Defining predictors of responsiveness to advanced therapies in Crohn's disease and ulcerative colitis: protocol for the IBD-RESPONSE and nested CD-metaRESPONSE prospective, multicentre, observational cohort study in precision medicine.

INTRODUCTION: Characterised by chronic inflammation of the gastrointestinal tract, inflammatory bowel disease (IBD) symptoms including diarrhoea, abdominal pain and fatigue can significantly impact patient's quality of life. Therapeutic developments in the last 20 years have revolutionised treatment. However, clinical trials and real-world data show primary non-response rates up to 40%. A significant challenge is an inability to predict which treatment will benefit individual patients.Current understanding of IBD pathogenesis implicates complex interactions between host genetics and the gut microbiome. Most cohorts studying the gut microbiota to date have been underpowered, examined single treatments and produced heterogeneous results. Lack of cross-treatment comparisons and well-powered independent replication cohorts hampers the ability to infer real-world utility of predictive signatures.IBD-RESPONSE will use multi-omic data to create a predictive tool for treatment response. Future patient benefit may include development of biomarker-based treatment stratification or manipulation of intestinal microbial targets. IBD-RESPONSE and downstream studies have the potential to improve quality of life, reduce patient risk and reduce expenditure on ineffective treatments. METHODS AND ANALYSIS: This prospective, multicentre, observational study will identify and validate a predictive model for response to advanced IBD therapies, incorporating gut microbiome, metabolome, single-cell transcriptome, human genome, dietary and clinical data. 1325 participants commencing advanced therapies will be recruited from ~40 UK sites. Data will be collected at baseline, week 14 and week 54. The primary outcome is week 14 clinical response. Secondary outcomes include clinical remission, loss of response in week 14 responders, corticosteroid-free response/remission, time to treatment escalation and change in patient-reported outcome measures. ETHICS AND DISSEMINATION: Ethical approval was obtained from the Wales Research Ethics Committee 5 (ref: 21/WA/0228). Recruitment is ongoing. Following study completion, results will be submitted for publication in peer-reviewed journals and presented at scientific meetings. Publications will be summarised at www.ibd-response.co.uk. TRIAL REGISTRATION NUMBER: ISRCTN96296121.

Clinical, electrophysiologic and serologic evidence of cancer associated retinopathy preceding a diagnosis of breast cancer.

We report the case of a woman in her 50s who presented headaches, blurred vision, diplopia and loss of peripheral vision. She was treated for normal tension glaucoma based on optic nerve cupping prior to the development of diplopia. Records demonstrated visual field constriction over 4 months despite well-controlled intraocular pressures. Examination revealed decreased visual acuity and visual field constriction. The multifocal electroretinogram was abnormal. After a thorough review of her medical and family history, a concern for cancer-associated retinopathy developed. Blood samples were positive for antiretinal antibodies against 23 kDA and 46 kDA proteins. Cancer screening was recommended as the aetiology for retinopathy was unknown and revealed a left breast lump. Following lumpectomy with adjuvant chemoradiation, her visual acuity normalised and visual field defects completely resolved. This case serves to provide an example that distant systemic symptoms may be a manifestation of the underlying malignancy and the importance of clinical suspicion with prompt evaluation.

Mixed-methods study exploring health service access and social support linkage to the mental well-being of Canadian Indigenous pregnant persons during the COVID-19 pandemic.

