Development of a Tumour Growth Inhibition Model to Elucidate the Effects of Ritonavir on Intratumoural Metabolism and Anti-tumour Effect of Docetaxel in a Mouse Model for Hereditary Breast Cancer

In a mouse tumour model for hereditary breast cancer, we previously explored the anti-cancer effects of docetaxel, ritonavir and the combination of both and studied the effect of ritonavir on the intratumoural concentration of docetaxel. The objective of the current study was to apply pharmacokinetic (PK)-pharmacodynamic (PD) modelling on this previous study to further elucidate and quantify the effects of docetaxel when co-administered with ritonavir. PK models of docetaxel and ritonavir in plasma and in tumour were developed. The effect of ritonavir on docetaxel concentration in the systemic circulation of Cyp3a knock-out mice and in the implanted tumour (with inherent Cyp3a expression) was studied, respectively. Subsequently, we designed a tumour growth inhibition model that included the inhibitory effects of both docetaxel and ritonavir. Ritonavir decreased docetaxel systemic clearance with 8% (relative standard error 0.4%) in the co-treated group compared to that in the docetaxel only-treated group. The docetaxel concentration in tumour tissues was significantly increased by ritonavir with mean area under the concentration-time curve 2.5-fold higher when combined with ritonavir. Observed tumour volume profiles in mice could be properly described by the PK/PD model. In the co-treated group, the enhanced anti-tumour effect was mainly due to increased docetaxel tumour concentration; however, we demonstrated a small but significant anti-tumour effect of ritonavir addition (p value <0.001). In conclusion, we showed that the increased anti-tumour effect observed when docetaxel is combined with ritonavir is mainly caused by enhanced docetaxel tumour concentration and to a minor extent by a direct anti-tumour effect of ritonavir.

Development and validation of energy expenditure prediction models based on GT3X accelerometer data in 5- to 9-year-old children

Background: Accelerometry has been established as an objective method that can be used to assess physical activity behavior in large groups. The purpose of the current study was to provide a validated equation to translate accelerometer counts of the triaxial GT3X into energy expenditure in young children. Methods: Thirty-two children aged 5–9 years performed locomotor and play activities that are typical for their age group. Children wore a GT3X accelerometer and their energy expenditure was measured with indirect calorimetry. Twenty-one children were randomly selected to serve as development group. A cubic 2-regression model involving separate equations for locomotor and play activities was developed on the basis of model fit. It was then validated using data of the remaining children and compared with a linear 2-regression model and a linear 1-regression model. Results: All 3 regression models produced strong correlations between predicted and measured MET values. Agreement was acceptable for the cubic model and good for both linear regression approaches. Conclusions: The current linear 1-regression model provides valid estimates of energy expenditure for ActiGraph GT3X data for 5- to 9-year-old children and shows equal or better predictive validity than a cubic or a linear 2-regression model.

Fostering sustainable urban development in Nakuru, Kenya Rift Valley

The town of Nakuru—Kenya's fourth largest town—lies in a unique setting in the Great Rift Valley. Recent developments on the Menengai Crater, the Mau Escarpment, and the Bahati Highlands exemplify the impacts of poorly planned urban growth on mountain ecosystems. The Nakuru Local Urban Observatory (LUO) project was initiated by the Municipal Council of Nakuru in January 2003, in collaboration with the Centre for Development and Environment (CDE) of the University of Berne and the Intermediate Technology Development Group (ITDG), and with funding from the Swiss Agency for Development and Cooperation (SDC). The project aims to provide a framework for sustainable urban development practices by building technical skills and improving participation by local stakeholders in decision-making processes. The potentials of information technology (IT) are being tapped to provide up-to-date information to decision-makers and democratize access to information, in order to improve public participation. The overall objective is to find ways of achieving better urban management in order to mitigate non-sustainable development trends in the town and its surroundings.

