A Coupled FEM-BEM Approach for the Solution of the Free-Boundary Axi-Symmetric Plasma Equilibrium Problem

In this paper we present a coupled Finite Element Method – Boundary Element Method (FEM-BEM) approach for the solution of the free-boundary axi-symmetric plasma equilibrium problem. The proposed method, obtained from an improvement of the Hagenow-Lackner coupling method, allows to efficiently model the equilibrium problem in unbounded domains by discretizing only the plasma region; the external conductors can be modelled either as 2D or 3D models, according to the problem of interest. The paper explores different iterative methods for the solution of the nonlinear Grad-Shafranov equation, such as Picard, Newton-Raphson and Newton-Krylov, in order to provide a robust and reliable tool, able to handle large-scale problems (e.g. high resolution equilibria). This method has been implemented in the FRIDA code (FRee-boundary Integro-Differential Axisimmetric – https://github. om/matteobonotto/ FRIDA), together with a suitable Adaptive Integration Technique (AIT) for the computation of the source term. FRIDA has been successfully tested and validated against experimental data from RFX-mod device, and numerical equilibria of an ITER-like device.     

A novel fMRI paradigm to dissociate the behavioral and neural components of mixed‐strategy decision making from non‐strategic decisions in humans

During competitive interactions, such as predator–prey or team sports, the outcome of one's actions is dependent on both their own choices and those of their opponents. Success in these rivalries requires that individuals choose dynamically and unpredictably, often adopting a mixed strategy. Understanding the neural basis of strategic decision making is complicated by the fact that it recruits various cognitive processes that are often shared with non‐strategic forms of decision making, such as value estimation, working memory, response inhibition, response selection, and reward processes. Although researchers have explored neural activity within key brain regions during mixed‐strategy games, how brain activity differs in the context of strategic interactions versus non‐strategic choices is not well understood. We developed a novel behavioral paradigm to dissociate choice behavior during mixed‐strategy interactions from non‐strategic choices, and we used task‐based functional magnetic resonance imaging (fMRI) to contrast brain activation. In a block design, participants competed in the classic mixed‐strategy game, “matching pennies,” against a dynamic computer opponent designed to exploit predictability in players’ response patterns. Results were contrasted with a non‐strategic task that had comparable sensory input, motor output, and reward rate; thus, differences in behavior and brain activation reflect strategic processes. The mixed‐strategy game was associated with activation of a distributed cortico‐striatal network compared to the non‐strategic task. We propose that choosing in mixed‐strategy contexts requires additional cognitive demands present to a lesser degree during the control task, illustrating the strength of this design in probing function of cognitive systems beyond core sensory, motor, and reward processes.     

The Selection of a Pharmaceutical Salt—The Effect of the Acidity of the Counterion on Its Solubility and Potential Biopharmaceutical Performance

A roadmap for the selection of a pharmaceutical salt form for a development candidate is presented. The free base of the candidate did not have sufficient chemical stability for development. The initially selected salt form turned out to be undevelopable because it was unstable during scale-up synthesis and storage. The rationale for the new solid form screening and the criteria for selection are discussed. Before the final selection, the pH solubility profiles of the 2 new salts, a benzoate and a besylate, were compared. Atypical solubility behavior was observed for the benzoate salt in hydrochloric acid with and without normal saline. A scheme is proposed illustrating how the pKas of the counterion and active pharmaceutical ingredient, the medium composition, and final pH affect the solubility and solution equilibria of the 2 selected salt forms. This scheme also includes the equilibria between solution and solid phases in different pH ranges. The pharmaceutical importance of this research is that it sheds light on how the acidity of the counterion can affect the solubility of the selected salt form in the gastric environment. With a well-designed formulation strategy, this property potentially can be translated to optimal biopharmaceutical performance of the drug product.     

Drug Solubilization by Means of a Surface-Modified Edible Biopolymer Enabled by Hot Melt Extrusion

A coprocessing/formulation approach for increasing the solubility of poorly soluble drugs using solid dispersions is presented, whereby the active pharmaceutical ingredients (API) retains its crystalline state. The approach uses a biopolymer naturally produced as dendrimeric nanoparticles that has been surface-modified to act as a solubilizing agent. The solubilizing agent is enabled by hot melt extrusion to produce the solid dispersions. Four APIs, phenytoin (PHT), griseofulvin, ibuprofen, and loratadine were used as model compounds to evaluate solubility enhancement. The rank order in solubility enhancement follows that of the hydrophobicity of the APIs. The APIs remained predominantly crystalline after hot melt extrusion processing. However, APIs with weak crystal structure (ibuprofen and loratadine) underwent measurable crystallinity loss. The solubilizing power of the modified biopolymer increases with increasing hydrophobicity and strength of the crystal structure. The solubility is described in terms of a parallel liquid-phase partition-association. For one API (PHT), solubility enhancement was minimal. The dissimilar behavior of PHT is discussed in terms of the polarity match between the API and the hydrophobic microenvironment in the solubilizing agent. This approach is expected to apply to a large number of poorly soluble drugs, offering a complementary approach to existing processing and formulation drug solubilization methods.     

