Fetal gene therapy: opportunities and risks

Advances in human prenatal medicine and molecular genetics have allowed the diagnosis of many genetic diseases early in gestation. In-utero transplantation of allogeneic hematopoietic stem cells (HSC) has been successfully used as a therapy in different animal models and recently also in human fetuses. Unfortunately, clinical success of this novel treatment is limited by the lack of donor cell engraftment in non-immunocompromised hosts and is thus restricted to diseases where the fetus is affected by severe immunodeficiency. Gene therapy using genetically modified autologous HSC circumvents allogeneic HLA barriers and constitutes one of the most promising new approaches to correct genetic deficits in the fetus. Recent developments of strategies to overcome failure of efficient transduction of quiescent hematopoietic cells include the use of new vector constructs and transduction protocols. These improvements open new perspectives for gene therapy in general and for prenatal gene transfer in particular. The fetus may be especially susceptible for successful gene therapy due to the immunologic naiveté of the immature hematopoietic system during gestation, precluding an immune reaction towards the transgene. Ethical issues, in particular those regarding treatment safety, must be taken into account before clinical trials with fetal gene therapy in human pregnancies can be initiated.

Subcutaneous immunoglobulin: opportunities and outlook

Immunoglobulin (Ig) administration via the subcutaneous (s.c.) route has become increasingly popular in recent years. The method does not require venous access, is associated with few systemic side effects and has been reported to improve patients' quality of life. One current limitation to its use is the large volumes which need to be administered. Due to the inability of tissue to accept such large volumes, frequent administration at multiple sites is necessary. Most studies conducted to date have investigated the use of subcutaneous immunoglobulin (SCIg) in patients treated previously with the intravenous (i.v.) formulation. New data now support the use of s.c. administration in previously untreated patients with primary immunodeficiencies. SCIg treatment may further be beneficial in the treatment of autoimmune neurological conditions, such as multi-focal motor neuropathy; however, controlled trials directly comparing the s.c. and i.v. routes are still to be performed for this indication. New developments may further improve and facilitate the s.c. administration route. For example, hyaluronidase-facilitated administration increases the bioavailability of SCIg, and may allow for the administration of larger volumes at a single site. Alternatively, more concentrated formulations may reduce the volume required for administration, and a rapid-push technique may allow for shorter administration times. As these developments translate into clinical practice, more physicians and patients may choose the s.c. administration route in the future.

Information Systems Outsourcing. Enduring themes, global challenges, and process opportunities

he notion of outsourcing – making arrangements with an external entity for the provision of goods or services to supplement or replace internal efforts – has been around for centuries. The outsourcing of information systems (IS) is however a much newer concept but one which has been growing dramatically. This book attempts to synthesize what is known about IS outsourcing by dividing the subject into three interrelated parts: (1) Traditional Information Technology Outsourcing, (2) Information Technolgy Offshoring, and (3) Business Process Outsourcing. The book should be of interest to all academics and students in the field of Information Systems as well as corporate executives and professionals who seek a more profound analysis and understanding of the underlying factors and mechanisms of outsourcing.

Opportunities and limits of the ecosystem services framework in capturing the cultural dimension of sustainable regional and landscape development in protected areas

With regard to protected areas, the concepts of ecosystem services and the cultural dimension of sustainable development (SD) are increasingly under debate. This contribution analyses the role of cultural aspects within the ecosystem services framework using the Millennium Ecosystem Assessment classification as a reference. The limits of the ecosystem services framework in capturing the cultural dimension are highlighted. Potential ways of strengthening the position of cultural values within this framework are discussed.

Cohort-specific effects of the expansion of the welfare state on job opportunities: a longitudinal analysis of three birth cohorts in the Federal Republic of Germany

Ziel der Untersuchung war es, Einflüsse auf den Arbeitsmarkt der Bundesrepublik durch das Anwachsen des Wohlfahrtsstaates zu ermitteln. Zu diesem Zweck wurden zwischen 1981 und 1983 2.171 Männer und Frauen der Geburtskohorten 1929-31, 1939-41 und 1949-51 mit standardisierten Interviews befragt zu ihrem Lebensverlauf, speziell unter den Gesichtspunkten: Soziale Herkunft, Ausbildung, Beschäftigung, Familie, Mobilität. Insbesondere interessierte die Frage nach der Beschäftigung im öffentlichen Dienst oder in der Privatwirtschaft bzw. ob und wann ein Wechsel von einem in den anderen Bereich stattgefunden hat. Einige Ergebnisse: Die Bildungsexpansion in den 70er Jahren führte dazu, daß eine steigende Anzahl von Universitätsabsolventen im öffentlichen Dienst Beschäftigung fand; seit der Stagnation des Wohlfahrtsstaates ab ca. 1980 sind die Beschäftigungschancen für hochqualifizierte Berufsanfänger dort wieder gesunken. In der Privatwirtschaft wird unqualifizierte Beschäftigung durch höher qualifizierte ersetzt, während im öffentlichen Dienst bei geringerem Arbeitsplatzangebot weniger hochqualifizierte Berufsanfänger nachgefragt werden.