VariantscanR: an R-package as a clinical tool for variant filtering of known phenotype-associated variants in domestic animals.

BACKGROUND: Since the introduction of next-generation sequencing (NGS) techniques, whole-exome sequencing (WES) and whole-genome sequencing (WGS) have not only revolutionized research, but also diagnostics. The gradual switch from single gene testing to WES and WGS required a different set of skills, given the amount and type of data generated, while the demand for standardization remained. However, most of the tools currently available are solely applicable for human analysis because they require access to specific databases and/or simply do not support other species. Additionally, a complicating factor in clinical genetics in animals is that genetic diversity is often dangerously low due to the breeding history. Combined, there is a clear need for an easy-to-use, flexible tool that allows standardized data processing and preferably, monitoring of genetic diversity as well. To fill these gaps, we developed the R-package variantscanR that allows an easy and straightforward identification and prioritization of known phenotype-associated variants identified in dogs and other domestic animals. RESULTS: The R-package variantscanR enables the filtering of variant call format (VCF) files for the presence of known phenotype-associated variants and allows for the estimation of genetic diversity using multi-sample VCF files. Next to this, additional functions are available for the quality control and processing of user-defined input files to make the workflow as easy and straightforward as possible. This user-friendly approach enables the standardisation of complex data analysis in clinical settings. CONCLUSION: We developed an R-package for the identification of known phenotype-associated variants and calculation of genetic diversity.

Do locking plugs improve implant strength? Biomechanical comparison of polyaxial locking constructs with and without locking plugs in a fracture gap model.

BACKGROUND: The objective of this study was to investigate the effects of locking plugs and the biomechanical properties of a 3.5 mm 8-hole polyaxial locking plate in a fracture gap model. Our hypothesis was that locking plugs would increase the strength and stiffness of the construct. Twelve 3.5 mm 8-hole plates were used to evaluate two different construct designs (with locking plugs vs. without locking plugs) with validated bone substitutes in a 25 mm bridging osteosynthesis gap model. Each construct was subjected to a single cycle four-point bending load to failure using a servo-hydraulic testing machine. Bending stiffness, bending strength, and bending structural stiffness were calculated and compared using an unpaired Student´s t-test. RESULTS: The plating construct with locking plugs did not show any significant increase in terms of bending stiffness, bending strength, and bending structural stiffness compared to plating construct without locking plugs in a 25 mm gap fracture model during a single cycle four-point bending. CONCLUSIONS: Under the conditions tested, filling empty plate holes with locking plugs in bridging osteosynthesis does not increase stiffness or strength of the plate-bone construct.

Single energy metal artifact reduction performs better than virtual monoenergetic dual-energy reconstruction in CT of the equine proximal phalanx.

Metal artifacts in CT negatively impact the evaluation of surgical implants and the surrounding tissues. The aim of this prospective experimental study was to evaluate the ability of a single energy metal artifact reduction (SEMAR™, Canon) algorithm and virtual monoenergetic (VM) dual-energy CT (DECT) scanning techniques to reduce metal artifacts from stainless steel screws surgically inserted into the equine proximal phalanx. Seven acquisitions of 18 cadaver limbs were performed on a Canon Aquilion One Vision CT scanner (Helical +SEMAR, Volume +SEMAR, Standard Helical, Standard Volume and VM DECT at 135, 120, and 105 keV) and reconstructed in a bone kernel. Blinded subjective evaluation performed by three observers indicated a significant effect of acquisition in both adjacent tissues (P < 0.001) and distant tissues (P < 0.001) and the best metal artifact reduction was seen with Helical +SEMAR and Volume +SEMAR. The subjective overall preference of CT acquisition type was (1) Helical +SEMAR, (2) Volume +SEMAR, (3) VM DECT 135 keV, (4) VM DECT 120 keV, (5) VM DECT 105 keV, (6) Standard Helical, (7) Standard Volume (P < 0.001). Unblinded objective evaluation performed by one observer showed that VM DECT 120 keV, Helical +SEMAR, and Volume +SEMAR performed similarly and were objectively the best at reducing blooming artifact. Overall, the best metal artifact reduction was obtained with SEMAR, followed by VM DECT. However, VM DECT performance varies with energy level and was associated with decreased image quality in distant tissues and artifactual overcorrection of metal artifacts at high energy levels.

