Passenger Mutations in More Than 2,500 Cancer Genomes: Overall Molecular Functional Impact and Consequences.

The dichotomous model of "drivers" and "passengers" in cancer posits that only a few mutations in a tumor strongly affect its progression, with the remaining ones being inconsequential. Here, we leveraged the comprehensive variant dataset from the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) project to demonstrate that-in addition to the dichotomy of high- and low-impact variants-there is a third group of medium-impact putative passengers. Moreover, we also found that molecular impact correlates with subclonal architecture (i.e., early versus late mutations), and different signatures encode for mutations with divergent impact. Furthermore, we adapted an additive-effects model from complex-trait studies to show that the aggregated effect of putative passengers, including undetected weak drivers, provides significant additional power (∼12% additive variance) for predicting cancerous phenotypes, beyond PCAWG-identified driver mutations. Finally, this framework allowed us to estimate the frequency of potential weak-driver mutations in PCAWG samples lacking any well-characterized driver alterations.

The Genetic Discrimination Observatory: confronting novel issues in genetic discrimination.

Genetic discrimination (GD) is the differential or unfair profiling of an individual on the basis of genetic data. This article summarizes the actions of the Genetic Discrimination Observatory (GDO) in addressing GD and recent developments in GD since late 2020. It shows how GD can take many forms in today's rapidly evolving society.

Global longitudinal strain and plasma biomarkers for prognosis in heart failure complicated by diabetes: a prospective observational study.

BACKGROUND: Heart failure (HF) and diabetes are associated with increased incidence and worse prognosis of each other. The prognostic value of global longitudinal strain (GLS) measured by cardiovascular magnetic resonance (CMR) has not been established in HF patients with diabetes. METHODS: In this prospective, observational study, consecutive patients (n = 315) with HF underwent CMR at 3T, including GLS, late gadolinium enhancement (LGE), native T1, and extracellular volume fraction (ECV) mapping. Plasma biomarker concentrations were measured including: N-terminal pro B-type natriuretic peptide(NT-proBNP), high-sensitivity troponin T(hs-TnT), growth differentiation factor 15(GDF-15), soluble ST2(sST2), and galectin 3(Gal-3). The primary outcome was a composite of all-cause mortality or HF hospitalisation. RESULTS: Compared to those without diabetes (n = 156), the diabetes group (n = 159) had a higher LGE prevalence (76 vs. 60%, p < 0.05), higher T1 (1285±42 vs. 1269±42ms, p < 0.001), and higher ECV (30.5±3.5 vs. 28.8±4.1%, p < 0.001). The diabetes group had higher NT-pro-BNP, hs-TnT, GDF-15, sST2, and Gal-3. Diabetes conferred worse prognosis (hazard ratio (HR) 2.33 [95% confidence interval (CI) 1.43-3.79], p < 0.001). In multivariable Cox regression analysis including clinical markers and plasma biomarkers, sST2 alone remained independently associated with the primary outcome (HR per 1 ng/mL 1.04 [95% CI 1.02-1.07], p = 0.001). In multivariable Cox regression models in the diabetes group, both GLS and sST2 remained prognostic (GLS: HR 1.12 [95% CI 1.03-1.21], p = 0.01; sST2: HR per 1 ng/mL 1.03 [95% CI 1.00-1.06], p = 0.02). CONCLUSIONS: Compared to HF patients without diabetes, those with diabetes have worse plasma and CMR markers of fibrosis and a more adverse prognosis. GLS by CMR is a powerful and independent prognostic marker in HF patients with diabetes.

Is there an OAHI or O2 nadir that predicts the need for preoperative echocardiogram prior to adenotonsillectomy for children with severe obstructive sleep apnea?

