WP 89 - Coordination of national social security in the EU

*Abstract* The coordination of the national social security is one of the crucial fields of cooperation between EU Member States. The coordination is based on the principle of application of one legislation at a time in cases of employment being executed in one or more than one Member State. Persons moving within the EU are thus subject to the social security scheme of only one Member State. The rules aim to guarantee equal treatment and non discrimination by the application of the “lex loci laboris” principle. In 2004 the European legislator concluded modernised social security coordination rules (Regulation EC 883/2004) in order to simplify the current rules. The idea was also to limit the number of specific rules for different categories of professional activities. An Implementing Regulation was concluded in April 2009. In this paper the author explores the (possible) complications related to the new rules. The paper consists of an overview of the rules, of the basic changes and of pending questions. At the end a set of recommendations is formulated meant to contribute to the necessary tailor-made solutions. *Samenvatting* De coördinatie van de nationale sociale zekerheidstelsels vormt een cruciaal terrein van samenwerking tussen de lidstaten van de Europese Unie. Die coördinatie is gebaseerd op het uitgangspunt dat slechts één wetgeving van toepassing kan zijn in situaties waarbij in een of meerdere lidstaten gewerkt wordt. EU onderdanen die gebruik maken van het vrij verkeer kunnen zodoende slechts onderworpen zijn aan het sociale zekerheidsstelsel van een lidstaat. De regels dienen de gelijke behandeling te garanderen en discriminatie tegen te gaan door de toepassing van het “lex loci laboris” principe (het werklandbeginsel). De Europese wetgever besloot in 2004 tot een modernisering en vereenvoudiging van de coördinatieregels voor de sociale zekerheid (Verordening EC 883/2004). Achterliggende gedachte was tevens het terugbrengen van het aantal specifieke regels voor verschillende beroepscategorieën. De implementatiewetgeving werd afgerond in april 2009. In dit werkdocument behandelt de auteur enkele (mogelijke) complicaties die kunnen voortvloeien uit de nieuwe regels. De studie geeft een overzicht van de regelgeving, van de belangrijkste veranderingen en van open kwesties. Aan het eind worden aanbevelingen geformuleerd die een bijdrage beogen te zijn voor de noodzakelijke op maat gesneden oplossingen.

Release of proteins via ion exchange from albumin-heparin microspheres

Albumin-heparin and albumin microspheres were prepared as ion exchange gels for the controlled release of positively charged polypeptides and proteins. The adsorption isotherms of chicken egg and human lysozyme, as model proteins, on microspheres were obtained. An adsorption isotherm of chicken egg lysozyme on albumin-heparin microspheres was linear until saturation was abruptly reached,\ud \ud The adsorption isotherms of human lysozyme at low and high ionic strength were typical of adsorption isotherms of proteins on ion exchange gels. The adsorption of human lysozyme on albumin-heparin and albumin microspheres fit the Freundlich equation suggesting heterogeneous binding sites. This was consistent with the proposed multivalent, electrostatic interactions between human lysozyme and negatively charged microspheres. Scatchard plots of the adsorption processes of human lysozyme on albumin-heparin and albumin microspheres suggested negative cooperativity, while positive cooperativity was observed for chicken egg lysozyme adsorption on albumin-heparin microspheres.\ud \ud Human lysozyme loading of albumin-heparin microspheres was 3 times higher than with albumin microspheres, with long term release occurring via an ion exchange mechanism. Apparent diffusion coefficients of 2.1 × 10-1 and 3.9 × 10-11cm2/sec were obtained for the release of human lysozyme from albumin-heparin and albumin microspheres, respectively. The release was found to be independent of diffusion, since the rate determining step was likely an adsorption/desorption processes. An apparent diffusion coefficient of 4.1 × 10-12 cm2/sec was determined for the release of chicken egg lysozyme from albumin-heparin microspheres.\ud \ud Low release of the lysozymes from albumin-heparin microspheres was observed in deionized water, consistent with the proposed ion exchange release mechanism. Overall, albumin-heparin microspheres demonstrated enhanced ion exchange characteristics over albumin microspheres