The TNNT2:c.95-108G>A variant is common in Maine Coons and shows no association with hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is a common and potentially fatal heart disease in many cat breeds. An intronic variant in TNNT2, c.95-108G>A, was recently reported as the cause of HCM in the Maine Coon. The aim of this study was to determine this variant's allele frequency in different populations and its possible association with HCM. Based on 160 Maine Coon samples collected in Belgium, Italy, Sweden and the USA, the variant's allele frequency was estimated to be 0.32. Analysis of the 99 Lives feline whole genome sequencing database showed that the TNNT2 variant also occurs in other breeds, as well as mixed-breed cats. Comparison of 31 affected and 58 healthy cats did not reveal significantly increased odds for HCM in homozygotes. Based on the combined evidence and in agreement with the standards and guidelines for the interpretation of sequence variants, this variant is currently classified as a variant of unknown significance and should not be used for breeding decisions regarding HCM.

Shear wave velocity measurements obtained in different regions are repeatable for presumed normal canine lymph nodes: A pilot study.

Shear wave elastography (SWE) has been applied as a noninvasive method for predicting regional lymph node (LN) metastases in human and veterinary patients. However, published studies describing standardized protocols and repeatability of this technique are currently lacking. The objective of this prospective, pilot, observer agreement study was to determine whether different shear wave velocity (SWV) measurements obtained in different regions of presumed normal canine LNs would be repeatable. Two imagers consecutively performed shear wave elastography of submandibular, superficial inguinal, and popliteal LNs in 10, clinically healthy adult dogs. Ten elastograms of each LN were acquired by each imager. In each adequate elastogram, three regions of interest (ROIs) were placed in the softest and stiffest region of the LN. Additionally, one ROI was drawn covering the entire LN. In each ROI, mean, median, and maximum SWVs were calculated. Mean values for the mean, median, and maximum SWVs varied from 2.33 to 3.10 m/s, 2.32 to 3.10 m/s, and 2.61 to 4.09 m/s, respectively. Intra- and interobserver agreements were acceptable. Superficial inguinal LNs demonstrated the highest intra- and interobserver agreement, followed by the popliteal and the submandibular LNs, respectively. Using the different measurements (mean, median, or maximum SWVs) had no significant effect on the intra- and interobserver variability, neither did the region (softest, stiffest, or entire LN). Findings indicated that all evaluated measurements and regions could be used to obtain reliable elastography data of presumed normal canine LNs. Clinical trials in dogs with cancer are necessary to compare SWVs of metastatic LNs with the reported SWVs and evaluate whether various measurements and regions can also be used in metastatic LNs.

Veterinarians' Competence in Applying Basic Genetic Principles and Daily Implementation of Clinical Genetics: A Study in a University Environment.

Veterinarian competency in genetics is vital for a meaningful application of the rapidly growing number of genetic tests available for animals. We evaluated the use of genetic tests in the daily veterinary practice and the competency of university-employed veterinarians in applying basic principles of genetics in a clinical setting through an electronic survey with 14 cases and 7 statements on genetics. Ninety-one non-geneticist veterinarians from two veterinary faculties in two different countries responded. Almost half of the participants apply genetic tests during their daily work, with frequencies varying between weekly and once a year. The most common indication to request a genetic test was diagnostic testing of clinically ill patients. Although 80% of the veterinarians communicated the result of a genetic test themselves, only 56% of them found it "very to rather easy" to find the correct test, and only 32% of them always felt competent to interpret the result of the test. The number of correctly answered questions varied widely, with median scores of 9/14 (range: 0-14) and 5/7 (range: 0-7) for the cases and statements, respectively. Most difficulties were seen with recognition of pedigree inheritance patterns, while veterinarians scored better in breeding advice and probability of disease estimations. Veterinarians scored best on questions related to autosomal recessive inheritance, followed by complex, autosomal dominant, X-linked recessive, and X-linked dominant inheritance. This study exposed pain points in veterinarians' knowledge and has led to the formulation of recommendations for future education and communication between laboratories, geneticists, and veterinarians.

