We present the results of a numerical investigation of the mixing within drops caused by surface tension variations. With microfluidic applications in mind, we simulate drops surrounded by a fluid of ...equal density and viscosity. We investigate both stationary coalescing drops and steadily flowing drops, and study the influence of drop size ratio, viscous effects, and surface tension variations. We measure the mixing efficiency using the variance of the concentration distribution and find that surface tension variations may result in faster mixing than geometric effects.
Background
Ofatumumab is a high-efficacy disease-modifying therapy (DMT) approved for first-line treatment of relapsing-remitting multiple sclerosis (RRMS) in Canada.
Objective
The aim of this study ...was to evaluate the cost effectiveness of ofatumumab from a Canadian healthcare system perspective.
Methods
A Markov cohort model was run over 65 years using annual cycles, 1.5% annual discount rate, and 100% treatment discontinuation at 10 years. The British Columbia database informed natural history transition probabilities. Treatment efficacy for DMTs were sourced from a network meta-analysis. Clinical trial data were used to estimate probabilities for treatment-related adverse events. Health utilities and costs were obtained from Canadian sources (if available) and the literature.
Results
Among first-line indicated therapies for RRMS, ofatumumab was dominant (more effective, lower costs) over teriflunomide, interferons, dimethyl fumarate, and ocrelizumab. Compared with glatiramer acetate and best supportive care, ofatumumab resulted in incremental cost-effectiveness ratios (ICERs) of $24,189 Canadian dollars per quality-adjusted life-year (QALY) and $28,014/QALY, respectively. At a willingness-to-pay threshold of $50,000/QALY, ofatumumab had a 64.3% probability of being cost effective. Among second-line therapies (scenario analysis), ofatumumab dominated natalizumab and fingolimod and resulted in an ICER of $50,969 versus cladribine.
Conclusions
Ofatumumab is cost effective against all comparators and dominant against all currently approved and reimbursed first-line DMTs for RRMS, except glatiramer acetate.
We simulate the evolution of the steady-state interface in the selective withdrawal regime. Selective withdrawal ends when the upward pull exerted by the viscous flow in the withdrawing liquid layer ...overcomes the downward force due to surface tension. The lower-layer dynamics are unimportant. The dominant contribution to the surface-tension force comes from the large area where the interface is weakly deflected, instead of the small area where the surface is most distorted. A scaling estimate based on this idea yields results that agree quantitatively with both simulations and previous experiments.
In this Brownian dynamics simulation study on the formation of aggregates made of spherical particles, we build on the well-established diffusion-limited cluster aggregation (DLCA) model. We include ...rotational effects, allow diffusivities to be size-dependent as is physically relevant, and incorporate settling under gravity. We numerically characterize the growth dynamics of aggregates and find that their radius of gyration, R g, grows approximately as R g ∼ t 1.02 for classical DLCA but slows to an approximate growth rate of R g ∼ t 0.71 when diffusivity is size-dependent. We also analyze the fractal structure of the resulting aggregates and find that their fractal dimension, d, decreases from d ≈ 1.8 for classical DLCA to d ≈ 1.7 when size-dependent rotational diffusion is included. The addition of settling effects further reduces the fractal dimension observed to d ≈ 1.6 and appears to result in aggregates with a vertical extent marginally smaller than their horizontal extent.
Transforming growth factor (TGF)-β1 plays an essential role in cell growth and differentiation. It is also considered as a gatekeeper of immune homeostasis with gene disruption leading to autoimmune ...and inflammatory diseases. TGF-β1 is produced as an inactive precursor polypeptide that can be efficiently secreted but correct proteolytic cleavage is an essential step for its activation. Assessment of the cleavage site has revealed a unique R-H-R-R sequence reminiscent of proprotein convertase (PC) recognition motifs and has previously demonstrated that this PC-like cleavage site is correctly cleaved by furin, a member of the PC family. Here we report that among PC members, furin more closely satisfies the requirements needed to fulfill the role of a genuine TGF-β1 convertase. Even though six members of the PC family have the ability to cleave TGF-β1, ectopic expression of α
1-antitrypsin Portland (α
1-AT-PDX), a potent furin inhibitor, blocked 80% of TGF-β1 processing mediated by endogenous enzymes as demonstrated in an
in vitro digestion assay. Genetic complementation of a furin-deficient LoVo cell line with the wild-type gene restores the production of mature and bioactivable TGF-β1. Moreover, both furin and TGF-β are coordinately expressed and regulated
in vitro and
in vivo in the hematopoietic and immune system, an important tissue target. These results demonstrate for the first time that furin is an authentic and adaptive TGF-β1-converting enzyme whereas other members of the PC family might substitute or supplement furin activity. Our study advances our comprehension of the complexity of the TGF-β system and should facilitate the development of therapeutically useful TGF-β inhibitors.
L'art populaire est le reflet d'une société, de la perspective de ses créateurs, dont les approches sont tantôt traditionnelles et rationnelles, tantôt indisciplinées et débridées. D'hier ou ...d'aujourd'hui, l'art populairen révèle toute son expressivité, met en valeur la beauté des objets anciens.Du coq à l'âme : L'art populaire au Québecvient circonscrire l'art populaire et présenter son évolution dans le temps, depuis sa forme traditionnelle, fort ancienne, jusqu'à sa forme indisciplinée, plus récente, du graffiti.Cet ouvrage est le résultat de plusieurs années de recherche et de rencontres avec des créateurs, des collectionneurs et des chercheurs, tous passionnés de cette forme de créativité originale et authentique.Une magnifique synthèse de la production et de l'évolution de l'art populaire, l'histoire culturelle et sociale et la créativité d'artistes québécois, souvent peu reconnus.L'anthropologue Jean-François Blanchette jette un regard historique et photographique sur les collections d'art populaire québécois du Musée canadien de l'histoire, dont la très prestigieuse collection de Nettie Covey Sharpe, acquise en 2002.
Drop coalescence was studied using numerical simulations. Liquid drops were made to coalesce with a body of the same liquid, either a reservoir or a drop of different size, each with negligible ...impact velocity. We considered either gas or liquid as a surrounding fluid, and experimental results are discussed for the gas–liquid set-up. Under certain conditions, a drop will not fully coalesce with the liquid reservoir, leaving behind a daughter drop. Partial coalescence is observed for systems of low viscosity, characterized by a small Ohnesorge number, where capillary waves remain sufficiently vigourous to distort the drop significantly. For drops coalescing with a flat interface, we determine the critical Ohnesorge number as a function of Bond number, as well as density and viscosity ratios of the fluids. Studying the coalescence of two drops of different sizes reveals that partial coalescence may occur in low-viscosity systems provided the size ratio of the drops exceeds a certain threshold. We also determine the extent to which the process of partial coalescence is self-similar and find that the viscosity of the drop has a large effect on the droplet's vertical velocity after pinch off. Finally, we report on the formation of satellite droplets generated after a first pinch off and on the ejection of a jet of tiny droplets during coalescence of a parent drop significantly deformed by gravity.
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