PURPOSE: To investigate threshold values for obstructive apnea-hypopnea index (OAHI) and nadir oxygen saturation (NspO2) in children with severe obstructive sleep apnea (OSA) to identify children most appropriate for preoperative echocardiography. METHODS: A multi-institutional retrospective chart review was performed on children who underwent echocardiography and polysomnogram within a year. Children with severe OSA as defined by OAHI > 10 or NspO2 < 80% were included. Receiver operator curves and Youden's J index were used to assess the discriminatory ability and threshold values of OAHI and NspO2 for right heart strain (RHS) on echocardiography. RESULTS: A total of 173 prepubertal (< 10 years) children and 71 postpubertal (≥ 10 years) children of age were included. RHS was seen in 9 (5%) prepubertal children and 4 (6%) postpubertal children. In prepubertal children, OAHI and NspO2 were poor predictors of RHS (area under the curve [AUC] 0.53 [95%CI 0.45-0.61], p = 0.748; AUC 0.56 [95%CI 0.48-0.64], p = 0.609). In postpubertal children, threshold values of 55 events/hour and 69% were strong predictors for RHS (AUC 0.88 [95%CI 0.78-0.95], p < 0.001; AUC 0.92 [95%CI 0.83-0.97], p < 0.001). CONCLUSION: In children with severe OSA, evidence of RHS is low. Postpubertal children with OAHI > 55 and NspO2 < 69% appear most appropriate for echocardiography. Clinicians should weigh the risks and benefits of preoperative echocardiography for each child with these threshold values in mind.

Concordance of International Regulation of Pediatric Health Research.

OBJECTIVE: To assess the comparability of international ethics principles and practices used in regulating pediatric research as a first step in determining whether reciprocal deference for international ethics review is feasible. Prior studies by the authors focused on other aspects of international health research, such as biobanks and direct-to-participant genomic research. The unique nature of pediatric research and its distinctive regulation by many countries warranted a separate study. STUDY DESIGN: A representative sample of 21 countries was selected, with geographical, ethnic, cultural, political, and economic diversity. A leading expert on pediatric research ethics and law was selected to summarize the ethics review of pediatric research in each country. To ensure the comparability of the responses, a 5-part summary of pediatric research ethics principles in the US was developed by the investigators and distributed to all country representatives. The international experts were asked to assess and describe whether principles in their country and the US were congruent. Results were obtained and compiled in the spring and summer of 2022. RESULTS: Some of the countries varied in their conceptualization or description of one or more ethical principles for pediatric research, but overall, the countries in the study demonstrated a fundamental concordance. CONCLUSIONS: Similar regulation of pediatric research in 21 countries suggests that international reciprocity is a viable strategy.

Subdiffraction focusing with a long focal length using a terahertz-wave super-oscillatory lens.

This Letter describes a super-oscillatory lens (SOL), with concentric ring-type metallic slits photolithographically fabricated on a glass substrate, that can function at subterahertz frequencies. The SOL has been investigated both experimentally and theoretically and demonstrates a spatial resolution of 1.5 mm (0.5λ), which is 0.45 times the diffraction limit, with a focal length of 75 mm (25λ) at 100 GHz (λ=3mm). Furthermore, the depth of focus of the lens was measured to be 47 mm, which is 10.8 times larger than that of a conventional lens. This type of SOL, with subdiffraction focusing, is thus highly effective for use in industrial inspections with millimeter and terahertz waves.

Multiparametric exercise stress cardiovascular magnetic resonance in the diagnosis of coronary artery disease: the EMPIRE trial.

BACKGROUND: Stress cardiovascular magnetic resonance (CMR) offers assessment of ventricular function, myocardial perfusion and viability in a single examination to detect coronary artery disease (CAD). We developed an in-scanner exercise stress CMR (ExCMR) protocol using supine cycle ergometer and aimed to examine the diagnostic value of a multiparametric approach in patients with suspected CAD, compared with invasive fractional flow reserve (FFR) as the reference gold standard. METHODS: In this single-centre prospective study, patients who had symptoms of angina and at least one cardiovascular disease risk factor underwent both ExCMR and invasive angiography with FFR. Rest-based left ventricular function (ejection fraction, regional wall motion abnormalities), tissue characteristics and exercise stress-derived (perfusion defects, inducible regional wall motion abnormalities and peak exercise cardiac index percentile-rank) CMR parameters were evaluated in the study. RESULTS: In the 60 recruited patients with intermediate CAD risk, 50% had haemodynamically significant CAD based on FFR. Of all the CMR parameters assessed, the late gadolinium enhancement, stress-inducible regional wall motion abnormalities, perfusion defects and peak exercise cardiac index percentile-rank were independently associated with FFR-positive CAD. Indeed, this multiparametric approach offered the highest incremental diagnostic value compared to a clinical risk model (χ2 for the diagnosis of FFR-positive increased from 7.6 to 55.9; P < 0.001) and excellent performance [c-statistic area under the curve 0.97 (95% CI: 0.94-1.00)] in discriminating between FFR-normal and FFR-positive patients. CONCLUSION: The study demonstrates the clinical potential of using in-scanner multiparametric ExCMR to accurately diagnose CAD. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03217227, Registered 11 July 2017-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03217227?id=NCT03217227&draw=2&rank=1&load=cart.

