Effect of reaction rate periodicity on detonation propagation

As an alternative to homogeneous reaction rates, we implement "synthetic" hot-spots through a depletion rate that is a function of the local pressure multiplied by a periodic function of the spatial coordinates. We investigate through numerical simulations how the detonation propagation is affected by the heterogeneous rate

Coarsening Strategies for Unstructured Multigrid Techniques with Application to Anisotropic Problems

Over the years, multigrid has been demonstrated as an efficient technique for solving inviscid flow problems. However, for viscous flows, convergence rates often degrade. This is generally due to the required use of stretched meshes (i.e., the aspect ratio AR = Δy/Δx < < 1) in order to capture the boundary layer near the body. Usual techniques for generating a sequence of grids that produce proper convergence rates on isotropic meshes are not adequate for stretched meshes. This work focuses on the solution of Laplace's equation, discretized through a Galerkin finite-element formulation on unstructured stretched triangular meshes. A coarsening strategy is proposed and results are discussed

A Level Set Approach to Eulerian-Lagrangian Coupling

We present a numerical method for coupling an Eulerian compressible flow solver with a Lagrangian solver for fast transient problems involving fluid-solid interactions. Such coupling needs arise when either specific solution methods or accuracy considerations necessitate that different and disjoint subdomains be treated with different (Eulerian or Lagrangian)schemes. The algorithm we propose employs standard integration of the Eulerian solution over a Cartesian mesh. To treat the irregular boundary cells that are generated by an arbitrary boundary on a structured grid, the Eulerian computational domain is augmented by a thin layer of Cartesian ghost cells. Boundary conditions at these cells are established by enforcing conservation of mass and continuity of the stress tensor in the direction normal to the boundary. The description and the kinematic constraints of the Eulerian boundary rely on the unstructured Lagrangian mesh. The Lagrangian mesh evolves concurrently, driven by the traction boundary conditions imposed by the Eulerian counterpart. Several numerical tests designed to measure the rate of convergence and accuracy of the coupling algorithm are presented as well. General problems in one and two dimensions are considered, including a test consisting of an isotropic elastic solid and a compressible fluid in a fully coupled setting where the exact solution is available

Shock and detonation modeling with the Mie-Grüneisen equation of state

We consider the numerical simulation of inviscid reactive flows with application to high density explosive detonation. The numerical model is based on the Euler equations and the Mie-Grüneisen equation of state extended to treat chemical energy release and expanded states. The equations are computed with a Roe-Glaister solver on a Cartesian mesh. We present results for two substances, a binder and an explosive. Our solution method is verified against the exact solution of the shock tube problem for solid materials. We show under what conditions a "physical" expansion shock can appear in this example. We then address the problem of modeling expanded states, and show results for a two-dimensional shock distraction around a sharp corner. In the last part of the paper, we introduce a detonation model that extends the Mie-Grüneisen equation of state to enable high explosive simulations without the complexity of mixture equations of state. We conclude with two examples of corner-turning computations carried out with a pressure-dependent reaction rate law

Cannabinoids in the treatment of epilepsy: current status and future prospects

Cannabidiol (CBD) is one of the prominent phytocannabinoids found in Cannabis sativa, differentiating from Δ9-tetrahydrocannabinol (THC) for its non-intoxicating profile and its antianxiety/antipsychotic effects. CBD is a multi-target drug whose anti-convulsant properties are supposed to be independent of endocannabinoid receptor CB1 and might be related to several underlying mechanisms, such as antagonism on the orphan GPR55 receptor, regulation of adenosine tone, activation of 5HT1A receptors and modulation of calcium intracellular levels. CBD is a lipophilic compound with low oral bioavailability (6%) due to poor intestinal absorption and high first-pass metabolism. Its exposure parameters are greatly influenced by feeding status (ie, high fatcontaining meals). It is mainly metabolized by cytochrome P 450 (CYP) 3A4 and 2C19, which it strongly inhibits. A proprietary formulation of highly purified, plant-derived CBD has been recently licensed as an adjunctive treatment for Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS), while it is being currently investigated in tuberous sclerosis complex. The regulatory agencies’ approval was granted based on four pivotal double-blind, placebocontrolled, randomized clinical trials (RCTs) on overall 154 DS patients and 396 LGS ones, receiving CBD 10 or 20 mg/kg/day BID as active treatment. The primary endpoint (reduction in monthly seizure frequency) was met by both CBD doses. Most patients reported adverse events (AEs), generally from mild to moderate and transient, which mainly consisted of somnolence, sedation, decreased appetite, diarrhea and elevation in aminotransferase levels, the last being documented only in subjects on concomitant valproate therapy. The interaction between CBD and clobazam, likely due to CYP2C19 inhibition, might contribute to some AEs, especially somnolence, but also to CBD clinical effectiveness. Cannabidivarin (CBDV), the propyl analogue of CBD, showed anti-convulsant properties in pre-clinical studies, but a plant-derived, purified proprietary formulation of CBDV recently failed the Phase II RCT in patients with uncontrolled focal seizures