High intake of sugars and starch, low number of meals and low roughage intake are associated with Equine Gastric Ulcer Syndrome in a Belgian cohort.

Equine gastric ulcer syndrome (EGUS) is a pathological condition affecting the glandular and squamous regions of the stomach. It is characterized by non-specific clinical signs, behavioural changes or can also be found without any overt clinical manifestations. Nutritional factors such as intermittent feeding, high sugars and starch intake, large amounts of straw as forage and prolonged time without access to forage have all been associated with an increased risk of equine squamous gastric disease (ESGD). The aim of this study was to investigate which nutritional practices are commonly seen in clinical ESGD cases in Belgium. Medical records of 27 horses referred to the equine nutritional service at Ghent University (2013-2018) due to equine gastric ulcer lesions were reviewed. Twenty-one healthy horses referred for dietary evaluation during the same period were selected as control cases (CC). Dietary evaluation was performed on an individual basis. Forage/concentrate ratio on dry matter basis, forage content in the diet, total dietary sugars and starch intake per day and per meal were analysed. Retrospective descriptive and statistical analyses were performed. Significantly, higher amounts of forage intake (%DM per BW) in the CC vs. ESGD group were noted (p ≤ .05) with average values of 1.39 (SD ± 0.27) and 1.27 (SD ± 0.70) respectively. There were no significant differences for sugars and starch intake in g/kg BW/day (p = .18). However, the sugars and starch intake per meal (g/kg BW/meal) in the CC group (average value 1.06, SD ± 0.56) was significantly (p < .001) lower than in the EGUS group (average value 1.85 SD ± 0.78). Forage intake below the recommended absolute minimum value as well as high sugars and starch intake were most commonly associated with EGUS in the present case series. An adequate diet formulation taking into account these main nutritional factors is therefore essential to avoid gastric problems in horses.

Veterinarians' Competence in Applying Basic Genetic Principles and Daily Implementation of Clinical Genetics: A Study in a University Environment.

Veterinarian competency in genetics is vital for a meaningful application of the rapidly growing number of genetic tests available for animals. We evaluated the use of genetic tests in the daily veterinary practice and the competency of university-employed veterinarians in applying basic principles of genetics in a clinical setting through an electronic survey with 14 cases and 7 statements on genetics. Ninety-one non-geneticist veterinarians from two veterinary faculties in two different countries responded. Almost half of the participants apply genetic tests during their daily work, with frequencies varying between weekly and once a year. The most common indication to request a genetic test was diagnostic testing of clinically ill patients. Although 80% of the veterinarians communicated the result of a genetic test themselves, only 56% of them found it "very to rather easy" to find the correct test, and only 32% of them always felt competent to interpret the result of the test. The number of correctly answered questions varied widely, with median scores of 9/14 (range 0-14) and 5/7 (range 0-7) for the cases and statements, respectively. Most difficulties were seen with recognition of pedigree inheritance patterns, while veterinarians scored better in breeding advice and probability of disease estimations. Veterinarians scored best on questions related to autosomal recessive inheritance, followed by complex, autosomal dominant, X-linked recessive, and X-linked dominant inheritance. This study exposed pain points in veterinarians' knowledge and has led to the formulation of recommendations for future education and communication between laboratories, geneticists, and veterinarians.

