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Background: The transgender patient seeking transition from male to female suffers a significant stigma from the prominent male thyroid cartilage. Natal men and women may seek elective reduction of the “Adam's apple” as well. There are various techniques for performing chondrolaryngoplasty, but these techniques and their associated outcomes are poorly described in the literature. Methods: A literature review was performed for articles related to esthetic chondrolaryngoplasty. Data related to outcomes and complications were extracted. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. The authors also present the case of a transgender 58 year-old male-to-female patient who underwent chondrolaryngoplasty. Results: Four case series, including 69 patients who had esthetic chondrolaryngoplasty, were identified that met inclusion criteria. Qualitative assessment of patient satisfaction was reported in two studies (n = 62), with a 98.4% satisfaction rate. The most common complications were odynophagia in 20.3% of patients, hoarseness in 36.2% of patients, and laryngospasm in 1.4% of patients. Of patients that had postoperative hoarseness, 96% had resolution within 20 days. In our patient's case, chondrolaryngoplasty was performed with a tracheal shave in combination with high-speed burring for fine contouring. The patient experienced hoarseness for 1 week postoperatively that self-resolved. Conclusion: Overall, chondrolaryngoplasty for reduction of the thyroid cartilage appears to be a safe and effective procedure. The complications that occurred in identified case series were mild and self-limiting. Although serious complications are certainly possible, we were not able to identify their occurrence in the literature. Recent modifications in chondrolaryngoplasty involve protecting the anterior commissure tendon to prevent iatrogenic voice modification. Keywords: Chondrolaryngoplasty, Facial feminization, Male-to-female, Tracheal shave, Transgender

Background:. Chest masculinization surgery is increasing in prevalence. However, the ideal location of the nipple-areolar complex (NAC) is unknown. Our purpose was to determine the most aesthetically favorable male NAC position for use in chest masculinization through crowdsourcing. Methods:. Using Adobe Photoshop CC 2017, 8 locations for the NAC were created based on previous literature descriptions. Amazon Mechanical Turk was utilized as a crowdsourcing interface—respondents were asked to rank the top 3 most favorable and least favorable images. Analysis of variance with subsequent Tukey HSD was used for a statistical comparison of favorability scores for different NAC localizations. Values were considered significant with P < 0.05. Results:. Eight hundred nineteen respondents participated in the survey. NAC positions of Images C (mean score = 1.9222) and A (mean score = 1.7365) received higher favorability scores than those of Images D, E, F, G, and H (all P < 0.05). There were no significant differences between Images C and A (C versus A: P = 0.6412). NAC localizations from Images G (mean score = −2.0353) and H (mean score = −1.6908) received lower favorability scores than Images A, B, C, D, E, and F (all P < 0.05). There were no significant differences between Images G and H (P = 0.2279). Conclusions:. Most respondents preferred Images C and A, and few favored Images G and H, suggesting that lateral NAC placement is favored over more medial localizations. Additionally, both Images C and A utilize relatively inferior NAC placements. Therefore, we recommend a location inferior and lateral to the NAC. Ultimately, NAC localization during chest masculinization will be the result of shared decision-making between the patient and the surgeon to fulfill each patient’s aesthetic goals.

Oligodendrocyte precursor cells (OPCs) have long been regarded as progenitors of oligodendrocytes, yet recent advances have illuminated their multifaceted nature including their emerging immune functions. This review seeks to shed light on the immune functions exhibited by OPCs, spanning from phagocytosis to immune modulation and direct engagement with immune cells across various pathological scenarios. Comprehensive understanding of the immune functions of OPCs alongside their other roles will pave the way for targeted therapies in neurological disorders.