OBJECTIVES: This study aimed to explore how the unprecedented stressors associated with the COVID-19 pandemic may have contributed to heightened levels of depression and anxiety among pregnant Indigenous persons, and identify protective individual-level factors. DESIGN: The current study used a mixed-methods design including standardised questionnaires and open-ended response questions. Using hierarchical regression models, we examined the extent to which COVID-19-related factors of service disruption (ie, changes to prenatal care, changes to birth plans and social support) were associated with mental well-being. Further, through qualitative analyses of open-ended questions, we examined the coping strategies used by pregnant Indigenous persons in response to the pandemic. SETTING: Participants responded to an online questionnaire consisting of standardised measures from 2020 to 2021. PARTICIPANTS: The study included 336 self-identifying Indigenous pregnant persons in Canada. RESULTS: Descriptive results revealed elevated rates of clinically relevant depression (52.7%) and anxiety (62.5%) symptoms among this population. 76.8% of participants reported prenatal care service disruptions, including appointment cancellations. Thematic analyses identified coping themes of staying informed, social and/or cultural connections and activities, and internal mental well-being strategies. Disruptions to services and decreased quality of prenatal care negatively impacted mental well-being of Indigenous pregnant persons during the COVID-19 pandemic. CONCLUSIONS: Given the potential for mental well-being challenges to persist and long-term effects of perinatal distress, it is important to examine the quality of care that pregnant individuals receive. Service providers should advance policies and practices that promote relationship quality and health system engagement as key factors linked to well-being during the perinatal period for Indigenous persons.

Established and Emerging Research Trends in Norway Lobster, Nephrops norvegicus.

The burrowing crustacean decapod Nephrops norvegicus is a significant species in European Atlantic and Mediterranean fisheries. Research over the decades has mainly focused on behavioral and physiological aspects related to the burrowing lifestyle, since animals can only be captured by trawls when engaged in emergence on the seabed. Here, we performed a global bibliographic survey of all the scientific literature retrieved in SCOPUS since 1965, and terminology maps were produced with the VOSviewer software to reveal established and emerging research areas. We produced three term-map plots: term clustering, term citation, and term year. The term clustering network showed three clusters: fishery performance, assessment, and management; biological cycles in growth, reproduction, and behavior; and finally, physiology and ecotoxicology, including food products. The term citation map showed that intense research is developed on ecotoxicology and fishery management. Finally, the term year map showed that the species was first studied in its morphological and physiological aspects and more recently in relation to fishery and as a food resource. Taken together, the results indicate scarce knowledge on how burrowing behavior and its environmental control can alter stock assessment, because of the poor use of current and advanced monitoring technologies.

Surgical outcomes in only eye cataract surgery.

INTRODUCTION: Performing cataract surgery in the setting of only one seeing-eye has significant benefits but also potential negative consequences for both patient and surgeon. This study investigates the surgical outcomes in patients undergoing cataract surgery on their only seeing-eye. METHODS: A retrospective analysis was conducted in a single tertiary centre of all adult patients who had undergone cataract surgery on their only eye, where the fellow eye had a vision of 1.0 LogMAR or worse. Complication rates and visual outcomes were compared against data from the National Ophthalmology Database (NOD) Audit. RESULTS: 918 patients underwent cataract surgery on their only seeing-eye and had their postoperative visual acuity recorded. The overall unadjusted complication rate was 4.0% (versus 2.5% from NOD data) with the rate of posterior capsule rupture (PCR) being 1.9% (versus 1.14% from NOD data). 72.5% (versus 91.5% from NOD data) of patients attained a post-operative visual acuity of 0.3 LogMAR or better. The grade of surgeon performing the surgery did not have a statistically significant effect on the risk of complications. DISCUSSION: In this cohort of only-eye patients undergoing cataract surgery, there was a small increased risk of operative complications including an increased, unadjusted risk of PCR, and fewer eyes achieved 0.3 LogMAR vision post-operatively compared to the NOD audit data. Grade of surgeon did not have an impact on the complication rate, indicating that with appropriate supervision, trainee surgeons may gain experience in only-eye surgery without additional risk to the patient. Further multicentre studies are recommended to assess reproducibility across units.

Constructing Health State Descriptions for Low-Risk Thyroid Cancer: Stakeholder Engagement and Formative Qualitative Research.