Transthoracic echocardiography and cardiac biomarkers in healthy captive male and female squirrel monkeys (Saimiri spp.).

BACKGROUND: Echocardiography is the most frequently used non -invasive diagnostic tool to evaluate cardiac anatomy and function in domestic species but increasingly also in non -domestic species, especially since cardiac disease is being recognized as an important cause of death in captive primates. The purpose of this cross -sectional study was to investigate the feasibility of transthoracic echocardiography in healthy squirrel monkeys as well as to provide species specific normal values for standard echocardiographic measurements. A secondary aim was to determine plasma and serum levels of the cardiac biomarkers, N -terminal pro -brain natriuretic peptide (NT -proBNP) and cardiac troponin T (cTnT). Furthermore, a commercial, non -invasive, smartphone -based ECG (AliveCor Vet TM) monitoring device was used to evaluate the heart rate and rhythm and to diagnose possible arrhythmias. RESULTS: In this study, transthoracic echocardiography of 14 squirrel monkeys was performed in right and left lateral recumbency. Similar standard right parasternal and left apical images were obtained as in dogs and cats and normal values for routine two -dimensional, time motion mode and Doppler mode measurements were generated. Thirteen animals were considered healthy and one squirrel monkey was identified with significant aortic dilation and regurgitation and consequently values obtained from this animal were not used when species specific normal values were calculated. NT -ProBNP and cTnT concentrations were available for 7 of the 13 healthy monkeys with NT -proBNP concentrations below detection limit in all animals and a mean cTnT concentration of 0.049 ng/mL. Electrocardiography was performed in all squirrel monkeys. The mean heart rate was 172 bpm. Frequent supraventricular premature beats were diagnosed in the squirrel monkey suffering from significant aortic dilation and regurgitation. CONCLUSION: This study presents echocardiographic normal values and additional cardiovascular data in anaesthetised Saimiri monkeys, fundamental from both the perspective of zoo animal health care as well as scientific research, since the squirrel monkey is often used as an animal model for human disease.

Dose-Dependent Effects of Dietary Xylooligosaccharides Supplementation on Microbiota, Fermentation and Metabolism in Healthy Adult Cats.

In order to investigate the effect and appropriate dose of prebiotics, this study evaluated the effect of two levels of xylooligosaccharides (XOS) in cats. Twenty-four healthy adult cats were divided into three groups: no-XOS control diet with 1% cellulose; low XOS supplementation (LXOS) with 0.04% XOS and 0.96% cellulose; and high XOS supplementation (HXOS) with 0.40% XOS and 0.60% cellulose. Both XOS groups increased blood 3-hydroxybutyryl carnitine levels and decreased hexadecanedioyl carnitine levels. Both XOS treatments displayed an increased bacterial abundance of Blautia, Clostridium XI, and Collinsella and a decreased abundance of Megasphaera and Bifidobacterium. LXOS groups increased fecal pH and bacterial abundance of Streptococcus and Lactobacillus, decreased blood glutaryl carnitine concentration, and Catenibacterium abundance. HXOS group showed a more distinct microbiome profile and higher species richness, and an increased bacterial abundance of Subdoligranulum, Ruminococcaceae genus (unassigned genus), Erysipelotrichaceae genus, and Lachnospiraceae. Correlations between bacterial abundances and blood and fecal parameters were also observed. In conclusion, XOS could benefit feline gut health by altering microbiota; its effects dependant on the dose. The higher-dose XOS increased bacterial populations that possibly promoted intestinal fermentation, while the lower dose altered populations of carbohydrate-metabolic microbiota and possibly modulated host metabolism. Low-dose prebiotics may become a trend in future studies.

THORACIC RADIOGRAPHY AND TRANSTHORACIC ECHOCARDIOGRAPHY IN CLINICALLY HEALTHY RING-TAILED LEMURS (LEMUR CATTA).