Obstructive sleep apnea during rapid eye movement sleep in patients after percutaneous coronary intervention: a multicenter study.

PURPOSE: Obstructive sleep apnea (OSA) during the rapid eye movement (REM) stage of the sleep cycle is associated with intense hypoxemia and cardiovascular instability. We characterized OSA during REM sleep in patients after percutaneous coronary intervention. METHODS: In this multicenter study, 204 patients who had undergone percutaneous coronary intervention in the prior 6 to 36 months were recruited for in-laboratory polysomnography. The primary measure was respiratory events during REM sleep. The patients were divided into 2 groups: (1) OSA during REM sleep (≥ 15 events/h) and (2) absence of OSA during REM sleep (< 15 events/h). RESULTS: Based on the overall apnea-hypopnea index ≥ 15, 148 patients (74.0%) had OSA. After excluding patients with failed polysomnography or REM sleep < 30 min, 163 patients formed the cohort for this analysis. OSA during REM sleep was diagnosed in 132 patients (81%). Compared with the patients without OSA during REM sleep, those with OSA during REM sleep had a higher body mass index (p = 0.003) and systolic blood pressure (p = 0.041), and a higher prevalence of diabetes mellitus (p = 0.029). Logistic regression analysis, including age, sex, diabetes mellitus, indication for percutaneous coronary intervention, and indication for multi-vessel percutaneous coronary intervention, showed that diabetes mellitus was the only independent predictor of OSA during REM sleep (odds ratio 2.83; 95% CI, 1.17 to 6.83; p = 0.021). CONCLUSION: In patients treated with percutaneous coronary intervention, there was a high prevalence of OSA during REM sleep. Diabetes mellitus was an independent predictor of OSA during REM sleep.

Association between computer-aided lung auscultation and treatment failure risk in calves treated for respiratory disease.

The use of computer-aided lung auscultation (CALA, Whisper Veterinary Stethoscope; Merck Animal Health, Madison, New Jersey, USA) is a relatively new approach to assist in confirming the diagnosis of bovine respiratory disease (BRD). For this prospective cohort study at 1 feedlot in the United States, a CALA score was generated for 2726 feeder cattle (calf-fed Holsteins and mixed-breed beef animals) at the time of the first BRD diagnosis and treatment. All cattle were treated according to the same BRD protocol prescribed for that facility and the protocol was not influenced by the CALA score. Data were collected for 120 d after enrollment. In this study, the risk of BRD retreatment and the risk of BRD mortality were each significantly (P < 0.05) associated with the CALA score at the time of first BRD diagnosis and treatment, and those risks increased (numerically and in some cases statistically) as the CALA score increased.

Association entre l'auscultation pulmonaire assistée par ordinateur et le risque d'échec du traitement chez les veaux traités pour une maladie respiratoire. L'utilisation de l'auscultation pulmonaire assistée par ordinateur (CALA, Whisper Veterinary Stethoscope; Merck Animal Health, Madison, New Jersey, USA) est une approche relativement nouvelle pour aider à confirmer le diagnostic de maladie respiratoire bovine (BRD). Pour cette étude de cohorte prospective dans un parc d'engraissement aux États-Unis, un score CALA a été généré pour 2726 bovins d'engraissement (veau Holstein et bovins de race mixte) au moment du premier diagnostic et traitement de la BRD. Tous les bovins ont été traités selon le même protocole BRD prescrit pour ce site et le protocole n'a pas été influencé par le score CALA. Les données ont été collectées pendant 120 jours après l'inscription. Dans cette étude, le risque de retraitement pour BRD et le risque de mortalité associée au BRD étaient chacun significativement (P < 0,05) associés au score CALA au moment du premier diagnostic et traitement BRD, et ces risques augmentaient (numériquement et dans certains cas statistiquement) à mesure que le score CALA augmentait.(Traduit par Dr Serge Messier).

