Rapid improvements in sequencing and array-based platforms are resulting in a flood of diverse genome-wide data, including data from exome and whole-genome sequencing, epigenetic surveys, expression profiling of coding and noncoding RNAs, single nucleotide polymorphism (SNP) and copy number profiling, and functional assays. Analysis of these large, diverse data sets holds the promise of a more comprehensive understanding of the genome and its relation to human disease. Experienced and knowledgeable human review is an essential component of this process, complementing computational approaches. This calls for efficient and intuitive visualization tools able to scale to very large data sets and to flexibly integrate multiple data types, including clinical data. However, the sheer volume and scope of data pose a significant challenge to the development of such tools.

Integrative Genomics Viewer

African swine fever (ASF) recently has spread beyond sub-Saharan Africa to the Trans-Caucasus region, parts of the Russian Federation and Eastern Europe. In this new epidemiological scenario, the disease has similarities, but also important differences, compared to the situation in Africa, including the substantial involvement of wild boar. A better understanding of this new situation will enable better control and prevent further spread of disease. In this article, these different scenarios are compared, and recent information on the pathogenesis of ASF virus strains, the immune response to infection and prospects for developing vaccines is presented. Knowledge gaps and the prospects for future control are discussed.

African swine fever: A re-emerging viral disease threatening the global pig industry

African swine fever.

African swine fever is a devastating disease that can result in death in almost all infected pigs. The continuing spread of African swine fever from Africa to Europe and recently to the high-pig production countries of China and others in Southeast Asia threatens global pork production and food security. The African swine fever virus is an unusual complex DNA virus and is not related to other viruses. This has presented challenges for vaccine development, and currently none is available. The virus is extremely well adapted to replicate in its hosts in the sylvatic cycle in East and South Africa. Its spread to other regions, with different wildlife hosts, climatic conditions, and pig production systems, has revealed unexpected epidemiological scenarios and different challenges for control. Here we review the epidemiology of African swine fever in these different scenarios and methods used for control. We also discuss progress toward vaccine development and research priorities to better understand this complex disease and improve control.

/pdf/african-swine-fever-epidemiology-and-control-2oi66ouw25.pdf

African Swine Fever Epidemiology and Control

African swine fever virus (ASFV) is the sole member of the family Asfarviridae, and the only known DNA arbovirus. Since its identification in Kenya in 1921, ASFV has remained endemic in Africa, maintained in a sylvatic cycle between Ornithodoros soft ticks and warthogs (Phacochoerus africanus) which do not develop clinical disease with ASFV infection. However, ASFV causes a devastating and economically significant disease of domestic (Sus scrofa domesticus) and feral (Sus scrofa ferus) swine. There is no ASFV vaccine available, and current control measures consist of strict animal quarantine and culling procedures. The virus is highly stable and easily spreads by infected swine, contaminated pork products and fomites, or via transmission by the Ornithodoros vector. Competent Ornithodoros argasid soft tick vectors are known to exist not only in Africa, but also in parts of Europe and the Americas. Once ASFV is established in the argasid soft tick vector, eradication can be difficult due to the long lifespan of Ornithodoros ticks and their proclivity to inhabit the burrows of warthogs or pens and shelters of domestic pigs. Establishment of endemic ASFV infections in wild boar populations further complicates the control of ASF. Between the late 1950s and early 1980s, ASFV emerged in Europe, Russia and South America, but was mostly eradicated by the mid-1990s. In 2007, a highly virulent genotype II ASFV strain emerged in the Caucasus region and subsequently spread into the Russian Federation and Europe, where it has continued to circulate and spread. Most recently, ASFV emerged in China and has now spread to several neighboring countries in Southeast Asia. The high morbidity and mortality associated with ASFV, the lack of an efficacious vaccine, and the complex makeup of the ASFV virion and genome as well as its lifecycle, make this pathogen a serious threat to the global swine industry and national economies. Topics covered by this review include factors important for ASFV infection, replication, maintenance, and transmission, with attention to the role of the argasid tick vector and the sylvatic transmission cycle, current and future control strategies for ASF, and knowledge gaps regarding the virus itself, its vector and host species.