OVERVIEW: This paper describes stakeholder involvement and formative qualitative research in the creation of health state descriptions (HSDs) or vignettes for low-risk thyroid cancer. The aim of this project was to engage stakeholders in the contribution of a novel set of HSDs, an important first step in the process of assessing value in thyroid cancer health states. METHODS: We draw upon formative, descriptive qualitative methods, following a multi-stage framework of data collection. We conducted individual semi-structured interviews, cognitive interviews, and focus groups with thyroid cancer patients, community providers, academic subspecialists, and participants with no thyroid cancer diagnosis (N = 31). The HSDs went through several iterations over the course of a year, in collaboration with a highly engaged community advisory board, laying the groundwork for HSDs that are comprehensible, comparable, and appropriate for stated-preference research. FINDINGS: Thyroid cancer survivors compared their experiences with those described in the HSDs. Feedback included concern for the emotional well-being of study participants who would be reading them. Providers were attuned to the need for clinical accuracy and made suggestions to reflect their clinical experience, including for patients with complications or disease progression. The pilot participants with no thyroid cancer were particularly valuable in promoting the need to simplify language and maximize readability. DISCUSSION: Stakeholder engagement was critical to being responsive to feedback as the iterations were refined and presented. Continuous engagement and consultation with multiple sources strengthened the HSDs. A secondary outcome from this project is that stakeholders expressed interest in adapting the HSDs into decision aids for people newly diagnosed with low-risk thyroid cancer.

An overview of international genetic evaluations of show jumping in sport horses.

The breeding of sport horses to compete in the Olympic disciplines of show jumping, eventing, and dressage is fast becoming a global industry with the increased use of reproductive technologies, including artificial insemination and embryo transfer. Reproductive technologies have facilitated the dissemination of genetics from elite horses across multiple countries and breeds as breeders are no longer limited by location. Due to this increased level of crossbreeding, there is an increased need for estimated breeding values (EBVs) for sport horse performance that can be compared across breeds and countries. However, the implementation of across-breed or across-country genetic evaluations has been limited by the differences in each studbook's individual breeding programs and genetic evaluations. Consequently, the aim of this review was to compare the genetic evaluations for show jumping of sport horse studbooks worldwide. The top sport horse studbooks in the world according to the World Breeding Federation for Sport Horses Studbook Rankings 2019 were contacted by email to request information on their current breeding programs and genetic evaluations. Twenty-six of the 51 studbooks contacted replied to this request but only 18 of these studbooks conducted their own genetic evaluations or were part of a larger genetic evaluation in their country of origin. The other eight studbooks were not involved in genetic evaluations at present but expressed an interest in the implementation of such in the future. Overall, many differences were identified among the genetic evaluations of each studbook or each country. The definition of show jumping performance differed within each evaluation and the methods and models utilized also differed. Despite some stallions and mares being registered in multiple studbooks or having progeny in multiple studbooks, these differences make comparison of EBVs across studbooks difficult. Further transparency and collaboration of sport horse studbooks with organizations such as Interstallion, will be essential to facilitate any future implementation of international genetic evaluations for show jumping performance.

Mobilising a workforce to combat COVID-19: An account, reflections, and lessons learned.

With the declaration of coronavirus 2019 (COVID-19) as a pandemic, intensive care units across the globe began to prepare for large numbers of patients. For many years, UK Intensive Care Units (ICUs) have been at high capacity, while facing staffing shortages. In order to prepare for the predicted increased work caring for large numbers with COVID-19, staff were redeployed from other clinical areas to help. Many of these staff had no previous ICU experience. In this article, we share our experiences redeploying medical staff from an extensive range of backgrounds, and how we utilised those staff to maximise use of their existing skills, together with reflections from a variety of redeployed staff members.

The Quality of Operative Performance Narrative Feedback: A Retrospective Data Comparison Between End of Rotation Evaluations and Workplace-based Assessments.

OBJECTIVE: To describe the quality of operative performance feedback using evaluation tools commonly used by general surgery residency training programs. SUMMARY OF BACKGROUND DATA: The majority of surgical training programs administer an evaluation through which faculty members may rate and comment on trainee operative performance at the end of the rotation (EOR). Many programs have also implemented the system for improving and measuring procedural learning (SIMPL), a workplace-based assessment tool with which faculty can rate and comment on a trainee's operative performance immediately after a case. It is unknown how the quality of narrative operative performance feedback delivered with these tools compares. METHODS: The authors collected EOR evaluations and SIMPL narrative comments on trainees' operative performance from 3 university-based surgery training programs during the 2016-2017 academic year. Two surgeon raters categorized comments relating to operative skills as being specific or general and as encouraging and/or corrective. Comments were then classified as effective, mediocre, ineffective, or irrelevant. The frequencies with which comments were rated as effective were compared using Chi-square analysis. RESULTS: The authors analyzed a total of 600 comments. 10.7% of EOR and 58.3% of SIMPL operative performance evaluation comments were deemed effective (P < 0.0001). CONCLUSIONS: Evaluators give significantly higher quality operative performance feedback when using workplace-based assessment tools rather than EOR evaluations.

