Assessing the impact of climate change on vector-borne viruses in the EU through the elicitation of expert opinion

Expert opinion was elicited to undertake a qualitative risk assessment to estimate the current and future risks to the European Union (EU) from five vector-borne viruses listed by the World Organization for Animal Health. It was predicted that climate change will increase the risk of incursions of African horse sickness virus (AHSV), Crimean-Congo haemorrhagic fever virus (CCHFV) and Rift Valley fever virus (RVFV) into the EU from other parts of the world, with African swine fever virus (ASFV) and West Nile virus (WNV) being less affected. Currently the predicted risks of incursion were lowest for RVFV and highest for ASFV. Risks of incursion were considered for six routes of entry (namely vectors, livestock, meat products, wildlife, pets and people). Climate change was predicted to increase the risk of incursion from entry of vectors for all five viruses to some degree, the strongest effects being predicted for AHSV, CCHFV and WNV. This work will facilitate identification of appropriate risk management options in relation to adaptations to climate change

The Effect of Electronic Cigarette User Modifications and E-liquid Adulteration on the Particle Size Profile of an Aerosolized Product

Electronic cigarettes (e-cigarettes) are an alternate nicotine delivery system that generate a condensation aerosol to be inhaled by the user. The size of the droplets formed in the aerosol can vary and contributes to drug deposition and ultimate bioavailability in the lung. The growing popularity of e-cigarette products has caused an increase in internet sources promoting the use of drugs other than nicotine (DOTNs) in e-cigarettes. The purpose of this study was to determine the effect of various e-cigarette and e-liquid modifications, such as coil resistance, battery voltage, and glycol and drug formulation, on the aerosol particle size. E-liquids containing 12 mg/mL nicotine prepared in glycol compositions of 100% propylene glycol (PG), 100% vegetable glycerin (VG), or 50:50 PG:VG were aerosolized at three voltages and three coil resistances. Methamphetamine and methadone e-liquids were prepared at 60 mg/mL in 50:50 PG:VG and all e-liquids were aerosolized onto a 10 stage Micro-Orifice Uniform Deposit Impactor. Glycol deposition correlated with drug deposition, and the majority of particles centered between 0.172–0.5 μm in diameter, representing pulmonary deposition. The 100% PG e-liquid produced the largest aerosol particles and the 100% VG and 50:50 PG:VG e-liquids produced ultra-fine particles \u3c0.3 μm. The presence of ultrafine particles indicates that drugs can be aerosolized and reach the pulmonary alveolar regions, highlighting a potential for abuse and risk of overdose with DOTNs aerosolized in an e-cigarette system

Modelling the species jump: towards assessing the risk of human infection from novel avian influenzas

The scientific understanding of the driving factors behind zoonotic and pandemic influenzas is hampered by complex interactions between viruses, animal hosts and humans. This complexity makes identifying influenza viruses of high zoonotic or pandemic risk, before they emerge from animal populations, extremely difficult and uncertain. As a first step towards assessing zoonotic risk of Influenza, we demonstrate a risk assessment framework to assess the relative likelihood of influenza A viruses, circulating in animal populations, making the species jump into humans. The intention is that such a risk assessment framework could assist decisionmakers to compare multiple influenza viruses for zoonotic potential and hence to develop appropriate strain-specific control measures. It also provides a first step towards showing proof of principle for an eventual pandemic risk model. We show that the spatial and temporal epidemiology is as important in assessing the risk of an influenza A species jump as understanding the innate molecular capability of the virus.We also demonstrate data deficiencies that need to be addressed in order to consistently combine both epidemiological and molecular virology data into a risk assessment framework

Qualitative import risk assessment : a proposed method for estimating the aggregated probability of entry of infection

