A Systematic Review of Delayed High-Grade Atrioventricular Block After Transcatheter Aortic Valve Implantation.

Background: High-grade atrioventricular block (HGAVB) is common after transcatheter aortic valve implantation (TAVI), often necessitating permanent pacemaker (PPM) implantation. Delayed HGAVB has varying definitions but typically refers to onset 48 hours after TAVI or following discharge and may cause syncope and sudden cardiac death. This review estimates the incidence of delayed HGAVB and identifies limitations of current literature. Methods: A systematic review was performed of the following online databases: Medline, Cochrane, Web of Science, and Scopus. Studies that labelled the outcome of "delayed" or "late" atrioventricular block after TAVI were included; patients with previous PPM or aortic valve surgery were excluded. Initial search yielded 775 studies, which, after screening, was narrowed to 19 studies. Results: Nineteen studies with 14,898 patients were included. Mean age was 81.7 years, and 46.3% were male. Mean Society of Thoracic Surgeons (STS) score was 5.6%, and 31.3% of patients had known atrial fibrillation. The most common access site was transfemoral (84.8%), whereas balloon-expandable valves were used in 62.1%, self-expanding valves in 34.0%, and mechanically expanding valves in 3.9% of cases. The incidence of delayed HGAVB ranged from 1.7% to 14.6%, with significant methodologic heterogeneity noted among the included studies. Conclusions: Delayed HGAVB is a common and potentially serious complication of TAVI, with similar risk factors to acute HGAVB. With a move toward an early discharge strategy post-TAVI, further prospective study of delayed HGAVB is warranted to improve understanding of predisposing factors, incidence, timing, and implications.

Contexte: L'apparition d'un bloc atrioventriculaire de haut degré (BAVHD) est fréquente après l'implantation valvulaire aortique par cathéter (IVAC), ce qui nécessite souvent l'implantation d'un stimulateur cardiaque permanent. Les définitions d'un BAVHD tardif varient, mais elles font habituellement référence à l'apparition du bloc 48 heures après l'IVAC ou après le congé de l'hôpital. Le bloc peut alors provoquer une syncope et une mort subite d'origine cardiaque. Cette analyse vise à estimer l'incidence de la formation d'un BAVHD tardif et à définir les lacunes dans les publications actuelles. Méthodologie: Une analyse des études publiées dans les bases de données en ligne suivantes a été menée : Medline, Cochrane, Web of Science et Scopus. Les études dont le libellé comprenait l'issue du bloc atrioventriculaire tardif ou éloigné (« delayed ¼ ou « late ¼) ont été retenues. Les patients qui avaient antérieurement reçu un stimulateur cardiaque permanent ou subi une intervention chirurgicale de la valve aortique ont été exclus. La recherche initiale a permis de recenser 775 études, nombre qui a été réduit à 19 après l'application des critères de sélection. Résultats: Dix-neuf études totalisant 14 898 patients ont été retenues. L'âge moyen était 81,7 ans, et 46,3 % des patients étaient des hommes. Le score STS (Society of Thoracic Surgeons) moyen était de 5,6 %, et 31,3 % des patients avaient une fibrillation auriculaire. Le point d'accès le plus fréquent était par l'artère fémorale (84,8 %). Des valves expansibles par ballonnet ont été utilisées dans 62,1 % des cas, des valves auto-expansibles dans 34,0 % des cas et des valves expansibles mécaniquement dans 3,9 % des cas. L'incidence du BAVHD tardif variait de 1,7 % à 14,6 %, mais la méthodologie était très hétérogène d'une étude à l'autre. Conclusions: Le BAVHD tardif est une complication fréquente et potentiellement grave de l'IVAC, et ses facteurs de risque sont comparables à ceux du BAVHD aigu. Étant donné la volonté d'adopter une stratégie de congé précoce après une IVAC, une autre étude prospective sur le BAVHD tardif s'impose pour mieux comprendre les facteurs prédisposants, l'incidence, la chronologie et les implications.

Machine learning to identify endometrial biomarkers predictive of pregnancy success following artificial insemination in dairy cows.