Introduction Traumatic rib fractures present a considerable risk to patient well-being, contributing to morbidity and mortality in trauma patients. To address the risks associated with rib fractures, evidence-based interventions have been implemented, including effective pain management, pulmonary hygiene, and early walking. Vancouver General Hospital, a level 1 trauma center in British Columbia, Canada, developed a comprehensive multidisciplinary chest trauma clinical practice guideline (CTCPG) to optimize the management of patients with rib fractures. This prospective cohort study aimed to assess the impact of the CTCPG on pain management interventions and patient outcomes.Methods The study involved patients admitted between January 1, 2021 and December 31, 2021 (post-CTCPG cohort) and a historical control group admitted between November 1, 2018 and December 31, 2019 (pre-CTCPG cohort). Patient data were collected from patient charts and the British Columbia Trauma Registry, including demographics, injury characteristics, pain management interventions, and relevant outcomes.Results Implementation of the CTCPG resulted in an increased use of multimodal pain therapy (99.4% vs 96.1%; p=0.03) and a significant reduction in the incidence of delirium in the post-CTCPG cohort (OR 0.43, 95% CI 0.21 to 0.80, p=0.0099). There were no significant differences in hospital length of stay, ICU (intensive care unit) days, non-invasive positive pressure ventilation requirement, ventilator days, pneumonia incidence, or mortality between the two cohorts.Discussion Adoption of a CTCPG improved chest trauma management by enhancing pain management and reducing the incidence of delirium. Further research, including multicenter studies, is warranted to validate these findings and explore additional potential benefits of the CTCPG in the management of chest trauma patients.Level of evidence IIb.

High levels of lipoprotein(a) [Lp(a)] are causal for atherosclerotic cardiovascular disease (ASCVD). Lp(a) is the most prevalent inherited dyslipidemia and strongest genetic ASCVD risk factor. This risk persists in the presence of at target, guideline-recommended, LDL-C levels and adherence to lifestyle modifications. Epidemiological and genetic evidence supporting its causal role in ASCVD and calcific aortic stenosis continues to accumulate, although various facets regarding Lp(a) biology (genetics, pathophysiology, and expression across race/ethnic groups) are not yet fully understood. The evolving nature of clinical guidelines and consensus statements recommending universal measurements of Lp(a) and the scientific data supporting its role in multiple disease states reinforce the clinical merit to start population screening for Lp(a) now. There is a current gap in the implementation of recommendations for primary and secondary cardiovascular disease (CVD) prevention in those with high Lp(a), in part due to a lack of protocols for management strategies. Importantly, targeted apolipoprotein(a) [apo(a)]-lowering therapies that reduce Lp(a) levels in patients with high Lp(a) are in phase 3 clinical development. This review focuses on the identification and clinical management of patients with high Lp(a). Specifically, we highlight the clinical value of measuring Lp(a) and its use in determining Lp(a)-associated CVD risk by providing actionable guidance, based on scientific knowledge, that can be utilized now to mitigate risk caused by high Lp(a).

Today, there exists a large number of different embedded hardware platforms for accelerating the inference of Deep Neural Networks (DNNs). To enable rapid application development, a number of prediction frameworks have been proposed to estimate the DNN inference latency on a wide range of hardware platforms. This work presents a novel smart padding benchmarking method, which allows the profiling of hardware platforms without requiring detailed per-layer reports. To mitigate the measurement inaccuracies inherent in the black-box approach, a confidence framework comprising three metrics has been developed. These metrics not only enhance the interpretation of prediction results but also significantly contribute to the refinement of the estimation framework itself, as they facilitate to improve the coverage of the training dataset for relevant layers and detect weaknesses in the training dataset. Empirical results demonstrate the method’s robustness, with average prediction errors minimized to below 10% for smart padding benchmarking-based ANNETTE predictions for the Jetson Xavier, NXP i.MX93, and NXP i.MX8M+.

ObjectiveTo identify, quantify and compare clinical and concurrent imaging findings of occipital hypoplasia (OH), syringomyelia (SM) and atlanto-occipital overlapping (AO) in dogs with or without brachycephaly.MethodsA focused systematic search for literature was performed in the Web of Science™, PubMed and Google Scholar databases. Both authors screened and classified the identified articles using EndNote and appraised the articles using the Critical Appraisal Skills Program checklists. The main clinical and concurrent imaging features were extracted and evaluated for coexistence of OH, SM, AO, and other imaging findings.ResultsThirty-one articles were included in this minireview. For articles focusing on descriptions of OH, SM and AO, 249 dogs had at least one of these conditions, and 3 of these 249 dogs (1%) had coexistence of all three conditions. For articles focusing on descriptions of the dogs, OH, SM, and AO were identified in 552/19/11/11, 574/2/0/6, and 100/0/0/0 small brachycephalic, small non-brachycephalic, large brachycephalic, and large non-brachycephalic breeds, respectively. For all small brachycephalic dogs, the percentages of affected animals were 40% for OH (p = 0.01), 42% for SM (p

