CGIAR research program on grain legumes

EXECUTIVE SUMMARY Background and context The Grain Legumes CRP was established to bring all research and development work on grain legumes within the CGIAR system under one umbrella. It was set up to provide public goods outcomes to serve the needs of the sustainable production and consumption of grain legumes in the developing world, capitalising upon their properties that enhance the natural resource base upon which production so unequivocally depends. The choice of species and research foci were finalised following extensive consultation with all stakeholders (though perhaps fewer end users), and cover all disciplines that contribute to long-lasting solutions to the issues of developing country production and consumption. ICRISAT leads Grain Legumes and is partnered by the CGIAR centers ICARDA, IITA and CIAT and a number of other important partners, both public and private, and of course farmers in the developed and developing world. Originally in mid-2012 Grain Legumes was structured around eight Product Lines (PL) (i.e. technological innovations) intersecting five Strategic Components (SC) (i.e. arranged as components along the value chain). However, in 2015, it was restructured along a more R4D output model leading to Intermediate Development Outcomes (IDOs). Thus five Flagship Projects (FP) more closely reflecting a systematic pipeline of progression from fundamental science, implementation of interventions and the development of capacity and partnerships to promote and adopt impactful outcomes: FP1) Managing Productivity through crop interactions with biotic and abiotic constraints; FP2) Determination of traits that address production constraints and opportunities; FP3) Trait Deployment of those traits through breeding; FP4) Seed Systems, post-harvest processing and nutrition; FP5) Capacity-Building and Partnerships. Another three cross-cutting FPs analyse the broader environment surrounding the adoption of outputs, the capitalising of investments in genomics research, and a focus on the Management and Governance of Grain Legumes: FP6) Knowledge, impacts, priorities and gender organisation; FP7) Tools and platforms for high throughput genotyping and bioinformatics; and FP8) Management and Governance. Five FPs focus on R4D; FPs 5 and 6 are considered cross-cutting; FP 7 has a technical focus and FP 8 has an overarching objective. Over the three year period since its inception in July 1012, Grain Legumes has had a total budget of $140 million, with $62M originally to come from W1/W2 and the remaining $78M to come from W3/bilateral. In actuality only $45M came from W1/W2 but $106M from W3/bilateral corresponding to 106% of expectation. Purpose, scope and objectives of the external evaluation Principally, the evaluation of Grain Legumes is to ensure that the program is progressing in an effective manner towards addressing the system-level outcomes of the CGIAR as they relate to grain legumes. In essence, the evaluation aims to provide essential evaluative information for decision-making by Program Management and its funders on issues such as extension, expansion and structuring of the program and adjustments in relevant parts of the program. Subsequent to the formal signing of the agreed terms of reference, the evaluation team was also invited to comment upon the mooted options for merging and/or disaggregating of Grain Legumes. The audiences are therefore manifold, from the CGIAR Fund Council and Consortium, the Boards of Trustees of the four component CGIAR centres, the Grain Legumes Steering, Management and Independent Advisory Committees, to the researchers and others involved in the delivery of R4D outcomes and their partner organisations. The evaluation was not only summative in measuring results from Grain Legumes at arm’s length; it was also formative in promoting learning and improvements, and developmental in nurturing adaption to transformational change with time. The evaluation report was written in a manner that allows for engagement of key partners and funders in a dialogue as to how to increase ownership and a common understanding of how the goals are to be achieved. We reviewed research undertaken before the CRPs but leading to impacts during Grain Legumes, and research commenced over the past 2.5 years. For related activities pre- and post-commencement of Grain Legumes, we reviewed the relevance of activities and their relation to CGIAR and the Grain Legumes goals, whether they were likely to lead to the outcomes and impacts as documented in the Grain Legumes proposal, and the quality of the science underpinning the likelihood to deliver outcomes. Throughout, we were cognisant of the extent of the reach of CGIAR centres’ activities, and those of stakeholders upon which the impact of CGIAR R4D depends. Within our remit we evaluated the original and modified management and governance structures, and all the processes/responsibilities managed within those structures. Besides the evaluation of the technical and managerial issues of Grain Legumes, we addressed cross-cutting issues of gender sensitivity, capacity building and the creation and nurturing of partnerships. The evaluation also has the objective to provide information relating to the development of full proposals for the new CRP funding cycle. The evaluation addressed six overarching questions developed from the TOR questions (listed in the Inception Report, 2015 [http://1drv.ms/1POQSZh] and others including cross-cutting issues, phrasing them within the context of traditional evaluation criteria: 1. Relevance: Global development, urbanisation and technological innovation are progressing rapidly, are the aims and focus of Grain Legumes coherent, robust, fit for purpose and relevant to the global community? 