Quality-by-Design-Based Development of n-Propyl-Gallate-Loaded Hyaluronic-Acid-Coated Liposomes for Intranasal Administration

The present study aimed to develop n-propyl gallate (PG)-encapsulated liposomes through a novel direct pouring method using the quality-by-design (QbD) approach. A further aim was to coat liposomes with hyaluronic acid (HA) to improve the stability of the formulation in nasal mucosa. The QbD method was used for the determination of critical quality attributes in the formulation of PG-loaded liposomes coated with HA. The optimized formulation was determined by applying the Box–Behnken design to investigate the effect of composition and process variables on particle size, polydispersity index (PDI), and zeta potential. Physiochemical characterization, in vitro release, and permeability tests, as well as accelerated stability studies, were performed with the optimized liposomal formulation. The optimized formulation resulted in 90 ± 3.6% encapsulation efficiency, 167.9 ± 3.5 nm average hydrodynamic diameter, 0.129 ± 0.002 PDI, and −33.9 ± 4.5 zeta potential. Coated liposomes showed significantly improved properties in 24 h in an in vitro release test (>60%), in vitro permeability measurement (420 μg/cm²) within 60 min, and also in accelerated stability studies compared to uncoated liposomes. A hydrogen-peroxide-scavenging assay showed improved stability of PG-containing liposomes. It can be concluded that the optimization of PG-encapsulated liposomes coated with HA has great potential for targeting several brain diseases.     

Operational risk: Emerging markets,sectors and measurement

The role of decision support systems in mitigating operational risks in firms is well established. However, there is a lack of investment in decision support systems in emerging markets, even though inadequate operational risk management is a key cause of discouraging external investment. This has also been exacerbated by insufficient understanding of operational risk in emerging markets, which can be attributed to past operational risk measurement techniques, limited studies on emerging markets and inadequate data.     

Real-World Forward Rate Dynamics With Affine Realizations

We investigate the existence of affine realizations for Lévy driven interest rate term structure models under the real-world probability measure, which so far has only been studied under an assumed risk-neutral probability measure. For models driven by Wiener processes, all results obtained under the risk-neutral approach concerning the existence of affine realizations are transferred to the general case. A similar result holds true for models driven by compound Poisson processes with finite jump size distributions. However, in the presence of jumps with infinite activity we obtain severe restrictions on the structure of the market price of risk; typically, it must even be constant.     

北江干流沉积物重金属污染生态风险评价

通过北江干流水体沉积物重金属含量,研究其典型污染物的潜在生态风险。采集了北江干流韶关至清远段7份沉积物样品,经混酸消解后,以电感耦合等离子体质谱仪测定沉积物中重金属含量,并对沉积物重金属分布特征进行了分析。同时利用Hakanson的潜在生态危害指数（RI）评价模式,对北江干流沉积物重金属生态风险进行了评价。评价结果表明,北江干流沉积物中重金属综合生态危害程度均表现为很高级别,其生态危害因子Pb、Cd已成为北江干流突发性水污染事故潜在预警因子。     

Organophosphate esters by GC–MS: An optimized method for aquatic risk assessment

Organophosphate esters used as flame retardants and plasticizers are ubiquitous contaminants in surface waters. Many studies indicate that these compounds are neurotoxicants, endocrine disruptors, and may affect reproduction and development of aquatic organisms. Thus, analytical methods that allow accurate quantification of these contaminants at environmentally relevant concentrations are desirable for risk assessment studies. In this study, a method based on solid phase extraction and gas chromatography coupled to mass spectrometry was developed for determination of organophosphate esters in river water extracts. Multivariate optimization was used to determine the best conditions for injection of larger volumes of sample in a Programmable Temperature Vaporization inlet. Furthermore, the matrix effect on the instrumental response was evaluated and compensated by association of extraction‐blank‐matched calibration and isotopically labeled focus standards. The method quantification limits ranged from 0.009 to 0.11 µg/L, staying below the predicted non‐effect concentration for the aquatic compartment for all analytes, which is a requisite for using in risk assessment studies. The method was applied to freshwater samples collected in rivers from the Sao Paulo State, Brazil, and eight out of the ten target organophosphate esters were quantified, being tris(2‐chloroisopropyl) phosphate and tris(phenyl) phosphate the most frequently detected compounds.     