Unmixing Symmetries.

The low-lying spectra of atomic nuclei display diverse behaviors, for example, rotational bands, which can be described phenomenologically by simple symmetry groups such as spatial SU(3). This leads to the idea of dynamical symmetry, where the Hamiltonian commutes with the Casimir operator(s) of a group, and is block diagonal in subspaces defined by the group's irreducible representations or irreps. Detailed microscopic calculations, however, show these symmetries are in fact often strongly mixed and the wave function fragmented across many irreps. More commonly, the fragmentation across members of a band are similar, which is called a quasidynamical symmetry. In this Letter I explicitly, albeit numerically, construct unitary transformations from a quasidynamical symmetry to a dynamical symmetry, adapting the similarity renormalization group (SRG) in order to transform away the symmetry-mixing parts of the Hamiltonian. The standard SRG produces unsatisfactory results, forcing the induced dynamical symmetry to be dominated by high-weight irreps irrespective of the original decomposition. Using spectral distribution theory to rederive and diagnose standard SRG, I introduce a new form of SRG. The new SRG transforms a quasidynamical symmetry to a dynamical symmetry, that is, unmixes the mixed symmetries, with intuitively more appealing results.

Ensuring trustworthy use of artificial intelligence and big data analytics in health insurance.

Technological advances in big data (large amounts of highly varied data from many different sources that may be processed rapidly), data sciences and artificial intelligence can improve health-system functions and promote personalized care and public good. However, these technologies will not replace the fundamental components of the health system, such as ethical leadership and governance, or avoid the need for a robust ethical and regulatory environment. In this paper, we discuss what a robust ethical and regulatory environment might look like for big data analytics in health insurance, and describe examples of safeguards and participatory mechanisms that should be established. First, a clear and effective data governance framework is critical. Legal standards need to be enacted and insurers should be encouraged and given incentives to adopt a human-centred approach in the design and use of big data analytics and artificial intelligence. Second, a clear and accountable process is necessary to explain what information can be used and how it can be used. Third, people whose data may be used should be empowered through their active involvement in determining how their personal data may be managed and governed. Fourth, insurers and governance bodies, including regulators and policy-makers, need to work together to ensure that the big data analytics based on artificial intelligence that are developed are transparent and accurate. Unless an enabling ethical environment is in place, the use of such analytics will likely contribute to the proliferation of unconnected data systems, worsen existing inequalities, and erode trustworthiness and trust.

Les progrès technologiques en matière de big data (un terme qui désigne de grandes quantités de données extrêmement variées, provenant de différentes sources et pouvant être traitées rapidement), de sciences de l'information et d'intelligence artificielle peuvent améliorer le fonctionnement du système de santé, mais aussi promouvoir des soins personnalisés et servir l'intérêt public. Néanmoins, ces technologies ne permettront pas de remplacer les composantes fondamentales du système de santé, comme le leadership éthique et la bonne gouvernance, ni d'éviter la nécessité de créer un environnement déontologique et réglementaire solide. Le présent document se penche sur la définition de cet environnement déontologique et réglementaire solide pour l'analyse des big data dans le domaine de l'assurance maladie, et fournit à titre d'exemple les mécanismes de protection et de participation qu'il convient d'instaurer. En premier lieu, imposer un cadre de gouvernance précis et efficace est essentiel au traitement des données. Des normes juridiques doivent être promulguées, tandis que les assureurs doivent être encouragés et incités à adopter une approche centrée sur l'humain, tant dans leur conception que dans leur utilisation de l'analyse des big data et de l'intelligence artificielle. Deuxièmement, il faut mettre en place un processus clair et responsable afin d'expliquer quels types d'informations sont susceptibles d'être employés et à quelles fins. Troisièmement, les personnes concernées doivent avoir la possibilité de déterminer de quelle manière leurs données personnelles sont gérées et régies, en étant activement impliquées dans ce processus. Et quatrièmement, les assureurs et les organes de gouvernance, dont les régulateurs et législateurs, doivent collaborer pour faire en sorte que l'analyse des big data basée sur l'intelligence artificielle soit correcte et transparente. À moins d'établir un environnement éthique, l'usage d'une telle analyse entraînera probablement la prolifération de systèmes de données non connectés, l'aggravation des inégalités actuelles ainsi qu'une perte de confiance et de fiabilité.