Development and Application of a Semi quantitative Scoring Method for Ultrastructural Assessment of Acute Stress in Pancreatic Islets.

BACKGROUND: Pancreas and islet transplantation outcomes are negatively impacted by injury to the endocrine cells from acute stress during donor death, organ procurement, processing, and transplant procedures. Here, we report a novel electron microscopy scoring system, the Newcastle Pancreas Endocrine Stress Score (NPESS). METHODS: NPESS was adapted and expanded from our previously validated method for scoring pancreatic exocrine acinar cells, yielding a 4-point scale (0-3) classifying ultrastructural pathology in endocrine cell nuclei, mitochondria, endoplasmic reticulum, cytoplasmic vacuolization, and secretory granule depletion, with a maximum additive score of 15. We applied NPESS in a cohort of deceased organ donors after brainstem (DBD) and circulatory (DCD) death with a wide range of cold ischemic times (3.6-35.9 h) including 3 donors with type 1 and 3 with type 2 diabetes to assess islets in situ (n = 30) in addition to pancreata (n = 3) pre- and postislet isolation. RESULTS: In DBD pancreata, NPESS correlated with cold ischemic time (head: r = 0.55; P = 0.02) and mirrored exocrine score (r = 0.48; P = 0.01). When stratified by endocrine phenotype, cells with granules of heterogeneous morphology had higher scores than α, ß, and δ cells (P < 0.0001). Cells of mixed endocrine-exocrine morphology were observed in association with increased NPESS (P = 0.02). Islet isolation was associated with improved NPESS (in situ: 8.39 ± 0.77 [Mean ± SD]; postisolation: 5.44 ± 0.31; P = 0.04). CONCLUSIONS: NPESS provides a robust method for semiquantitative scoring of subcellular ultrastructural changes in human pancreatic endocrine cells in situ and following islet isolation with utility for unbiased evaluation of acute stress in organ transplantation research.

Diagnostic Evaluation of Visual Snow.

Introduction: To determine which patients with visual snow (VS) and VS syndrome (VSS) require standard ophthalmologic testing including automated visual field and which patients require further testing such as macular spectral domain optical coherence tomography (SD-OCT), electrophysiology, and neuroimaging. Materials and Methods: We retrospectively reviewed 52 consecutive patients at three institutions with VS and VSS including the University of Alabama, Callahan Eye Hospital, the University of Missouri-Kansas City School of Medicine, and the Little Rock Eye Clinic from the years 2015 to 2021. We collected historical information, examination findings, ophthalmic testing, electrophysiology, and neuroimaging. Results: Of the 52 patients with VS and VSS, eight of the 52 cases met the clinical criteria for VSS. The ages ranged from 7 to 79 years, with a mean age of 25 years (SD = 14.0). There were 22 males and 30 females. Color vision was tested in 51 cases and was normal in 47 cases (92%). A funduscopic exam was performed in all 52 cases and was normal in 46 cases (88%). The macular SD-OCT was normal in all of the 19 cases that it was performed (100%). A Humphrey visual field was performed in 50 cases and was normal in 43 (86%). A visually evoked potential (VEP) was normal in 18 of the 19 cases where it was obtained (95%). The full-field electroretinography (ffERG) was obtained in 28 cases and was normal in 25 (89%). The multifocal electroretinography (mfERG) was normal in 11 of 12 cases (92%). Only four patients accounted for all of the abnormal electrophysiological tests. In the 37 cases that had an MRI, 29 were normal (78%). Only one patient revealed a lesion in the visual pathway (right optic nerve enhancement in an optic neuritis patient). Conclusions: Patients with VS and VSS, if typical in presentation and with normal testing, do not require a workup beyond a thorough history, neuro-ophthalmologic examination, and automated perimetry. If this testing is abnormal, then ancillary testing is required.