/pdf/african-swine-fever-virus-an-emerging-dna-arbovirus-3s5wfwgsiz.pdf

African Swine Fever Virus: An Emerging DNA Arbovirus.

African swine fever is a highly contagious viral disease of mandatory declaration to the World Organization for Animal Health (OIE). The lack of available vaccines makes its control difficult; thus, African swine fever virus (ASFV) represents a major threat to the swine industry. Inactivated vaccines do not confer solid protection against ASFV. Conversely, live attenuated viruses (LAV), either naturally isolated or obtained by genetic manipulation, have demonstrated reliable protection against homologous ASFV strains, although little or no protection has been demonstrated against heterologous viruses. Safety concerns are a major issue for the use of ASFV attenuated vaccine candidates and have hampered their implementation in the field so far. While trying to develop safer and efficient ASFV vaccines, we found that the deletion of the viral CD2v (EP402R) gene highly attenuated the virulent BA71 strain in vivo Inoculation of pigs with the deletion mutant virus BA71ΔCD2 conferred protection not only against lethal challenge with the parental BA71 but also against the heterologous E75 (both genotype I strains). The protection induced was dose dependent, and the cross-protection observed in vivo correlated with the ability of BA71ΔCD2 to induce specific CD8+ T cells capable of recognizing both BA71 and E75 viruses in vitro Interestingly, 100% of the pigs immunized with BA71ΔCD2 also survived lethal challenge with Georgia 2007/1, the genotype II strain of ASFV currently circulating in continental Europe. These results open new avenues to design ASFV cross-protective vaccines, essential to fight ASFV in areas where the virus is endemic and where multiple viruses are circulating.IMPORTANCE African swine fever virus (ASFV) remains enzootic in most countries of Sub-Saharan Africa, today representing a major threat for the development of their swine industry. The uncontrolled presence of ASFV has favored its periodic exportation to other countries, the last event being in Georgia in 2007. Since then, ASFV has spread toward neighboring countries, reaching the European Union's east border in 2014. The lack of available vaccines against ASFV makes its control difficult; so far, only live attenuated viruses have demonstrated solid protection against homologous experimental challenges, but they have failed at inducing solid cross-protective immunity against heterologous viruses. Here we describe a new LAV candidate with unique cross-protective abilities: BA71ΔCD2. Inoculation of BA71ΔCD2 protected pigs not only against experimental challenge with BA71, the virulent parental strain, but also against heterologous viruses, including Georgia 2007/1, the genotype II strain of ASFV currently circulating in Eastern Europe.

/pdf/ba71dcd2-a-new-recombinant-live-attenuated-african-swine-31h1eefsbw.pdf

BA71ΔCD2: a New Recombinant Live Attenuated African Swine Fever Virus with Cross-Protective Capabilities

Accidental extubation in prone position: Report of two cases and proposal of an algorithm for airway management.

BACKGROUND
Recommendations on the diagnosis and management of myocardial injury in noncardiac surgery (MINS) show remarkable variability. Mortality reports also vary. We aimed to describe mortality and major adverse cardiovascular and cerebrovascular event (MACCE) rates in patients with silent MINS treated with postoperative aspirin-statin therapy and with cardiology follow-up.


METHODS
Prospective descriptive cohort study of patients aged 45 years or older scheduled for noncardiac surgery with high risk for cardiovascular complications from May 2017 to April 2019. Aspirin-statin therapy and cardiology follow-up were prescribed for patients with silent (asymptomatic) MINS. The primary outcome was one-year mortality in patients with silent MINS. Secondary outcomes were mortality in MINS patients with perioperative myocardial infarction (PMI) or chronic myocardial injury (CMI) and MACCE.