2. Efficiency: Is the structure and effectiveness of leadership across Grain Legumes developing efficient partnership management and project management across PLs? 3. Quality of science: Is Grain Legumes utilising a wide range of technologies in a way that will increase our fundamental understanding of the biology that underpins several PLs; and are collected data used in the most effective way? 4. Effectiveness: Are Product Lines strategic contributors to the overarching aims and vision for Grain Legumes? 5. Impact: Are the impact pathways that underlie each PL well defined, measureable and achievable; and are they sufficiently defined in terms of beneficiaries? Does progress towards achieving outputs and outcomes from the major research areas indicate a lasting benefit for CGIAR and the communities it serves? 6. Sustainability: Is Grain Legumes managing the increasing level of restricted funding in terms of program quality and effectiveness, including attracting and retaining quality staff? Questions for the evaluation of governance and management focused on accountability, transparency, the effectiveness and success of program execution, change management processes and communication methods, taking account of the effects of CGIAR reform. The three crosscutting issues were considered as follows: i) gender balance in program delivery, e.g. whether each PL is able to contribute to the increased income, food security, nutrition, environmental and resource conservation for resource-poor women and men existing in rural livelihoods; ii) are internal and external capacity gaps identified/met, is capacity effectively developed within each product line, and are staff at all levels engaged in contributing ideas towards capacity building; and iii) is there effective involvement of partners in research and activity programming, what are the criteria for developing partnerships, how they are formalised and how is communication between partners and within Grain Legumes managed? It was not in remit to search for output, outcomes or impact, however as highlighted later, much of our time was spent on searching for information to support claims of impact, since Grain Legumes had no effective dedicated M&E in place at the time of undertaking the review. Approach and methodology The evaluation was conducted when Grain Legumes had been operational for approximately 3 years. The approach and methodology followed that outlined in the Inception Report [http://1drv.ms/1POQSZh]. The CCEE Team based its findings, conclusions and recommendations on data collection from several sources:  review of program documents, communications with the CO, minutes and presentations from all management and governance committee meetings  review of previous assessments and evaluations  sampling of Grain Legume projects in 7 countries1  more than 66 face to face interviews, a further 133 persons in groups and 4 phone/Skype conversations: ICRISAT, ICARDA, CIAT and IITA staff, partners and stakeholders. Meetings with one Independent Science and Partnership Council (ISPC) member.  meetings with over 100 people in 16 external groups, such as farmers’ groups  online survey completed by 126 (33.4%) scientists who contribute to Grain Legumes and a number of non-CGIAR partners and Management representatives  bibliometric review of 10 publications within each PL to qualitatively assess the design, conduct, analysis and presentation of results  quantitative and qualitative self-assessment of the contributions of each of the PLs to the six criteria and 3 cross-cutting issues of evaluation mentioned above completed by PLCs (see below). We reviewed the Logical Framework that underpins the desired Goals, or Impacts of Grain Legumes, and the links between the outputs and inputs as they related to the organisational units of Grain Legumes. The logical framework approach to planning and management of Grain Legumes activities implies a linear process, leading from activities, outputs, outcomes, to impacts, but within such an approach there may be room for a more systems dynamics approach allowing for feedback at every step and within every step, in order to refine and improve upon the respective activities as new results, ideas, and directions come to light. We then developed a matrix that summarised quantitatively and qualitatively the contributions of each of the PLs to the six criteria and 3 cross-cutting issues of evaluation mentioned above. Main findings and conclusions Grain legume production and consumption remain of great importance to the food security of not inconsiderable populations in the developing world, and merit sustained research investment. We conclude that Grain Legumes continues to contribute significant returns to research investments by the CGIAR, and such investment should continue. The global research community looks to the CGIAR for leadership in Grain legumes, but needs to be assured of value adding when bringing CGIAR centres under the expected umbrella of synergy. However, there is considerable scope for improving the efficiency with which outcomes are achieved. We note that an absence of an effective M&E has hampered the assessment of the effectiveness of proposed impact pathways. Likewise progress has been hampered by the limited numbers of research partnerships with Advanced Institutes and by budgetary constraints (lamented for their stifling effects on continuation of ongoing exciting research). The unworkable management structure constrains the CRP Director’s leadership role; responsibility without authority will never