Biodegradable Poly(2-Dimethylamino Ethylamino)Phosphazene for In Vivo Gene Delivery to Tumor Cells. Effect of Polymer Molecular Weight

Purpose. Previously, we have shown that complexes of plasmid DNA with the biodegradable polymer poly(2-dimethylamino ethylamino)phosphazene (p(DMAEA)-ppz) mediated tumor selective gene expression after intravenous administration in mice. In this study, we investigated the effect of p(DMAEA)-ppz molecular weight on both in vitro and in vivo tumor transfection, as well as on complex induced toxicity. Materials and Methods. p(DMAEA)-ppz with a broad molar mass distribution was fractionated by preparative size exclusion chromatography. Polyplexes consisting of plasmid DNA and the collected polymer fractions were tested for biophysical properties, (cyto)toxicity and transfection activity. Results. Four p(DMAEA)-ppz fractions were collected with weight average molecular weights ranging from 130 to 950 kDa, and with narrow molecular mass distributions (Mw/Mn from 1.1 to 1.3). At polymer-to-DNA (N/P) ratios above 6, polyplexes based on these polymers were all positively charged (zeta potential 25–29 mV), and had a size of 80–90 nm. The in vitro cytotoxicity of the polyplexes positively correlated with polymer molecular weight. The in vitro transfection activity of the different polyplexes depended on their N/P ratio, and was affected by the degree of cytotoxicity, as well as the colloidal stability of the different polyplexes. Intravenous administration of polyplexes based on the high molecular weight polymers led to apparent toxicity, as a result of polyplex-induced erythrocyte aggregation. On the other hand, administration of polyplexes based on low molecular weight p(DMAEA)-ppz_s (Mw130 kDa) did not show signs of toxicity and resulted in tumor selective gene expression. Conclusion. Polymer molecular weight fractionation enabled us to optimize the transfection efficiency/ toxicity ratio of p(DMAEA)-ppz polyplexes for in vitro and in vivo tumor transfection. KEY WORDS: biodegradable; cationic polymer; DNA; molecular weight; tumor gene delivery

Band structure related wave function symmetry of amphoteric Si dopants in GaAs

Autocompensated Si-doped GaAs is studied with cross-sectional scanning tunneling spectroscopy (X-STS). The local electronic contrasts of substitutional Si(Ga) donors and Si(As) acceptors under the (110) cleavage plane are imaged with high resolution. Si(Ga) donor atoms exhibit radially symmetric contrasts. Si(As) acceptors have anisotropic features. The anisotropic acceptor contrasts are traced back to a tunnel process at the valence band edge. They reflect the probability density distribution of the localized acceptor hole state.Comment: 10 pages, 3 figure

Ethnic diversity outpatient clinic in paediatrics

<p>Abstract</p> <p>Background</p> <p>The health status of chronic sick ethnic minority children in the Netherlands is unequal compared with indigenous Dutch children. In order to optimize the health care for these children a specific patient-oriented clinic in ethnic-cultural diversity: the Mosaic Outpatient Clinic (MOC) was integrated in the general Paediatric Outpatient Departments (POPD) of three hospitals in Amsterdam.</p> <p>Methods</p> <p>Feasibility of the MOC, factors influencing the health care process and encountered bottlenecks in health care were studied in ethnic minority children with asthma, diabetes type 1 or metabolic disease originating from Morocco, Turkey and Surinam. Feasibility was determined by the number of patients attended, support from the paediatric medical staff and willingness of the patients to participate. Influences on the health care process comprised parents' level of knowledge of disease, sense of disease severity, level of effort, linguistic skills, health literacy, adherence to treatment and encountered bottlenecks in the health care process. Moreover, the number of admissions and visits to the POPD in the years before, during and after the MOC were analysed.</p> <p>Results</p> <p>In 2006 a total of 189 ethnic minority children were seen. Integration of the MOC within the general POPD of the hospital is feasible. The ability of the parents to speak and understand Dutch was found to be 58%, functional health literacy was 88%; sufficient knowledge of disease and sense of disease severity were 59% and 67%, respectively.</p> <p>The main bottlenecks in the healthcare process: poor knowledge of disease, limited sense of disease severity and low health literacy in the parents proved to be the best predictors for decreased adherence. After attending the MOC there was a decrease in the number of admissions and visits to the POPD for asthma while the number of visits increased in patients with diabetes and the amount of no-shows decreased in patients with a metabolic disease.</p> <p>Conclusion</p> <p>Integration of a MOC in the general POPD is feasible and appreciated by the parents, provides more insight in the problems ethnic minority children and their parents face and shows promising directions for optimizing adherence in these children.</p

The Proposed OECD Multilateral Instrument Amending Tax Treaties

In this article, the authors consider some of the practical issues relating to the introduction of the OECD multilateral instrument amending tax treaties, which has been proposed within the context of the OECD/G20 Base Erosion and Profit Shifting Project

