The risk of infection by African swine fever virus in European swine through boar movement and legal trade of pigs and pig meat

African swine fever (ASF) is currently spreading westwards throughout Europe and eastwards into China, with cases occurring in both wild boar and domestic pigs. A generic risk assessment framework is used to determine the probability of first infection with ASF virus (ASFV) at a fine spatial scale across European Union Member States. The framework aims to assist risk managers across Europe with their ASF surveillance and intervention activities. Performing the risk assessment at a fine spatial scale allows for hot-spot surveillance, which can aid risk managers by directing surveillance or intervention resources at those areas or pathways deemed most at risk, and hence enables prioritization of limited resources. We use 2018 cases of ASF to estimate prevalence of the disease in both wild boar and pig populations and compute the risk of initial infection for 2019 at a 100 km2 cell resolution via three potential pathways: legal trade in live pigs, natural movement of wild boar, and legal trade in pig meat products. We consider the number of pigs, boar and amount of pig meat entering our area of interest, the prevalence of the disease in the origin country, the probability of exposure of susceptible pigs or boar in the area of interest to introduced infected pigs, boar, or meat from an infected pig, and the probability of transmission to susceptible animals. We provide maps across Europe indicating regions at highest risk of initial infection. Results indicate that the risk of ASF in 2019 was predominantly focused on those regions which already had numerous cases in 2018 (Poland, Lithuania, Hungary, Romania, and Latvia). The riskiest pathway for ASFV transmission to pigs was the movement of wild boar for Eastern European countries and legal trade of pigs for Western European countries. New infections are more likely to occur in wild boar rather than pigs, for both the pig meat and wild boar movement pathways. Our results provide an opportunity to focus surveillance activities and thus increase our ability to detect ASF introductions earlier, a necessary requirement if we are to successfully control the spread of this devastating disease for the pig industry

Characterization of the Human Risk of Salmonellosis Related to Consumption of Pork Products in Different E.U. Countries Based on a QMRA

In response to the European Food Safety Authority's wish to assess the reduction of human cases of salmonellosis by implementing control measures at different points in the farm-to-consumption chain for pork products, a quantitative microbiological risk assessment (QMRA) was developed. The model simulated the occurrence of Salmonella from the farm to consumption of pork cuts, minced meat, and fermented ready-to-eat sausage, respectively, and a dose-response model was used to estimate the probability of illness at consumption. The QMRA has a generic structure with a defined set of variables, whose values are changed according to the E.U. member state (MS) of interest. In this article we demonstrate the use of the QMRA in four MSs, representing different types of countries. The predicted probability of illness from the QMRA was between 1 in 100,000 and 1 in 10 million per serving across all three product types. Fermented ready-to-eat sausage imposed the highest probability of illness per serving in all countries, whereas the risks per serving of minced meat and pork chops were similar within each MS. For each of the products, the risk varied by a factor of 100 between the four MSs. The influence of lack of information for different variables was assessed by rerunning the model with alternative, more extreme, values. Out of the large number of uncertain variables, only a few of them have a strong influence on the probability of illness, in particular those describing the preparation at home and consumption

Assessing the effect of on-farm and abattoir interventions in reducing human salmonellosis from pig meat consumption in the EU

Pigs are commonly infected with Salmonella spp. at the slaughterhouse, and the consumption of pig meat is hypothesised to be an important contributor to human salmonellosis. The European Union (EU) will shortly set targets for the reduction of Salmonella in pigs at slaughter for each Member State (MS), and each MS is expected to put in place a National Control Plan (NCP) in order to achieve their targets. If MSs are to realise their targets then practical interventions that consistently work must be identified

Cross-validation of generic risk assessment tools for animal disease incursion based on a case study for African swine fever