lead to effective outcomes. Good fortune is responsible for many of the successes of Grain Legumes, underpinned by a devoted work force across the participating CGIAR centres and partners. The quality of the science is not uniformly high, and we believe that mentoring of scientists should be given priority where quality is poor. Simplified yet informative reporting is an imperative to this. World class science underpins the identification of, and molecular basis for, traits important for yield improvement and this expertise should be extended to all grain legume species, capitalising upon the germplasm collections. The linking of Grain Legumes with regional research and development consortia has been very successful, with outcomes aligning with those of Grain Legumes. We see that with declining funding consolidation of research effort based on likely successes will be necessary, and welcome the move afoot to incorporate grain legumes into an agri-food system focused on successful value chains that deliver sustainable outcomes. Relevance and Strategy Grain Legumes has geographic and disciplinary relevance, addressing the major supply chain issues of variety development seed system and agronomy, with some attention to quality and postharvest marketing systems. The CRP has provided the opportunity to cut ongoing and to initiate new research. Research funded by the Gates Foundation (Anon, 2014) suggests that the need for improvement is greatest in Africa and advocates reducing the number of crop by country combinations when resources are sparse. The lesser research investment in Latin America, however, is not in line with the regions’ dependency on legumes. In spite of the fact that there is no evidence of strong inter-partner CGIAR centre or internal synergy, the program is still moving ahead on most fronts in line with the overall project logframe. This is in spite of continual pushing and pulling by in particular donors and the CO. However, to quantify real impact, we believe Grain Legumes must have access to reliable baseline data on production and consumption, and this is missing. Similarly, there is little evidence of the proposed ‘Inclusive Market Oriented Development’ (IMOD) framework being used to assist with priority setting. The product lines, eight of which cover most of the historical programmes in place in the partner CGIAR centres at the commencement of the Grain Legumes, do not cover all the constraints for formal constraints analysis was not undertaken at the inception of the Grain Legumes, and some of this additionally identified research is undertaken under the umbrella of the FPs; this needs to be rationalised. We found the PLs to be isolated in activity, even with minimally-integrated activities within each PL, with little evidence of synergy between PLs. Even though the SCs should ensure a systems approach, as with the new FPs, we did not get a feel that this is so. The underplaying of agronomy, and production practices may be one reason for this. We believe that treating legume crops as if they were horticultural crops will increase farmer returns from investment. The choice of Flagship Projects makes sense, with the flow of activity firstly around crop management and agronomy followed by the logical sequence of trait discovery, incorporation into improved varieties, dissemination of those varieties through appropriate seed chains leading to market impacts, and the capacity building required at all steps. One obvious omission, however, is the lack of a central and strategic policy on the role of transgenics in Grain Legumes. We found four notable comparative advantages for Grain Legumes: the access to germplasm of component species, the use of the phenotyping facility at ICRISAT, the approach for village level industry for IPM, and the emphasis on hybrid pigeonpea. Efficiency Each centre has strong control of, and emphasis on, their ‘species’ domains, and ownership of the same detracts from possible synergy. Without synergy or value add, the Grain Legumes brings with it no comparative advantage over each centre continuing their own pre-CRP research agendas. We found little evidence of integration of programmes between centres and almost no cross-centre authorship of publications, such as could have occurred with the integrated cross-centre approaches to stress tolerance including crop modelling: the one publication (Gaur et al., 2015) on heat tolerance by ICRISAT, CIAT and ICARDA does not provide any keys to inter-centre collaboration. The integration of each centre with NARS and university research programmes is good, but the cross-centre links with NARS are poor. A better coordinated integration with Grain Legumes, , rather than through the individual centres, may reduce transactions costs for NARS, Monitoring and evaluation is, as noted throughout our report, one area of Grain Legumes research management that has not been given the attention it should have received. If it had have received proper attention, some of the issues of poor efficiency might have been nipped in the bud. A strong monitoring and evaluation system would have provided the baseline data and set the milestones that would have allowed both efficiency and effectiveness to be better appraised. We found no attempt to define comparative advantages of the CGIAR centres and their R4D activities, although practice showed the better grasp of CIAT in developing innovative seed distribution systems. During field visits and interviews, the CCEE Team observed shortcomings in the communication processes within Grain Legumes and with the broader scientific community and the public. For example, the public face of the program