Children and Their Parents: A Comparative Study of the Legal Position of Children with Regard to Their Intentional and Biological Parents in English and Dutch Law

This is a book about children and their parents. There are many different kinds of children and at least about as many different kinds of parents. In addition to the many different disciplines that study children and their parents, such as sociology, psychology, child studies and gender studies, to name but a few, this study concerns a legal question with regard to the parent-child relationship, namely how the law assigns parents to children. This subject is approached in a comparative legal perspective and covers England and The Netherlands. The book contains a detailed comparison and analysis of the manner in which the law in the two jurisdictions assigns the status of legal parent and/or attributes parental responsibility to the child’s biological and intentional parents. The concept ‘procreational responsibility’, which is introduced in the concluding chapter of the book, may be used as a tool to assess and reform existing regulations on legal parent-child relationships. The structure of the book, which is based on a categorisation of different family types in a ‘family tree’, enables the reader to have easy access to family-specific information.FdR – Publicaties zonder aanstelling Universiteit Leide

Some Reflections on the Proposed Revisions to the OECD Model and Commentaries, and on the Multilateral Instrument, with Respect to Fiscally Transparent Entities

This material was first published by Sweet &amp; Maxwell Limited in Angelo Nikolakakis, Stephane Austry, John Avery Jones, Philip Baker, Peter Blessing, Robert Danon, Shefali Goradia, Johann Hattingh, Koichi Inoue, Juergen Luedicke, Guglielmo Maisto, Toshio Miyatake, Kees van Raad, Richard Vann and Bertil Wiman, “Some Reflections on the Proposed Revisions to the OECD Model and Commentaries, and on the Multilateral Instrument, With Respect to Fiscally Transparent Entities”, British Tax Review, Vol. 2017, No. 3, pp. 295-373, 2017 and is reproduced by agreement with the Publishers. This article sets out some reflections of the authors on those aspects of the OECD’s October 2015 final report on Neutralising the Effects of Hybrid Mismatch Arrangements (the Hybrids Report) that relate to revisions to the OECD Model to add a specific provision on fiscally transparent entities (as a new Article 1(2)), and to build on the Commentaries already in place in this regard (the HR Proposals). It also considers the similar and related provisions contained in the multilateral instrument to implement the tax treaty related BEPS measures (the MLI) that was released on 24 November 2016. The authors conduct an extensive review of the issues and raise a number of interpretive and technical questions, as well as policy considerations. This review is set against the backdrop of an examination of similar provisions (or provisions with similar purposes) in the US Models and in various existing bilateral treaties, as well as under domestic laws, of the countries represented by the authors. The authors also provide some observations with respect to potential scope and drafting or implementation of alternatives, with a view to contributing to the ongoing international debate and reform project

New materials and devices for preventing catheter-related infections

Catheters are the leading source of bloodstream infections for patients in the intensive care unit (ICU). Comprehensive unit-based programs have proven to be effective in decreasing catheter-related bloodstream infections (CR-BSIs). ICU rates of CR-BSI higher than 2 per 1,000 catheter-days are no longer acceptable. The locally adapted list of preventive measures should include skin antisepsis with an alcoholic preparation, maximal barrier precautions, a strict catheter maintenance policy, and removal of unnecessary catheters. The development of new technologies capable of further decreasing the now low CR-BSI rate is a major challenge. Recently, new materials that decrease the risk of skin-to-vein bacterial migration, such as new antiseptic dressings, were extensively tested. Antimicrobial-coated catheters can prevent CR-BSI but have a theoretical risk of selecting resistant bacteria. An antimicrobial or antiseptic lock may prevent bacterial migration from the hub to the bloodstream. This review discusses the available knowledge about these new technologies

Economic evaluation alongside a single RCT of an integrative psychotherapeutic nursing home programme

__Abstract__ There is an 80% prevalence of two or more psychiatric symptoms in psychogeriatric patients. Multiple psychiatric symptoms (MPS) have many negative effects on quality of life of the patient as well as on caregiver burden and competence. Irrespective of the effectiveness of an intervention programme, it is important to take into account its economic aspects

Features of home and neighbourhood and the liveability of older South Africans

While older people live in developing countries, little is known about the relative importance of features of their communities in influencing their liveability. We examinecomponents of home and neighbourhood among older South Africans. Linear regression analyses revealed that features of home (basic amenities, household composition, financial status and safety) and neighbourhood (ability to shop for groceries, participate in organizations and feel safe from crime) are significantly associated with life satisfaction. Approaches to liveability that are person-centred and also set within contexts beyond home and neighbourhood are needed to addressboundaries between home and neighbourhood; incorporate personal resources into liveability models and import broader environmental contexts such as health and social policy