Sublabel-Accurate Relaxation of Nonconvex Energies

We propose a novel spatially continuous framework for convex relaxations based on functional lifting. Our method can be interpreted as a sublabel-accurate solution to multilabel problems. We show that previously proposed functional lifting methods optimize an energy which is linear between two labels and hence require (often infinitely) many labels for a faithful approximation. In contrast, the proposed formulation is based on a piecewise convex approximation and therefore needs far fewer labels. In comparison to recent MRF-based approaches, our method is formulated in a spatially continuous setting and shows less grid bias. Moreover, in a local sense, our formulation is the tightest possible convex relaxation. It is easy to implement and allows an efficient primal-dual optimization on GPUs. We show the effectiveness of our approach on several computer vision problems

Release of macromolecules from albumin-heparin microspheres

Hydrophilic microspheres based on albumin-heparin conjugates have been prepared as a macromolecular delivery system. The soluble albumin-heparin conjugate was synthesized and crosslinked in a water-in-oil emulsion with glutaraldehyde to form microspheres in the same manner as for albumin microsphere preparation. The microspheres were characterized in terms of their size and swelling properties. The loading of macromolecules into albumin-heparin microspheres was carried out concurrently and after microsphere preparation. FITC-dextran was applied as a model macromolecule. A higher loading content was achieved when loading was carried out concurrently with microsphere preparation than when loaded subsequently. Prolonged release of FITC-dextran from albumin-heparin microspheres was achieved and attributed to the high molecular weight of the macromolecule. The release of FITC-dextran was modulated by crosslinking density, loading content and the method of drug incorporation. Apparently, the mechanism of FITC-dextran release from albumin-heparin microspheres was dependent on the method of drug incorporation. For release of FITC-dextran from the microspheres, assuming negligible interactions, a diffusion coefficient of 1.7 × 10¿9 cm2/s was determined

Preparation and characterization of albumin-heparin microspheres

Albumin-heparin microspheres were prepared by a two-step process which involved the preparation of a soluble albumin-heparin conjugate, followed by formation of microspheres from this conjugate or by a double cross-linking technique involving both coupling of soluble albumin and heparin and microsphere stabilization in one step. The first technique was superior since it allowed better control over the composition and the homogeneity of the microspheres. Microspheres could be prepared with a diameter of 5¿35¿m. The size could be controlled by adjusting the emulsification conditions. The degree of swelling of the microspheres was sensitive to external stimuli, and increased with increasing pH and decreasing ionic strength of the medium

Adriamycin-loaded albumin-heparin conjugate microspheres for intraperitoneal chemotherapy

Adriamycin-loaded albumin-heparin conjugate microspheres (ADR-AHCMS) were evaluated as possible intraperitoneal (i.p.) delivery systems for site-specific cytotoxic action. The biocompatibility of the microspheres after intraperitoneal injection was tested first. 1 day after i.p. administration of empty as well as drug-loaded AHCMS to male Balb/c mice, only a moderate increase in i.p. neutrophils was measured. 3 days after injection neutrophil levels were comparable with the controls. No significant increases in the numbers of other cell types were observed, indicating an acute inflammatory response which can be considered to be mild. Antitumour efficacy was tested in an L1210 tumour-bearing mouse model and in a CC531 tumour-bearing rat model. The use of ADR-AHCMS leads to longer survival times of mice and improved tumour growth delay in rats, as compared with untreated controls and free drug treated animals. In both animal models higher adriamycin doses were initially tolerated if the drug was formulated in microspheres, although long-term adriamycin toxicity effects were evident in all treated groups. Doses and dosage schedules may be optimized to further reduce the toxic effects of the drug

Preparation and characterization of microspheres of albumin-heparin conjugates

Albumin-heparin microspheres have been prepared as a new drug carrier. A soluble albumin-heparin conjugate was synthesized by forming amide bonds between human serum albumin and heparin. After purification the albumin-heparin conjugate was crosslinked in a water-in-oil emulsion to form albumin-heparin microspheres. The composition of the conjugate was determined by amino acid analysis. The swelling properties of albumin-heparin microspheres were investigated as a function of pH and ionic strength and compared with albumin microspheres. Albumin-heparin and albumin microspheres exhibited stimuli-sensitive swelling. Both microsphere systems exhibited low swelling at low pH and high swelling at higher pH caused by ionization of amino acids of serum albumin. The swelling of albumin-heparin microspheres was more sensitive toward ionic strength than that of albumin microspheres. This was due to the greater negative charge of the albumin-heparin microspheres. Surfaces of albumin-heparin and albumin microspheres were characterized by ESCA, contact angle measurements, electrophoresis, and scanning electron microscopy. Surface analysis indicated the presence of heparin at the albumin-heparin microsphere/water interface