The objective was to identify a set of genes whose transcript abundance is predictive of a cow's ability to become pregnant following artificial insemination (AI). Endometrial epithelial cells from the uterine body were collected for RNA sequencing using the cytobrush method from 193 first-service Holstein cows at estrus prior to AI (day 0). A group of 253 first-service cows not used for cytobrush collection were controls. There was no effect of cytobrush collection on pregnancy outcomes at day 30 or 70 or on pregnancy loss between day 30 and 70. There were 2 upregulated and 214 downregulated genes (FDR < 0.05, absolute fold change >2-fold) for cows pregnant at day 30 versus those that were not pregnant. Functional terms overrepresented in the downregulated genes included those related to immune and inflammatory responses. Machine learning for fertility biomarkers with the R package BORUTA resulted in identification of 57 biomarkers that predicted pregnancy outcome at day 30 with an average accuracy of 77%. Thus, machine learning can identify predictive biomarkers of pregnancy in endometrium with high accuracy. Moreover, sampling of endometrial epithelium using the cytobrush can help understand functional characteristics of the endometrium at AI without compromising cow fertility. Functional characteristics of the genes comprising the set of biomarkers is indicative that a major determinant of cow fertility, at least for first insemination after calving, is immune status of the uterus, which, in turn, is likely to reflect the previous history of uterine disease.

Node-degree aware edge sampling mitigates inflated classification performance in biomedical random walk-based graph representation learning.

Motivation: Graph representation learning is a family of related approaches that learn low-dimensional vector representations of nodes and other graph elements called embeddings. Embeddings approximate characteristics of the graph and can be used for a variety of machine-learning tasks such as novel edge prediction. For many biomedical applications, partial knowledge exists about positive edges that represent relationships between pairs of entities, but little to no knowledge is available about negative edges that represent the explicit lack of a relationship between two nodes. For this reason, classification procedures are forced to assume that the vast majority of unlabeled edges are negative. Existing approaches to sampling negative edges for training and evaluating classifiers do so by uniformly sampling pairs of nodes. Results: We show here that this sampling strategy typically leads to sets of positive and negative examples with imbalanced node degree distributions. Using representative heterogeneous biomedical knowledge graph and random walk-based graph machine learning, we show that this strategy substantially impacts classification performance. If users of graph machine-learning models apply the models to prioritize examples that are drawn from approximately the same distribution as the positive examples are, then performance of models as estimated in the validation phase may be artificially inflated. We present a degree-aware node sampling approach that mitigates this effect and is simple to implement. Availability and implementation: Our code and data are publicly available at https://github.com/monarch-initiative/negativeExampleSelection.

Meta-analysis to determine efficacy of colony-stimulating factor 2 for improving pregnancy success after embryo transfer in cattle.

Results have been inconsistent as to whether addition of colony stimulating factor 2 (CSF2) to culture medium improves embryo competence for establishment of pregnancy in cattle and humans. The purpose of the current study was to use all available experiments in cattle concerning effects of CSF2 on pregnancy success after transfer into recipient cattle. The approach was to perform a meta-analysis of all published data sets as well as data from an unpublished experiment described for the first time here. Meta-analysis failed to support the hypothesis that addition of CSF2 to embryo culture medium improves competence of bovine blastocysts to increase pregnancy or calving rates after transfer into recipient females. Thus, its general use as a culture medium additive to increase pregnancy success after embryo transfer is not recommended.

NPSV-deep: a deep learning method for genotyping structural variants in short read genome sequencing data.

MOTIVATION: Structural variants (SVs) play a causal role in numerous diseases but can be difficult to detect and accurately genotype (determine zygosity) with short-read genome sequencing data (SRS). Improving SV genotyping accuracy in SRS data, particularly for the many SVs first detected with long-read sequencing, will improve our understanding of genetic variation. RESULTS: NPSV-deep is a deep learning-based approach for genotyping previously reported insertion and deletion SVs that recasts this task as an image similarity problem. NPSV-deep predicts the SV genotype based on the similarity between pileup images generated from the actual SRS data and matching SRS simulations. We show that NPSV-deep consistently matches or improves upon the state-of-the-art for SV genotyping accuracy across different SV call sets, samples and variant types, including a 25% reduction in genotyping errors for the Genome-in-a-Bottle (GIAB) high-confidence SVs. NPSV-deep is not limited to the SVs as described; it improves deletion genotyping concordance a further 1.5 percentage points for GIAB SVs (92%) by automatically correcting imprecise/incorrectly described SVs. AVAILABILITY AND IMPLEMENTATION: Python/C++ source code and pre-trained models freely available at https://github.com/mlinderm/npsv2.