High serum osteopontin levels are associated with prevalent fractures and worse lipid profile in post-menopausal women with type 2 diabetes

Purpose: Patients with type 2 diabetes (T2DM) have increased fracture risk. Osteopontin (OPN) is a protein involved in bone remodeling and inflammation. The aim of this study was to evaluate the association of OPN with fracture prevalence and with metabolic parameters in post-menopausal women with T2DM. Methods: Sixty-four post-menopausal women with T2DM (age 67.0 ± 7.8 years, diabetes duration 8.9 ± 6.7 years), enrolled in a previous study, were followed up (3.6 ± 0.9 years). Previous fragility fractures were recorded. The FRAX score (without BMD) was calculated and biochemical parameters (plasma glucose, HbA1c, lipid profile and renal function) were assessed. Serum 25OH-vitamin D, calcium, PTH and OPN were evaluated at baseline. The association between OPN and fracture prevalence at baseline was evaluated by a logistic model. Results: OPN levels were higher in patients with previous fractures (n.25) than in patients without previous fractures at baseline (n.39) (p = 0.006). The odds of having fractures at baseline increased by 6.7 (1.9–31.4, 95% CI, p = 0.007) for each increase of 1 ng/ml in OPN levels, after adjustment for vitamin D and HbA1c levels. Fracture incidence was 4.7%. Higher OPN associated with a decrease in HDL-cholesterol (p = 0.048), after adjustment for age, basal HDL-cholesterol, basal and follow-up HbA1c and follow-up duration. 25OH-vitamin D associated with an increase in FRAX-estimated probability of hip fracture at follow-up (p = 0.029), after adjustment for age, 25OH-vitamin D and time. Conclusions: In post-menopausal women with T2DM, OPN might be a useful marker of fracture and worse lipid profile

Normotensive offspring with non-dipper hypertensive parents have abnormal sleep pattern.

The objective of this study was to determine whether abnormal microstructure of sleep in non-dipper hypertensive patients was present in their offspring. Subjects included 11 normotensive offspring of non-dipper hypertensive parents (FH + ND), 6 of dipper hypertensive parents (FH + D) and 5 of normotensive parents (Controls). We measured blood pressure beat-to-beat by Finapres and all stages of sleep by polysomnographically recording simultaneously during spontaneous nocturnal sleep. We analysed blood pressure pattern for 4-min long random periods while the subjects were awake and during all stages of sleep; sleep efficiency (SE), sleep latency (SL), delta-sleep latency (delta-SL), REM sleep latency (REM-SL), Stage 1, Stage 2, Stage 3, Stage 4 and REM duration and percentage values, and microstructural aspects of sleep (arousal and microarousal temporization and features). FH + D and controls showed a fall in blood pressure greater than 10% in all stages of NREM sleep and in the FH + ND blood pressure fall in less than 10% of waking values in all NREM stages. REM sleep and heart rate were similar in the three groups during all stages of sleep. FH + ND showed the same number of arousals but more microarousals than FH + D and controls (p < 0.0001). Microarousals induced several stage shifts through lighter sleep. For this reason, FH + ND spent more time in stage 2 than FH + D and controls. In conclusion, offspring of non-dipper hypertension parents showed a greater number of microarousals than the other two groups

Auditive direct in utero observation (Audio): A randomized controlled trial for a prenatal demonstration of fetal hearing

Introduction: The objective of this randomized controlled study was to demonstrate whether acoustic stimulation in utero is associated with fetal reactivity which is documentable by car-diotocography. Materials and methods: A monocentric randomized controlled trial was performed at a single university tertiary hospital between September 2016 and July 2017. This study was registered as a randomized clinical trial on clinicaltrail.gov (registration number NCT04622059). Unselected pregnancies at term of gestation were consecutively recruited for the purpose of this study. After 10 min of normal cardiotocography without accelerations (non-stress-test with a basal frequency between 110 and 150 beats/min, normal variability between 6 and 15 b/min, no accelerations, and no fetal movements), fetuses were randomized at a 1:1 ratio to either of the two groups. Fetuses in group A (n = 105) received acoustic stimulation after 10 min from the beginning of the CTG, whereas fetuses in group B received no stimulation (n = 105). The outcome variables investigated were the lapse of time between the beginning of the CTG and the occurrence of the first accelera-tion, and the lapse of time between the beginning of the CTG and the first fetal movement noticed. Results: The lapse of time between the beginning of the CTG and the occurrence of the first acceleration was significantly shorter in the group with acoustic stimulation compared to the other group (14.87 ± 5.01 vs. 21.90 ± 6.94 min, p-value &lt; 0.001 log-rank test). Similarly, the lapse of time between the beginning of the CTG and the occurrence of the first fetal movement was significantly shorter in group A compared to group B (17.77 ± 7.62 vs. 23.28 ± 7.61 min, p-value &lt; 0.001, log-rank test). Fetal cardiac acceleration and the occurrence of a fetal movement during the first 20 min of the CTG were more frequently recorded in group A compared to group B (respectively, 15% vs. 5% and 20% vs. 8%). Conclusion: This RCT showed an early fetal reaction following auditive stimulus, documentable by cardiotocography. Further research is needed to investigate a possible role of acoustic stimulation in utero for the prenatal diagnosis of congenital hypoacusis