on the internet is out of date. Survey findings, however, suggest that information is shared freely and routinely within the PL within which scientists work. Some external issues, such as those with funding, low W1/W2 and poor sustainability of funding (especially if funding is top heavy with a few agencies), undermine research investment and confidence of partners in the system (e.g. as voiced by researchers working on crops and countries not included in TL III and the cessation of ongoing competitively-funded projects especially in India), but other issues attributable to the governance and management of the Grain Legumes, such as opaque integration of W3/bilaterals with W1/W2 funding require attention. Offsetting this, the existence of the Grain Legumes did mobilise additional funding [that it would not have if Grain Legumes did not exist]. We were concerned that Grain Legumes is simply not recognised outside of the CRP, with a limited www presence and centres promote themselves, rather than Grain Legumes (with exception in IITA). This is not a good move if one wishes to increase investment in the Grain Legumes. Although funding agencies require cost:benefit ratios, for example for each PL we faced difficulty in determining comparative value for money between investment in different types of research, and in being able to clearly attribute research and development outcomes to financial investment. There was also a time CCEE frame issue too. There is poor interaction with the private sector, notably in areas where they have a comparative financial advantage. We questioned in particular the apparent lack of interaction with the major agro-chemical companies, with respect to the development of herbicide tolerant (HT) grain legumes and the lack of evidence that the regulatory and trade aspects related to herbicide tolerant crops had been considered. Quality of science The quality of the science is highly variable across Grain Legumes, with pockets of real excellence that are linked to good levels of productivity, whereas other PLs are struggling to deliver quality publications, and outputs and outcomes that are based on these. There is much evidence of gradualism in terms of research output and outcomes, i.e. essentially the same activities that were ongoing at the time of the launch of Grain Legumes are still in place. However, there are examples of game changers including those from valuable investments in genomics, phenotyping, and bio-control. We were pleased to see large proportions of collaboration on publications with non-CGIAR centres, reflecting cooperation with partners in developed and developing countries. The value of collaboration when ensuring quality of science cannot be stressed highly enough both within the CRP, and with other global and national partners. PLs should be given incentives to collaborate with other CRPs and external institutions. There is little cohesion between PLs and with other CRPs as evidenced by publications, although there are some exceptions. We suspect the reasons for this are driven by funding. Productivity from the different PLs is also highly variable and it is not clear what other activities staff are engaged in since, in some PLs, they do not appear to lead to quality publications. Effectiveness Grain Legumes has been very effective in addressing component issues of research, but not the continuum from variety development to legumes on someone’s dinner plate. Our overall assessment of the effectiveness of Grain Legumes in stimulating synergy, innovation and impact indicate that gradualism is more prevalent than innovation. It also shows, as do publications, that there is little integration of disciplines or a focus on ‘systems’. The absence of socio-economists from research teams is evident in the general lack of an end user focus. However, research on genomics, plant breeding and seed systems have made great strides forward, on the brink of delivering impact. Agronomy has been a poor sister, but some of the competitive grants within Grain Legumes have unearthed some potential game changers, such as objective use of transplanting as an agronomic practice. As mentioned earlier, the lack of effective M&E (however, this was part of some major projects such as TL II/TL III), and therefore the ability to monitor impact pathways and achievement of impact, implies no systematic management of data. This creates difficulty when attempting to evaluate the achievement of the Grain Legumes objectives. One might have expected at least one attempt to try to develop publications between centres arguing for similar biologies/research approaches, bringing species together under one umbrella, but we did not find any evidence for this. It is most unfortunate that, due to budgetary cuts, the new ‘schemes’, e.g. competitive grants and scholarships, were cut off before gaining a foothold. With 8 species addressed by Grain Legumes, it is not unexpected that there will be little evidence of shared protocols across centres/species. One rare example was that hosted by the United States Department of Agriculture (USDA) on shared methods for phenotyping of legume germplasm. Researchers from CIAT, IITA, ICRISAT and three USDA stations attended, focusing in simple canopy temperature and root morphology measurements. It is our belief that as a set of research centres, the CGIAR centres should be focusing on the research for which they have a comparative advantage. While imposing the restructure to FPs, which is fine for development objectives and outcomes (funded through W3/bilateral), it is less so for a research institute, and the structure should not detract from the more basic work expected