The ability of contemporary cardiologists to judge the ischemic impact of a coronary lesion visually

BACKGROUND: Landmark trials showed that invasive pressure measurement (Fractional Flow Reserve, FFR) was a better guide to coronary stenting than visual assessment. However, present-day interventionists have benefited from extensive research and personal experience of mapping anatomy to hemodynamics. AIMS: To determine if visual assessment of the angiogram performs as well as invasive measurement of coronary physiology. METHODS: 25 interventional cardiologists independently visually assessed the single vessel coronary disease of 200 randomized participants in The Objective Randomized Blinded Investigation with optimal medical Therapy of Angioplasty in stable angina trial (ORBITA). They gave a visual prediction of the FFR and Instantaneous Wave-free Ratio (iFR), denoted vFFR and viFR respectively. Each judged each lesion on 2 occasions, so that every lesion had 50 vFFR, and 50 viFR assessments. The group consensus visual estimates (vFFR-group and viFR-group) and individual cardiologists' visual estimates (vFFR-individual and viFR-individual) were tested alongside invasively measured FFR and iFR for their ability to predict the placebo-controlled reduction in stress echo ischemia with stenting. RESULTS: Placebo-controlled ischemia improvement with stenting was predicted by vFFR-group (p < 0.0001) and viFR-group (p < 0.0001), vFFR-individual (p < 0.0001) and viFR-individual (p < 0.0001). There were no significant differences between the predictive performance of the group visual estimates and their invasive counterparts: p = 0.53 for vFFR vs FFR and p = 0.56 for viFR vs iFR. CONCLUSION: Visual assessment of the angiogram by contemporary experts, provides significant additional information on the amount of ischaemia which can be relieved by placebo-controlled stenting in single vessel coronary artery disease.

The importance of nonobstructive plaque characteristics in symptomatic and asymptomatic coronary artery disease.

BACKGROUND: We examined obstructive and nonobstructive plaque volumes in populations with subclinical and clinically manifested coronary artery disease (CAD) using quantitative computed tomography (QCT). METHODS: 855 participants with CAD (274 asymptomatic individuals, 254 acute chest pain patients without acute coronary syndrome (ACS), and 327 patients with ACS) underwent QCT of proximal coronary segments to assess participant-level plaque volumes of dense calcium, fibrous, fibrofatty, and necrotic core tissue. RESULTS: Nonobstructive (<50% stenosis) plaque volumes were greater than obstructive plaque volumes, irrespective of population (all p<0.0001): Asymptomatic individuals (mean (95% CI)): 218 [190-250] vs. 16 [12-22] mm3; acute chest pain patients without ACS: 300 [263-341] vs. 51 [41-62] mm3; patients with ACS: 370 [332-412] vs. 159 [139-182] mm3. After multivariable adjustment, nonobstructive fibrous and fibrofatty tissue volumes were greater in acute chest pain patients without ACS compared to asymptomatic individuals (fibrous tissue: 122 [107-139] vs. 175 [155-197] mm3, p<0.01; fibrofatty tissue: 44 [38-50] vs. 71 [63-80] mm3, p<0.01. Necrotic core tissue was greater in ACS patients (29 [26-33] mm3) compared to both asymptomatic individuals (15 [13-18] mm3, p<0.0001) and acute chest pain patients without ACS (21 [18-24] mm3, p<0.05). Nonobstructive dense calcium volumes did not differ between the three populations: 29 [24-36], 29 [23-35], and 41 [34-48] mm3, p>0.3 respectively. CONCLUSION: Nonobstructive CAD was the predominant contributor to total atherosclerotic plaque volume in both subclinical and clinically manifested CAD. Nonobstructive fibrous, fibrofatty and necrotic core tissue volumes increased with worsening clinical presentation, while nonobstructive dense calcium tissue volumes did not.

The ability of contemporary cardiologists to judge the ischemic impact of a coronary lesion visually.