In the absence of sufficient numerical data, qualitative risk assessment is recognised as an important tool for providing risk managers with evidence-based predictions on which to formulate their decisions. Such approaches have been used in the area of animal health for import risk assessment for both livestock and zoonotic pathogens. Very few qualitative import risk assessments have, however, considered the aggregated probability of introduction, that is, the probability of at least one infected/contaminated entry per group of import units. Those that have are generally based on specific cases and do not follow a generic approach. In this paper, we consider whether or not it is feasible to develop a generic method and under what circumstances such an approach could be applied in practice. Our conclusion is that it would be difficult to specify a generic method because any such approach would rely on specifying numerical bounds for qualitative categories of probability as well as an idea of the number of imports and would thus be case-specific. As an alternative we propose a way of using case by case information to create a simple graphical reference tool which removes some of the subjectivity that is often associated with deriving qualitative risk. The reference tool considers various qualitative categories of individual probability and determines the relationship between this probability, the number of imports and the aggregated probability of entry. Applying the reference tool to a previously published case-study demonstrated some differences in conclusions and suggests that more subjective approaches can under-estimate probability and thus risk. It is concluded that this approach may be useful for future qualitative assessments of aggregated probability, provided that bounds for qualitative probabilities can be defined for the specific case situation

A risk assessment for Salmonella in pigs in Great Britain

Along with poultry, pig meat has been identified as a potential source of human food borne Salmonella infection. In order to minimise the risk of human illness, a number of EU countries have initiated Salmonella monitoring programmes for pigs (e.g. Denmark, Germany, UK) and EU requirements for control of Salmonella in pigs will be based on the results of recent surveys together with risk assessment and economic studies that are under way . However, control programmes cannot be successful unless practical interventions are available for pig fanners and producers to implement. Therefore, as part of a large risk-based study investigating control of Salmonella in pigs, a full British farm-to-consumption risk assessment has been developed in order to predict the impact of interventions upon the risk of human disease. The interventions investigated within the risk assessment were: vaccination, feeding of organic acids, rodent control, anal bunging and washing and drying of the carcass at dehairing

Neutral tritium gas reduction in the KATRIN differential pumping sections

The KArlsruhe TRItium Neutrino experiment (KATRIN) aims to measure the effective electron anti-neutrino mass with an unprecedented sensitivity of $0.2\,\mathrm{eV}/\mathrm{c}^2$, using $\beta$-electrons from tritium decay. The electrons are guided magnetically by a system of superconducting magnets through a vacuum beamline from the windowless gaseous tritium source through differential and cryogenic pumping sections to a high resolution spectrometer and a segmented silicon pin detector. At the same time tritium gas has to be prevented from entering the spectrometer. Therefore, the pumping sections have to reduce the tritium flow by more than 14 orders of magnitude. This paper describes the measurement of the reduction factor of the differential pumping section performed with high purity tritium gas during the first measurement campaigns of the KATRIN experiment. The reduction factor results are compared with previously performed simulations, as well as the stringent requirements of the KATRIN experiment.Comment: 19 pages, 4 figures, submitted to Vacuu

Prognostic Role of Gene Mutations in Chronic Myelomonocytic Leukemia Patients Treated With Hypomethylating Agents

Somatic mutations contribute to the heterogeneous prognosis of chronic myelomonocytic leukemia (CMML). Hypomethylating agents (HMAs) are active in CMML, but analyses of small series failed to identify mutations predicting response or survival. We analyzed a retrospective multi-center cohort of 174 CMML patients treated with a median of 7 cycles of azacitidine (n = 68) or decitabine (n = 106). Sequencing data before treatment initiation were available for all patients, from Sanger (n = 68) or next generation (n = 106) sequencing. Overall response rate (ORR) was 52%, including complete response (CR) in 28 patients (17%). In multivariate analysis, ASXL1 mutations predicted a lower ORR (Odds Ratio [OR] = 0.85, p = 0.037), whereas TET2mut/ASXL1wt genotype predicted a higher CR rate (OR = 1.18, p = 0.011) independently of clinical parameters. With a median follow-up of 36.7 months, overall survival (OS) was 23.0 months. In multivariate analysis, RUNX1mut (Hazard Ratio [HR] = 2.00, p = .011), CBLmut (HR = 1.90, p = 0.03) genotypes and higher WBC (log10(WBC) HR = 2.30, p = .005) independently predicted worse OS while the TET2mut/ASXL1wt predicted better OS (HR = 0.60, p = 0.05). CMML-specific scores CPSS and GFM had limited predictive power. Our results stress the need for robust biomarkers of HMA activity in CMML and for novel treatment strategies in patients with myeloproliferative features and RUNX1 mutations. Keywords: Chronic myelomonocytic leukemia, Hypomethylating agents, Somatic mutations, Prognosi

