Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

institutional framework of in action against land degradation

While econometric and spatial data are increasingly helpful to quantify and locate the extent and costs of land degradation, there is still little understanding of the contextual factors that determine or influence the land users' practices that aggravate or counteract land degradation. In this chapter, we take an institutional economic approach to analyse the persistence of degrading practices, the low adoption of sustainable land management (SLM), or the eventual organisational reaction to land degradation. The chapter reviews four examples of land degradation in different contexts to reveal the multiple driving forces and contextual factors. We then propose a conceptual framework to better understand the incentive structure and factors determining the land users' decision making. A layered analysis of the social phenomena is applied, following Williamson (2000). The chapter shows how actions at different layers can help improve land management. The chapter concludes with practical recommendations for the institutional economic analysis of land degradation

10 Jahre Chemikaliengesetz Bilanz und Perspektiven

10 Jahre Chemikaliengesetz bedeutet ein Jahrzehnt stuermischer Rechtsentwicklung: Was Anfang der 80er Jahre noch Neuland war, ist heute ein umfangreiches Rechtsgebiet mit ausgefeilten untergesetzlichen Detailregelungen, fest verzahnt mit den uebrigen Bereichen des Umweltrechts und Bestandteil einer Gesamtkonzeption zur Chemikaliensicherheit, die internationale Ausstrahlungskraft hat. Aktuell befindet sich das Chemikalienrecht in einer Phase, der ''inneren Verfestigung und Komplettierung''. Eingeleitet wurde sie durch die Novelle von 1990, mit der auf der Grundlage der ersten Vollzugserfahrungen im Rahmen der bestehenden EG-rechtlichen Vorgaben gezielt Schwachstellen beseitigt wurden. Im zweiten Schritt dieser Phase sind, die zwischenzeitlich erfolgten, bzw. derzeit erfolgenden Ueberarbeitungen und Ergaenzungen der EG-rechtlichen Vorgaben umzusetzen. Weitere rechtliche Regelungen duerften im Bereich der Verbote und Beschraenkungen zu erwarten sein. Sie sind bisher ueberwiegend einzelfallbezogen und reaktiv angelegt. Wichtig waere vor allem die Entwicklung eines einheitlichen, an sachlichen Gesichtspunkten ausgerichteten Kriterienkatalogs. Es geht darum, gezielt und vorsorgeorientiert die fuer eine nachhaltige umweltvertraegliche Entwicklung erforderlichen Rahmenbedingungen fuer die Stofffluesse unserer Industriegesellschaft zu schaffen. (orig./HSCH)The chemical substances act is ten years old. These ten years have witnessed a stormy development in legislation on chemicals: what was new ground still at the beginning of the eighties, is now a vast area of law complemented by detailed individual regulations at the administrative level, firmly interlocked with the other areas of environmental law, and part of an overall concept for the safety of chemicals enjoying an international reputation. Currently, the chemical substances act is in a phase of inner consolidation and completion. This phase was ushered in by the proposed amendment of 1990, an amendment aimed to eliminate weak points on the basis of first experiences with the implementation of legal requirements existing under EC law. In the second part of this phase, revisions or completions which have meanwhile been effected or are being effected in community law must be integrated. Further legal regulations are to be expected in the area of prohibitions and restrictions. These are, so far, mainly attuned to individual cases and reactive in nature. Most important of all is the development of a uniform and appropriate catalogue of criteria. The aim must be to create the necessary boundary conditions for the use of chemicals in our industrial society ensuring sustainable, environmentally compatible development for a long time to come. (orig./HSCH)SIGLEAvailable from TIB Hannover: T94B139 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman

A Game Theoretic Approach to Analyse Cooperation Between Rural Households in Northern Nigeria

Much research focuses on development of new agricultural technologies to reduce poverty levels of the large population of smallholder farms in Sub Saharan Africa. In this paper we argue that smallholders can also increase their production in a different way, namely by using their resources more efficiently through cooperation. This is obtained by grouping their (heterogeneous) resources and making joint decisions based on the aggregate resources. Afterwards, the gains of the joint production are divided, such that each farmer remains independent. This type of cooperation is modeled using linear programming and cooperative game theory. While linear programming establishes insight in optimal farm plans for farmers that cooperate, game theory is used to generate fair divisions of the extra gain that is established by cooperation. The model is applied to a village in Northern Nigeria. Households are clustered based on socio-economic parameters, and we explore cooperation. The optimal farm plan of the cooperative (i.e., farmers cooperate) contains more crops with high market and nutritional value, such as cowpea and sugarcane. We show that the gross margin of the cooperative is 12% higher than the sum of the individual gross margins. To divide these gains, we consider four established solution concepts from game theory that divide these extra gains: the Owen value, Shapley value, compromise value and nucleolus. An interesting result is that all farmers gain from cooperation and that the four solution concepts give similar results. Finally, we show how the provision of micro-credit can be used to stimulate cooperation in practice, benefiting the least-endowed farmers as well.