NSG (NOD/Scid IL2Rγnull) mice reconstituted with PBMCs donated by patients with ulcerative colitis or Crohn’s disease highly reflect the respective pathological phenotype. To determine whether these findings could be applicable to atopic dermatitis (AD) and psoriasis vulgaris (PV), PBMCs isolated from patients with AD and PV were first subjected to immunological profiling. Subsequently, NSG mice were reconstituted with these PBMCs. Hierarchical clustering and network analysis revealed a distinct profile of patients with AD and PV with activated CD4+ T cells (CD69, CD25) occupying a central position in the AD network and CD4+ CD134+ cells acting as the main hub in the PV network. After dermal application of DMSO, both NSG mice reconstituted with PBMCs from donors with AD (ie, NSG-AD mice) and NSG mice reconstituted with PBMCs from donors with PV (ie, NSG-PV mice) exhibited increased clinical, skin, and histological scores. Immunohistochemical analysis, frequencies of splenic human leukocytes, and cytokine expression levels indicated that CD4+ CD69+ cells, M1 and TSLP receptor–expressing monocytes, switched B cells, and monocyte chemoattractant protein 3 were the driving factors of inflammation in NSG-AD mice. In contrast, inflammation in NSG-PV mice was characterized by an increase in fibroblasts in the epidermis, frequencies of CD1a-expressing monocytes, and IL-17 levels. Therefore, the pathological phenotypes of NSG-AD mice and NSG-PV mice differ and partially reflect the respective human diseases.

Abstract Background Dilated cardiomyopathy (DCM) is a life-threatening heart disease and a common cause of heart failure due to systolic dysfunction and subsequent left or biventricular dilatation. A significant number of cases have a genetic etiology; however, as a complex disease, the exact genetic risk factors are largely unknown, and many patients remain without a molecular diagnosis. Methods We performed GWAS followed by whole-genome, transcriptome, and immunohistochemical analyses in a spontaneously occurring canine model of DCM. Canine gene discovery was followed up in three human DCM cohorts. Results Our results revealed two independent additive loci associated with the typical DCM phenotype comprising left ventricular systolic dysfunction and dilatation. We highlight two novel candidate genes, RNF207 and PRKAA2, known for their involvement in cardiac action potentials, energy homeostasis, and morphology. We further illustrate the distinct genetic etiologies underlying the typical DCM phenotype and ventricular premature contractions. Finally, we followed up on the canine discoveries in human DCM patients and discovered candidate variants in our two novel genes. Conclusions Collectively, our study yields insight into the molecular pathophysiology of DCM and provides a large animal model for preclinical studies.

In the past, feline infectious peritonitis (FIP) caused by feline coronavirus (FCoV) was considered fatal. Today, highly efficient drugs, such as GS-441524, can lead to complete remission. The currently recommended treatment duration in the veterinary literature is 84 days. This prospective randomized controlled treatment study aimed to evaluate whether a shorter treatment duration of 42 days with oral GS-441524 obtained from a licensed pharmacy is equally effective compared to the 84-day regimen. Forty cats with FIP with effusion were prospectively included and randomized to receive 15 mg/kg of GS-441524 orally every 24h (q24h), for either 42 or 84 days. Cats were followed for 168 days after treatment initiation. With the exception of two cats that died during the treatment, 38 cats (19 in short, 19 in long treatment group) recovered with rapid improvement of clinical and laboratory parameters as well as a remarkable reduction in viral loads in blood and effusion. Orally administered GS-441524 given as a short treatment was highly effective in curing FIP without causing serious adverse effects. All cats that completed the short treatment course successfully were still in complete remission on day 168. Therefore, a shorter treatment duration of 42 days GS-441524 15 mg/kg can be considered equally effective.