of an international CGIAR centre (or set of centres as in a CRP). Impact It is well known that research does not always lead to scientific breakthroughs. Also, activities such as plant breeding are long term; making impacts difficult to assess. We believe that sufficient progress with genomics and associated research has been made to warrant impact, but we are unable to quantify the levels of impact, or the timeframe for the same. Work in Grain Legumes has enormous potential for real impact in scientific research, commercial, farming, smallholder and household communities, much of which is being realised. However, the PLs need to become more adept at providing convincing cases that are strongly evidenced for these impacts, as this is likely to be a key factor in leveraging future funding. Claimed gains must be referenced against baseline data, and these are not always readily available. The CCEE Team realises that such impact evaluation represents a significant drain on resources, and Grain Legumes should determine whether the balance of costs to benefits favours such investment. Interviews conducted by the CCEE during site visits showed that PLs are quantifying the area of adoption of varieties, but in most cases they are not measuring the impact on environment, health/nutrition. Since the health and nutritional benefits and the environmental gains from growing legumes are major arguments for supporting grain legume research, the community is currently missing substantial opportunities to strengthen its own case for continued support. Whilst there are some impressive examples of considering the whole value chain, e.g. white beans from production through to export; in the main, the pipeline to end user is somewhat piece-meal, with no clear definition of the end user nor differential responsibility of Grain Legumes and of partners. The lack of robust time-defined impact pathways is highlighted in Section 7.4, and even though developed for PL5, timeframes are essential for measuring progress against prediction. Sustainability In summary, there is general acknowledgement that future funding is likely to become more limited, specifically in W1&2 and there is understandable concern over the support for the staff and basic infrastructure that underpin the Grain Legumes programme. For example, it is reported that staffing in parts of CIAT has been dependent on W1&2 and that this is too unstable to re-establish a critical mass. The present system whereby W3 and bilateral projects do not pay a realistic level of overheads means that such projects are being effectively subsidised by W1&2. This position is not sustainable in the long term as there will be a progressive but definite loss of basic skills and resources in the core centres. The only obvious options to prevent this outcome include a severe reduction in the fixed costs of the centres and/or a refusal to accept W3 and bilateral funding with an inadequate overhead component. In the latter case, there is an obvious danger that funders will move their resources away from the CGIAR system towards other, perhaps less expensive, suppliers of research, and possibly more relevant development expertise. This issue must be addressed. As the Grain Legumes moves into the future, and if sustainable funding cannot be assured, decisions must be made concerning a reduction in activities, keeping some caretaker breeding maintenance, and focus (as has TL III) on fewer species and a reduced geographic focus. Cross cutting issues: Gender, capacity building and partnerships Gender is not mainstreamed, but there is some evidence that this is improving, especially with dedicated gender specialists and the slow integration of gender across CRPs. There is a need to approach gender through the vision of agriculture as a social practice, with recognition of what changes will be acceptable culturally and what not, and capitalising upon the perceived and actual features of production and processing that grain legumes are primarily women-based crops. Gender awareness may be high among Scientists, but it appears to be a predominantly passive attribute with few proactively seeking opportunities for gender equity. It is, however, a sound sensitivity base on which to build. Nevertheless, examples of notable gender initiatives were identified during field visits. For example, in Benin, the development of biocontrol technologies has enthusiastically integrated diversity, engaging with women farmers’ and youths while maintaining cultural norms. Women are gathering and processing, youths are taking the product to market. The implication is that several groups benefit, rather than domination by the majority group. In Malawi, innovative approaches have been developed to improving nutrition for children, such as incorporating nutrient enriched bean flour products into snacks. In India, scientists collaborating with gender scientists and socio-economists are identifying the impact of mechanical harvesting on agricultural labour and the potential displacement of female labourers. In Kenya, a novel initiative is improving the accessibility of certified seed for new varieties. Seed suppliers have introduced small packs of grain legume seed at low unit cost, which are being purchased by young people and women. Capacity building efforts for external partners are not clearly aligned with the research mandate and delivery of Grain Legumes. However, there are a number of training activities that are being undertaken by Grain Legumes, largely through the W3/bilateral project. Gender balance never reaches parity, but it appears that efforts are made to include female participants. Within the evaluation