Nonlinear Advection-Diffusion-Reaction Phenomena Involved in the Evolution and Pumping of Oil in Open Sea: Modeling, Numerical Simulation and Validation Considering the Prestige and Oleg Naydenov Oil Spill Cases.

The main goal of this article is to improve upon a previous model used to simulate the evolution of oil spots in the open sea and the effect of a skimmer ship pumping oil out from the spots. The concentration of the pollutant is subject to the effects of wind and sea currents, diffusion, and the pumping action of a skimmer (i.e., cleaning) ship that follows a pre-assigned trajectory. This implies that the mathematical model is of the advection-diffusion-reaction type. A drawback of our previous model was that diffusion was propagating with infinite velocity; in this article, we use an improved modeling relying on a nonlinear diffusion term, implying that diffusion propagates with finite velocity. To reduce numerical diffusion when approximating the advection part of the model, we consider second order discretization schemes with nonlinear flux limiters. We consider also absorbing boundary conditions to insure accurate results near the boundary. To reduce CPU time we use an operator-splitting scheme for the time discretization. Finally, we also introduce the modeling of coastlines and dynamic sources of pollutant. The novel approach we advocate in this article is validated by comparing our numerical results with real life measurements from the Oleg Naydenov and the Prestige oil spills, which took place in Spain in 2015 and 2002, respectively

Modeling and optimization of activated sludge bioreactors for wastewater treatment taking into account spatial inhomogeneities

In this work, we study optimal and suboptimal control strategies for the treatment of a polluted water resource by using aside a continuous bioreactor. The control consists in choosing the inlet volumetric flow rate for filling the bioreactor with contaminated water from a considered resource (lake, reservoir, water-table, …). The treated outflow returns to the resource. We tackle an optimization problem which aims to minimize the time needed to reach a prescribed minimal value of contamination in the resource by choosing the input flow. Next, we study the influence of inhomogeneities of concentrations in the bioreactor, considering a system based on partial differential equations which describe its dynamics. We show that applying the optimal feedback control derived for perfectly mixed bioreactor does not allow to reach the target with small diffusion parameters as it drives the bioreactor to washout (the bioreactor equilibrium with no biomass). In this case, a suboptimal feedback (which reaches the target in finite time) is obtained with the help of a Hybrid Genetic Algorithm. Furthermore, we consider that the fluid flow velocity of the water entering into the bioreactor follows either a uniform or a nonuniform profile, showing that the optimal volumetric flow rates obtained with the uniform profile are not optimal if the profile is nonuniform, even when high diffusion coefficients are considered in the model

What Matters Most to Patients and Rheumatologists? A Discrete Choice Experiment in Rheumatoid Arthritis

Introduction: To determine patient and rheumatologist preferences for rheumatoid arthritis (RA) treatment attributes in Spain and to evaluate their attitude towards shared decision-making (SDM). Methods: Observational, descriptive, exploratory and cross-sectional study based on a discrete choice experiment (DCE). To identify the attributes and their levels, a literature review and two focus groups (patients [P] = 5; rheumatologists [R] = 4) were undertaken. Seven attributes with 2–4 levels were presented in eight scenarios. Attribute utility and relative importance (RI) were assessed using a conditional logit model. Patient preferences for SDM were assessed using an ad hoc questionnaire. Results: Ninety rheumatologists [52.2% women; mean years of experience 18.1 (SD: 9.0); seeing an average of 24.4 RA patients/week (SD: 15.3)] and 137 RA patients [mean age: 47.5 years (SD: 10.7); 84.0% women; mean time since diagnosis of RA: 14.2 years (SD: 11.8) and time in treatment: 13.2 years (SD: 11.2), mean HAQ score 1.2 (SD: 0.7)] participated in the study. In terms of RI, rheumatologists and RA patients viewed: time with optimal QoL: R: 23.41%/P: 35.05%; substantial symptom improvement: R: 13.15%/P: 3.62%; time to onset of treatment action: R: 16.24%/P: 13.56%; severe adverse events: R: 10.89%/P: 11.20%; mild adverse events: R: 4.16%/P: 0.91%; mode of administration: R: 25.23%/P: 25.00%; and added cost: R: 6.93%/P: 10.66%. Nearly 73% of RA patients were involved in treatment decision-making to a greater or lesser extent; however, 27.4% did not participate at all. Conclusion: Both for rheumatologists and patients, the top three decision-making drivers are time with optimal quality, treatment mode of administration and time to onset of action, although in different ranking order. Patients were willing to be more involved in the treatment decision-making process

The domestication syndrome in Phoenix dactylifera seeds : toward the identification of wild date palm populations