Los avances tecnológicos relativos a los macrodatos (es decir, grandes cantidades de datos muy variados de muchas fuentes diversas que pueden procesarse rápidamente), las ciencias de los datos y la inteligencia artificial pueden mejorar las funciones del sistema sanitario y promover la atención personalizada y el bien público. No obstante, estas tecnologías no sustituirán los componentes fundamentales del sistema sanitario, como el liderazgo ético y la gobernanza, ni evitarán la necesidad de un entorno ético y normativo sólido. En el presente documento se examina cómo podría ser un entorno ético y normativo sólido para el análisis de macrodatos en el ámbito de los seguros médicos, y se describen ejemplos de mecanismos de protección y participación que deberían establecerse. En primer lugar, es fundamental contar con un marco claro y eficaz de gestión de datos. Es necesario promulgar normas jurídicas y alentar e incentivar a las aseguradoras para que adopten un enfoque centrado en el ser humano en el diseño y la aplicación de análisis de macrodatos e inteligencia artificial. En segundo lugar, es necesario un proceso claro y responsable para explicar cómo y qué información se puede utilizar. En tercer lugar, se debe facultar a las personas cuyos datos puedan ser utilizados mediante su participación activa en la determinación de cómo se pueden gestionar y regular sus datos personales. En cuarto lugar, las aseguradoras y los órganos de gobierno, incluidos los reguladores y los responsables de formular políticas, deben colaborar para garantizar que los análisis de macrodatos basados en la inteligencia artificial que se elaboren sean transparentes y precisos. A menos que exista un entorno ético adecuado, el uso de esos análisis probablemente contribuirá a la proliferación de sistemas de datos sin conexión, empeorará las desigualdades existentes y reducirá la fiabilidad y la confianza.

Quality of Life Following Molecular Marker Testing for Indeterminate Thyroid Nodules.

OBJECTIVE: Thyroid cancer has a disproportionately negative effect on the quality of life (QOL) compared to malignancies with a worse prognosis. The QOL of patients with indeterminate thyroid nodules has not been previously evaluated. We aimed to assess the impact of molecular test results on the QOL of patients with indeterminate thyroid nodules. METHODS: A short version of the Thyroid-Related Patient-Reported Outcome (ThyPro-39) was used to assess the QOL of patients who underwent thyroid fine needle aspiration (FNA) biopsy throughout UCLA Health from May, 2016, to June, 2017. All patients with indeterminate biopsy results underwent molecular testing with either Afirma Gene Expression Classifier or ThyroSeq v2 at the time of the initial biopsy. The QOL associated with symptoms of goiter, anxiety, depression, and impaired daily life were analyzed. RESULTS: Of 825 consented patients, 366 completed the assessment (44.4% response rate). FNA results included 76% benign, 7% malignant, and 17% indeterminate. There were no differences in QOL between patients with a benign FNA and patients with an indeterminate result with benign molecular testing. In patients with an indeterminate FNA, symptoms of goiter (20.5 versus 10.4; P = .033) and depression (33.3 versus 21.0; P = .026) were worse for patients with suspicious versus benign molecular test results; however, no significant differences were observed in anxiety or impaired daily life. CONCLUSION: A benign molecular test result may provide reassurance for patients with indeterminate thyroid nodules that the risk of malignancy is low. Long-term follow-up is necessary to determine if benign molecular test results maintain improved QOL.

How Does Replacement of the Axial Histidine Ligand in Cytochrome c Peroxidase by Nδ-Methyl Histidine Affect Its Properties and Functions? A Computational Study.