Burrow emergence rhythms of Nephrops norvegicus by UWTV and surveying biases.

Underwater Television (UWTV) surveys provide fishery-independent stock size estimations of the Norway lobster (Nephrops norvegicus), based directly on burrow counting using the survey assumption of "one animal = one burrow". However, stock size may be uncertain depending on true rates of burrow occupation. For the first time, 3055 video transects carried out in several Functional Units (FUs) around Ireland were used to investigate this uncertainty. This paper deals with the discrimination of burrow emergence and door-keeping diel behaviour in Nephrops norvegicus, which is one of the most commercially important fisheries in Europe. Comparisons of burrow densities with densities of visible animals engaged in door-keeping (i.e. animals waiting at the tunnel entrance) behaviour and animals in full emergence, were analysed at time windows of expected maximum population emergence. Timing of maximum emergence was determined using wave-form analysis and GAM modelling. The results showed an average level of 1 visible Nephrops individual per 10 burrow systems, depending on sampling time and depth. This calls into question the current burrow occupancy assumption which may not hold true in all FUs. This is discussed in relation to limitations of sampling methodologies and new autonomous robotic technological solutions for monitoring.

Identification of genomic regions that exhibit sexual dimorphism for size and muscularity in cattle.

Sexual dimorphism, the phenomenon whereby males and females of the same species are distinctive in some aspect of appearance or size, has previously been documented in cattle for traits such as growth rate and carcass merit using a quantitative genetics approach. No previous study in cattle has attempted to document sexual dimorphism at a genome level; therefore, the objective of the present study was to determine whether genomic regions associated with size and muscularity in cattle exhibited signs of sexual dimorphism. Analyses were undertaken on 10 linear-type traits that describe the muscular and skeletal characteristics of both males and females of five beef cattle breeds: 1,444 Angus (AA), 6,433 Charolais (CH), 1,129 Hereford, 8,745 Limousin (LM), and 1,698 Simmental. Genome-wide association analyses were undertaken using imputed whole-genome sequence data for each sex separately by breed. For each single-nucleotide polymorphism (SNP) that was segregating in both sexes, the difference between the allele substitution effect sizes for each sex, in each breed separately, was calculated. Suggestively (P ≤ 1 × 10-5) sexually dimorphic SNPs that were segregating in both males and females were detected for all traits in all breeds, although the location of these SNPs differed by both trait and breed. Significantly (P ≤ 1 × 10-8) dimorphic SNPs were detected in just three traits in the AA, seven traits in the CH, and three traits in the LM. The vast majority of all segregating autosomal SNPs (86% in AA to 94% in LM) had the same minor allele in both males and females. Differences (P ≤ 0.05) in allele frequencies between the sexes were observed for between 36% (LM) and 66% (AA) of the total autosomal SNPs that were segregating in both sexes. Dimorphic SNPs were located within a number of genes related to muscularity and/or size including the NAB1, COL5A2, and IWS1 genes on BTA2 that are located close to, and thought to be co-inherited with, the MSTN gene. Overall, sexual dimorphism exists in cattle at the genome level, but it is not consistent by either trait or breed.

Development and validation of a quantitative electron microscopy score to assess acute cellular stress in the human exocrine pancreas.