Abstract Argumentation is crucial to fostering scientific reasoning and problem-solving in science education. However, researchers and teachers still report problems facilitating argumentation in the classroom. This may be influenced by the design of the corresponding professional development programs (PDPs) and the focus of the underlying research. To describe the state of the research regarding science teacher PDPs on facilitating argumentation, we systematically reviewed publications from the last 20 years in terms of their design, with selected low- and high-inference characteristics, for example, in terms of the addressed professional competence and the argumentation framework. The results illustrate a broad spectrum of teacher PDPs on argumentation in terms of formal-structural aspects (e.g., sample size) and interests (e.g., methodology). We found, for example, that pre-service teachers’ argumentation PDPs are less frequent than in-service teachers’ argumentation PDPs and that research rarely focuses on situation-specific competencies, such as professional vision or decision-making. Additionally, we report challenges in analyzing the argumentation framework and discuss possible reasons for this. We critically evaluate these and other findings, point to fruitful directions for further research and reviews, and inform practitioners of professional development of argumentation.

Objective: G-protein-coupled receptor (GPCR) kinases (GRKs) abrogate GPCR signaling by promoting receptor desensitization and internalization. Accumulating evidence suggests that GRK2 represents an important regulator of GPCR-mediated effects on systemic glucose metabolism, obesity, and insulin resistance. Despite the key role of the liver in maintaining euglycemia, the potential metabolic relevance of hepatic GRK2 has yet to be examined. Thus, the goal of this study was to explore the potential role of hepatic GRK2 in maintaining glucose homeostasis and other key metabolic functions. Methods: To address this question, we generated mice that showed a ∼90% reduction in GRK2 protein expression selectively in hepatocytes (Hep-GRK2-KO mice) and subjected these mice, together with their control littermates, to systematic metabolic phenotyping studies. Results: We found that Hep-GRK2-KO mice maintained on regular chow did not differ significantly from their control littermates in glycemia, glucose tolerance, insulin sensitivity, in vivo gluconeogenesis, and glucagon-induced hyperglycemia. We obtained similar findings when we analyzed Hep-GRK2-KO mice and control littermates consuming an obesogenic high-fat diet. Likewise, plasma levels of insulin, glucagon, free fatty acids, and ketone bodies remained unaffected by the lack of hepatocyte GRK2. The same was true when we examined the expression levels of key genes regulating hepatic glucose and fatty acid metabolism. Conclusion: In summary, our data suggest that hepatocyte GRK2 is dispensable for systemic glucose homeostasis and other key metabolic functions in both lean and obese mice. This finding suggests that drug development efforts aimed at inhibiting GRK2 to improve impaired glucose homeostasis and insulin sensitivity need to focus on other metabolically important tissues.

The article deals with the pedagogical content knowledge of mathematical modelling as part of the professional competence of pre-service teachers. With the help of a test developed for this purpose from a conceptual model, we examine whether this pedagogical content knowledge can be promoted in its different facets--especially knowledge about modelling tasks and about interventions--by suitable university seminars. For this purpose, the test was administered to three groups in a seminar for the teaching of mathematical modelling: (1) to those respondents who created their own modelling tasks for use with students; (2) to those trained to intervene in mathematical modelling processes; and (3) participating students who are not required to address mathematical modelling. The findings of the study--based on variance analysis--indicate that certain facets (knowledge of modelling tasks, modelling processes, and interventions) have increased significantly in both experimental groups but to varying degrees. By contrast, pre-service teachers in the control group demonstrated no significant change to their level of pedagogical content knowledge.