Cardiac disease has been recognized as a major cause of death in captive nonhuman primates, which necessitates diagnostic (imaging) techniques to screen for and diagnose preclinical and clinical stages of possible cardiac conditions. Echocardiography is currently the most commonly used diagnostic tool for evaluation of cardiac anatomy and function. Complete with thoracic radiography and blood levels of two cardiac biomarkers, N-terminal probrain natriuretic peptide (NT-proBNP) and cardiac troponin T (cTnT), it gives an extensive examination of the cardiorespiratory system. The purpose of this cross-sectional cohort study is to describe normal thoracic anatomy using thoracic radiography, and to provide normal values for echocardiographic measurements in 20 ring-tailed lemurs (Lemur catta). Additionally, cardiac biomarkers were determined. Three radiographic projections of the thoracic cavity and a complete transthoracic echocardiography were performed in 20 clinically healthy ring-tailed lemurs during their annual health examinations. Similar standard right parasternal and left apical echocardiographic images were obtained as described in dogs and cats and normal values for routine two-dimensional (2D-), time-motion (M-) and Doppler mode measurements were generated. Furthermore, a noninvasive smartphone base ECG recording and blood concentrations of cardiac biomarkers were obtained. Other radiographic measurements are provided for the skeletal and respiratory systems such as the trachea to inlet ratio and tracheal inclination. Knowledge of the normal radiographic thoracic and echocardiographic anatomy and function are fundamental for the diagnosis and follow-up of cardiac disease in affected individuals and for species screening, and will be of added value in future research in and conservation of this endangered species.

High-frequency ultrasound, computed tomography and computed tomography arthrography of the cranial cruciate ligament, menisci and cranial meniscotibial ligaments in 10 radiographically normal canine cadaver stifles.

BACKGROUND: Bilateral non-traumatic cranial cruciate disease is frequently seen in originally unilateral cruciate pathology. Untreated cranial cruciate ligament disease and concurrent meniscal lesions cause progressive osteoarthritis and pain of the stifle joint. Early presurgical diagnosis is important, but remains difficult. The purpose of this ex vivo study was (1) to describe the ultrasonographic appearance of the canine cranial cruciate ligament (CrCrL), menisci and meniscal ligaments using a high-frequency linear transducer, (2) to determine the length of the CrCrL seen on ultrasonography (US) and (3) to describe and compare the appearance of the CrCrL, menisci and meniscal ligaments on US, computed tomography (CT) and computed tomography arthrography (CTA). RESULTS: US and CT examinations were performed on 10 radiographically normal cadaveric stifles of adult dogs weighing more than 15 kg, followed by macroscopic and histologic evaluations. The CrCrL had a parallel hyperechoic fibrillar pattern at the insertion on the tibia and a hypoechoic structure more proximally in all stifles. This pattern was visible over 35% (median) of the total length of the ligament, with 50% (median) of the total length CrCrL that could be outlined. All medial menisci and 8 out of 10 of the lateral menisci showed hypoechoic lines within their bodies oriented obliquely to the direction of the ultrasound beam. Fifteen of the 20 cranial meniscotibial ligaments were detected, showing a hyperechoic fibrillar pattern. Normal macro- and microscopic appearance was observed in all menisci, with the radial bundles of collagen fibers at the level of and with similar orientation as the intrameniscal hypoechoic lines on US. The CrCrL, menisci and meniscal ligaments were of intermediate density on CT, but marked improvement of the border detection was obtained using CTA. Contrast within the CrCrL was observed in 4/10 stifles using CT and confirmed in 3/4 stifles on histology. One of these ligaments had a partial tear (5-10%) on macroscopic evaluation. None of the menisci showed any abnormalities on CTA. CONCLUSIONS: Normal canine menisci are heterogeneous on high-frequency US and a fibrillar pattern may be observed in the cranial meniscotibial ligaments and the distal portion of the CrCrL. Linear areas of contrast may be detected within the cranial cruciate ligament of radiographically normal stifles.