Chronic myelomonocytic leukemia in younger patients : molecular and cytogenetic predictors of survival and treatment outcome

In patients with chronic myelomonocytic leukemia (CMML), age>65 years is an adverse prognostic factor. Our objective in the current study was to examine risk factors for survival and treatment outcome in 261 'young' adults with CMML, as defined by age \u2a7d65 years. In multivariable analysis, lower HB (P=0.01), higher circulating blast % (P=0.002), ASXL1 (P=0.0007) and SRSF2 mutations (P=0.008) and Mayo-French cytogenetic stratification (P=0.04) negatively impacted survival. Similarly, leukemia-free survival was independently affected by higher circulating blast % (P<0.0001), higher bone marrow blast % (P=0.0007) and the presence of circulating immature myeloid cells (P=0.0002). Seventy-five (29%) patients received hypomethylating agents (HMA), with the median number of cycles being 5, and the median duration of therapy being 5 months. The over-all response rate was 40% for azacitidine and 30% for decitabine. Fifty-three (24%) patients underwent an allogeneic hematopoietic stem cell transplant (AHSCT), with a response rate of 56% and a non-relapse mortality of 19%. Survival in young adults with CMML, although higher than in older patients, is poor and even worse in the presence of ASXL1 and SRSF2 mutations. Treatment outcome was more impressive with AHSCT than with HMA and neither was influenced by ASXL1/SRSF2 mutations or karyotype

Improved Upper Limit on the Neutrino Mass from a Direct Kinematic Method by KATRIN.

We report on the neutrino mass measurement result from the first four-week science run of the Karlsruhe Tritium Neutrino experiment KATRIN in spring 2019. Beta-decay electrons from a high-purity gaseous molecular tritium source are energy analyzed by a high-resolution MAC-E filter. A fit of the integrated electron spectrum over a narrow interval around the kinematic end point at 18.57&nbsp;keV gives an effective neutrino mass square value of (-1.0_{-1.1}^{+0.9})  eV^{2}. From this, we derive an upper limit of 1.1&nbsp;eV (90%&nbsp;confidence level) on the absolute mass scale of neutrinos. This value coincides with the KATRIN sensitivity. It improves upon previous mass limits from kinematic measurements by almost a factor of 2 and provides model-independent input to cosmological studies of structure formation

Influenza at the animal-human interface : a review of the literature for virological evidence of human infection with swine or avian influenza viruses other than A(H5N1)

Factors that trigger human infection with animal influenza virus progressing into a pandemic are poorly understood. Within a project developing an evidence-based risk assessment framework for influenza viruses in animals, we conducted a review of the literature for evidence of human infection with animal influenza viruses by diagnostic methods used. The review covering Medline, Embase, SciSearch and CabAbstracts yielded 6,955 articles, of which we retained 89; for influenza A(H5N1) and A(H7N9), the official case counts of the World Health Organization were used. An additional 30 studies were included by scanning the reference lists. Here, we present the findings for confirmed infections with virological evidence. We found reports of 1,419 naturally infected human cases, of which 648 were associated with avian influenza virus (AIV) A(H5N1), 375 with other AIV subtypes, and 396 with swine influenza virus (SIV). Human cases naturally infected with AIV spanned haemagglutinin subtypes H5, H6, H7, H9 and H10. SIV cases were associated with endemic SIV of H1 and H3 subtype descending from North American and Eurasian SIV lineages and various reassortants thereof. Direct exposure to birds or swine was the most likely source of infection for the cases with available information on exposure