Legal Framework for Cross-Regional Networks: The Case of Services and Migration

Paper prepared by Marion Panizzon and Charlotte Sieber-Gasser for the International Conference on the Political Economy of Liberalising Trade in Services, Hebrew University of Jerusalem, 14-15 June 2010 Recent literature has shed light on the economic potential of cross-border networks. These networks, consisting of expatriates and their acquaintances from abroad and at home, provide the basis for the creation of cross-border value added chains and therewith the means for turning brain drain into brain circulation. Both aspects are potentially valuable for economic growth in the developing world. Unilateral co-development policies operating through co-funding of expatriate business ventures, but also bilateral agreements liberalising circular migration for a limited set of per-sons testify to the increasing awareness of governments about the potential, which expatriate networks hold for economic growth in developing countries. Whereas such punctual efforts are valuable, viewed from a long term perspective, these top-down, government mandated Diaspora stimulation programs, will not replace, this paper argues, the market-driven liberalisation of infrastructure and other services in developing countries. Nor will they carry, in the case of circular labour migration, the political momentum to liberalise labour market admission for those non-nationals, who will eventually emerge as the future transnational entrepreneurs. It will take a combination of mode 4 and infrastructure services openings-cum regulation for countries at both sides of the spectrum to provide the basis and precondition for transnational business and entrepreneurial networks to emerge and translate into cross-border, value added production chains. Two key issues are of particular relevance in this context: (i) the services sector, especially in infrastructure, tends to suffer from inefficiencies, particularly in developing countries, and (ii) labour migration, a highly complex issue, still faces disproportionately rigid barriers despite well-documented global welfare gains. Both are hindrances for emerging markets to fully take advantage of the potential of these cross-border networks. Adapting the legal framework for enhancing the regulatory and institutional frameworks for services trade, especially in infrastructure services sectors (ISS) and labour migration could provide the incentives necessary for brain circulation and strengthen cross-border value added chains by lowering transaction costs. This paper analyses the shortfalls of the global legal framework – the shallow status quo of GATS commitments in ISS and mode 4 particular – in relation to stimulating brain circulation and the creation of cross-border value added chains in emerging markets. It highlights the necessity of adapting the legal framework, both on the global and the regional level, to stimulate broader and wider market access in the four key ISS sectors (telecommunications, transport, professional and financial services) in developing countries, as domestic supply capacity, global competitiveness and economic diversification in ISS sectors are necessary for mobilising expatriate re-turns, both physical and virtual. The paper argues that industrialised, labour receiving countries need to offer mode 4 market access to wider categories of persons, especially to students, graduate trainees and young professionals from abroad. Further-more, free trade in semi-finished products and mode 4 market access are crucial for the creation of cross-border value added chains across the developing world. Finally, the paper discusses on the basis of a case study on Jordan why the key features of trade agreements, which promote circular migration and the creation of cross-border value added chains, consist of trade liberalisation in services and liberal migration policies.

Multi-vessel stenting during primary percutaneous coronary intervention for acute myocardial infarction. A single-center experience

BACKGROUND: Recanalization of the culprit lesion is the main goal of primary angioplasty for acute ST-segment elevation myocardial infarction (STEMI). Patients presenting with acute myocardial infarction and multivessel disease are, therefore, usually subjected to staged procedures, with the primary percutaneous coronary intervention (PCI) confined to recanalization of the infarct-related artery (IRA). Theoretically at least, early relief of stenoses of non-infarct-related arteries could promote collateral circulation, which could help to limit the infarct size. However, the safety and feasibility of such an approach has not been adequately established. METHODS: In this single-center prospective study we examined 73 consecutive patients who had an acute STEMI and at least one or more lesions > or = 70% in a major epicardial vessel other than the infarct-related artery. In the first 28 patients, forming the multi-vessel (MV) PCI group, all lesions were treated during the primary procedure. In the following 45 patients, forming the culprit-only (CO) PCI group, only the culprit lesion was treated during the initial procedure, followed by either planned-staged or ischemia-driven revascularization of the non-culprit lesions. Fluoroscopy time and contrast dye amount were compared between both groups, and patients were followed up for one year for major adverse cardiac events (MACE) and other significant clinical events. RESULTS: The two groups were well balanced in terms of clinical characteristics, number of diseased vessels and angiographic characteristics of the culprit lesion. In the MV-PCI group, 2.51 lesions per patient were treated using 2.96 +/- 1.34 stents (1.00 lesions and 1.76 +/- 1.17 stents in the CO-PCI group, both p < 0.001). The fluoroscopy time increased from 10.3 (7.2-16.9) min in the CO-PCI group to 12.5 (8.5-19.3) min in the MV-PCI group (p = 0.22), and the amount of contrast used from 200 (180-250) ml to 250 (200-300) ml, respectively (p = 0.16). Peak CK and CK-MB were significantly lower in patients of the MV-PCI group (843 +/- 845 and 135 +/- 125 vs 1652 +/- 1550 and 207 +/- 155 U/l, p < 0.001 and 0.01, respectively). Similar rates of major adverse cardiac events at one year were observed in the two groups (24% and 28% in multi-vessel and culprit treatment groups, p = 0.73). The incidence of new revascularization in both infarct- and non-infarct-related arteries was also similar (24% and 28%, respectively, p = 0.73). CONCLUSION: We may state from this limited experience that a multi-vessel stenting approach for patients with acute STEMI and multi-vessel disease is feasible and probably safe during routine clinical practice. Our data suggest that this approach may help to limit the infarct size. However, larger studies, perhaps using drug-eluting stents, are still needed to further evaluate the safety and efficiency of this procedure, and whether it is associated with a lower need of subsequent revascularization and lower costs.