GADA titer-related risk for organ-specific autoimmunity in LADA subjects subdivided according to gender (NIRAD study 6).

CONTEXT: Latent autoimmune diabetes in adults (LADA) includes a heterogeneous population wherein, based on glutamic acid decarboxylase antibody (GADA) titer, different subgroups of subjects can be identified. OBJECTIVE: The aim of the present study was to evaluate GADA titer-related risk for β-cell and other organ-specific autoimmunity in LADA subjects. METHODS: Adult-onset autoimmune diabetes subjects (n=236) and type 2 diabetes (T2DM) subjects (n=450) were characterized for protein tyrosine phosphatase (IA-2IC and IA-2(256-760)), zinc transporter 8 (ZnT8), thyroid peroxidase, (TPO), steroid 21-hydroxylase (21-OH), tissue transglutaminase (tTG), and antiparietal cell (APC) antibodies. RESULTS: High GADA titer compared to low GADA titer showed a significantly higher prevalence of IA-2IC, IA-2(256-760), ZnT8, TPO, and APC antibodies (P≤0.04 for all comparison). 21-OH antibodies were detected in 3.4% of high GADA titer. A significant decreasing trend was observed from high GADA to low GADA and to T2DM subjects for IA-2(256-760), ZnT8, TPO, tTG, and APC antibodies (P for trend≤0.001). TPO was the only antibody showing a different prevalence between gender; low GADA titer and T2DM female patients had a higher frequency of TPO antibody compared to males (P=0.0004 and P=0.0006, respectively), where the presence of high GADA titer conferred an odds ratio of 8.6 for TPO compared to low GADA titer. After subdividing high and low GADA titer subjects according to the number of antibodies, we observed that 73.3% of high GADA titer subjects were positive for at least one or more antibodies, compared to 38.3% of low GADA titer (P<0.0001). CONCLUSIONS: In LADA subjects, high GADA titer was associated with a profile of more severe autoimmunity and, in male gender, specifically predisposed to thyroid autoimmunity. A regular screening for other antibodies is recommended in LADA patients according to GADA titer and gender

Preliminary bioassays on the susceptibility of stone fruits rootstocks to Capnodis tenebrionis (L.).

Capnodis tenebrionis (L.) (Coleoptera: Buprestidae), the so called Mediterranean flat-headed root-borer, is an economically important phytophagous pest species mainly on stone fruit trees (apricot, plum, cherry, peach and nectarine). Chemicals and Entomopathogenic nematodes are used for the control of adults and neonate larvae, respectively. Further control means are under investigations in order to have more options within Integrated Pest Control strategies. This study is aimed at investigating the susceptibility of rootstocks to the larvae of C. tenebrionis. Two bioassays were carried out during 2016 and 2017. A first bioassay was based on the evaluation of a potential antixenosis action expressed by neonate larvae infesting twigs of rootstocks (Marianna 26, Barrier, Adesoto, Mylaboran 29C, GF677, Garnem, Cab 6P, Max Ma60 and Colt). This bioassay allowed to process a high number of different rootstocks in a short time. It has a preliminary value. The second bioassay assessed the antibiosis influence of the rootstocks through the breeding of larvae (since the neonate ones) on artificial diets containing bark flour of Adesoto, Cab 6P, Colt, Garnem, GF677, Max Ma60, Montclar and 29C rootstock. The first bioassay showed that Colt, Mylaboran 29C and GF677 were the most susceptible rootstocks to larval infestation of C. tenebrionis and Max Ma60 was less favorable to the pest. Concerning the effects of the diet, larvae reared on a diet containing Montclar, Cab 6P and GF 677 bark flour had a mean daily increase of their weight higher that those reared on cortex tissues of other genotypes whereas Garnem and Colt had a lower increase