timeframe it was not possible to conduct external surveys to further validate or review external capacity building efforts in Grain Legumes. Training of scientists is significant, with >40 benefiting. Postgraduate training is varied across PLs, and there is some opportunity to increase the numbers being supervised. We consider that support for postgraduates at ICRISAT could be better coordinated, satisfying more of the students’ needs. It is important, however, to follow up investments in capacity building by monitoring effectiveness, career progressions and so on. Training activities appear to be rather centre-specific, not following a coordinated programme managed by, nor at the level of, the Grain Legumes. Numbers of persons trained and their gender are important, but a measure of the effectiveness of the training is more important. Although optimism is expressed by the great majority of Research Managers that partnerships were working well to leverage knowledge and research capacities, scientists have a less favourable view, particularly in terms of their incentives to participate. It seems likely that the activities taking place within Grain Legumes were, in the most part, continuations of previous collaborations. This is not surprising in light of the reduction in the emphasis on partnerships as Grain Legumes evolved to a funded project, and the consequent lack of opportunity and ambition for establishing novel partnerships. Where they exist, partnerships are good on the whole, especially with US. They could be expanded where comparative advantages exist (for example with Canada and Australia for machine harvestable legumes), but some earlier identified partnerships, e.g. with Turkey, have not been capitalised upon. Others experience problems of variety access (the embargo on exports of some sources of materials from India), yet others do have relevance e.g. imported Brazilian varieties in pre-release in Ethiopia (even though two of the three are from CIAT materials). Governance and Management The standard format of committee structure and responsibilities is common to other CRPs, as are the attendant problems. One of the major problems is that the Grain Legumes Director has responsibility but no authority; hence, even with the support of the RMC, the Director is unable to ‘direct’ in the literal sense of the work the activities of Grain Legumes. We also see the same sense of helplessness with the role of the PLCs. They have responsibility but no authority in managing the affairs of their PL, and they have no access to funds with which to promote intellectual collaboration and cooperation. Minutes from governance and management meetings do not reflect the compromised weak position of the Director and the associated difficulties in the management of Grain Legumes. Nor do the minutes reflect concerns about the amount of time spent by scientists in meetings for planning, integration, evaluation and reporting. Many scientists reported significant opportunity costs in participating in the ongoing imposed [by the CO] evolution of Grain Legumes and CRPs in general. The changes brought in by the CO have not helped promote any greater authority and capacity of the Grain Legumes Director to direct. Likewise, they do not address any of the issues with the conflict of interest in having the Lead Centre chair the Steering Committee. Indeed, we believe that the combining of the Steering Committee with the Independent Advisory Committee, besides becoming unwieldy in number, annuls any sense of independence in advice offered to the Grain Legumes management. We have concerns with the declining proportion of W1/W2 funds (as expressed in the section on Sustainability), and believe that when basic financial planning takes place, integration of W1/W2 and W3/bilateral sources must occur, and be linked to anticipated outcomes and impacts. This will ensure a close alignment of collaborators’ and partners’ objectives and contributions to that of the Grain Legumes. We also queried the process for, and the formality, or lack of, surrounding, the approval of annual budgets, and the level of priority setting when budgets are cut. Recommendations for Grain Legumes The CCEE Team makes the following recommendations, critical issues are highlighted in bold, and those that require action by an entity other than the Grain Legumes Research Management Committee or Project Management united are identified in a footnote. Relevance and Strategy Recommendation 1: A period of consistency is necessary to raise confidence, morale and trust across scientists, managers and partners to foster the assembly of enduring Grain Legumes outcomes2.  There needs to be a concerted effort to undertake baseline studies and to implement a robust M&E activity during this period. Without these data the foundation for integrated research in grain legumes is jeopardised.  There is a strong need to link more closely with the private sector, especially where there are financial and other comparative advantages to do so. Recommendation 2: The agronomic and physiological trait targets of Grain Legumes (tolerance to changing climate patterns, to the pests and diseases of today and of the future, incorporation of quality traits and adaptations to intensive production systems [machine-harvestability and herbicide tolerance], and short season high yielding characters) are all worthy of continued investment when selecting for improved varieties.  