Investigating crop origins is a priority to understand the evolution of plants under domestication, develop strategies for conservation and valorization of agrobiodiversity and acquire fundamental knowledge for cultivar improvement. The date palm(Phoenix dactylifera L.) belongs to the genus Phoenix, which comprises 14 species morphologically very close, sometimes hardly distinguishable. It has been cultivated for millennia in the Middle East and in North Africa and constitutes the keystone of oasis agriculture. Yet, its origins remain poorly understood as no wild populations are identified. Uncultivated populations have been described but they might represent feral, i.e. formerly cultivated, abandoned forms rather than truly wild populations. In this context, this study based on morphometrics applied to 1625 Phoenix seeds aims to (1) differentiate Phoenix species and (2) depict the domestication syndrome observed in cultivated date palm seeds using other Phoenix species as a "wild" reference. This will help discriminate truly wild from feral forms, thus providing new insights into the evolutionary history of this species. Seed size was evaluated using four parameters: length, width, thickness and dorsal view surface. Seed shape was quantified using outline analyses based on the Elliptic Fourier Transform method. The size and shape of seeds allowed an accurate differentiation of Phoenix species. The cultivated date palm shows distinctive size and shape features, compared to other Phoenix species: seeds are longer and elongated. This morphological shift may be interpreted as a domestication syndrome, resulting from the long-term history of cultivation, selection and human-mediated dispersion. Based on seed attributes, some uncultivated date palms from Oman may be identified as wild. This opens new prospects regarding the possible existence and characterization of relict wild populations and consequently for the understanding of the date palm origins. Finally, we here describe a pipeline for the identification of the domestication syndrome in seeds that could be used in other crops

Antihypertensive Mechanism of Lactoferrin-Derived Peptides: Angiotensin Receptor Blocking Effect

Texto del artículo, no incluye figuras ni tablas.Looking for antihypertensive mechanisms beyond ACE inhibition, we assessed whether lactoferrin (LF)-derived peptides can act as receptor blockers to inhibit vasoconstriction induced by angiotensin II or endothelin-1. The lactoferricin B (LfcinB)-derived peptide LfcinB20–25 (RRWQWR), the low molecular weight LF hydrolysate (LFH < 3 kDa), and two peptides identified in LFH < 3 kDa (LIWKL and RPYL) were tested in ex vivo assays of vasoactive responses. The peptide RPYL was tested in radioligand receptor binding assays. Both LFH < 3 kDa and individual peptides inhibited angiotensin II-induced vasoconstriction. RPYL showed the highest ex vivo inhibitory effect and also inhibited binding of [125I]-(Sar1,Ile8)-angiotensin II to AT1 receptors. By contrast, neither LFH < 3 kDa nor RPYL inhibited endothelin-1 and depolarization-induced vasoconstrictions. In conclusion, LF-derived peptides selectively inhibit angiotensin II-induced vasoconstriction by blocking angiotensin AT1 receptors. Therefore, inhibition of angiotensin II-induced vasocontriction is suggested as a mechanism contributing along with ACE inhibition to the antihypertensive effect of some LF-derived peptides.This work was supported by Grants AGL2010-21009 from Ministerio de Educación y Ciencia – FEDER, Consolider Ingenio 2010, Fun-C-Food, CSD2007-00063, and network RETICS INVICTUS – RD12/0014/0004 from Instituto de Salud Carlos III. R. Fernández-Musoles is the recipient of a fellowship from Ministerio de Educación y Ciencia (BES-2008-004472).Peer reviewe

Muscle-Type Nicotinic Receptor Blockade by Diethylamine, the Hydrophilic Moiety of Lidocaine

Lidocaine bears in its structure both an aromatic ring and a terminal amine, which can be protonated at physiological pH, linked by an amide group. Since lidocaine causes multiple inhibitory actions on nicotinic acetylcholine receptors (nAChRs), this work was aimed to determine the inhibitory effects of diethylamine (DEA), a small molecule resembling the hydrophilic moiety of lidocaine, on Torpedo marmorata nAChRs microtransplanted to Xenopus oocytes. Similarly to lidocaine, DEA reversibly blocked acetylcholine-elicited currents (IACh) in a dose-dependent manner (IC50 close to 70 μM), but unlike lidocaine, DEA did not affect IACh desensitization. IACh inhibition by DEA was more pronounced at negative potentials, suggesting an open-channel blockade of nAChRs, although roughly 30% inhibition persisted at positive potentials, indicating additional binding sites outside the pore. DEA block of nAChRs in the resting state (closed channel) was confirmed by the enhanced IACh inhibition when pre-applying DEA before its co-application with ACh, as compared with solely DEA and ACh co-application. Virtual docking assays provide a plausible explanation to the experimental observations in terms of the involvement of different sets of drug binding sites. So, at the nAChR transmembrane (TM) domain, DEA and lidocaine shared binding sites within the channel pore, giving support to their open-channel blockade; besides, lidocaine, but not DEA, interacted with residues at cavities among the M1, M2, M3, and M4 segments of each subunit and also at intersubunit crevices. At the extracellular (EC) domain, DEA and lidocaine binding sites were broadly distributed, which aids to explain the closed channel blockade observed. Interestingly, some DEA clusters were located at the α-γ interphase of the EC domain, in a cavity near the orthosteric binding site pocket; by contrast, lidocaine contacted with all α-subunit loops conforming the ACh binding site, both in α-γ and α-δ and interphases, likely because of its larger size. Together, these results indicate that DEA mimics some, but not all, inhibitory actions of lidocaine on nAChRs and that even this small polar molecule acts by different mechanisms on this receptor. The presented results contribute to a better understanding of the structural determinants of nAChR modulation.This work was supported by grants BFU2012-31359, BFU2012-39092-C02-01, BFU2011-25920, and CSD2008-00005 from the MINECO and PROMETEO/2014/11 from GVA (Spain)

