Evaluation of topical bioavailability in human stratum corneum in vivo by tape stripping using a direct sprectroscopic method

The objective of this thesis was to develop a spectrophotometric methodology for simultaneous determination of a sunscreening agent and relative stratum corneum tissue density in skin tape strips. This methodology was then employed to investigate the effect of different vehicles and their application time on the penetration of the sunscreening agent into the stratum corneum (SC) and the ability of these vehicles to create a reservoir. Tape stripping of the stratum corneum from the skin is a relatively non-invasive and useful technique used for bioavailability and dermatopharmacokinetic studies of topically-applied drugs. As model compound the sunscreening agent 3-(4-Methylbenzylidene)camphor (4-MBC) was chosen because of its high absorbance potential (A 930-990 at 299 nm) and its high affinity to the SC which may be inferred by its low solubility in water (0.00013 g in 100 mL). To be able to conduct SC measurements directly on a tape by UV/VIS spectroscopy, a Perkin Elmer UV/VIS spectrophotometer was modified providing a uniform measurement area of 1 cm2 to measure the absorbance through the sample as a result of light scattering by the SC on the tapes. A spectroscopic UV/VIS method determining the model compound 4-MBC and SC simultaneously in skin tape strips was then developed directly on tape strips and validated according to the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) guidelines. For SC measurements this technique has distinct advantages in terms of facile sample handling procedures when compared with previously described methods such as tape strip weighing, protein determination and extraction procedures which are laborious and are susceptible to analytical artifacts. The validation parameters of the UV/VIS method were compared to those of a conventional solvent extraction/HPLC method. The data of the two analytical methods were found to be equally accurate and precise in determining sunscreen abundance in the corneocyte layers removed by tape stripping. However, the direct spectrophotometric technique obviates the need for any tape extraction process prior to analysis of 4-MBC and SC, and is sensitive enough for the accurate determination of low analyte concentrations on the tape strips since there is no loss of analyte in the sample handling protocol. The validation was further completed by comparing the data of an in vivo tape stripping experiment measured by the UV/VIS method and the solvent extraction/HPLC method. For this purpose the tape stripping procedure has been optimized and standardized using a strict protocol to minimize the variability of the tape stripping data. The 4-MBC delivery from a 2% and 4% 4-MBC emulsions was then investigated in vivo using five human volunteers. A dose of 2 mg/cm2 was applied to the volar forearm for one hour. The tapes were analyzed be the new UV/VIS method by determining simultaneously the 4-MBC abundance and the relative density of SC. The tapes were then extracted and the 4-MBC concentrations obtained by direct spectrophotometric quantification were verified by HPLC. The linear correlation factor was 0.974 and statistical analysis confirmed that there was no statistical difference (p>0.05) between the two analytical procedures. The total mass of compound delivered from a vehicle was calculated by summating the 4-MBC abundance determined per tape and area of tape strip. Thereby, the first tape was always discarded. The results showed a statistically significant (p<0.05) influence of the dosing strength (2% vs 4%) of the formulations on the penetration of 4-MBC. This investigation revealed that the newly developed spectroscopic method is rapid, precise and as accurate as a conventional HPLC method for the in vivo determination of sunscreening agent delivery from topical applied formulations. Finally, the delivery of 4-MBC from several representative vehicles was compared using the direct spectrophotometric determination method and according to GCP procedures. To be able to detect vehicle effects on the penetration of 4-MBC into the SC, all vehicles used in the study were saturated with 4-MBC. In the first experiment the influence of propylene glycol and mineral oil and of their application time on 4-MBC penetration was investigated in five volunteers. Although the solubility of 4-MBC was approximately 3.5 times lower in propylene glycol than in mineral oil, the 4-MBC delivery into the SC was significantly higher from propylene glycol. This observation can be explained by the ability of propylene glycol to decrease SC permeability. The number of tape strips required to completely remove the SC in the presence of the propylene glycol was significantly lower revealing a loosening of corneocytes and thus a facilitated penetration of 4-MBC into the SC. The application time showed no influence on the 4-MBC penetration. In a further experiment, PEG 400 vehicles containing 0%, 10% and 50% Transcutol®CG were evaluated in ten subjects for their ability to create a reservoir of 4-MBC in the skin. This was evaluated seven hours post vehicle application. The solubility of 4-MBC increased with increasing Transcutol®CG concentration in the vehicle. The 4-MBC delivery from the three vehicles was proportional to the 4-MBC concentration in the vehicle. The vehicles containing 0% and 10% Transcutol®CG showed no difference in the 4-MBC amount measured in the SC seven hours post application compared to the 4-MBC amount measured in the SC one hour post application. For PEG 400 containing 50% Transcutol®CG the 4-MBC amount remaining in the SC seven hours post application was smaller than one hour post application. This study clearly demonstrated that this methodology is, therefore, capable of detecting differences in the extent of reservoir formation of the sunscreen when applied to the skin in different delivery vehicles

