This research addresses the following question: ‘In the context of climate change, how do different actors narrate the uncertain, ambiguous and risky future of maize agriculture, and what are the implications?' A multi-sited and institutional ethnography approach was adopted in order to look critically at how knowledge and narratives of future change in Kenyan maize agriculture are constructed by a variety of actors. The thesis describes: contested narratives of climate change and climate change impacts (through an analysis of the global climate impact modelling endeavour); contested narratives of change on smallholder farms (based on two case study sites in Kenya); contested narratives of pro-poor technological interventions (including the development of genetically modified drought tolerant maize); and contested narratives of technology regulation (with a focus on Kenyan biosafety policy). It is shown that narratives are contested in multiple sites and by a variety of actors and, although the resolution of these contestations often fall along familiar lines of power and elite capture, there are examples in which alternative perspectives find agency. This is the case not only in national policy-making arenas and the board-rooms of international development initiatives, but also in the fields and communities of smallholder farmers, the offices of national research centres, and the operations of civil society organisations. It is argued that, within these diverse settings, critical analysis of the constructed nature of knowledge is a necessary foundation on which to open up the negotiation of Kenya's agricultural future to multiple alternatives.

Normalt sett skyddar komplementsystemet kroppen mot infektioner och patogener. Vid vissa typer av njursjukdomar, framför allt vid C3-glomerulopati, förekommer autoantikroppar som kallas ”nephritic factors” (NeF). Sådana antikroppar stabiliserar enzymkomplex (konvertas) i komplementsystemet, vilket leder till destruktiv komplementaktivering via den alternativa vägen. Syftet med studien var att utveckla minst en metod för att analysera C5NeF på kliniska prover.  C5NeF In-House ELISA analyserade bindning av C5NeF till C5-konvertas. Analys av C5-klyvning i löslig fas kvantifierade mängden C5a som bildats vid stabilisering av C5-konvertas. Cut-off för analyserna bestämdes genom analys av prover från 20 friska blodgivare. Tolv patientprover med möjlig förekomst av C5NeF analyserades. För att utesluta falskt positiv reaktion i C5NeF in-house ELISA analyserades även förekomst av antikroppar mot specifika enskilda komplementproteiner. Åtta patientprover var positiva i C5NeF In-House ELISA, fem patientprover uppvisade positivt resultat för C3NeF, vilket inte var oväntat utifrån tidigare publikationer som visat att det är vanligt att patienter med C5NeF också ofta är positiva för C3NeF. Tre patientprover erhöll positivt resultat i endast C5NeF In-House ELISA och två av dessa var positiva i analys av C5-klyvning i löslig fas. Studien resulterade i etablering av en metod för analys av C5NeF. / Normally the complement system protects the body from infections and pathogens. In certain types of kidney diseases, mainly C3-glomerulopathy, autoantibodies called ”Nephritic Factors” (NeF) are found. NeFs stabilize enzyme complexes (convertases) in the complement system, an event which leads to destructive complement activation via the alternative pathway. The purpose of this study was to develop at least one method to analyse C5NeF on clinical samples.  C5NeF In-House ELISA analysed binding of C5NeF to C5 convertases. Analysis of C5-cleavage in the soluble phase measured the amount of C5a formed when C5-convertase was stabilized. Cut-off for the analyses was determined through analysis of 20 blood donor samples from healthy individuals. Twelve patient samples with possible C5NeF were analysed. To exclude false positive results in C5NeF In-House ELISA analysis of antibodies against specific single complement factors was performed.  Eight patient samples were positive in C5NeF In-House ELISA, five patient samples showed positive result for C3NeF, a finding which was not unexpected as previous publications have shown that concomitant presence of C3NeF and C5NeF is common in C3-glomerulopathy. Where most patients are positive for both C3NeF and C5NeF. Three patient samples received positive result in only C5NeF In-House ELISA and two of these samples were positive in the analysis of C5-cleavage in soluble phase. In conclusion, in this study a method to examine C5NeF was developed.