Enmein的平衡溶解度、油水分配系数及环糊精包合作用的研究

目的 测定Enmein的平衡溶解度、油水分配系数,考察环糊精对其包合作用,为制剂研究奠定基础。方法 采用HPLC测定Enmein在不同溶剂中的平衡溶解度;采用摇瓶法测定Enmein在不同条件下的油水分配系数;以羟丙基-β-环糊精（HP-β-CD）、羟丙基-γ-环糊精（HP-γ-CD）2种材料制备Enmein包合物,经溶解度试验,比较溶解性能的变化。结果 （25±0.5）℃振摇24 h,Enmein在纯水中溶解度为（239.32±4.99）μg·mL^-1,在多种常见的有机溶剂中微溶,在常用的药用油溶剂中不溶;正辛醇-水体系中,测得Enmein油水分配系数P为4.64,不同生理pH环境及环糊精材料,对其lgP影响不大;经过2种材料包合后,Enmein的溶解度有所提高,其中以HP-γ-CD的增溶效果最好。结论 Enmein在水、常见的药用油溶剂中溶解性均不好;消化道生理pH变化及包合材料对Enmein的吸收影响不大;用Enmein的HP-γ-CD包合物为原料制备制剂,有利于提高其生物利用度。     

基于博弈论的我国分级诊疗制度分析与政策建议

目的研究我国建立分级诊疗制度的困境以及相关解决政策建议。方法利用博弈论和帕累托改进理论分析促进分级诊疗制度的实施方法。结果分级诊疗的难点在于未能实现帕累托改进,即患者和政府可以在分级诊疗制度中节约成本,但医生并未得到相应的激励,因此,缺乏下沉积极性。结论若能够让政府和患者节省的一部分费用补贴给大医院医生,则这些医生就会下沉到基层医疗机构,即可以实现帕累托改进,建立分级诊疗就医秩序。     

Regulation of erythrocyte function: Multiple evolutionary solutions for respiratory gas transport and its regulation in fish

Gas transport concepts in vertebrates have naturally been formulated based on human blood. However, the first vertebrates were aquatic, and fish and tetrapods diverged hundreds of millions years ago. Water‐breathing vertebrates live in an environment with low and variable O₂ levels, making environmental O₂ an important evolutionary selection pressure in fishes, and various features of their gas transport differ from humans. Erythrocyte function in fish is of current interest, because current environmental changes affect gas transport, and because especially zebrafish is used as a model in biomedical studies, making it important to understand the differences in gas transport between fish and mammals to be able to carry out meaningful studies. Of the close to thirty thousand fish species, teleosts are the most species‐numerous group. However, two additional radiations are discussed: agnathans and elasmobranchs. The gas transport by elasmobranchs may be closest to the ancestors of tetrapods. The major difference in their haemoglobin (Hb) function to humans is their high urea tolerance. Agnathans differ from other vertebrates by having Hbs, where cooperativity is achieved by monomer‐oligomer equilibria. Their erythrocytes also lack the anion exchange pathway with profound effects on CO₂ transport. Teleosts are characterized by highly pH sensitive Hbs, which can fail to become fully O₂‐saturated at low pH. An adrenergically stimulated Na⁺/H⁺ exchanger has evolved in their erythrocyte membrane, and plasma‐accessible carbonic anhydrase can be differentially distributed among their tissues. Together, and differing from other vertebrates, these features can maximize O₂ unloading in muscle while ensuring O₂ loading in gills.     

Considerations in applying the general equilibrium approach to environmental health assessment

There are currently two commonly used approaches to assessing economic impacts of health damage resulting from environmental pollution： human capital approach （HCA） and willingness-to-pay （WTP）. WTP can be further divided into averted expenditure approach （AEA）, hedonlc wage approach （HWA）, contingent valuation approach （CVA） and hedonlc price approach （HPA）. A general review of the principles behind these approaches by the authors indicates that these methods are incapable of unveiling the mechanism of health impact from the point of view of national economy. On a basis of economic system, the shocks brought about by health effects of environmental pollution change the labor supply and medical expenditure, which in turn affects the level of production activity in each sector and the total final consumption pattern of the society. The general equilibrium approach within the framework of macroeconomic theory is able to estimate the health impact on national economy comprehensively and objectively. Its mechanism and applicability are discussed in detail by the authors.     

The coupling of diffusion,migration and chemical equilibrium during the voltammetric reduction of weak polyprotic acids1

A theoretical model is presented for the coupling of diffusion, migration and chemical equilibrium during the voltammetric reduction of weak polyprotic acids. The dissociation reaction of a neutral acid is assumed to influence only the apparent diffusion coefficients of the hydrogen ion and its conjugate base anions. For typical values of equilibrium constants of dissociation reactions and analytical concentration, polyprotic acids behave as either monoprotic acids or diprotic acids, which agrees well with experimental results. A semi-quantitative explanation based on a diffusion layer treatment is proposed for this phenomenon. It is also shown that the ratio of limiting current at low concentration of supporting electrolyte to diffusion-limited current depends on the initial equilibrium concentrations of all species in the solution but not on the kinetics of the dissociation reactions. Furthermore the movement of the uncharged species (the neutral acid) can be influenced by an electric field through the coupling effected by the chemical equilibrium.     

彭筱平教授治疗失眠经验

失眠是现代人常见的一种疾病,虽不致命但严重影响人们的生活质量,现代医学中多用药物治疗失眠,辅助心理治疗、物理治疗等,药物治疗病情容易反复,停药后容易出现反弹或加重等情况,物理及心理治疗适用人群极为有限,难以从根本解决失眠的问题,故而从中医中药上寻求帮助。彭筱平教授熟读《黄帝内经》《伤寒论》等经典著作,从阴阳角度提出了治疗失眠应重视阴不足的病机,根据心、肝、肾、脾胃的脏腑生理病理特性分析了以上几脏易于出现阴不足病机而至失眠,从营卫角度分析了营阴与失眠密切相关,在治疗过程中除了清热养滋阴血安神等治法外,提出了个人用药特色——白芍,白芍用药可以入营阴,有滋阴养血柔肝和营的功效,运用上述滋阴养血和营之法治疗失眠,临床上收效甚佳。