Therapeutic Area: ASCVD/CVD Risk Reduction Background: Elevated lipoprotein(a) [Lp(a)] is the most common inherited dyslipidemia leading to an increased risk of atherosclerotic cardiovascular disease (ASCVD). Several cohort studies have reported elevated Lp(a) prevalence in the general population; however, there is a paucity of data in those with established ASCVD. This sub-analysis of the Lp(a)HERITAGE study (NCT03887520) assessed Lp(a) levels in United States (US) participants with ASCVD, stratified by race, ethnicity, and sex. Methods: This cross-sectional study assessed the prevalence of elevated Lp(a) in adult participants (18–80 years of age) with a history of myocardial infarction or ischemic stroke ≥3 months to ≤10 years prior to enrollment (April 2019–July 2021) or symptomatic peripheral artery disease, across 192 US sites. Lp(a) and low-density lipid-cholesterol (LDL-C) levels were obtained using US central laboratory or historical data. Results: In total, 8,295 US participants were enrolled. The sub-analysis included 7,679 participants with Lp(a) measured in nmol/L, of which 66.4% were male, 80.5% were White, 16.9% were Black, and 8.0% had Hispanic ethnicity. Compared with the overall population, median Lp(a) was >2.5-fold higher in Black participants (132.0 vs 52.1 nmol/L) and was 21.8% lower in Hispanic participants (40.7 vs 52.1 nmol/L); in females, median Lp(a) levels were >1.5-fold higher than in male participants (69.4 vs 45.6 nmol/L) (Table). Overall, 33.3% of participants had Lp(a) ≥125 nmol/L. Prevalence of Lp(a) ≥125 nmol/L was highest among Black participants (52.0%) and lowest among Hispanic participants (25.6%); a greater proportion of females had Lp(a) ≥125 nmol/L compared with males (38.9% vs 30.4%) (Table). Conclusions: In the Lp(a)HERITAGE study, 33.3% of US participants with established ASCVD had Lp(a) levels ≥125 nmol/L. Compared with the overall population, the proportion of patients with Lp(a) ≥125 nmol/L was higher in Black (52.0%) and female (38.9%) participants and was lower in Hispanic participants (25.6%). These findings support more aggressive Lp(a) screening strategies among patients with established ASCVD, particularly female or Black patients. Furthermore, elevated Lp(a) levels can be used to inform the intensification of lifestyle and other risk factor management in clinical practice and may have implications for potential future therapies targeting Lp(a).

Abstract Background Three‐dimensional (3D) echocardiography and 2‐dimensional (2D) strain measurements of the right ventricle (RV) are important indices in humans with pulmonary hypertension (PH) and need further evaluation in dogs with PH. Objectives To evaluate various RV size and function indices in dogs with PH and to examine differences between pre‐ and postcapillary PH. Animals A total of 311 client‐owned dogs: 100 dogs with PH, 31 with postcapillary and 69 with precapillary PH, and 211 healthy control dogs. Methods Retro‐ and prospective, multicenter study. Size and function of the RV was determined using several indices, derived using dedicated RV software, including 3D RV end‐diastolic volume (EDVn), end‐systolic volume (ESVn), ejection fraction, 2D global and free wall RV longitudinal strain (RVLS), end‐diastolic area, end‐systolic area, fractional area change, tricuspid annular plane systolic excursion, and tissue Doppler imaging‐derived systolic myocardial velocity of the lateral tricuspid annulus (S′n). Results The EDVn (1.8 vs 2.5 mL/kg0.942, P

Abstract Background Reablement is a multi-professional and internationally established home-based health care service for mainly older people with the aim to reduce the need for long-term care and to promote self-determination. However, it is unknown which factors would facilitate the implementation of reablement in health care services. Therefore, the aim of this work was to identify relevant factors for the implementation process and to elucidate their importance based on the perspectives of experts. Methods Within an exploratory sequential mixed-methods design, a literature search followed by framework analysis was carried out using the five domains of the Consolidated Framework of Implementation Research (CFIR) to collect potentially relevant factors for implementation of reablement. A survey was then drawn up encompassing the factors identified. Within the survey international reablement – experts were asked to rate the relevance of these factors . Results The literature search identified 58 publications that served as sources for the framework analysis, where 40 potentially relevant factors were clustered into the five CFIR domains. These 40 factors were rated by experts in an online-survey. Based on the analysis of survey-data, 35 factors were considered as relevant for implementation of reablement services. The CFIR-domain characteristics of individuals, including teamwork and communication skills, was seen as most relevant. Conclusions The implementation of reablement services is complex and requires the consideration of numerous factors, especially regarding the CFIR-domain characteristics of individuals. From the perspective of the survey´s participants one important factor of a successful implementation was the engagement of the persons involved. It requires team members with a strong, shared vision. Communication skills are highly important to promote teamwork and intensive training is needed to establish these skills. Further research on the implementation of reablement services is essential to realize its full potential.

