Probing the Effects of the Well-mixed Assumption on Viral Infection Dynamics

Viral kinetics have been extensively studied in the past through the use of spatially well-mixed ordinary differential equations describing the time evolution of the diseased state. However, emerging spatial structures such as localized populations of dead cells might adversely affect the spread of infection, similar to the manner in which a counter-fire can stop a forest fire from spreading. In a previous publication (Beauchemin et al., 2005), a simple 2-D cellular automaton model was introduced and shown to be accurate enough to model an uncomplicated infection with influenza A. Here, this model is used to investigate the effects of relaxing the well-mixed assumption. Particularly, the effects of the initial distribution of infected cells, the regeneration rule for dead epithelial cells, and the proliferation rule for immune cells are explored and shown to have an important impact on the development and outcome of the viral infection in our model.Comment: LaTeX, 12 pages, 22 EPS figures, uses document class REVTeX 4, and packages float, graphics, amsmath, and SIunit

Attenuation of microvascular function in those with cardiovascular disease is similar in patients of Indian Asian and European descent

addresses: Institute of Biomedical and Clinical Science, Peninsula Medical School (Exeter), University of Exeter, UK. [email protected]: PMCID: PMC2823616types: Comparative Study; Journal Article; Multicenter Study; Research Support, Non-U.S. Gov't© 2010 Strain et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Indian Asians are at increased risk of cardiovascular death which does not appear to be explained by conventional risk factors. As microvascular disease is also more prevalent in Indian Asians, and as it is thought to play a role in the development of macrovascular disease, we decided to determine whether impaired microcirculation could contribute to this increased cardiovascular risk in Indian Asians

Modulational instability in a silicon-on-insulator directional coupler: Role of the coupling-induced group velocity dispersion

We report frequency conversion experiments in silicon-on-insulator (SOI) directional couplers. We demonstrate that the evanescent coupling between two subwavelength SOI waveguides is strongly dispersive and significantly modifies modulational instability (MI) spectra through the coupling induced group velocity dispersion (GVD). As the separation between two 380-nm-wide silicon photonic wires decreases, the increasing dispersion of the coupling makes the GVD in the symmetric supermode more normal and suppresses the bandwidth of the MI gain observed for larger separations

Effects of semaglutide on stroke subtypes in type 2 diabetes: post hoc analysis of the randomised SUSTAIN 6 & PIONEER 6

This is the final version. Available on open access from Lippincott, Williams & Wilkins via the DOI in this record Background: Glucagon-like peptide-1 receptor agonists, including semaglutide, may reduce stroke risk in people with type 2 diabetes (T2D). This post hoc analysis examined the subcutaneous and oral semaglutide effects, versus placebo, on stroke and its subtypes in people with T2D at high cardiovascular (CV) risk. Methods: SUSTAIN 6 and PIONEER 6 were randomised CV outcome trials of subcutaneous and oral semaglutide in people with T2D at high CV risk, respectively. Time to first stroke and stroke subtypes were analysed using a Cox proportional hazards model stratified by trial with pooled treatment as a factor. The impact of prior stroke, prior myocardial infarction or stroke, age, sex, systolic blood pressure, estimated glomerular filtration rate, and prior atrial fibrillation on treatment effects was assessed using interaction p-values. Risk of major adverse CV event (MACE) was analysed according to prior stroke. Results: 106/6480 participants had a stroke (1.0 event/100 patient-years of observation [PYO]). Semaglutide reduced incidence of any stroke versus placebo (0.8 vs 1.1 events/100 PYO; HR 0.68, 95%CI 0.46–1.00;p=0.048), driven by significant reductions in risk of small-vessel occlusion (0.3 vs 0.7 events/100 PYO; HR 0.51, 95%CI 0.29–0.89;p=0.017). HRs for risk of any stroke with semaglutide versus placebo were 0.60 (95%CI 0.37–0.99; 0.5 vs 0.9 events/100 PYO) and 0.89 (95%CI 0.47–1.69; 2.7 vs 3.0 events/100 PYO) in those without and with prior stroke, respectively. Except for prior atrial fibrillation (pinteraction=0.025), no significant interactions were observed between treatment effects on risk of any stroke and subgroups investigated, or between treatment effects on risk of MACE and prior stroke (pinteraction>0.05 for all). Conclusions: Semaglutide reduced incidence of any first stroke during the trials versus placebo in people with T2D at high CV risk, primarily driven by small-vessel occlusion prevention. Semaglutide treatment, versus placebo, lowered the risk of stroke irrespective of prior stroke at baseline. Clinical Trial Registration Information: SUSTAIN 6: NCT01720446 (https://clinicaltrials.gov/ct2/show/NCT01720446); PIONEER 6: NCT02692716 (https://clinicaltrials.gov/ct2/show/NCT02692716).Novo Nordisk A/S (Søborg, Denmark

EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion on the substantiation of a health claim related to E<em>ff</em>_EXT™ and maintenance of normal joint mobility pursuant to Article 13(5) of Regulation (EC) No 1924/2006

Following an application from Nutrilinks Sarl, submitted pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of Belgium, the Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to EffEXT™ and maintenance of normal joint mobility. The Panel considers that EffEXT™, which is standardised pure krill oil, is sufficiently characterised. The claimed effect proposed by the applicant is “contributes to support joint flexibility”. The Panel considers that maintenance of normal joint mobility is a beneficial physiological effect. The applicant identified one human intervention study as being pertinent to the health claim. The Panel notes that chronic inflammation was an inclusion criterion of the study, that a significant number of the patients recruited were reported to have confirmed diagnosis of osteoarthritis, rheumatoid arthritis, or of both cardiovascular disease and osteoarthritis, and that the WOMAC osteoarthritis questionnaire was administered only to patients with arthritic disease (osteoarthritis or rheumatoid arthritis). The Panel also notes that no evidence which could justify the extrapolation of the results, obtained in patients with joint diseases characterised by chronic inflammation, to the target population, subjects without chronic joint diseases, was provided by the applicant. The Panel considers that no conclusions can be drawn from this study for the scientific substantiation of the claim. The Panel concludes that a cause and effect relationship has not been established between the consumption of EffEXT™ and maintenance of normal joint mobility

EFSA NDA Panel (EFSA Panel on Dietetic Products, Nutrition and Allergies), 2013 . S tatement on the safety of ' Cetyl Myristoleate Complex ' as an ingredient in food supplements

Following a request from the European Commission, the Panel on Dietetic Products, Nutrition and Allergies was asked to update its opinion on the safety of ‘Cetyl Myristoleate Complex’ (CMC) as a novel food ingredient in the light of a new repeated dose 90-day oral toxicity study in mice. In its previous opinion of 2010, the Panel concluded that based on the available data, the safety of CMC as an ingredient in food supplements has not been established. This conclusion was based on the considerations that in the absence of appropriate data on absorption, distribution, metabolism and excretion, the provided toxicological data were insufficient. Whereas the applicant considers that the NOAEL of CMC in this new 90-day study was 1000 mg/kg body weight (bw), the highest dose tested, the Panel considers that this study and study report has many shortcomings to be a reliable source of information supporting the absence of adverse effects of the parent material CMC. The Panel concludes that the safety of 'Cetyl Myristoleate Complex' has not been established

EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion on the substantiation of a health claim related to ♀EFAX™ and reduction of menstrual discomfort pursuant to Article 13(5) of Regulation (EC) No 1924/2006

Following an application from Nutrilinks Sarl submitted for authorisation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of Cyprus, the Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to ♀EFAX™ and reduction of menstrual discomfort. The food, ♀EFAX™, which is standardised pure krill oil and is the subject of the health claim, is sufficiently characterised. The claimed effect, reduction of menstrual discomfort, is a beneficial physiological effect. No human intervention studies from which conclusions could be drawn for the scientific substantiation of the claim were provided by the applicant. A cause and effect relationship has not been established between the consumption of ♀EFAX™ and reduction of menstrual discomfort