The pancreas is particularly sensitive to acute cellular stress, but this has been difficult to evaluate using light microscopy. Pancreatic ischaemia associated with deceased organ donation negatively impacts whole-organ and isolated-islet transplantation outcomes. Post-mortem changes have also hampered accurate interpretation of ante-mortem pancreatic pathology. A rigorous histological scoring system accurately quantifying ischaemia is required to experimentally evaluate innovations in organ preservation and to increase rigour in clinical/research evaluation of underlying pancreatic pathology. We developed and validated an unbiased electron microscopy (EM) score of acute pancreatic exocrine cellular stress in deceased organ donor cohorts (development [n = 28] and validation [n = 16]). Standardised assessment led to clearly described numerical scores (0-3) for nuclear, mitochondrial and endoplasmic reticulum (ER) morphology and intracellular vacuolisation; with a maximum (worst) aggregate total score of 12. In the Validation cohort, a trend towards higher scores was observed for tail versus head regions (nucleus score following donation after brainstem death [DBD]: head 0.67 ± 0.19; tail 0.86 ± 0.11; p = 0.027) and donation after circulatory death (DCD) versus DBD (mitochondrial score: DCD (head + tail) 2.59 ± 0.16; DBD (head + tail) 2.38 ± 0.21; p = 0.004). Significant mitochondrial changes were seen ubiquitously even with short cold ischaemia, whereas nuclear and vacuolisation changes remained mild even after prolonged ischaemia. ER score correlated with cold ischaemia time (CIT) following DBD (pancreatic tail region: r = 0.796; p = 0.018). No relationships between CIT and EM scores were observed following DCD. In conclusion, we have developed and validated a novel EM score providing standardised quantitative assessment of subcellular ultrastructural morphology in pancreatic acinar cells. This provides a robust novel tool for gold standard measurement of acute cellular stress in studies evaluating surrogate measures of peri-transplant ischaemia, organ preservation technologies and in samples obtained for detailed pathological examination of underlying pancreatic pathology.

Cardiovascular and Metabolic Responses to Carbon Dioxide Euthanasia in Conscious and Anesthetized Rats.

Euthanasia is a necessary component in research and must be conducted humanely. Currently, regulated CO2 exposure in conscious rats is acceptable, but data are divided on whether CO2 alone is more distressing than anesthesia prior to CO2. To evaluate distress in rats, we compared physiologic responses to CO2 euthanasia with and without isoflurane preanesthesia. Male Sprague-Dawley rats were implanted with telemetry devices to measure mean arterial pressure (MAP), heart rate (HR), and blood glucose. Animals recovered for 2 wk and were then exposed to either 5% isoflurane (n = 6) or 100% CO2 (n = 7; calculated 30% chamber volume/min displacement) in their home cages to induce loss of consciousness. Euthanasia was then completed with CO2 in both groups. MAP and HR increased when the gas delivery lids were placed on the home cages of both groups. Both MAP and HR gradually decreased with isoflurane exposure. MAP increased and HR decreased with CO2 exposure. Glucose levels remained stable throughout the procedure, except for a small drop in conscious animals initially exposed to 100% CO2. These data suggest that both gases affect the measured parameters in a similar manner, and that environmental factors, such as gas delivery lid placement, also change these measurements.

Genetic control of temperament traits across species: association of autism spectrum disorder risk genes with cattle temperament.

BACKGROUND: Temperament traits are of high importance across species. In humans, temperament or personality traits correlate with psychological traits and psychiatric disorders. In cattle, they impact animal welfare, product quality and human safety, and are therefore of direct commercial importance. We hypothesized that genetic factors that contribute to variation in temperament among individuals within a species will be shared between humans and cattle. Using imputed whole-genome sequence data from 9223 beef cattle from three cohorts, a series of genome-wide association studies was undertaken on cattle flight time, a temperament phenotype measured as the time taken for an animal to cover a short-fixed distance after release from an enclosure. We also investigated the association of cattle temperament with polymorphisms in bovine orthologs of risk genes for neuroticism, schizophrenia, autism spectrum disorders (ASD), and developmental delay disorders in humans. RESULTS: Variants with the strongest associations were located in the bovine orthologous region that is involved in several behavioural and cognitive disorders in humans. These variants were also partially validated in independent cattle cohorts. Genes in these regions (BARHL2, NDN, SNRPN, MAGEL2, ABCA12, KIFAP3, TOPAZ1, FZD3, UBE3A, and GABRA5) were enriched for the GO term neuron migration and were differentially expressed in brain and pituitary tissues in humans. Moreover, variants within 100 kb of ASD susceptibility genes were associated with cattle temperament and explained 6.5% of the total additive genetic variance in the largest cattle cohort. The ASD genes with the most significant associations were GABRB3 and CUL3. Using the same 100 kb window, a weak association was found with polymorphisms in schizophrenia risk genes and no association with polymorphisms in neuroticism and developmental delay disorders risk genes. CONCLUSIONS: Our analysis showed that genes identified in a meta-analysis of cattle temperament contribute to neuron development functions and are differentially expressed in human brain tissues. Furthermore, some ASD susceptibility genes are associated with cattle temperament. These findings provide evidence that genetic control of temperament might be shared between humans and cattle and highlight the potential for future analyses to leverage results between species.