Resource degradation, low agricultural productivity, and poverty in sub-Saharan Africa: pathways out of the spiral

Sub-Saharan Africa (SSA) has the lowest agricultural productivity in the world, while almost half of the population lives below US$1 per day. The biggest development policy challenge is to find appropriate solutions to end hunger and poverty in the region. Building on several years of empirical research conducted in East Africa, this paper identifies potential strategies for sustainable development in this region. In general, the empirical evidence reviewed confirms that different strategies are needed in different development domains of SSA. Nevertheless, some elements will be common to all successful strategies, including assurance of peace and security, a stable macroeconomic environment, provision of incentives through markets where markets function, development of market institutions where they do not, and public and private investment in an appropriate mix of physical, human, natural, and social capital. The differences in strategies across these domains mainly reflect differences in the mix of those investments as influenced by different comparative advantages. Copyright 2005 International Association of Agricultural Economics.

On the Use of Agricultural System Models for Exploring Technological Innovations Across Scales in Africa: A Critical Review

The major challenge of the 21st century is to achieve food security under, roughly, a doubling in food demand by 2050 compared to present, and producing the additional food under marked shifts in climatic risks and with environmentally sound farming practices. Sustainable intensification of agricultural production is required that meets the dual goal of improved environmental sustainability and economic efficiency. Ex ante evaluation of technological innovations to support agricultural production and food security taking into account the various future risks can substantially contribute to achieve this. Here we perceive technological innovations as new or improved agro-technologies and –management practices, such as new breeds, integrated soil fertility practices or labour-saving technologies meeting the goals of sustainable intensification. In this report we present results from three systematic reviews: one on the use of biophysical modelling, the second and third on the use of bio-economic modelling at farm scale and agro-economic modelling at higher aggregation levels, for ex ante evaluation of the effects of (agro ) Technological Innovations (ag-TIs) on sustainable agriculture and food security indicators. To this end, we searched the SCOPUS database for journal articles published between 1996 and 2015. We considered modelling studies at different spatial scales with particular attention to local to national scale studies for the twelve PARI focal countries in Africa . But we also included studies for all other African countries as well as a few studies at supra-national/continental scale. Both, “quick wins” as well as long term benefits from ag-TIs were of interest. The various ag-TIs were furthermore grouped into four classes: (1) water/soil moisture (2) soil nutrients/conservation (3) crop/cropping system, (4) other ag-TIs or (5) combinations of 1 to 4. For each paper, we tried to identify the primary ag-TI analysed, and if there was equal emphasis to more than one, we classified them as combinations. It should be borne in mind that there is some subjectivity in classifying the papers in this way. Results. After various steps of refining “search strings”, screening on relevance and supplementing databases from additional sources, we found 140 relevant biophysical modelling studies, whereby coverage of sub-regions and ag-TIs varied markedly. Most studies were found for East and West Africa, followed by Southern Africa; hardly anything was found for Northern and Middle Africa . A similar pattern appeared for the integrated agro-economic modelling studies at farm scale, for which we found 40 relevant ones. Agro-economic modelling studies at higher aggregation levels showed a somewhat different pattern – and more generally contained little detail on technological innovations. Regarding the share of different primary agro-technologies explored in the biophysical studies we found 45 on crop management, 35 on combined agro-technologies, 31 on soil nutrient management and conservation, 23 on water/soil moisture management, and 6 on other technologies. We found similar shares among the various agro-technology groups for the integrated agro-economic modelling studies at farm scale. Looking at the outcomes from ex ante evaluations we found that many studies are (mostly) positive on effects of single and “conventional” ag-Tis. The majority of biophysical studies is performed at “field scale” and focuses on the effects on productivity (sometimes yield stability); many of these studies were performed in climate variability and change /adaptation research context. Most agro-economic modelling studies that look specifically at ex ante evaluations of ag-TIs are performed at farm or regional (sub-national) scales. While the number of biophysically oriented studies has grown exponentially over the considered period 1996-2015, this is not the case for the agro-economic modelling studies. Looking in more detail at the twelve focal countries of PARI (=Programme of Accompanying Research on Agricultural Innovations) we also find an unbalanced distribution, with most studies found in Kenya, Ethiopia, Mali and Ghana (biophysical modelling studies), and respectively in Kenya and Uganda (agro-economic modelling studies), whereas nothing or little was found for both types of studies in Togo, Zambia and Nigeria. Very few of the biophysically-oriented studies include other information than effects on crop yields, and there are few studies for both biophysical and agro-economic modelling that comprise multi-scale or higher scale analyses; if multi-scale, there are more studies that scale up from field/farm to regional/sub-national level than from field/farm to nation scale or beyond. There is definitely a need to overcome the lack of meaningful integrated multi-scale modelling along the lines proposed in chapters 5-6 of this report. Moreover, less than half of all integrated /agro-economic modelling studies at farm scale explicitly address risk – another clear shortcoming, which requires attention by the research community. A more general conclusion is that there is no application yet of true transdisciplinary research approaches in practice. Hence, there is need for participatory, collaborative (cross-sectoral) and combined modelling approaches with adequate stakeholder involvement throughout the research process. In this respect, some lessons might be learned from pioneering work conducted in Asia and Europe