There needs to be a common strategy, implemented across centres and species, as to how to address these trait targets through conventional and modern breeding approaches, but only if adequate funding is assured and secured and if a consistency and unity of purpose can be achieved across a large-scale. This should take the form of cross-species coordinated research programmes to address these breeding targets that cooperate across centres and make efficient use of facilities and other resources.  The CRP should undertake a detailed strategic review of the role of transgenics across the range of targets in the mandate crops. Efficiency Recommendation 3: The lack of an effective M&E process is a significant omission, not least in terms of more efficient use of resources and the lack of baseline data with which to measure impact, and must be rectified.  Reinforcing Recommendation 1, an effective M&E system initially directed towards baseline studies must be implemented.  Transaction costs may be reduced through bilateral projects, which are seen as more cost effective than W1/W2 where transaction costs are disproportionately higher. Recommendation 4: To improve communication and coordination within the CRP, and with a broader audience:  There is a priority need for a central database containing, names of staff associated with Grain Legumes and their time commitments, their responsibilities, and involvement in CRP activities, their progress and achievements, their publications, plans of training, travel, and other opportunities for interaction.  Regular global meetings of staff involved in managing PLs, the entire CRP management staff and the IAC are essential for effective coordination of all activity within Grain Legumes.  The website must be given a complete overhaul and improvement and then regular maintenance must be provided to keep it current. Quality of Science Recommendation 5: It is essential to continue investment in good science and to institute a change from gradualism in research output and outcomes to an expectation of innovative and concrete achievements that can be attributed clearly to people, centres and core facilities.  A cost:benefit analysis and subsequent strategic planning must be undertaken to justify further investment in the genomics and phenotyping facilities at ICRISAT especially as such technologies advance rapidly. Strategic planning and coordination must also be implemented for capitalising on the investment in crop simulation modelling. (The phenotyping facility of ICRISAT needs to focus on delivering some outcomes, not only outputs.)  PLs should be given incentives to collaborate with other CRPs and external institutions. The CCEE recommends special recognition of high quality collaborative papers, thereby encouraging increased quality of the research programmes and widening the penetration of research impacts.  More importance should be placed on the quality of publication, rather than quantity of outputs and there should be recognition of other types of outputs from Grain Legumes. The CRP Director must be party to this.  If staff are engaged in activities that relate more to impact than publication then this needs to be monitored and recorded and a clearer understanding developed of what constitutes a pathway to impact and how success of such activities can be evaluated. A system must be devised and incorporated into the M&E to enable recognition of other types of outputs (non- publication based) from Grain Legumes, e.g. varieties for breeders. Effectiveness Recommendation 6: To develop greater synergy, Grain Legumes should review management processes and the direction of research activities. In particular, far more extensive integration of research and knowledge exchange should take place across both African and Asian continents so that the best aspects of both can be shared. A multidisciplinary approach is recommended that considers processing solutions, as well as breeding solutions, to capitalise upon the nutritional benefits of the grain legume crops. We recommend:  A better collaboration with social scientists at the design stage of experiments in order to improve the utility of the work carried out and to understand its reach.  Supporting3 the adoption of best practice electronic data collection, central storage and open access, particularly of genomic data, for public use.  Given the focus on the link between phenotyping and genotyping, we note that there is a lack of congruence between the populations that are being phenotyped and those being genotyped, and therefore these could be better aligned within each species.  Concentrating investment external to Grain Legumes on scaling up production of varieties with the most promising trait profiles to meet the basic seed requirement.  Developing a more holistic approach that coordinates an understanding of the disease pathology and epidemiology, and of new chemicals before they become commercially available, together with agronomic practice such that recommendations can be made for growers. Continuing work to establish whether agronomic factors hold true in different environments and to assess GxE effects within breeding programmes. Such rigorous trial practices should be used to inform the evaluation of breeding lines and to provide phenotype data to associate with markers for traits such as heat, drought and herbicide tolerance.  Considering grain legumes as if they were vegetable crops in terms of the strategy for intensification of production, both from the management perspective and for seed systems, will be a useful development objective into the future. This will bring about more rapid intensification and is likely to increase farmer returns from investment. Recommendation 7: The CGIAR centres should focus in on the research for which they have a comparative advantage. While imposing the restructure to FPs, which is fine for development objectives and outcomes (funded through W3/bilateral) it is less so for a research institute, and should not detract from the more basic work expected of an international CGIAR centre (or set of centres in a CRP).  