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A deficiência da proteína C5 do sistema complemento humano é rara com 38 casos relatados na literatura e freqüentemente associada a severas infecções provocadas por bactérias Neisseria. O objetivo do trabalho é caracterizar imunológica e geneticamente esta deficiência encontrada pela primeira vez em brasileiros. Por imunodifusão dupla obtivemos níveis expressivos de C3, C4, C6, C7, C8, C9, Fator B, Fator H e Fator I em todos os membros desta família, a proteína C5 não foi detectada no soro de três irmãos: II:9, II:4 e II:5. Por ELISA a concentração de C5 nestes indivíduos foi (0,9; 1,0; 1,3 µg/ml, 45- 190 µg/ml). Soros destes probandos não apresentam atividade hemolítica mediada pelo sistema complemento. O cDNA de C5 dos indivíduos I:1, I:2, II:4 e II:9 apresenta a deleção do éxon 30. Causada pela substituição de GAG4028 por GAA4028 no último nucleotídeo deste éxon que leva a um erro no splicing. Este defeito provavelmente produz uma proteína incompleta e destinada à degradação. / The deficiency of the C5 component of the complement system is rare with 38 described cases in the literature. This deficiency is frequently associated with severe infections, especially caused by Neisseria. Our objective is to characterize immunologically and genetically this deficiency, the first of its type described in the Brazilian population.We noted that C3, C4, C6, C7, C8, C9, Factor B, Factor H and Factor I have expressive levels in all the individuals sera of this family. C5 was absent in individuals II:4, II:5 and II:9. By ELISA a C5 concentration in this individuals were 0,9; 1,0; 1,3 µg/ml (normal: 45 - 190 µg/ml). Their serum doesn´t present hemolytic activity mediated by complement system. The C5 cDNA from individuals I:1, I:2, II:4 and II:9 has éxon 30 deleted. Caused by the substitution of GAG4028 for a GAA4028 in the last codon of exon 30. This defect was responsible for the deficiency of C5 in this family and this deletion would probably produce an unstable protein destined for degradation.

A deficiência da proteína C5 do sistema complemento humano é rara com 38 casos relatados na literatura e freqüentemente associada a severas infecções provocadas por bactérias Neisseria. O objetivo do trabalho é caracterizar imunológica e geneticamente esta deficiência encontrada pela primeira vez em brasileiros. Por imunodifusão dupla obtivemos níveis expressivos de C3, C4, C6, C7, C8, C9, Fator B, Fator H e Fator I em todos os membros desta família, a proteína C5 não foi detectada no soro de três irmãos: II:9, II:4 e II:5. Por ELISA a concentração de C5 nestes indivíduos foi (0,9; 1,0; 1,3 µg/ml, 45- 190 µg/ml). Soros destes probandos não apresentam atividade hemolítica mediada pelo sistema complemento. O cDNA de C5 dos indivíduos I:1, I:2, II:4 e II:9 apresenta a deleção do éxon 30. Causada pela substituição de GAG4028 por GAA4028 no último nucleotídeo deste éxon que leva a um erro no splicing. Este defeito provavelmente produz uma proteína incompleta e destinada à degradação. / The deficiency of the C5 component of the complement system is rare with 38 described cases in the literature. This deficiency is frequently associated with severe infections, especially caused by Neisseria. Our objective is to characterize immunologically and genetically this deficiency, the first of its type described in the Brazilian population.We noted that C3, C4, C6, C7, C8, C9, Factor B, Factor H and Factor I have expressive levels in all the individuals sera of this family. C5 was absent in individuals II:4, II:5 and II:9. By ELISA a C5 concentration in this individuals were 0,9; 1,0; 1,3 µg/ml (normal: 45 - 190 µg/ml). Their serum doesn´t present hemolytic activity mediated by complement system. The C5 cDNA from individuals I:1, I:2, II:4 and II:9 has éxon 30 deleted. Caused by the substitution of GAG4028 for a GAA4028 in the last codon of exon 30. This defect was responsible for the deficiency of C5 in this family and this deletion would probably produce an unstable protein destined for degradation.