Accumulation of selected metals in the fruits of medicinal plants grown in urban environment of Islamabad,Pakistan

The present study is based on the measurement of selected metals (Ca, Cd, Co, Cr, Cu, Fe, Mg, Mn, Pb, Sr and Zn) in the fruits of eight medicinal plants (Carrisa opeca, Phyllanthus emblica, Solanum nigrum, Zizyphus nummularia, Zizyphus mauritiana, Physalis minima, Opuntia dillenii and Phoenix dactylifera) and relevant soil samples by atomic absorption spectrometry. Highest average concentrations of Cu (14.4 mg/kg), Cr (19.0 mg/kg), and Zn (125 mg/kg) were found in the fruits of P. minima, C. opeca and Z. nummularia, respectively, while O. dillenii showed the elevated mean levels of Cd (3.49 mg/kg), Sr (61.4 mg/kg), Mg (0.21%), Ca (6.62%) and Mn (44.6 mg/kg). However, highest average levels of Pb (41.7 mg/kg) and Co (38.4 mg/kg) were found in Z. mauritiana. Overall, most of the fruit samples showed higher contributions of Ca and Mg, followed by Fe, Zn, Co and Pb. In the case of soil samples, highest concentration was observed for Ca, followed by Fe, Mg, Mn and Sr, while lowest concentration was shown by Cd. Bioaccumulation factors exhibited significantly higher accumulation of Co (0.813–1.829) and Pb (0.060–2.350) from the soil to the fruits. Principal component analysis revealed significant anthropogenic contributions of Pb, Fe and Co in the fruit samples. Contamination factors and enrichment factors of Cd and Pb in the soil indicated very high contamination and extreme enrichment of these metals.     

The uncertain premium principle based on the distortion function

In this paper, we discuss the premium principle in uncertain environment. First, the net premium principle for uncertain risks is presented within the framework of uncertainty theory. With the help of distortion function, a new uncertain premium principle is derived from the uncertain net premium. Some properties of uncertain distortion premium principle are proved. Furthermore, a sufficient and necessary condition that an uncertain premium principle is an uncertain distortion premium principle has been characterized. Finally, some examples are given to illustrate the calculations of the uncertain distortion premium.     

Modelling Operational Risk Losses with Graphical Models and Copula Functions

The management of Operational Risk has been a difficult task due to the lack of data and the high number of variables. In this project, we treat operational risks as multivariate variables. In order to model them, copula functions are employed, which are a widely used tool in finance and engineering for building flexible joint distributions. The purpose of this research is to propose a new methodology for modelling Operational Risks and estimating the required capital. It combines the use of graphical models and the use of copula functions along with hyper-Markov law. Historical loss data of an Italian bank is used, in order to explore the methodology’s behaviour and its potential benefits.      

The credit risk+ model with general sector correlations

We consider an enhancement of the credit risk⁺ model to incorporate correlations between sectors. We model the sector default rates as linear combinations of a common set of independent variables that represent macro-economic variables or risk factors. We also derive the formula for exact VaR contributions at the obligor level.     

Valuation and risk assessment of participating life insurance in the presence of credit risk

In participating life insurance, management decisions regarding the asset composition can substantially impact the value of a policy from the policyholders’ perspective as well as the insurer’s risk situation. Due to the long-term guarantees often embedded in these contracts, life insurers typically invest a considerable portion of their capital in long-term assets such as corporate and government bonds. Besides interest rate risk, the value of these bond investments is thus particularly influenced by credit risk. Thus, the aim of this paper is to examine the impact of market risk associated with the asset composition on fair valuation and risk assessment with focus on credit risk and its interaction with equity risk and interest rate risk. Our analysis emphasizes that the consideration of credit risk associated with bonds has a strong impact on the fair valuation and risk measurement in the context of participating life insurance contracts, even in case of higher grade bond exposures.