Public private partnership contracts financing by covered bonds

The provision of public properties that generate income for the public sector, used as securitization in government bonds, is under consideration both from public and private sector during the last few years. The efficient exploitation of the long term contracts under Public Private Partnership schemes (either infrastructures or other real assets) that produce steady cash inflows can result to a lower cost of borrowing-funding for the State, by linking the efficiently priced future expected cash flows of PPP’s, with a special form of sovereign covered bonds issued by the Government. This paper, after a review of covered bonds advantages and recent market developments, examines the major parameters that governmental authorities should review and assess in order to achieve optimal pricing from a market point of view of PPP contracts. Such parameters include Primary Objectives of the public sector, expectations about future developments in inflation, growth and interest rates, availability of government funding and key objectives about management of Public deficit and Public debt, as well as the pricing sensitivities of PPP contracts expected cash flows on some of these factors. Also the paper develops and assesses the possible uses of PPP contracts for the purposes of enhancing the credit quality of new Sovereign Covered Bonds (Linked with PPP contracts), together with the broader objective of efficiently mobilizing the Public assets portfolio in delivering to the State, efficiently priced and optimal Public services and under specific conditions, lower cost of funding or refinancing for the State, compared to the unsecured senior debt obligations of the Government. The standard market model of the public sector in pricing PPP’s projects is extended and connected to optimization of quantitative objectives of the Public Sector in order to achieve specific targets under different assumptions about the underlying variables. Issues of legislation, marketability and liquidity of the proposed schemes as well as mutual benefits for the market participants are highlighted as well as market practices from the private sector covered bond market.peer-reviewe

Feasibility of the development of cruise terminal in Lavrio port under concession scheme

Cruise industry is an economic activity experiencing a noticeable growth during the last years worldwide. The efficient exploitation of existing ports and related infrastructures for the development and expansion of this tourism segment of the Greek economy can provide multidimensional benefits. This paper examines the fundamentals qualitative parameters of the port of Lavrio in order to be established as a cruise terminal, decreasing Piraeus port congestion. Efficient cooperation between public sector as owner of infrastructures and private entities providing knowledge and know how in cruise industry can produce high quality services for the clients, ensuring Value for Money and profit maximization for the involved parties. The paper examines the potential for the development of a home port in Lavrio via concession agreement and presents the major parameters that should be evaluated from the public sector for the selection of the optimal bidder. This case study is evaluated in order to examine the feasibility of the investment for the private sector and the potential benefits for the public sector, under specific assumptions under the case study scenario.peer-reviewe

The Greek maritime cluster as a driving force for the economy’s restarting

Clusters as a geographical concentration of independent activities have been for a long time recognized as a crucial instrument for promoting industrial development, in-novation, competitiveness and growth. A vast literature and worldwide experience has emerged and is associated with the most dynamic economies. The maritime industries and services compromise of a wide range of sectoral activities producing internationally tradable goods and services in a most competitive world en-vironment. In Greece, the shipping sector traditionally has a sizeable contribution to the Greek economy mainly by its revenues from seaborne transportation services. At the same time, the contribution from the other categories of the maritime cluster in domestic value added is relatively limited. There is a significant scope to benefit from more bal-anced maritime activities, with appropriate policies providing huge business opportu-nities and generating production, value added, employment, direct in the maritime sec-tor and the rest of the economy through multiplied indirect effects. By this paper, we aim to present the economic importance of the Greek maritime cluster to the economy and its related macroeconomic aggregates, as also in the country's ex-ternal balance, competitiveness, economic confidence and stability. We are going to attempt to explore future prospects and appropriate policy instruments in the main field of the Greek maritime cluster, by which the unexploited opportunities can contribute to the country's effort exiting from the current crisis.peer-reviewe

Residual value and its importance in concession agreements for infrastructure problems