Introduktion: Paroxysmal nokturn hemoglobinuri (PNH) är en kronisk, förvärvad, mycket sällsynt sjukdom som kännetecknas av komplementmedierad intravaskulär hemolys och är potentiellt livshotande. Sjukdomen börjar med en störning hos en hematopoetisk stamcell vilket leder till att patienter med PNH får röda blodceller som är känsliga för aktiverat komplementsystem och membranattackkomplexet (MAC). PNH kan ge symtom som exempelvis anemi, trombos och trötthet. PNH kan behandlas med komplementhämmare som förhindrar komplementaktivering och därmed komplementmedierad intravaskulär hemolys. Den först utvecklade komplementhämmaren eculizumab är en C5-hämmare som kontrollerar intravaskulär hemolys. Många patienter visar dock tecken på extravaskulär hemolys under behandling med eculizumab. Därför utvecklades det en C3-hämmare pegcetacoplan som ska även blockera extravaskulär hemolys. Syfte: Syftet med detta arbete var att studera pegcetacoplans effektivitet i komplementhämmare-naiva patienter och effektivitet i jämförelse med eculizumab vid behandling av PNH. Syftet var även att analysera skillnader i effektivitet mellan pegcetacoplan och eculizumab vid behandling av PNH. Metod: Detta examensarbete var ett litteraturarbete där sex vetenskapliga artiklar inkluderades baserat på inklusions- och exklusionskriterier. Inklusionskriterier var klinisk studie som analyserade pegcetacoplans effektivitet hos patienter med PNH. Exklusionskriterier var bland annat post hoc-analyser och fallrapporter. Artikelsökning gjordes i databasen PubMed med sökorden ”paroxysmal nocturnal hemoglobinuria pegcetacoplan”. Resultat: Pegcetacoplan-behandling ledde till och/eller bibehöll förbättringar gällande bland annat hemoglobinnivåer och LDH-nivåer hos patienter med PNH i alla sex studier. I PHAROAH och PADDOCK/PALOMINO visades en ökning av klonal distribution av typ II och typ III röda blodceller och minskning av C3 på typ II och typ III celler, vilket tolkades som att pegcetacoplan skyddar dessa celler från extravaskulär hemolys. I PRINCE var pegcetacoplan överlägsen kontrollgruppen med stödjande behandling gällande flera utfallsvariabler. I PEGASUS visade både eculizumab och pegcetacoplan effektivitet gällande bland annat LDH-nivåer men pegcetacoplan visade bättre effektivitet än eculizumab gällande hemoglobinnivåer och retikulocytantal. I uppföljningsstudien till PEGASUS och i förlängningsstudien OLE upprätthöll pegcetacoplan de tidigare uppnådda förbättringarna. Diskussion och slutsatser: Resultatet från dessa studier tyder på att pegcetacoplan är ett effektivt läkemedel med ihållande effektivitet vid behandling av PNH gällande kontroll av både intravaskulär och extravaskulär hemolys oavsett tidigare behandling med komplement-hämmare eller inte. Blockering av extravaskulär hemolys var den viktigaste skillnaden i effektivitet mellan pegcetacoplan och eculizumab. Dock skulle trovärdigheten av dessa slutsatser kunna förstärkas om det gjordes fler studier utan påverkan av Apellis Pharmaceuticals. / Introduction: Paroxysmal nocturnal hemoglobinuria (PNH) is a chronic, acquired, rare disease characterized by complement-mediated intravascular hemolysis and is potentially life-threatening. The disease begins with a disorder of a hematopoietic stem cell, which results in patients with PNH having red blood cells that are sensitive to complement activation and the membrane attack complex (MAC). PNH can cause symptoms such as anemia, thrombosis and fatigue. PNH can be treated with complement inhibitors that prevent complement activation and thereby complement-mediated intravascular hemolysis. The first complement inhibitor developed, eculizumab, is a C5 inhibitor that controls intravascular hemolysis. However, many patients show signs of extravascular hemolysis during treatment with eculizumab. Therefore, a C3 inhibitor pegcetacoplan was developed that should also block extravascular hemolysis. Aim: The aim of this study was to evaluate the efficacy of pegcetacoplan in complement inhibitor-naïve patients and efficacy in comparison with eculizumab in the treatment of PNH. The aim was also to analyze differences in effectiveness between pegcetacoplan and eculizumab in the treatment of PNH. Method: This thesis was a literature review in which six scientific articles were analyzed. Inclusion criteria were clinical trial analyzing the efficacy of pegcetacoplan in patients with PNH. Exclusion criteria included post hoc analyzes and case reports. An article search was made in the PubMed database with the keywords "paroxysmal nocturnal hemoglobinuria pegcetacoplan". Results: Pegcetacoplan treatment led to and/or maintained improvements in, among other things, hemoglobin levels and LDH levels in patients with PNH in all six studies. In the PHAROAH and PADDOCK/PALOMINO studies, an increase in the clonal distribution of type