BACKGROUND: Landmark trials showed that invasive pressure measurement (Fractional Flow Reserve, FFR) was a better guide to coronary stenting than visual assessment. However, present-day interventionists have benefited from extensive research and personal experience of mapping anatomy to hemodynamics. AIMS: To determine if visual assessment of the angiogram performs as well as invasive measurement of coronary physiology. METHODS: 25 interventional cardiologists independently visually assessed the single vessel coronary disease of 200 randomized participants in The Objective Randomized Blinded Investigation with optimal medical Therapy of Angioplasty in stable angina trial (ORBITA). They gave a visual prediction of the FFR and Instantaneous Wave-free Ratio (iFR), denoted vFFR and viFR respectively. Each judged each lesion on 2 occasions, so that every lesion had 50 vFFR, and 50 viFR assessments. The group consensus visual estimates (vFFR-group and viFR-group) and individual cardiologists' visual estimates (vFFR-individual and viFR-individual) were tested alongside invasively measured FFR and iFR for their ability to predict the placebo-controlled reduction in stress echo ischemia with stenting. RESULTS: Placebo-controlled ischemia improvement with stenting was predicted by vFFR-group (p < 0.0001) and viFR-group (p < 0.0001), vFFR-individual (p < 0.0001) and viFR-individual (p < 0.0001). There were no significant differences between the predictive performance of the group visual estimates and their invasive counterparts: p = 0.53 for vFFR vs FFR and p = 0.56 for viFR vs iFR. CONCLUSION: Visual assessment of the angiogram by contemporary experts, provides significant additional information on the amount of ischaemia which can be relieved by placebo-controlled stenting in single vessel coronary artery disease.

Anesthesiologists' skills in emergency cricothyroidotomy mandate a brush-up training after 3 months-A randomized controlled trial.

BACKGROUND: In the Difficult Airway Society's 2015 "cannot intubate, cannot oxygenate" guideline, the emergency cricothyroidotomy is the final option when managing an unanticipated difficult airway. How often training for maintenance of this skill is required for anesthesiologists remains unknown. We aimed to assess if specialist-trained anesthesiologists' skills improved from a brush-up intervention and if skills were retained after 3 months. METHODS: In this multicenter, randomized, controlled trial, participants were randomized to either a simulation-based brush-up or no brush-up. Both groups performed a mannequin-based technical skills emergency cricothyroidotomy test twice and were assessed by a blinded rater using a structured assessment tool that included time, positioning, palpation, appropriate employment of instruments, and stepwise progression. After 3 months of non-training, participants completed identical tests of retention. RESULTS: A total of 54 anesthesiologists were included from three hospitals in the Region of Southern Denmark. Thirty-seven percent of the participants had received skills training in emergency cricothyroidotomy in the prior 12 months. The intervention group (N = 27) performed better in the initial tests, with a mean time of 51.5 s (SD = 10.82), a total score per minute of 15.9 points (SD = 4.91), and 93% passing both initial tests compared to the control group (N = 27) with a mean time of 76.8 s (SD = 35.82), a total score per minute of 6.6 (SD = 4.68) and only 15% passing both initial tests. The intervention group managed to retain overall performance in retention tests in terms of performance time (48.9 s, p = .26), total score per minute (13.6 points, p = .094), and passing the tests (75%, p = .059). CONCLUSION: Exposure to simulation-based brush-up training in emergency cricothyroidotomy improved anesthesiologists' technical performance and was overall retained after 3 months. Some loss of skill concerning specific items was observed, highlighting the need for regular training in emergency cricothyroidotomy. Simulation-based training should be prioritized to improve and maintain technical skills in infrequent high-stakes procedures.

Ambulance and helicopter response time. Association with patient outcome and illness severity: Protocol of a systematic literature review and meta-analysis.

BACKGROUND: Response time for emergency medical service units is a key performance indicator. Studies have shown reduced response time association with improved outcome for specific critical conditions. To achieve short response time, emergency vehicles utilize lights and sirens, and crews are allowed to be non-compliant with traffic rules, posing a risk for accident. The purpose of the systematic review and meta-analysis is to provide an overview of the current body of evidence regarding the association, if any, between ambulance and helicopter response time and major complications and mortality in patients conveyed by ambulance and/or helicopter. Our secondary aim will be to enhance knowledge in the field of criteria-based dispatch to provide decision makers with evidence to optimize dispatch of limited resources. RESEARCH QUESTIONS: What is the association between overall emergency medical services unit response time and patient outcomes, major complications, and time-critical conditions? What is the internal and external validity of the included literature? METHODS: We plan the systematic review and meta-analysis to be in accordance with the Cochrane Handbook and Joanna Briggs Institute Manual for Systematic Reviews. The methodology will include formulating the review questions using a Population, Exposure, and Outcome framework. Every study design is eligible, including qualitative, quantitative, and mixed-methods designs. We will include all articles in English, Scandinavian, German, French and Portuguese in this systematic review. RESULTS: We will publish results from the systematic review and meta-analysis in a peer-reviewed journal and we will present the results at scientific conferences and meetings. Results will also be available at www.ahrtemis.dk. CONCLUSION: We will base our conclusions on the findings of the review and meta-analysis.