Heme peroxidases have important functions in nature related to the detoxification of H2O2. They generally undergo a catalytic cycle where, in the first stage, the iron(III)-heme-H2O2 complex is converted into an iron(IV)-oxo-heme cation radical species called Compound I. Cytochrome c peroxidase Compound I has a unique electronic configuration among heme enzymes where a metal-based biradical is coupled to a protein radical on a nearby Trp residue. Recent work using the engineered Nδ-methyl histidine-ligated cytochrome c peroxidase highlighted changes in spectroscopic and catalytic properties upon axial ligand substitution. To understand the axial ligand effect on structure and reactivity of peroxidases and their axially Nδ-methyl histidine engineered forms, we did a computational study. We created active site cluster models of various sizes as mimics of horseradish peroxidase and cytochrome c peroxidase Compound I. Subsequently, we performed density functional theory studies on the structure and reactivity of these complexes with a model substrate (styrene). Thus, the work shows that the Nδ-methyl histidine group has little effect on the electronic configuration and structure of Compound I and little changes in bond lengths and the same orbital occupation is obtained. However, the Nδ-methyl histidine modification impacts electron transfer processes due to a change in the reduction potential and thereby influences reactivity patterns for oxygen atom transfer. As such, the substitution of the axial histidine by Nδ-methyl histidine in peroxidases slows down oxygen atom transfer to substrates and makes Compound I a weaker oxidant. These studies are in line with experimental work on Nδ-methyl histidine-ligated cytochrome c peroxidases and highlight how the hydrogen bonding network in the second coordination sphere has a major impact on the function and properties of the enzyme.

Comparative diversity of microbiomes and Resistomes in beef feedlots, downstream environments and urban sewage influent.

BACKGROUND: Comparative knowledge of microbiomes and resistomes across environmental interfaces between animal production systems and urban settings is lacking. In this study, we executed a comparative analysis of the microbiota and resistomes of metagenomes from cattle feces, catch basin water, manured agricultural soil and urban sewage. RESULTS: Metagenomic DNA from composite fecal samples (FC; n = 12) collected from penned cattle at four feedlots in Alberta, Canada, along with water from adjacent catchment basins (CB; n = 13), soil (n = 4) from fields in the vicinity of one of the feedlots and urban sewage influent (SI; n = 6) from two municipalities were subjected to Illumina HiSeq2000 sequencing. Firmicutes exhibited the highest prevalence (40%) in FC, whereas Proteobacteria were most abundant in CB (64%), soil (60%) and SI (83%). Among sample types, SI had the highest diversity of antimicrobial resistance (AMR), and metal and biocide resistance (MBR) classes (13 & 15) followed by FC (10 & 8), CB (8 & 4), and soil (6 & 1). The highest antimicrobial resistant (AMR) gene (ARG) abundance was harboured by FC, whereas soil samples had a very small, but unique resistome which did not overlap with FC & CB resistomes. In the beef production system, tetracycline resistance predominated followed by macrolide resistance. The SI resistome harboured ß-lactam, macrolide, tetracycline, aminoglycoside, fluoroquinolone and fosfomycin resistance determinants. Metal and biocide resistance accounted for 26% of the SI resistome with a predominance of mercury resistance. CONCLUSIONS: This study demonstrates an increasing divergence in the nature of the microbiome and resistome as the distance from the feedlot increases. Consistent with antimicrobial use, tetracycline and macrolide resistance genes were predominant in the beef production system. One of the feedlots contributed both conventional (raised with antibiotics) and natural (raised without antibiotics) pens samples. Although natural pen samples exhibited a microbiota composition that was similar to samples from conventional pens, their resistome was less complex. Similarly, the SI resistome was indicative of drug classes used in humans and the greater abundance of mercury resistance may be associated with contamination of municipal water with household and industrial products.

Plasmid Distribution among Escherichia coli from Livestock and Associated Wastewater: Unraveling Factors That Shape the Presence of Genes Conferring Third-Generation Cephalosporin Resistance.