This paper utilizes the concept of the agency of material objects, proposed as a tenet by several historians of science in the late twentieth century. It argues that scientific instruments have agency in the field due to their value and fragility, both of which attributes served to dictate a social hierarchy of activity. Furthermore, the resulting numerical outputs served to discriminate between various groups. The principal focus is the role of instruments used by travellers sponsored by the Royal Geographical Society, London, but it also looks at the role of instruments on a larger triangulation; the project to survey the African part of the arc of the 30th meridian east of Greenwich. Seeing the instruments as material objects allows insights into the social arrangements and interactions taking place. It is argued that instruments, and the results of instrument use, entrenched existing power hierarchies, imparting greater prestige to those who were previously endowed with privilege. It is argued the instruments contributed to ‘othering’ both in the field and in the publications resulting from the expeditions. [ABSTRACT FROM AUTHOR]

The development of animal models reflecting the pathologies of ulcerative colitis (UC) and Crohn’s disease (CD) remains a major challenge. The NOD/SCID/IL2rγnull (NSG) mouse strain, which is immune-compromised, tolerates the engraftment of human peripheral blood mononuclear cells (PBMC) derived from patients with UC (NSG-UC) or CD (NSG-CD). This offers the opportunity to examine the impact of individual immunological background on the development of pathophysiological manifestations. When challenged with ethanol, NSG-UC mice exhibited a strong pro-inflammatory response, including the development of edemas, influx of human T cells, B cells and monocytes into the mucosa and submucosa, and elevated expression of the inflammatory markers CRP and CCL-7. Fibrotic alterations were characterized by an influx of fibroblasts and a thickening of the muscularis mucosae. In contrast, the development of pathological manifestations in NSG-CD mice developed without challenge and was signified by extensive collagen deposition between the muscularis propria and muscularis mucosae, as observed in the areas of strictures in CD patients. Vimentin-expressing fibroblasts supplanting colonic crypts and elevated expression of HGF and TGFß corroborated the remodeling phenotype. In summary, the NSG-UC and NSG-CD models partially reflect these human diseases and are powerful tools to examine the mechanism underlying the inflammatory processes in UC and CD.

Muscarinic acetylcholine receptors are well-known for their crucial involvement in hippocampus-dependent learning and memory, but the exact roles of the various receptor subtypes (M1–M5) are still not fully understood. Here, we studied how M1 and M3 receptors affect plasticity at the mossy fiber (MF)–CA3 pyramidal cell synapse. In hippocampal slices from M1/M3 receptor double knockout (M1/M3-dKO) mice, the signature short-term plasticity of the MF–CA3 synapse was not significantly affected. However, the rather unique NMDA receptor-independent and presynaptic form of long-term potentiation (LTP) of this synapse was much larger in M1/M3-deficient slices compared to wild-type slices in both field potential and whole-cell recordings. Consistent with its presynaptic origin, induction of MF-LTP strongly enhanced the excitatory drive onto single CA3 pyramidal cells, with the effect being more pronounced in M1/M3-dKO cells. In an earlier study, we found that the deletion of M2 receptors in mice disinhibits MF-LTP in a similar fashion, suggesting that endogenous acetylcholine employs both M1/M3 and M2 receptors to constrain MF-LTP. Importantly, such synergism was not observed for MF long-term depression (LTD). Low-frequency stimulation, which reliably induced LTD of MF synapses in control slices, failed to do so in M1/M3-dKO slices and gave rise to LTP instead. In striking contrast, loss of M2 receptors augmented LTD when compared to control slices. Taken together, our data demonstrate convergence of M1/M3 and M2 receptors on MF-LTP, but functional divergence on MF-LTD, with the net effect resulting in a well-balanced bidirectional plasticity of the MF–CA3 pyramidal cell synapse.