In recent years, several generic risk assessment (RA) tools have been developed that can be applied to assess the incursion risk of multiple infectious animal diseases allowing for a rapid response to a variety of newly emerging or re-emerging diseases. Although these tools were originally developed for different purposes, they can be used to answer similar or even identical risk questions. To explore the opportunities for cross-validation, seven generic RA tools were used to assess the incursion risk of African swine fever (ASF) to the Netherlands and Finland for the 2017 situation and for two hypothetical scenarios in which ASF cases were reported in wild boar and/or domestic pigs in Germany. The generic tools ranged from qualitative risk assessment tools to stochastic spatial risk models but were all parameterized using the same global databases for disease occurrence and trade in live animals and animal products. A comparison of absolute results was not possible, because output parameters represented different endpoints, varied from qualitative probability levels to quantitative numbers, and were expressed in different units. Therefore, relative risks across countries and scenarios were calculated for each tool, for the three pathways most in common (trade in live animals, trade in animal products, and wild boar movements) and compared. For the 2017 situation, all tools evaluated the risk to the Netherlands to be higher than Finland for the live animal trade pathway, the risk to Finland the same or higher as the Netherlands for the wild boar pathway, while the tools were inconclusive on the animal products pathway. All tools agreed that the hypothetical presence of ASF in Germany increased the risk to the Netherlands, but not to Finland. The ultimate aim of generic RA tools is to provide risk-based evidence to support risk managers in making informed decisions to mitigate the incursion risk of infectious animal diseases. The case study illustrated that conclusions on the ASF risk were similar across the generic RA tools, despite differences observed in calculated risks. Hence, it was concluded that the cross-validation contributed to the credibility of their results.info:eu-repo/semantics/publishedVersio

Application of non-HDL cholesterol for population-based cardiovascular risk stratification: results from the Multinational Cardiovascular Risk Consortium.

BACKGROUND: The relevance of blood lipid concentrations to long-term incidence of cardiovascular disease and the relevance of lipid-lowering therapy for cardiovascular disease outcomes is unclear. We investigated the cardiovascular disease risk associated with the full spectrum of bloodstream non-HDL cholesterol concentrations. We also created an easy-to-use tool to estimate the long-term probabilities for a cardiovascular disease event associated with non-HDL cholesterol and modelled its risk reduction by lipid-lowering treatment. METHODS: In this risk-evaluation and risk-modelling study, we used Multinational Cardiovascular Risk Consortium data from 19 countries across Europe, Australia, and North America. Individuals without prevalent cardiovascular disease at baseline and with robust available data on cardiovascular disease outcomes were included. The primary composite endpoint of atherosclerotic cardiovascular disease was defined as the occurrence of the coronary heart disease event or ischaemic stroke. Sex-specific multivariable analyses were computed using non-HDL cholesterol categories according to the European guideline thresholds, adjusted for age, sex, cohort, and classical modifiable cardiovascular risk factors. In a derivation and validation design, we created a tool to estimate the probabilities of a cardiovascular disease event by the age of 75 years, dependent on age, sex, and risk factors, and the associated modelled risk reduction, assuming a 50% reduction of non-HDL cholesterol. FINDINGS: Of the 524 444 individuals in the 44 cohorts in the Consortium database, we identified 398 846 individuals belonging to 38 cohorts (184 055 [48·7%] women; median age 51·0 years [IQR 40·7-59·7]). 199 415 individuals were included in the derivation cohort (91 786 [48·4%] women) and 199 431 (92 269 [49·1%] women) in the validation cohort. During a maximum follow-up of 43·6 years (median 13·5 years, IQR 7·0-20·1), 54 542 cardiovascular endpoints occurred. Incidence curve analyses showed progressively higher 30-year cardiovascular disease event-rates for increasing non-HDL cholesterol categories (from 7·7% for non-HDL cholesterol <2·6 mmol/L to 33·7% for ≥5·7 mmol/L in women and from 12·8% to 43·6% in men; p<0·0001). Multivariable adjusted Cox models with non-HDL cholesterol lower than 2·6 mmol/L as reference showed an increase in the association between non-HDL cholesterol concentration and cardiovascular disease for both sexes (from hazard ratio 1·1, 95% CI 1·0-1·3 for non-HDL cholesterol 2·6 to <3·7 mmol/L to 1·9, 1·6-2·2 for ≥5·7 mmol/L in women and from 1·1, 1·0-1·3 to 2·3, 2·0-2·5 in men). The derived tool allowed the estimation of cardiovascular disease event probabilities specific for non-HDL cholesterol with high comparability between the derivation and validation cohorts as reflected by smooth calibration curves analyses and a root mean square error lower than 1% for the estimated probabilities of cardiovascular disease. A 50% reduction of non-HDL cholesterol concentrations was associated with reduced risk of a cardiovascular disease event by the age of 75 years, and this risk reduction was greater the earlier cholesterol concentrations were reduced. INTERPRETATION: Non-HDL cholesterol concentrations in blood are strongly associated with long-term risk of atherosclerotic cardiovascular disease. We provide a simple tool for individual long-term risk assessment and the potential benefit of early lipid-lowering intervention. These data could be useful for physician-patient communication about primary prevention strategies. FUNDING: EU Framework Programme, UK Medical Research Council, and German Centre for Cardiovascular Research

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)