Major and less important parameters affecting the efficiency of the Public Private Partnerships (PPPs) in Infrastructure development have been discussed and analyzed thoroughly in International research. Issues related to the Residual Value factor are under consideration recently, mainly from countries and organizations that have implemented PPPs years ago and now they have to manage risks associated with Residual Value. Efficiency in Residual Value is close related with the proper quality of the provided services by the infrastructure, ensures Value for Money and maximizes the returns on investment. The specific risk is more important to the concession projects where the infrastructure returns to the beneficial owner after the expiration of the contractual period. The paper examines the influence, importance and treatment of the Residual Value parameter in leasehold concession agreements, since this type of concessions have been analyzed less that the schemes related to Built Operate Transfer (BOT) contracts. Residual value risk and its management is an issue that should be taken into consideration from the tendering phase of the project during the optimal selection of the preferred bidder.peer-reviewe

From Habit-Forming to Habit-Breaking Availability : Experiences on Electronic Gambling Machine Closures During COVID-19

Electronic gambling machines (EGMs) are among the most harmful forms of gambling. The structural characteristics of EGMs prolong and reinforce gambling similarly to other habit-forming technologies. In Finland, the wide availability of EGMs in non-casino locations is likely to further reinforce the habit-creating nature of gambling offer by incorporating EGMs into everyday practices. The COVID-19 pandemic changed the landscape of gambling in Finland. The most visible change was the closure of land-based EGMs in non-casino environments, arcades, and the casino in March 2020. Since then, the status of EGMs has varied depending on the pandemic situation. The current qualitative study focuses on how Finnish past-year gamblers experience prolonged EGM closures and occasional re-openings 1 year into the pandemic. The data consist of responses to an online questionnaire eliciting experiences (N = 187) as well as interviews (N = 27, conducted in groups or alone). To aid our analysis, we employ the sociological pragmatist theory of the concept of "habit." The analysis focuses on gambler experiences on EGM shutdowns and re-openings, and views on whether closures have contributed to abstaining from gambling or to shifting to other gambling products. Policy implications of the results are discussed.Peer reviewe

Problem gambling and support preferences among Finnish prisoners: a pilot study in an adult correctional population

Purpose The purpose of this paper is to explore the prevalence of potential problem gambling among Finnish prisoners; the associations between problem gambling and demographics, substance use and crime-related factors; and problem gamblers’ support preferences.Design/methodology/approach Prisoners (n=96) from two Finnish prisons were recruited between December 2017 and January 2018. The estimated response rate was 31 percent. Gambling problems were measured using the Brief Biosocial Gambling Screen. The participants were asked to report their gambling both for one year prior to their incarceration and for the past year. The independent variables were demographics (age, gender and marital status), substance use (alcohol, smoking and narcotics) and crime-related factors (crime type, prison type and previous sentence). Statistical significance (p) was determined using Fischer’s exact test.Findings Past-year pre-conviction problem gambling prevalence was 16.3 percent and past-year prevalence 15 percent. Age, gender, smoking, alcohol or illicit drug use were not associated with past-year problem gambling before sentencing. One-third of the prisoners (33.3 percent) who were sentenced for a property crime, financial crime or robbery were problem gamblers. One-quarter (24 percent) of all participants showed an interest in receiving support by identifying one or more support preferences. The most preferred type of support was group support in its all forms.Research limitations/implications It is recommended that correctional institutions undertake systematic screening for potential problem gambling, and implement tailored intervention programs for inmates with gambling problems.Originality/value This study provides a deeper understanding of problem gambling in prisons. Problem gambling is associated with crime and also seems to be linked with serving a previous sentence. Early detection and tailored interventions for problem gambling may help to reduce reoffending rates.Peer reviewe

Online Gambling, Regulation, and Risks: A Comparison of Gambling Policies in Finland and the Netherlands

The purpose of this article is to compare the different regulatory approaches taken by Finland and the Netherlands in response to the pressures of European Union law, unlicensed gambling, and the harmful effects which can arise from gambling. The two Member States represent two different models of gambling regulation. According to Kingma, the models refer to different attitudes and concerns towards gambling in different timeframes. We argue that Finland fits the “alibi model” of gambling regulation, whereas the Netherlands aligns with the “risk model”. Both countries have decided to restrict the cross-border movement of gambling services, even though Finland has opted for a monopoly system and the Netherlands is heading towards a licensing system. We employ the “Multiple Streams Approach” to explain why Finland and the Netherlands have taken different political and legislative paths in the regulation of gambling services. For several years, Finnish gambling policy has focused on channeling demand towards domestic online gambling sites, which have been represented as more secure than foreign online gambling sites. The Netherlands seeks to channel 80 percent of demand to locally licensed online operators. Both Finland and the Netherlands seek the same objective: to protect consumers from the excesses of gambling in part by reducing the presence of unlicensed operators in their respective national markets