The effect of lacosamide in peripheral neuropathic pain: A randomized, double-blind, placebo-controlled, phenotype-stratified trial.

BACKGROUND: Neuropathic pain is common and difficult to treat. The sodium channel blocker lacosamide is efficacious in animal models of pain, but its effect on neuropathic pain in humans is inconclusive. METHODS: In a multicentre, randomized, double-blinded placebo-controlled phenotype stratified trial, we examined if lacosamide produced better pain relief in patients with the irritable nociceptor phenotype compared to those without. The primary outcome was the change in daily average pain from baseline to last week of 12 weeks of treatment. Secondary and tertiary outcomes included pain relief, patient global impression of change and presence of 30% and 50% pain reduction. RESULTS: The study was prematurely closed with 93 patients included and 63 randomized to lacosamide or placebo in a 2:1 ratio, of which 49 fulfilled the per protocol criteria and was used for the primary objective. We did not find a better effect of lacosamide in patients with the irritable nociceptor phenotype, the 95% CI for the primary objective was 0.41 (-1.2 to 2.0). For all patients randomized, lacosamide had no effect on the primary outcome, but significantly more patients were responders to lacosamide than during placebo, with an NNT of 4.0 (95% CI 2.3-16.1) and 5.0 (95% CI 2.8-24.5) for 30% and 50% pain reduction respectively. We did not identify any predictors for response. Lacosamide was generally well tolerated. CONCLUSION: We could not confirm that lacosamide was more efficacious in patients with the irritable nociceptor type, but the study was prematurely closed, so we cannot exclude a small difference. SIGNIFICANCE: Treatment of neuropathic pain is often a trial and error process. Little is known about which patient benefit from which kind of medication. The sodium channel blocker lacosamide shows variable effect on neuropathic pain. Pain sensory phenotype, as defined by quantitative sensory testing, did not predict response to treatment with lacosamide.

The function of alternative splicing in the proteome: rewiring protein interactomes to put old functions into new contexts.

Alternative splicing affects more than 95% of multi-exon genes in the human genome. These changes affect the proteome in a myriad of ways. Here, we review our understanding of the breadth of these changes from their effect on protein structure to their influence on interactions. These changes encompass effects on nucleic acid binding in the nucleus to protein-carbohydrate interactions in the extracellular milieu, altering interactions involving all major classes of biological molecules. Protein isoforms have profound influences on cellular and tissue physiology, for example, by shaping neuronal connections, enhancing insulin secretion by pancreatic beta cells and allowing for alternative viral defense strategies in stem cells. More broadly, alternative splicing enables repurposing proteins from one context to another and thereby contributes to both the evolution of new traits as well as the creation of disease-specific interactomes that drive pathological phenotypes. In this Review, we highlight this universal character of alternative splicing as a central regulator of protein function with implications for almost every biological process.

Molnupiravir Revisited-Critical Assessment of Studies in Animal Models of COVID-19.

Molnupiravir, a prodrug known for its broad antiviral activity, has demonstrated efficacy in animal models of COVID-19, prompting clinical trials, in which initial results indicated a significant effect against the disease. However, subsequent clinical studies did not confirm these findings, leading to the refusal of molnupiravir for permanent market authorization in many countries. This report critically assessed 22 studies published in 18 reports that investigated the efficacy of molnupiravir in animal models of COVID-19, with the purpose of determining how well the design of these models informed human studies. We found that the administered doses of molnupiravir in most studies involving animal COVID-19 models were disproportionately higher than the dose recommended for human use. Specifically, when adjusted for body surface area, over half of the doses of molnupiravir used in the animal studies exceeded twice the human dose. Direct comparison of reported drug exposure across species after oral administration of molnupiravir indicated that the antiviral efficacy of the dose recommended for human use was underestimated in some animal models and overestimated in others. Frequently, molnupiravir was given prophylactically or shortly after SARS-CoV-2 inoculation in these models, in contrast to clinical trials where such timing is not consistently achieved. Furthermore, the recommended five-day treatment duration for humans was exceeded in several animal studies. Collectively, we suggest that design elements in the animal studies under examination contributed to a preference favoring molnupiravir, and thus inflated expectations for its efficacy against COVID-19. Addressing these elements may offer strategies to enhance the clinical efficacy of molnupiravir for the treatment of COVID-19. Such strategies include dose increment, early treatment initiation, administration by inhalation, and use of the drug in antiviral combination therapy.