[Nursing unit: nurses co-ordinating hospital care--an answer to new challenges in acute medicine]

Some patients at university hospital no longer need frequent medical treatment but complex professional nursing care. At University Hospital (Inselspital) Bern a Nursing Unit with six beds was run as a pilot project based on experiences in British Nursing Development Units. The care concept was specifically developed and based on a definition of professional nursing, an evidence-based practice approach, resource oriented self management, and caring. Primary nursing was used, and the primary nurse was responsible for the coordination and steering of patient care. The project was evaluated prospectively. During the pilot phase, 37 patients were cared for on the NU. On average, 85% of the beds were occupied, patients were hospitalized for 21.5 days and had a mean age of 68.9 years. They were older than the University Hospital's average patient, and cases were more complex than the University Hospital's average case. The nurses' experiences were mainly positive. Their enhanced responsibility and the structured care process were seen as a challenge allowing them to enlarge their abilities. With this project, the University Hospital built up innovative services for patients with complex nursing problems. The project showed that well trained nurses can take on more responsibility for this patient group than in the context of conventional care models.

Transdisciplinary co-production of knowledge in the development of organic agriculture in Switzerland

The present study analyses transdisciplinary co-production of knowledge in the development of organic farming in Switzerland by using Fleck's theory of thought styles and thought collectives. Three different phases can be identified throughout the historical development. The initial phase lasting from the beginning of the 1920s to the early 1970s contains numerous characteristics of diverse well-established definitions and concepts of transdisciplinarity and represents a successful transdisciplinary process, which has not been perceived as such in the past and present scientific discussion. The second and third phases show an increasing segregation of thought collectives, caused by internal changes such as the establishment of specialised research institutions and external processes like agriculture policy and market development. These developments led to a decreasing degree of transdisciplinarity. We observe an ambiguous trend: the continuously growing and today well-established positive societal recognition of an initially rather little accepted newcomer movement is associated with the gradual loss of its very valuable forms of knowledge co-production and the related philosophical background. In order to maintain the various forms of transdisciplinary co-production of knowledge, one has to reflect not only their results or outcome but also the whole cooperation process, which has led to these results. The understanding of the historical development and characteristic features of knowledge co-production as presented in this study will help to reinforce transdisciplinary research in organic agriculture and research on transdisciplinarity in general.

Psoriasis beyond the skin: an expert group consensus on the management of psoriatic arthritis and common co-morbidities in patients with moderate-to-severe psoriasis

BACKGROUND Psoriatic arthritis (PsA) and co-morbidities of psoriasis represent a significant clinical and economic burden for patients with moderate-to-severe psoriasis. Often these co-morbidities may go unrecognized or undertreated. While published data are available on the incidence and impact of some of them, practical guidance for dermatologists on detection and management of these co-morbidities is lacking. OBJECTIVE To prepare expert recommendations to improve the detection and management of common co-morbidities in patients with moderate-to-severe psoriasis. METHODS A systematic literature review was conducted on some common co-morbidities of psoriasis-cardiovascular (CV) diseases (including obesity, hypertension, hyperglycaemia and dyslipidaemia), psychological co-morbidities (including depression, alcohol abuse and smoking) and PsA-to establish the incidence and impact of each. Data gaps were identified and a Delphi survey was carried out to obtain consensus on the detection and management of each co-morbidity. The expert panel members for the Delphi survey comprised 10 dermatologists with substantial clinical expertise in managing moderate-to-severe psoriasis patients, as well as a cardiologist and a psychologist (see appendix) with an interest in dermatology. Agreement was defined using a Likert scale of 1-7. Consensus regarding agreement for each statement was defined as ≥75% of respondents scoring either 1 (strongly agree) or 2 (agree). RESULTS The expert panel members addressed several topics including screening, intervention, monitoring frequency, and the effects of anti-psoriatic treatment on each co-morbidity. Consensus was achieved on 12 statements out of 22 (3 relating to PsA, 4 relating to psychological factors, 5 relating to CV factors). The panel members felt that dermatologists have an important role in screening their psoriasis patients for PsA and in assessing them for psychological and CV co-morbidities. In most cases, however, patients should be referred for specialist management if other co-morbidities are detected. CONCLUSION This article provides useful and practical guidance for the detection and management of common co-morbidities in patients with moderate-to-severe psoriasis.

