Embryonic and fetal development: fundamental research.

Much progress has been made over the past decades in the development of in vitro techniques for the assessment of chemically induced effects in embryonic and fetal development. In vitro assays have originally been developed to provide information on the mechanism of action of normal development, and have hence more adequately been used in fundamental research. These assays had to undergo extensive modification to be used in developmental toxicity testing. The present paper focuses on the rat whole embryo culture system, but also reviews modifications that were undertaken for the in vitro chick embryo system and the aggregate cultures of fetal rat brain cells. Today these tests cannot replace the existing in vivo developmental toxicity tests. They can, however, be used to screen chemicals for further development or further testing. In addition, these in vitro tests provide valuable information on the mechanisms of developmental toxicity and help to understand the relevancy of findings for humans. In vitro systems, combined with selected in vivo testing and pharmacokinetic investigations in animals and humans, can thus provide essential information for human risk assessment.

Small Cities, Neoliberal Governance and Sustainable Development in the Global South : A Conceptual Framework and Research Agenda

Development and environmental issues of small cities in developing countries have largely been overlooked although these settlements are of global demographic importance and often face a "triple challenge"; that is, they have limited financial and human resources to address growing environmental problems that are related to both development (e.g., pollution) and under-development (e.g., inadequate water supply). Neoliberal policy has arguably aggravated this challenge as public investments in infrastructure generally declined while the focus shifted to the metropolitan "economic growth machines". This paper develops a conceptual framework and agenda for the study of small cities in the global south, their environmental dynamics, governance and politics in the current neoliberal context. While small cities are governed in a neoliberal policy context, they are not central to neoliberalism, and their (environmental) governance therefore seems to differ from that of global cities. Furthermore, "actually existing" neoliberal governance of small cities is shaped by the interplay of regional and local politics and environmental situations. The approach of urban political ecology and the concept of rural-urban linkages are used to consider these socio-ecological processes. The conceptual framework and research agenda are illustrated in the case of India, where the agency of small cities in regard to environmental governance seems to remain limited despite formal political decentralization.

Vaccinia immune globulin: current policies, preparedness, and product safety and efficacy.

In 1980 the World Health Organization declared that smallpox was eradicated from the world, and routine smallpox vaccination was discontinued. Nevertheless, samples of the smallpox virus (variola virus) were retained for research purposes, not least because of fears that terrorist groups or rogue states might also have kept samples in order to develop a bioweapon. Variola virus represents an effective bioweapon because it is associated with high morbidity and mortality and is highly contagious. Since September 11, 2001, countries around the world have begun to develop policies and preparedness programs to deal with a bioterror attack, including stockpiling of smallpox vaccine. Smallpox vaccine itself may be associated with a number of serious adverse events, which can often be managed with vaccinia immune globulin (VIG). VIG may also be needed as prophylaxis in patients for whom pre-exposure smallpox vaccine is contraindicated (such as those with eczema or pregnant women), although it is currently not licensed in these cases. Two intravenous formulations of VIG (VIGIV Cangene and VIGIV Dynport) have been licensed by the FDA for the management of patients with progressive vaccinia, eczema vaccinatum, severe generalized vaccinia, and extensive body surface involvement or periocular implantation following inadvertent inoculation.

Research and development, where people are exposed to nanomaterials

OBJECTIVES: Many nanomaterials (materials with structures smaller than 100 nm) have chemical, physical and bioactive characteristics of interest for novel applications. Considerable research efforts have been launched in this field. This study aimed to study exposure scenarios commonly encountered in research settings. METHODS: We studied one of the leading Swiss universities and first identified all research units dealing with nanomaterials. After a preliminary evaluation of quantities and process types used, a detailed analysis was conducted in units where more than a few micrograms were used per week. RESULTS: In the investigated laboratories, background levels were usually low and in the range of a few thousand particles per cubic centimeter. Powder applications resulted in concentrations of 10,000 to 100,000 particles/cm(3) when measured inside fume hoods, but there were no or mostly minimal increases in the breathing zone of researchers. Mostly low exposures were observed for activities involving liquid applications. However, centrifugation and lyophilization of nanoparticle-containing solutions resulted in high particle number levels (up to 300,000 particles/cm(3)) in work spaces where researchers did not always wear respiratory protection. No significant increases were found for processes involving nanoparticles bound to surfaces, nor were they found in laboratories that were visualizing properties and structure of small amounts of nanomaterials. CONCLUSIONS: Research activities in modern laboratories equipped with control techniques were associated with minimal releases of nanomaterials into the working space. However, the focus should not only be on processes involving nanopowders but should also be on processes involving nanoparticle-containing liquids, especially if the work involves physical agitation, aerosolization or drying of the liquids.

Strategies to promote translational research within the European Organisation for Research and Treatment of Cancer (EORTC) Head and Neck Cancer Group: a report from the Translational Research Subcommittee.