A key concern with agricultural wastewater storage ponds is that they may provide an environment conducive for horizontal exchange of antibiotic resistance genes (ARGs), thereby facilitating the emergence of antibiotic resistant pathogens. Central to this exchange are mobile genetic elements like plasmids; yet, the factors shaping their presence in agricultural environments remain poorly understood. Here, using Escherichia coli as a model bacterium, we examined genetic backgrounds and plasmid profiles of generic fecal and wastewater isolates and those possessing blaCTX-M and blaCMY-2 genes (which confer resistance to third-generation cephalosporins) to delineate factors shaping the environmental persistence of plasmid-associated ARGs in beef cattle feedlots. The wastewater environment exerted minimal influence on plasmid repertoires, as the number of plasmids and distribution of different incompatibility groups did not differ between generic fecal and wastewater isolates. The blaCTX-M and blaCMY-2 genes were associated with IncF and IncA/C plasmids, respectively, and host isolates possessing these ARGs had fewer plasmids than generic isolates, suggesting ARG-bearing plasmids may associate predominantly with such hosts to compensate for the metabolic burden imposed by these plasmids. Phylogeny also appeared to be a factor for blaCTX-M genes, as their bacterial hosts were restricted to particular genetic lineages, including the environmentally adapted ET-1 clade, as noted previously for these genes. Ultimately, these findings have important implications for evaluating human health risks of agricultural wastewater with respect to environmental persistence of ARGs and may help identify options for improving wastewater treatment.

Lumen Apposing Metal Stents (LAMSs) for Drainage of Pancreatic and Gallbladder Collections: A Meta-analysis.

BACKGROUND AND AIMS: Endoscopic ultrasound-guided transmural drainage using lumen apposing metal stents (LAMSs) is becoming a popular and promising therapeutic approach for drainage of intra-abdominal fluid collections. There has been an increasing number of studies evaluating LAMS for drainage of pancreatic pseudocysts (PP), walled-off pancreatic necrosis (WOPN), and gallbladder (GB) drainage. The aim of this meta-analysis is to analyze the literature to date regarding the clinical success, technical success, and adverse events of LAMS in treatment of pancreatic fluid collections and GB drainage. METHODS: A comprehensive search of multiple literature databases through November 2016 was performed. Human studies with at least 10 subjects that examined the clinical success, technical success, and adverse events of LAMS in treating PP, WOPN, and GB drainage were included. RESULTS: A total of 993 patients (608-WOPN; 204-PP; 181-GB drainage) underwent drainage from 20 trials. For drainage of WOPN, the pooled technical success was 98.9% [95% confidence interval (CI): 98.2% to 99.7%] and clinical success was 90% (95% CI: 87% to 93%) (τ=0.001). For drainage of PP, the pooled technical success was 97% (95% CI: 95% to 99%) and clinical success was 98% (95% CI: 96% to 100%), (τ=0.001). For GB drainage, the pooled technical success was 95% (95% CI: 91% to 99%) and clinical success was 93% (95% CI: 90% to 97%), (τ=0.001). Total adverse events occurred in 11% of patients with higher complication rates observed in GB drainage. There was no evidence of publication bias in this meta-analysis. CONCLUSIONS: Endoscopic ultrasound-guided transmural drainage using LAMS is becoming a widely accepted therapeutic approach for the treatment of PP, WOPN, and GB drainage with high clinical and technical success rates and acceptable adverse events. Further prospective randomized trials reporting long-term clinical efficacy and cost-effectiveness are needed to validate LAMS as a therapeutic modality for pancreatic and GB collections.

Incidence and predictors of left ventricular thrombus by cardiovascular magnetic resonance in acute ST-segment elevation myocardial infarction treated by primary percutaneous coronary intervention: a meta-analysis.