Echocardiographic and hemodynamic indices of myocardial contractility simultaneously evaluated in telemetered beagle dogs: A HESI-sponsored cross-company evaluation.

INTRODUCTION: Alterations in cardiac contractility can have significant clinical implications, highlighting the need for early detection of potential liabilities. Pre-clinical methods to assess contractility are typically invasive and their translation to human measures of cardiac function are not well defined. Clinically, cardiac function is most often measured non-invasively using echocardiography. The objective of these studies was to introduce echocardiography into standard large animal cardiovascular safety pharmacology studies and determine the feasibility of this combination. METHODS: A consortia of laboratories combined their data sets for evaluation. At each site, telemetered beagle dogs, in a 4 × 4 Latin square crossover study design (n = 4), were administered either pimobendan (positive inotrope) or atenolol (negative inotrope) orally at clinically relevant dose levels. Standard telemetry parameters were collected (heart rate, mean arterial blood pressure, etc.) continuously over 24 h, as well as derived contractility endpoints: QA interval and LV +dP/dtmax. At Tmax, echocardiography was performed in conscious dogs with minimal restraint to collect contractility parameters: ejection fraction (EF) and fractional shortening (FS). RESULTS: Correlations between telemetry and echo contractility endpoints showed that, in general, a change in LV +dP/dtmax of 1000 mmHg/s translates to a 5.2% change in EF and a 4.2% change in FS. Poor correlations were shown between QA interval derived simultaneously, to both EF and FS. DISCUSSION: Comparing data from telemetry-only groups to those that included echocardiography collections showed no effect in the ability to interpret test article-related effects, providing the foundation for the inclusion of echocardiography without compromising standard telemetry data quality.

Genomic Regions Associated With Skeletal Type Traits in Beef and Dairy Cattle Are Common to Regions Associated With Carcass Traits, Feed Intake and Calving Difficulty.

Linear type traits describing the skeletal characteristics of an animal are moderately to strongly genetically correlated with a range of other performance traits in cattle including feed intake, reproduction traits and carcass merit; thus, type traits could also provide useful insights into the morphological differences among animals underpinning phenotypic differences in these complex traits. The objective of the present study was to identify genomic regions associated with five subjectively scored skeletal linear traits, to determine if these associated regions are common in multiple beef and dairy breeds, and also to determine if these regions overlap with those proposed elsewhere to be associated with correlated performance traits. Analyses were carried out using linear mixed models on imputed whole genome sequence data separately in 1,444 Angus, 1,129 Hereford, 6,433 Charolais, 8,745 Limousin, 1,698 Simmental, and 4,494 Holstein-Friesian cattle, all scored for the linear type traits. There was, on average, 18 months difference in age at assessment of the beef versus the dairy animals. While the majority of the identified quantitative trait loci (QTL), and thus genes, were both trait-specific and breed-specific, a large-effect pleiotropic QTL on BTA6 containing the NCAPG and LCORL genes was associated with all skeletal traits in the Limousin population and with wither height in the Angus. Other than that, little overlap existed in detected QTLs for the skeletal type traits in the other breeds. Only two QTLs overlapped the beef and dairy breeds; both QTLs were located on BTA5 and were associated with height in both the Angus and the Holstein-Friesian, despite the difference in age at assessment. Several detected QTLs in the present study overlapped with QTLs documented elsewhere that are associated with carcass traits, feed intake, and calving difficulty. While most breeding programs select for the macro-traits like carcass weight, carcass conformation, and feed intake, the higher degree of granularity with selection on the individual linear type traits in a multi-trait index underpinning the macro-level goal traits, presents an opportunity to help resolve genetic antagonisms among morphological traits in the pursuit of the animal with optimum performance metrics.