antigen and RNA. This study suggests that predominance of plasmacytic inflammation in cases of FIP uveitis reduces the odds of a confirmatory diagnosis through the viral detection methods available.

Development and evaluation of a survey instrument to assess veterinary medical record suitability for multi-center research studies.

Here we describe the development and evaluation of a survey instrument to assess the research suitability of veterinary electronic medical records (EMRs) through the conduct of two studies as part of the Dog Aging Project (DAP). In study 1, four reviewers used the instrument to score a total of 218 records in an overlapping matrix of pairs to assess inter-rater agreement with respect to appropriate format (qualification), identification match (verification), and record quality. Based upon the moderate inter-rater agreement with respect to verification and the relatively large number of records that were incorrectly rejected the instrument was modified and more specific instructions were provided. In study 2, a modified instrument was again completed by four reviewers to score 100 different EMRs. The survey scores were compared to a gold standard of board-certified specialist review to determine receiver operating curve statistics. The refined survey had substantial inter-rater agreement across most qualification and verification questions. The cut-off value identified had a sensitivity of 95 and 96% (by reviewer 1 and reviewer 2, respectively) and a specificity of 82% and 91% (by reviewer 1 and reviewer 2, respectively) to predict gold standard acceptance or rejection of the record. Using just qualification and verification questions within the instrument (as opposed to full scoring) minimally impacted sensitivity and specificity and resulted in substantial time savings in the review process.

Ecological lags govern the pace and outcome of plant community responses to 21st-century climate change.

Forecasting the trajectories of species assemblages in response to ongoing climate change requires quantifying the time lags in the demographic and ecological processes through which climate impacts species' abundances. Since experimental climate manipulations are typically abrupt, the observed species responses may not match their responses to gradual climate change. We addressed this problem by transplanting alpine grassland turfs to lower elevations, recording species' demographic responses to climate and competition, and using these data to parameterise community dynamics models forced by scenarios of gradual climate change. We found that shifts in community structure following an abrupt climate manipulation were not simply accelerated versions of shifts expected under gradual warming, as the former missed the transient rise of species benefiting from moderate warming. Time lags in demography and species interactions controlled the pace and trajectory of changing species' abundances under simulated 21st-century climate change, and thereby prevented immediate diversity loss.

Phenotypic plasticity promotes species coexistence.

Ecological explanations for species coexistence assume that species' traits, and therefore the differences between species, are fixed on short timescales. However, species' traits are not fixed, but can instead change rapidly as a consequence of phenotypic plasticity. Here we use a combined experimental-theoretical approach to demonstrate that plasticity in response to interspecific competition between two aquatic plants allows for species coexistence where competitive exclusion is otherwise predicted to occur. Our results show that rapid trait changes in response to a shift in the competitive environment can promote coexistence in a way that is not captured by common measures of niche differentiation.