Association of intraosseous and intravenous access with patient outcome in out-of-hospital cardiac arrest.

Here we report the results of a study on the association between drug delivery via intravenous route or intraosseous route in out-of-hospital cardiac arrest. Intraosseous drug delivery is considered an alternative option in resuscitation if intravenous access is difficult or impossible. Intraosseous uptake of drugs may, however, be compromised. We have performed a retrospective cohort study of all Danish patients with out-of-hospital cardiac arrest in the years 2016-2020 to investigate whether mortality is associated with the route of drug delivery. Outcome was 30-day mortality, death at the scene, no prehospital return of spontaneous circulation, and 7- and 90-days mortality. 17,250 patients had out-of-hospital cardiac arrest. 6243 patients received no treatment and were excluded. 1908 patients had sustained return of spontaneous circulation before access to the vascular bed was obtained. 2061 patients were unidentified, and 286 cases were erroneously registered. Thus, this report consist of results from 6752 patients. Drug delivery by intraosseous route is associated with increased OR of: No spontaneous circulation at any time (OR 1.51), Death at 7 days (OR 1.94), 30 days (2.02), and 90 days (OR 2.29). Intraosseous drug delivery in out-of-hospital cardiac arrest is associated with overall poorer outcomes than intravenous drug delivery.

What made primary health care resilient against COVID-19? A mixed-methods positive deviance study in Nigeria.

INTRODUCTION: The SARS-CoV-2 (COVID-19) pandemic overwhelmed some primary health care (PHC) systems, while others adapted and recovered. In Nigeria, large, within-state variations existed in the ability to maintain PHC service volumes. Identifying characteristics of high-performing local government areas (LGAs) can improve understanding of subnational health systems resilience. METHODS: Employing a sequential explanatory mixed-methods design, we quantitatively identified 'positive deviant' LGAs based on their speed of recovery of outpatient and antenatal care services to prepandemic levels using service volume data from Nigeria's health management information system and matched them to comparators with similar baseline characteristics and slower recoveries. 70 semistructured interviews were conducted with LGA officials, facility officers and community leaders in sampled LGAs to analyse comparisons based on Kruk's resilience framework. RESULTS: A total of 57 LGAs were identified as positive deviants out of 490 eligible LGAs that experienced a temporary decrease in PHC-level outpatient and antenatal care service volumes. Positive deviants had an average of 8.6% higher outpatient service volume than expected, and comparators had 27.1% lower outpatient volume than expected after the initial disruption to services. Informants in 12 positive deviants described health systems that were more integrated, aware and self-regulating than comparator LGAs. Positive deviants were more likely to employ demand-side adaptations, whereas comparators primarily focused on supply-side adaptations. Barriers included long-standing financing and PHC workforce gaps. CONCLUSION: Sufficient flexible financing, adequate PHC staffing and local leadership enabled health systems to recover service volumes during COVID-19. Resilient PHC requires simultaneous attention to bottom-up and top-down capabilities connected by strong leadership.

Recurrent Valve Frame Infolding in the 34mm Self-Expanding Medtronic Evolut Pro+ Transcatheter Valve System: A Single Centre Experience.

BACKGROUND: Valve frame infolding (VFI) is a rare complication (1-3%) of transcatheter aortic valve implantation (TAVI), which primarily occurs in large sized self-expanding valves. We report the incidence of VFI in a small group of patients with highly calcified and extra-large aortic annuli, who underwent implantation of the newer generation 34mm Medtronic Evolut Pro+ (EP+) valve system. METHODS: A retrospective review was conducted on all patients presenting to a single centre experienced with TAVI in Sydney, NSW, Australia, between June and October 2022, for transfemoral TAVI using the Medtronic 34mm EP+ valve system. VFI was diagnosed using fluoroscopy, and pre-procedure computed tomography (CT) was analysed offline. RESULTS: VFI occurred in four of 10 patients who underwent TAVI using the 34mm EP+ system. Between VFI and non-VFI patients, the annular size, aortic angulation and total calcium volume was similar. Calcium distribution between the coronary cusps was symmetrical in non-VFI patients (37%, 33% and 30%), compared to 52% in the non-coronary cusp (NCC) in VFI patients. The mean ellipticity index was higher in VFI versus non-VFI patients (22% vs 14%). CONCLUSION: The 34mm Medtronic EP+ valve system is vital for safe and effective treatment of a niche subgroup of patients with extra-large annuli and extensive calcification, however operators should be aware of the increased incidence of VFI. Heavy eccentric calcification at the NCC, as well as using the cusp-overlap implant technique may exacerbate VFI, while multiplanar fluoroscopic screening may improve recognition.