Implementation and validation of an economic module for the epidemiological model Be-FAST to predict the costs generated by livestock diseases epidemics. Application to the Classical Swine Fever case in Spain.

Classical Swine Fever (CSF) is one of the most harmful livestock di-seases for the economy of the swine sector worldwide. Specifically in Spain, the costs in the two last CSF outbreaks (1997 and 2001) have been estimated above 108 million euros. In this work, we aim to evaluate the economic impact of important livestock disease epidemics, and particularly the CSF in Spain. This study starts with a preliminary classification of the costs associated with CSF epidemics. In order to estimate the expected costs of a given epidemic in a considered area, a new economic module has been integrated into the epidemiological model Be-FAST, a time-spatial stochastic spread mathematical model for studying the transmission of diseases within and between farms. The input data for economic parameters have been obtained from entities related with the swine industry in Spain. The new Be-FAST module is tested by comparing the results obtained with historical data from CSF epidemics in Spain. The outcomes show that severe CSF epidemics also have a strong economic impact with around 80% of the costs related to animal culling, while costs associated with control measures are directly associated with the number of infected farms and the duration of the epidemic. The results presented in this work are expected to provide valuable information to decision makers, including animal health officials and insurance companies, and can be extended to other livestock diseases or used to predict the economic impact of future outbreaks

A replication study confirms the association of TNFSF4 (OX40L) polymorphisms with systemic sclerosis in a large European cohort

&lt;p&gt;&lt;b&gt;Objectives&lt;/b&gt; The aim of this study was to confirm the influence of TNFSF4 polymorphisms on systemic sclerosis (SSc) susceptibility and phenotypic features.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methods&lt;/b&gt; A total of 8 European populations of Caucasian ancestry were included, comprising 3014 patients with SSc and 3125 healthy controls. Four genetic variants of TNFSF4 gene promoter (rs1234314, rs844644, rs844648 and rs12039904) were selected as genetic markers.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Results&lt;/b&gt; A pooled analysis revealed the association of rs1234314 and rs12039904 polymorphisms with SSc (OR 1.15, 95% CI 1.02 to 1.31; OR 1.18, 95% CI 1.08 to 1.29, respectively). Significant association of the four tested variants with patients with limited cutaneous SSc (lcSSc) was revealed (rs1234314 OR 1.22, 95% CI 1.07 to 1.38; rs844644 OR 0.91, 95% CI 0.83 to 0.99; rs844648 OR 1.10, 95% CI 1.01 to 1.20 and rs12039904 OR 1.20, 95% CI 1.09 to 1.33). Association of rs1234314, rs844648 and rs12039904 minor alleles with patients positive for anti-centromere antibodies (ACA) remained significant (OR 1.23, 95% CI 1.10 to 1.37; OR 1.12, 95% CI 1.01 to 1.25; OR 1.22, 95% CI 1.07 to 1.38, respectively). Haplotype analysis confirmed a protective haplotype associated with SSc, lcSSc and ACA positive subgroups (OR 0.88, 95% CI 0.82 to 0.96; OR 0.88, 95% CI 0.80 to 0.96; OR 0.86, 95% CI 0.77 to 0.97, respectively) and revealed a new risk haplotype associated with the same groups of patients (OR 1.14, 95% CI 1.03 to 1.26; OR 1.20, 95% CI 1.08 to 1.35; OR 1.23, 95% CI 1.07 to 1.42, respectively).&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusions&lt;/b&gt; The data confirm the influence of TNFSF4 polymorphisms in SSc genetic susceptibility, especially in subsets of patients positive for lcSSc and ACA.&lt;/p&gt