Abstract Background The benefits of pimobendan in the treatment of congestive heart failure (CHF) in cats with hypertrophic cardiomyopathy (HCM) have not been evaluated prospectively. Hypothesis/Objectives To investigate the effects of pimobendan in cats with HCM and recent CHF and to identify possible endpoints for a pivotal study. We hypothesized that pimobendan would be well‐tolerated and associated with improved outcome. Animals Eighty‐three cats with HCM and recently controlled CHF: 30 with and 53 without left ventricular outflow tract obstruction. Methods Prospective randomized placebo‐controlled double‐blind multicenter nonpivotal field study. Cats received either pimobendan (0.30 mg/kg q12h, n = 43), placebo (n = 39), or no medication (n = 1) together with furosemide (

Abstract Background Treatment is indicated in dogs with preclinical degenerative mitral valve disease (DMVD) and cardiomegaly (stage B2). This is best diagnosed using echocardiography; however, relying upon this limits access to accurate diagnosis. Objectives To evaluate whether cardiac biomarker concentrations can be used alongside other clinical data to identify stage B2 dogs. Animals Client‐owned dogs (n = 1887) with preclinical DMVD prospectively sampled in Germany, the United Kingdom, and the United States. Methods Dogs that met inclusion criteria and were not receiving pimobendan (n = 1245) were used for model development. Explanatory (multivariable logistic regression) and predictive models were developed using clinical observations, biochemistry, and cardiac biomarker concentrations, with echocardiographically confirmed stage B2 disease as the outcome. Receiver operating characteristic curves assessed the ability to identify stage B2 dogs. Results Age, appetite, serum alanine aminotransferase activity, body condition, serum creatinine concentration, murmur intensity, and plasma N‐terminal propeptide of B‐type natriuretic peptide (NT‐proBNP) concentration were independently associated with the likelihood of being stage B2. The discriminatory ability of this explanatory model (area under curve [AUC], 0.84; 95% confidence interval [CI], 0.82‐0.87) was superior to NT‐proBNP (AUC, 0.77; 95% CI, 0.74‐0.80) or the vertebral heart score alone (AUC, 0.76; 95% CI, 0.69‐0.83). A predictive logistic regression model could identify the probability of being stage B2 (AUC test set, 0.86; 95% CI, 0.81‐0.91). Conclusion and Clinical Importance Our findings indicate accessible measurements could be used to screen dogs with preclinical DMVD. Encouraging at‐risk dogs to seek further evaluation could result in a greater proportion of cases being appropriately managed.

Abstract Background Echocardiographic measurements play an important role in detecting cardiac enlargement and assessing cardiac function. In human cardiology, M‐mode measurements have been widely replaced by volumetric measurements of the left ventricle (LV) using Simpson's method of disc (SMOD). In veterinary cardiology, more large‐scale studies are necessary to generate reference intervals (RIs) for SMOD LV volume measurements. Objective To generate body size independent RIs for LV volume measurements in dogs. Animals Healthy adult dogs (n = 1331) of variable size and somatotype. Methods Prospective study. The SMOD was measured from the right parasternal long axis and the left apical 4‐chamber view in clinically healthy dogs. The SMOD measurements were normalized to various allometric scales (kg, kg2/3, or kg1/3). RIs for LV end‐diastolic volume (LVEDV) and LV end‐systolic volume (LVESV) using SMOD were estimated as prediction intervals of both a linear and an additive regression model. Additionally, after normalization to body weight, 95% RIs were determined using nonparametric methods with 2.5 and 97.5 percentiles serving as the lower and upper limits. Separate analyses were performed for 120 sighthound breeds and 1211 other breeds. Results Echocardiographic LV volumes correlated best with weight in kilograms. The additive model proved to be more flexible and accurate than the other 2 methods to generate RIs. Separate RIs for sighthound and all other breeds are provided. Conclusions and Clinical Importance Body size and breed‐independent RIs for LV volume measurements using SMOD were generated prospectively from a large and diverse population of dogs and are available for clinical use.