Renal perfusion parameters measured by contrast-enhanced ultrasound in healthy dogs demonstrate a wide range of variability in the long-term.

Contrast-enhanced ultrasound may be helpful for detecting early renal microvascular damage and dysfunction in dogs. However, before this noninvasive imaging method can be tested as an early-stage screening tool in clinical patients, an improved understanding of long-term variation in healthy animals is needed. In this prospective, secondary, longitudinal, serial measurements study, variability of contrast-enhanced ultrasound renal perfusion parameters was described for eight healthy dogs, using seven time points and a period of 83 weeks. Dogs were sedated with butorphanol (0.4 mg/kg), and contrast-enhanced ultrasound of each kidney was performed after an intravenous bolus injection of a microbubble contrast agent (0.04 mL/kg). Time-intensity curves were created from regions-of-interest drawn in the renal cortex and medulla. Intensity-related parameters representing blood volume and time-related parameters representing blood velocity were determined. A random-effects model using restricted maximum likelihood was used to estimate variance components. Within-dog coefficient of variation was defined as the ratio of the standard deviation over the mean. Time-related parameters such as time-to-peak, rise and fall time had lowest within-dog variability. Intensity-related parameters such as peak enhancement, wash-in and wash-out area under the curve, total area under the curve, and wash-in and washout rates had high within-dog variability (coefficient of variation > 45%). Authors therefore recommend the use of time-related parameters for future studies of renal perfusion. Within-dog variability for bilateral kidney measurements was extremely low, therefore contrast-enhanced ultrasound may be particularly useful for detecting unilateral changes in renal perfusion. Future studies are needed to compare contrast-enhanced ultrasound findings in healthy dogs versus dogs with renal disease.

Using variant databases for variant prioritization and to detect erroneous genotype-phenotype associations.

BACKGROUND: In the search for novel causal mutations, public and/or private variant databases are nearly always used to facilitate the search as they result in a massive reduction of putative variants in one step. Practically, variant filtering is often done by either using all variants from the variant database (called the absence-approach, i.e. it is assumed that disease-causing variants do not reside in variant databases) or by using the subset of variants with an allelic frequency > 1% (called the 1%-approach). We investigate the validity of these two approaches in terms of false negatives (the true disease-causing variant does not pass all filters) and false positives (a harmless mutation passes all filters and is erroneously retained in the list of putative disease-causing variants) and compare it with an novel approach which we named the quantile-based approach. This approach applies variable instead of static frequency thresholds and the calculation of these thresholds is based on prior knowledge of disease prevalence, inheritance models, database size and database characteristics. RESULTS: Based on real-life data, we demonstrate that the quantile-based approach outperforms the absence-approach in terms of false negatives. At the same time, this quantile-based approach deals more appropriately with the variable allele frequencies of disease-causing alleles in variant databases relative to the 1%-approach and as such allows a better control of the number of false positives. We also introduce an alternative application for variant database usage and the quantile-based approach. If disease-causing variants in variant databases deviate substantially from theoretical expectancies calculated with the quantile-based approach, their association between genotype and phenotype had to be reconsidered in 12 out of 13 cases. CONCLUSIONS: We developed a novel method and demonstrated that this so-called quantile-based approach is a highly suitable method for variant filtering. In addition, the quantile-based approach can also be used for variant flagging. For user friendliness, lookup tables and easy-to-use R calculators are provided.

Intra-arterial versus intra venous contrast-enhanced computed tomography of the equine head.