Identification of quantitative trait loci and associated candidate genes for pregnancy success in Angus-Brahman crossbred heifers.

BACKGROUND: In beef cattle, more than 50% of the energy input to produce a unit of beef is consumed by the female that produced the calf. Development of genomic tools to identify females with high genetic merit for reproductive function could increase the profitability and sustainability of beef production. RESULTS: Genome-wide association studies (GWAS) were performed using a single-step genomic best linear unbiased prediction approach on pregnancy outcome traits from a population of Angus-Brahman crossbred heifers. Furthermore, a validation GWAS was performed using data from another farm. Heifers were genotyped with the Bovine GGP F250 array that contains 221,077 SNPs. In the discovery population, heifers were bred in winter breeding seasons involving a single round of timed artificial insemination (AI) followed by natural mating for 3 months. Two phenotypes were analyzed: pregnancy outcome to first-service AI (PAI; n = 1,481) and pregnancy status at the end of the breeding season (PEBS; n = 1,725). The heritability was estimated as 0.149 and 0.122 for PAI and PEBS, respectively. In the PAI model, one quantitative trait locus (QTL), located between 52.3 and 52.5 Mb on BTA7, explained about 3% of the genetic variation, in a region containing a cluster of γ-protocadherin genes and SLC25A2. Other QTLs explaining between 0.5% and 1% of the genetic variation were found on BTA12 and 25. In the PEBS model, a large QTL on BTA7 was synonymous with the QTL for PAI, with minor QTLs located on BTA5, 9, 10, 11, 19, and 20. The validation population for pregnancy status at the end of the breeding season were Angus-Brahman crossbred heifers bred by natural mating. In concordance with the discovery population, the large QTL on BTA7 and QTLs on BTA10 and 12 were identified. CONCLUSIONS: In summary, QTLs and candidate SNPs identified were associated with pregnancy outcomes in beef heifers, including a large QTL associated with a group of protocadherin genes. Confirmation of these associations with larger populations could lead to the development of genomic predictions of reproductive function in beef cattle. Moreover, additional research is warranted to study the function of candidate genes associated with QTLs.

The Field's mass shooting: emergency medical services response.

BACKGROUND: Major incidents (MI) happen infrequently in Scandinavia and mass shootings are even less frequently occurring. Case reports and research are called for, as literature is scarce. On 3rd July 2022, a mass shooting took place at the shopping mall Field's in Copenhagen, Denmark. Three people were killed and seven injured by a gunman, firing a rifle inside the mall. A further 21 people suffered minor injuries during the evacuation of the mall. In this case report, we describe the emergency medical services (EMS) incident response and evaluate the EMS´ adherence to the MI management guidelines to identify possible areas of improvement. CASE PRESENTATION: Forty-eight EMS units including five Tactical Emergency Medical Service teams were dispatched to the incident. Four critically injured patients were taken to two trauma hospitals. The deceased patients were declared dead at the scene and remained there for the sake of the investigation. A total of 24 patients with less severe and minor injuries were treated at four different hospitals in connection with the attack. The ambulance resources were inherently limited in the initial phase of the MI, mandating improvisation in medical incident command. Though challenged, Command and Control, Safety, Communication, Assessment, Triage, Treatment, Transport (CSCATTT) principles were followed. CONCLUSIONS: The EMS response generally adhered to national guidelines for MI. The activation of EMS and the hospital preparedness program was relevant. Important findings were communication shortcomings; inherent lack of readily available ambulance resources in the initial critical phase; uncertainty regarding the number of perpetrators; uncertainty regarding number of casualties and social media rumors that unnecessarily hampered and prolonged the response. The incident command had to use non-standard measures to mitigate potential challenges.