II and type III red blood cells and a decrease in C3 on type II and type III cells were shown, which was interpreted as pegcetacoplan protecting these cells from extravascular hemolysis. In PRINCE, pegcetacoplan was superior to the supportive care control group on several outcome variables. In PEGASUS, both eculizumab and pegcetacoplan showed efficacy regarding, among other things, LDH levels, but pegcetacoplan showed higher efficacy than eculizumab regarding hemoglobin levels and reticulocyte count. In the follow-up study to PEGASUS and in the extension study OLE, pegcetacoplan maintained the previously achieved improvements. Discussion and conclusions: The results from these studies suggest that pegcetacoplan is an effective drug with sustained efficacy in the treatment of PNH regarding the control of both intravascular and extravascular hemolysis regardless of previous treatment with complement inhibitors or not. Blockade of extravascular hemolysis was the main difference in efficacy between pegcetacoplan and eculizumab. However, the credibility of these conclusions could be strengthened if more studies were conducted without the influence of Apellis Pharmaceuticals.

Since 1975, the extent of catching-up has been very different across Southern regions. Starting from the common arguments of growth theory, the paper wishes to show whether differences in regional income and growth can be attributed to different endowment in human capital, differences in private or public investment level, to structural imbalances, and labour force participation. The investigated panel consists of regional time series for the period 1975 to 1994 and includes NUTS II level regions of Greece, Spain, and the Italian South. Estimation of the impact of the variables on regional income is effected in a dynamic panel data model applying a GMM estimation procedure. The results indicate that the income level of Southern EU regions is largely determined by employment/educational levels and past public investment, while the impact of private investment is not significant. One may follow that EU regional policies should predominately focus on the human factor. Assistance to member countries to upgrade public infrastructures may be continued, but private investment incentives should be curbed. (author's abstract) / Series: Working Papers Series "Growth and Employment in Europe: Sustainability and Competitiveness"

This thesis examines the linkages between social protection and resilience to climate change among poor rural households. To date there is a very limited understanding of the potential role of social protection programmes in contributing to an increase in resilience of the rural poor with respect to climate change. An improved understanding of these links can help to build the knowledge base that is needed to help the poorest members of the society to adapt to the impacts of climate change. This gap in understanding is addressed in this thesis through a case study of the conditional cash transfer programme Oportunidades in two rural communities in Yucatan, Mexico, a region highly exposed to hurricanes and droughts. Qualitative and quantitative data were collected by means of household surveys, life-history interviews, key informant interviews, group discussions and participant observation. A social protection-resilience analytical framework was developed in order to guide the data collection and analysis. This framework is informed by a dynamic understanding of resilience, which integrates two resilience dimensions: the absorptive capacity (the ability to resist and recover from a shock) and the adaptive capacity (the ability to adapt to the effects of a shock). This framework is based on the proposition that social protection reduces vulnerability and, by doing so, this can also help to increase poor households resilience to climate change. The thesis found that the main role of Oportunidades is to provide a regular and predictable safety net that protects households from short-term risk, thus increasing households' absorptive capacity. The impact on the adaptive capacity of households is indirect and differentiated according to their respective poverty profiles. Furthermore, the research shows that certain features of the theory of change of Oportunidades, and its design, reduce the potential impact of the programme, creating trade-offs between the different resilience dimensions. This is the case because resilience to climate change and social protection literatures are derived from distinctive approaches, which frame vulnerability differently. The thesis concludes by making a case for social protection to be complemented by other interventions in a systemic approach that should explicitly consider climate change, in order to increase resilience and achieve sustainable poverty reduction.