INTRODUCTION: The incidence of left ventricular (LV) thrombus formation in ST-segment elevation myocardial infarction (STEMI) patients in the current era of primary percutaneous coronary intervention (PCI) is not well established. We performed a meta-analysis to assess the actual incidence and predictors of LV thrombus by cardiovascular magnetic resonance (CMR) in STEMI treated by primary PCI. METHODS: We searched MEDLINE and EMBASE databases up to February 2018. We included all studies published as a full-text article, reporting the incidence of LV thrombus by CMR within 1 month following acute STEMI in patients treated by primary PCI. A binary random-effects model was used to estimate the pooled incidence of LV thrombus. The diagnostic performance of transthoracic echocardiography (TTE) as compared with CMR was pooled to obtain the sensitivity and specificity of TTE with CMR as the gold standard. Embolic and bleeding complications of LV thrombus were also evaluated. RESULTS: Ten studies were included in the meta-analysis. The incidence of LV thrombus by CMR in all-comer STEMI patients (n = 2072) was 6.3% with 96% of LV thrombus occurring in those with anterior STEMI (12.2% incidence). When only anterior STEMI with LVEF< 50% were considered (n = 447), the incidence of LV thrombus was 19.2%. Compared with CMR, the sensitivity of TTE to detect LV thrombus was 29% with a specificity of 98%. The sensitivity of TTE increased to 70% in those with anterior STEMI and reduced LVEF. LV thrombus resolved in 88% of cases by 3 to 6 months. After 1-2 years follow-up, the embolic complication rate was similar at 1.5% (P = 0.25) but the bleeding complication rate was significantly higher (8.8% versus 0.5%, P < 0.001) in the LV thrombus group on triple therapy when compared to the no LV thrombus group on dual antiplatelet therapy. CONCLUSION: In the primary PCI era, CMR detection of an LV thrombus post-STEMI remains high with incidence of nearly 20% in anterior STEMI with depressed LVEF. Patients with LV thrombus treated by triple therapy had similar embolic complications but higher bleeding complications than those with no LV thrombus treated with dual antiplatelet therapy. A 3 month follow-up CMR scan to guide anticoagulation duration might help mitigate bleeding risk.

Cardiac magnetic resonance T1 and extracellular volume mapping with motion correction and co-registration based on fast elastic image registration.

OBJECTIVE: Our aim was to investigate the technical feasibility of a novel motion compensation method for cardiac magntic resonance (MR) T1 and extracellular volume fraction (ECV) mapping. MATERIALS AND METHODS: Native and post-contrast T1 maps were obtained using modified look-locker inversion recovery (MOLLI) pulse sequences with acquisition scheme defined in seconds. A nonrigid, nonparametric, fast elastic registration method was applied to generate motion-corrected T1 maps and subsequently ECV maps. Qualitative rating was performed based on T1 fitting-error maps and overlay images. Local deformation vector fields were produced for quantitative assessment. Intra- and inter-observer reproducibility were compared with and without motion compensation. RESULTS: Eighty-two T1 and 39 ECV maps were obtained in 21 patients with diverse myocardial diseases. Approximately 60% demonstrated clear quality improvement after motion correction for T1 mapping, particularly for the poor-rating cases (23% before vs 2% after). Approximately 67% showed further improvement with co-registration in ECV mapping. Although T1 and ECV values were not clinically significantly different before and after motion compensation, there was improved intra- and inter-observer reproducibility after motion compensation. CONCLUSIONS: Automated motion correction and co-registration improved the qualitative assessment and reproducibility of cardiac MR T1 and ECV measurements, allowing for more reliable ECV mapping.

A retrospective analysis of feedlot morbidity and mortality outcomes in calves born to dams with known viral vaccination history.

This retrospective analysis aimed to determine the effects of a maternal viral vaccination program (MVVP; Express Verified) on calf health during the feeding period. In low- and high-risk populations, calves born to dams vaccinated pre-breeding with program products had improved morbidity and mortality outcomes compared with non-program animals.

Analyse rétrospective de la morbidité dans des parcs d'engraissement et résultats de mortalité chez les veaux nés de mères ayant des antécédents de vaccination connus. Cette analyse rétrospective visait à déterminer les effets d'un programme maternel de vaccination virale (PMVV; Express Verified) sur la santé des veaux durant la période d'allaitement. Dans les populations à risque faible et élevé, les veaux nés de mères vaccinées avant l'accouplement avec des produits de programme présentaient des résultats améliorés de morbidité et de mortalité comparativement aux animaux à l'extérieur du programme.(Traduit par Isabelle Vallières).