BACKGROUND: The anatomical complexity of the horse's head limits the abilities of radiography. Computed tomography (CT) in combination with contrast enhanced CT is used more often for diagnosing various head pathology in horses. The objective of this study was to compare intravenous and intra-arterial contrast-enhancement techniques and describe normal and abnormal contrast enhancement in the horse's head. RESULTS: All 24 horses included in the study recovered without complication from the procedures. Compared to the pre-contrast studies, post-contrast studies showed significant contrast enhancement in the pituitary gland (IA: p < 0.0001; IV: p < 0.0001), IA nose septum (p = 0.002), nose mucosa (IA: p < 0.0001; IV: p = 0.02), parotid salivary gland (IA: p < 0.0001; IV p < 0.0001), cerebrum (IA: p < 0.0001; IV: p < 0.0001), rectus capitis muscle (IA: p < 0.0001; IV p = 0.001), IA temporal muscle (p < 0.0001), IA masseter muscle (p <0.0001) and IV brainstem (p = 0.01). No significant contrast enhancement was seen in the eye (IA: p = 0.23; IV p = 0.33), tongue (IA p = 0.2; IV p = 0.57), IA brainstem (p = 0.88), IV nose septum (p = 0.26), IV temporal muscle (p = 0.09) and IV masseter muscle (p = 0.46). Three different categories of abnormal enhancement were detected: a strong vascularised mass, an enhanced rim surrounding an unenhanced structure and an inflamed anatomical structure with abnormal contrast enhancement. CONCLUSION: Using the intra-arterial technique, similar contrast enhancement is achieved using less contrast medium compared to the intravenous technique. And a potential major advantage of the IA technique is the ability to evaluate lesions that are characterized by increased blood flow. Using the intravenous technique, a symmetrical and homogenous enhancement is achieved, however timing is more crucial and the contrast dosage is more of influence in the IV protocol. And a potential major advantage of the IV technique is the ability to evaluate lesions that are characterized by increased vascular permeability. Knowing the different normal contrast enhancement patterns will facilitate the recognition of abnormal contrast enhancements.

COMPUTED TOMOGRAPHIC FINDINGS IN CANINE ELBOWS ARTHROSCOPICALLY DIAGNOSED WITH EROSION OF THE MEDIAL COMPARTMENT: AN ANALYTICAL METHOD COMPARISON STUDY.

Medial compartment erosion is an advanced stage of medial coronoid disease, an important cause of elbow lameness in dogs, with treatment and the expected prognosis depending on the extent of the cartilage lesions. The identification of specific computed tomographic (CT) findings might facilitate the nonsurgical diagnosis and add to treatment decision making. Aims of this retrospective, analytical, method comparison study were to describe CT findings in elbows of dogs arthroscopically diagnosed with medial compartment erosion and to compare CT vs. arthroscopic findings. A total of 56 elbows met inclusion criteria. Elbows with focal (n = 13), diffuse (n = 11), and complete (n = 32) erosion were compared. Prevalence findings for CT lesions were as follows: periarticular osteophytosis (100%), abnormal shape of the medial coronoid process of the ulna (96.4%), and subchondral bone defect of the medial part of the humeral condyle (MHC; 96.4%). The three groups significantly differed for presence of medial coronoid process fragmentation, radial head subchondral bone sclerosis, and widening of the humeroulnar joint space. No significant agreement was found between CT and arthroscopy for presence of a subchondral bone defect of the MHC. A significant agreement was found between CT and arthroscopy for presence of fragmentation of the medial coronoid process. However, some of the calcified body/fragment(s) visualized on CT in the region of the medial coronoid process could not be identified via arthroscopy. Findings indicated that an accurate estimation of the extent of the elbow cartilage lesions still requires arthroscopic joint inspection.

An heuristic filtering tool to identify phenotype-associated genetic variants applied to human intellectual disability and canine coat colors.