Potentials and constraints of modeling for transdisciplinary co-producing strategies for sustainable water governance

Both climate change and socio-economic development will significantly modify the supply and consumption of water in future. Consequently, regional development has to face aggravation of existing or emergence of new conflicts of interest. In this context, transdisciplinary co-production of knowledge is considered as an important means for coping with these challenges. Accordingly, the MontanAqua project aims at developing strategies for more sustainable water management in the study area Crans-Montana-Sierre (Switzerland) in a transdisciplinary way. It strives for co-producing system, target and transformation knowledge among researchers, policy makers, public administration and civil society organizations. The research process basically consisted of the following steps: First, the current water situation in the study region was investigated. How much water is available? How much water is being used? How are decisions on water distribution and use taken? Second, participatory scenario workshops were conducted in order to identify the stakeholders’ visions of regional development. Third, the water situation in 2050 was simulated by modeling the evolution of water resources and water use and by reflecting on the institutional aspects. These steps laid ground for jointly assessing the consequences of the stakeholders’ visions of development in view of scientific data regarding governance, availability and use of water in the region as well as developing necessary transformation knowledge. During all of these steps researchers have collaborated with stakeholders in the support group RegiEau. The RegiEau group consists of key representatives of owners, managers, users, and pressure groups related to water and landscape: representatives of the communes (mostly the presidents), the canton (administration and parliament), water management associations, agriculture, viticulture, hydropower, tourism, and landscape protection. The aim of the talk is to explore potentials and constraints of scientific modeling of water availability and use within the process of transdisciplinary co-producing strategies for more sustainable water governance.

Development, implementation, and evaluation of a structured reporting web tool for abdominal aortic aneurysms

BACKGROUND The majority of radiological reports are lacking a standard structure. Even within a specialized area of radiology, each report has its individual structure with regards to details and order, often containing too much of non-relevant information the referring physician is not interested in. For gathering relevant clinical key parameters in an efficient way or to support long-term therapy monitoring, structured reporting might be advantageous. OBJECTIVE Despite of new technologies in medical information systems, medical reporting is still not dynamic. To improve the quality of communication in radiology reports, a new structured reporting system was developed for abdominal aortic aneurysms (AAA), intended to enhance professional communication by providing the pertinent clinical information in a predefined standard. METHODS Actual state analysis was performed within the departments of radiology and vascular surgery by developing a Technology Acceptance Model. The SWOT (strengths, weaknesses, opportunities, and threats) analysis focused on optimization of the radiology reporting of patients with AAA. Definition of clinical parameters was achieved by interviewing experienced clinicians in radiology and vascular surgery. For evaluation, a focus group (4 radiologists) looked at the reports of 16 patients. The usability and reliability of the method was validated in a real-world test environment in the field of radiology. RESULTS A Web-based application for radiological "structured reporting" (SR) was successfully standardized for AAA. Its organization comprises three main categories: characteristics of pathology and adjacent anatomy, measurements, and additional findings. Using different graphical widgets (eg, drop-down menus) in each category facilitate predefined data entries. Measurement parameters shown in a diagram can be defined for clinical monitoring and be adducted for quick adjudications. Figures for optional use to guide and standardize the reporting are embedded. Analysis of variance shows decreased average time required with SR to obtain a radiological report compared to free-text reporting (P=.0001). Questionnaire responses confirm a high acceptance rate by the user. CONCLUSIONS The new SR system may support efficient radiological reporting for initial diagnosis and follow-up for AAA. Perceived advantages of our SR platform are ease of use, which may lead to more accurate decision support. The new system is open to communicate not only with clinical partners but also with Radiology Information and Hospital Information Systems.