Head and neck squamous cell cancer (HNSCC) is the sixth leading cause of cancer-related deaths worldwide. These tumors are commonly diagnosed at advanced stages and mortality rates remain high. Even cured patients suffer the consequences of aggressive treatment that includes surgery, chemotherapy, and radiotherapy. In the past, in clinical trials, HNSCC was considered as a single disease entity. Advances in molecular biology with the development of genomic and proteomic approaches have demonstrated distinct prognostic HNSCC patient subsets beyond those defined by traditional clinical-pathological factors such as tumor subsite and stage [Cho W (ed). An Omics Perspective on Cancer Research. New York/Berlin: Springer 2010]. Validation of these biomarkers in large prospective clinical trials is required before their clinical implementation. To promote this research, the European Organisation for Research and Treatment of Cancer (EORTC) Head and Neck Cancer Program will develop the following strategies-(i) biobanking: prospective tissue collection from uniformly treated patients in the setting of clinical trials; (ii) a group of physicians, physician-scientists, and EORTC Headquarters staff devoted to patient-oriented head and neck cancer research; (iii) a collaboration between the basic scientists of the Translational Research Division interested in head and neck cancer research and the physicians of the Head and Neck Cancer Group; and (iv) funding through the EORTC Grant Program and the Network Core Institutions Consortium. In the present report, we summarize our strategic plans to promote head and neck cancer research within the EORTC framework.

The hotel industry and its importance in the technical and economic development of a region : the Lake Geneva case (1852-1914)

The historiography dedicated to tourism has emphasised how some socio-economic evolutions such as urbanisation, mechanisation of transport or the advent of leisure time in society have supported pleasure trips and therefore the development of the hotel industry. On the contrary, the research has too often neglected or at least minimised the impact of the hotel sector on a region's development. This contribution seeks to fill this gap by analysing the Geneva Lake region, one of the most important birthplaces of the European tourism. In this space not much touched by the first industrial revolution, the hotel business has in fact played the role of an economic motor, stimulating investment and employment. This dynamism provoked a domino effect on several other sectors of the economy (industry, bulding sector, banking). To please their customers, the hoteliers have not only given impulses on housing modernisation, but also to the revitalisation of transport, energy and communication networks. The necessity to remain on the state-of-the-art of technical issues, with the concern of competitiveness, has called forth an acceleration of the technology transfer and stimulated the constitution of technical know-how.

Single nucleotide polymorphisms, apoptosis, and the development of severe late adverse effects after radiotherapy.

PURPOSE: Evidence has accumulated in recent years suggestive of a genetic basis for a susceptibility to the development of radiation injury after cancer radiotherapy. The purpose of this study was to assess whether patients with severe radiation-induced sequelae (RIS; i.e., National Cancer Institute/CTCv3.0 grade, > or =3) display both a low capacity of radiation-induced CD8 lymphocyte apoptosis (RILA) in vitro and possess certain single nucleotide polymorphisms (SNP) located in candidate genes associated with the response of cells to radiation. EXPERIMENTAL DESIGN: DNA was isolated from blood samples obtained from patients (n = 399) included in the Swiss prospective study evaluating the predictive effect of in vitro RILA and RIS. SNPs in the ATM, SOD2, XRCC1, XRCC3, TGFB1, and RAD21 genes were screened in patients who experienced severe RIS (group A, n = 16) and control subjects who did not manifest any evidence of RIS (group B, n = 18). RESULTS: Overall, 13 and 21 patients were found to possess a total of <4 and > or =4 SNPs in the candidate genes. The median (range) RILA in group A was 9.4% (5.3-16.5) and 94% (95% confidence interval, 70-100) of the patients (15 of 16) had > or =4 SNPs. In group B, median (range) RILA was 25.7% (20.2-43.2) and 33% (95% confidence interval, 13-59) of patients (6 of 18) had > or =4 SNPs (P < 0.001). CONCLUSIONS: The results of this study suggest that patients with severe RIS possess 4 or more SNPs in candidate genes and low radiation-induced CD8 lymphocyte apoptosis in vitro.

Superior outcome of women with stage I/II cutaneous melanoma: pooled analysis of four European Organisation for Research and Treatment of Cancer phase III trials.

PURPOSE: Several studies observed a female advantage in the prognosis of cutaneous melanoma, for which behavioral factors or an underlying biologic mechanism might be responsible. Using complete and reliable follow-up data from four phase III trials of the European Organisation for Research and Treatment of Cancer (EORTC) Melanoma Group, we explored the female advantage across multiple end points and in relation to other important prognostic indicators. PATIENTS AND METHODS: Patients diagnosed with localized melanoma were included in EORTC adjuvant treatment trials 18832, 18871, 18952, and 18961 and randomly assigned during the period of 1984 to 2005. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% CIs for women compared with men, adjusted for age, Breslow thickness, body site, ulceration, performed lymph node dissection, and treatment. RESULTS: A total of 2,672 patients with stage I/II melanoma were included. Women had a highly consistent and independent advantage in overall survival (adjusted HR, 0.70; 95% CI, 0.59 to 0.83), disease-specific survival (adjusted HR, 0.74; 95% CI, 0.62 to 0.88), time to lymph node metastasis (adjusted HR, 0.70; 95% CI, 0.51 to 0.96), and time to distant metastasis (adjusted HR, 0.69; 95% CI, 0.59 to 0.81). Subgroup analysis showed that the female advantage was consistent across all prognostic subgroups (with the possible exception of head and neck melanomas) and in pre- and postmenopausal age groups. CONCLUSION: Women have a consistent and independent relative advantage in all aspects of the progression of localized melanoma of approximately 30%, most likely caused by an underlying biologic sex difference.