BACKGROUND: Identification of one or several disease causing variant(s) from the large collection of variants present in an individual is often achieved by the sequential use of heuristic filters. The recent development of whole exome sequencing enrichment designs for several non-model species created the need for a species-independent, fast and versatile analysis tool, capable of tackling a wide variety of standard and more complex inheritance models. With this aim, we developed "Mendelian", an R-package that can be used for heuristic variant filtering. RESULTS: The R-package Mendelian offers fast and convenient filters to analyze putative variants for both recessive and dominant models of inheritance, with variable degrees of penetrance and detectance. Analysis of trios is supported. Filtering against variant databases and annotation of variants is also included. This package is not species specific and supports parallel computation. We validated this package by reanalyzing data from a whole exome sequencing experiment on intellectual disability in humans. In a second example, we identified the mutations responsible for coat color in the dog. This is the first example of whole exome sequencing without prior mapping in the dog. CONCLUSION: We developed an R-package that enables the identification of disease-causing variants from the long list of variants called in sequencing experiments. The software and a detailed manual are available at https://github.com/BartBroeckx/Mendelian.

Intra- and interobserver agreement on radiographic phenotype in the diagnosis of canine hip dysplasia.

OBJECTIVE: To investigate the repeatability and reproducibility of the presence of a circumferential femoral head osteophyte (CFHO), a curvilinear caudolateral osteophyte (CCO), osteosclerosis of the cranial acetabular edge (Scler CrAE), degenerative joint disease (DJD), and the diagnosis of suspected canine hip dysplasia (CHD) in different groups of experienced observers. STUDY DESIGN: Cross-sectional study. SAMPLE POPULATION: Standard hip extended radiographs (n = 50). METHODS: Nine experienced observers were divided into 3 groups: surgeons (DECVS), radiologists (DECVDI), and non-board certified observers (NBC) and 2 subgroups (academics and non-academics). Cohen's kappa (κ) was calculated for CFHO, CCO, Scler CrAE, DJD, and suspected CHD, and weighted κ was calculated for DJD score to determine inter- and intraobserver agreement. RESULTS: Intraobserver agreement on CFHO, CCO, Scler CrAE, DJD, and suspected CHD ranged from slight to almost perfect, but was not significantly different between NBC, DECVS, and DECVDI. Radiologists and non-board certified observers had a more uniform scoring than surgeons on the overall DJD score, as did academics versus non-academics. Interobserver agreement for NBC was more uniform than that of radiologists and surgeons on CCO and DJD. NBC and radiologists scored more uniformly than surgeons on CFHO, and radiologists scored more uniformly than NBC and surgeons on Scler CrAE. Academics scored more uniformly than non-academics, but only significantly for Scler CrAE. CONCLUSIONS: Recognition of specific radiographic markers is only fairly reliable within and between experienced observers. Therefore, care must be taken to apply these traits in official screening, surgical decision-making and scientific research.

Quantifying the Stress in Stress Radiographs to Determine Sufficient Laxity of the Coxofemoral Joint: A Canine Hip Dysplasia Cadaveric Study.

OBJECTIVE: While it has been known for a long time that laxity in the hip joint is the primary cause of degenerative changes later on in canine hip dysplasia, limited data are available on the fundamental characteristics that define the procedure used to quantify this. The aim of this study was to evaluate the force-laxity relation to assess the repeatability of repeated cycles of stress on the hip joint and determine the force necessary tomeasure a sufficient proportion of laxity present in hip joints. MATERIALS AND METHODS: Thirty-four canine cadavers underwent a radiographic protocol including stress radiographs with increasing force using the Vezzoni modified Badertscher distension measuring device (VMBDmD). Three dogs underwent five repeat examinations. The laxity index (LI) and osteoarthritis were scored. RESULTS AND CONCLUSION: The curves and the maximal LI (LImax) were not significantly influenced by osteoarthritis, weight, gender, and side. The position of the VMBDmD influenced the curve but not the LImax. The force-laxity curve itself and the LImax were repeatable, which indicated that it did not cause permanent damage to the joint and also confirmed the practicability of the procedure. Ninety percent of hip joints reached sufficient laxity at a force of 95.32 N, which is realistically achievable. Further studies are necessary before extrapolating these results to patients and to further enlighten the biomechanics of stress radiographs.