Emerging foodborne diseases.

The epidemiology of foodborne diseases is rapidly changing. Recently described pathogens, such as Escherichia coli O157:H7 and the epidemic strain of Salmonella serotype Typhimurium Definitive Type 104 (which is resistant to at least five antimicrobial drugs), have become important public health problems. Well-recognized pathogens, such as Salmonella serotype Enteritidis, have increased in prevalence or become associated with new vehicles. Emergence in foodborne diseases is driven by the same forces as emergence in other infectious diseases: changes in demographic characteristics, human behavior, industry, and technology; the shift toward a global economy; microbial adaptation; and the breakdown in the public health infrastructure. Addressing emerging foodborne diseases will require more sensitive and rapid surveillance, enhanced methods of laboratory identification and subtyping, and effective prevention and control

Campylobacter jejuni--an emerging foodborne pathogen.

Campylobacter jejuni is the most commonly reported bacterial cause of foodborne infection in the United States. Adding to the human and economic costs are chronic sequelae associated with C. jejuni infection--Guillian-Barré syndrome and reactive arthritis. In addition, an increasing proportion of human infections caused by C. jejuni are resistant to antimicrobial therapy. Mishandling of raw poultry and consumption of undercooked poultry are the major risk factors for human campylobacteriosis. Efforts to prevent human illness are needed throughout each link in the food chain

Quantitative Regular Expressions for Arrhythmia Detection Algorithms

Motivated by the problem of verifying the correctness of arrhythmia-detection algorithms, we present a formalization of these algorithms in the language of Quantitative Regular Expressions. QREs are a flexible formal language for specifying complex numerical queries over data streams, with provable runtime and memory consumption guarantees. The medical-device algorithms of interest include peak detection (where a peak in a cardiac signal indicates a heartbeat) and various discriminators, each of which uses a feature of the cardiac signal to distinguish fatal from non-fatal arrhythmias. Expressing these algorithms' desired output in current temporal logics, and implementing them via monitor synthesis, is cumbersome, error-prone, computationally expensive, and sometimes infeasible. In contrast, we show that a range of peak detectors (in both the time and wavelet domains) and various discriminators at the heart of today's arrhythmia-detection devices are easily expressible in QREs. The fact that one formalism (QREs) is used to describe the desired end-to-end operation of an arrhythmia detector opens the way to formal analysis and rigorous testing of these detectors' correctness and performance. Such analysis could alleviate the regulatory burden on device developers when modifying their algorithms. The performance of the peak-detection QREs is demonstrated by running them on real patient data, on which they yield results on par with those provided by a cardiologist.Comment: CMSB 2017: 15th Conference on Computational Methods for Systems Biolog

Changed concepts and definitions of myeloproliferative neoplasms (MPN), myelodysplastic syndromes (MDS) and myelodysplastic/myeloproliferative neoplasms (MDS/MPN) in the updated 2008 WHO classification

The purpose of this overview is to discuss the changes in the 2008 WHO classification of myeloid neoplasms, with exclusion of acute myeloid leukaemia. Specific mutations or rearrangements leading to constitutive activation of growth factor receptors or cytoplasmic tyrosine kinases are now recognised as recurrent genetic events characterising the group of myeloproliferative neoplasms (MPN). A newly introduced subgroup consists of patients with persistent eosinophilia and myeloid or lymphoid proliferations harbouring specific genetic changes involving platelet-derived growth factor receptors alpha and beta (PDGFRA and PDGFRB) or fibroblast growth factor receptor 1 (FGFR1). The clinical relevance of recognising myeloid neoplasms with aberrant tyrosine kinase activity is based in novel treatment options with tyrosine kinase inhibitors. The myelodysplastic syndromes (MDS) without increased blasts are further divided into subtypes of refractory cytopaenias with unilineage dysplasia. A new provisional entity is refractory cytopaenia of childhood. Down syndrome- and therapy-related myeloid neoplasms, including MDS, were moved to the section of acute myeloid leukaemia and related precursor neoplasms

PCSK9 genetic variants and risk of type 2 diabetes: a mendelian randomisation study

BACKGROUND: Statin treatment and variants in the gene encoding HMG-CoA reductase are associated with reductions in both the concentration of LDL cholesterol and the risk of coronary heart disease, but also with modest hyperglycaemia, increased bodyweight, and modestly increased risk of type 2 diabetes, which in no way offsets their substantial benefits. We sought to investigate the associations of LDL cholesterol-lowering PCSK9 variants with type 2 diabetes and related biomarkers to gauge the likely effects of PCSK9 inhibitors on diabetes risk. METHODS: In this mendelian randomisation study, we used data from cohort studies, randomised controlled trials, case control studies, and genetic consortia to estimate associations of PCSK9 genetic variants with LDL cholesterol, fasting blood glucose, HbA1c, fasting insulin, bodyweight, waist-to-hip ratio, BMI, and risk of type 2 diabetes, using a standardised analysis plan, meta-analyses, and weighted gene-centric scores. FINDINGS: Data were available for more than 550 000 individuals and 51 623 cases of type 2 diabetes. Combined analyses of four independent PCSK9 variants (rs11583680, rs11591147, rs2479409, and rs11206510) scaled to 1 mmol/L lower LDL cholesterol showed associations with increased fasting glucose (0·09 mmol/L, 95% CI 0·02 to 0·15), bodyweight (1·03 kg, 0·24 to 1·82), waist-to-hip ratio (0·006, 0·003 to 0·010), and an odds ratio for type diabetes of 1·29 (1·11 to 1·50). Based on the collected data, we did not identify associations with HbA1c (0·03%, -0·01 to 0·08), fasting insulin (0·00%, -0·06 to 0·07), and BMI (0·11 kg/m2, -0·09 to 0·30). INTERPRETATION: PCSK9 variants associated with lower LDL cholesterol were also associated with circulating higher fasting glucose concentration, bodyweight, and waist-to-hip ratio, and an increased risk of type 2 diabetes. In trials of PCSK9 inhibitor drugs, investigators should carefully assess these safety outcomes and quantify the risks and benefits of PCSK9 inhibitor treatment, as was previously done for statins. FUNDING: British Heart Foundation, and University College London Hospitals NHS Foundation Trust (UCLH) National Institute for Health Research (NIHR) Biomedical Research Centre