RESULTS
We identified 766 eligible patients and enrolled 747. MINS occurred in 166 patients (22.2%); 151 (91%) had silent MINS and 15 (9%) had PMI. Thirty-one patients (4.1%) had CMI. One-year mortality was higher in patients with silent MINS (22.5%) than in patients with no MINS (7.8%) (P<0.001). One-year mortality rates in MINS patients with PMI or CMI were 27 and 19 %, respectively. MACCE were more frequent in patients with silent MINS at 30 days and one year (18 and 25%) than in patients with no MINS (6 and 12%, respectively).


CONCLUSIONS
Rates of mortality and MACCE in patients with silent MINS were high despite aspirin-statin therapy and cardiology follow-up. Further prospective research is needed to assess new postoperative care protocols that might effectively improve outcomes.

Mortality and incidence of cardiovascular events in patients treated with aspirin and statins at one year after myocardial injury in noncardiac surgery: a prospective observational study.

BACKGROUND
The best use of perioperative cardiac biomarkers assessment is still under discussion. Massive postoperative troponin surveillance can result in untenably high workloads and costs for health care systems and potentially harmful interventions for patients. In a cohort of patients at risk for major adverse cardiovascular and cerebrovascular events (MACCEs), we aimed to (1) determine whether preoperative biomarkers can identify patients at major risk for acute myocardial injury in noncardiac surgery, (2) develop a risk model for acute myocardial injury prediction, and (3) propose an algorithm to optimize postoperative troponin surveillance.


METHODS
Prospective, single-center cohort study enrolling consecutive adult patients (≥45 years) at risk for MACCE scheduled for intermediate-to-high-risk noncardiac surgery. Baseline high-sensitivity troponin T (hsTnT) and N-terminal fragment of pro-B-type natriuretic peptide (NT-proBNP), as well as hsTnT on the first 3 postoperative days were obtained. The main outcome was the occurrence of acute myocardial injury. Candidate predictors of acute myocardial injury were baseline concentrations of hsTnT ≥14 ng/L and NT-proBNP ≥300 pg/mL and preoperative and intraoperative variables. A multivariable risk model and a decision curve were constructed.


RESULTS
Of 732 patients, 42.1% had elevated hsTnT and 37.3% had elevated NT-proBNP levels at baseline. Acute myocardial injury occurred in 161 patients (22%). Elevated baseline hsTnT, found in 84% of patients with acute myocardial injury, was strongly associated with this outcome: odds ratio (OR), 12.08 (95% confidence interval [CI], 7.78-19.42). Logistic regression identified 6 other independent predictors for acute myocardial injury: age, sex, estimated glomerular filtration rate (eGFR) <45 mL·min-1·1.73 m-2, functional capacity <4 METs or unknown, NT-proBNP ≥300 pg/mL, and estimated intraoperative blood loss. The c-statistic for the risk model was 77% (95% CI, 0.73-0.81). The net benefit of the model began at a risk threshold of 7%.


CONCLUSIONS
Baseline determination of cardiac biomarkers in patients at risk for MACCE shortly before intermediate- or high-risk noncardiac surgery helps identify those with the highest risk for acute myocardial injury. A baseline hsTnT ≥14 ng/L indicates the need for postoperative troponin surveillance. In patients with baseline hsTnT <14 ng/L, our 6-predictor model will identify additional patients at risk for acute myocardial injury who may also benefit from postoperative surveillance.

Prediction of Acute Myocardial Injury in Noncardiac Surgery in Patients at Risk for Major Adverse Cardiovascular and Cerebrovascular Events: A Multivariable Risk Model.

Laia Bosch

Papers

BA71ΔCD2: a New Recombinant Live Attenuated African Swine Fever Virus with Cross-Protective Capabilities

Accidental extubation in prone position: Report of two cases and proposal of an algorithm for airway management.

Mortality and incidence of cardiovascular events in patients treated with aspirin and statins at one year after myocardial injury in noncardiac surgery: a prospective observational study.

Prediction of Acute Myocardial Injury in Noncardiac Surgery in Patients at Risk for Major Adverse Cardiovascular and Cerebrovascular Events: A Multivariable Risk Model.