Collaborative approaches should be explored within Grain Legumes, e.g. similar biologies/research approaches, bringing species together under one umbrella. Similarly better alignment is needed to address the lack of congruence between the populations that are being phenotyped and those being genotyped.  Despite positive impacts from research in genomics, plant breeding and seed systems, the lack of an effective M&E, already mentioned elsewhere, has reduced the ability to monitor impact pathways. This must be addressed.  The absence of socio-economists from research teams is evident in the general lack of an end user focus. Responsibilities of the different actors in the whole value chain must be considered and identified when developing impact targets, and the pathway leading to them, for individual projects. People with socio-economist skills must be part of the team from project inception so that appropriate frameworks are incorporated for measuring and influencing sociological and economic changes brought about by Grain Legumes research. Impact Recommendation 8: PLs need to become more adept at providing convincing cases in which impact is strongly evidenced, as this is likely to be a key factor in leveraging future funding.  Claimed gains must be referenced against baseline data, and these are not always readily available. The CCEE Team realises that such impact evaluation represents a significant drain on resources, and Grain Legumes should determine whether the balance of costs to benefits favours such investment.  It is essential that Grain Legumes provides training to staff on what constitutes impact and how it can be recorded.  Specific, rather than generalised, potential impacts arising from activity within Grain Legumes should be defined at the time of justifying the programme of work and a pathway to impact should form part of the documentation prepared ahead of a piece of research commencing. . In other words, centres should submit work plans to Grain Legumes before they are undertaken using W1/W2 funds Recommendation 9: The reporting activity must be streamlined to a single (brief) format that can be used to report to Grain Legumes, Centres and to donors for special project activities4. Sustainability Recommendation 10: As Grain Legumes moves into the future, and if sustainable funding cannot be assured, decisions must be made concerning a reduction in activities, keeping some caretaker breeding maintenance, and focus (as has TL III) on fewer species and a reduced geographic focus. Zeigler (Director General of IRRI) states “…time and effort would be better spent … making tough decisions about which programs deserve the precious support.”  The present system whereby W3 and bilateral projects do not pay a realistic level of overheads means that such projects are being effectively subsidised by W1&2 and there will be a progressive but definite loss of basic skills and resources in the core centres. To prevent this outcome it is necessary to significantly reduce the fixed costs of the centres and/or refuse to accept W3 and bilateral funding without an adequate overhead component.  In the absence of long term certainty, the scale of the budget allocated to each of the new CRPs should be very conservative, a feature that can only be achieved by restricting/reducing the scope, probably quite significantly. Cross cutting issues: Gender, capacity building and partnerships Recommendation 11: The challenge for Grain Legumes is to achieve pro-active gender mainstreaming, which facilitates opportunities for gender diversity within all activities, from employment processes through research to end users.  Strategic measurable gender indicators need to be embedded in research design, for instance, through specific IDOs for each of the flagships projects. Accurate baseline data are also required to facilitate M&E reviews of progress.  Implementation of the Gender Strategy is the responsibility of everyone, not solely the Gender Team. Thus, ownership could be encouraged by setting personal development for key personnel objectives with specific outcomes, e.g. employment practices or research outcomes.  Recognising the positive gender initiatives in progress or planned, feedback must be communicated and integrated into broader research planning to share opportunities, methods and outcomes.  In addition to promoting gender equity in research, Grain Legumes also needs to ensure that working environments are gender sensitive and that recruitment processes, including promotion opportunities are equitable. Gender imbalance in management should be actively examined to identify further opportunities for developing female leadership. Recommendation 12: It is recommended that a training plan be devised to ensure that capacity building efforts are more clearly aligned with the research mandate, delivery and timeframe of Grain Legumes. Moreover, we recommend that ICRISAT develop a strategy to treat their new cohort of researchers more equitably in the future. Recommendation 13: To develop a more coherent strategic programme designed to eliminate overlap and promote synergy between programmes with common aims, Grain Legumes should hold a meeting with a range of partners. Governance Recommendation 14: Governance processes should be re-assessed and the structure altered to ensure that the Grain Legumes Director has the authority and budget control to drive the execution of strategy.  The ISC should be truly independent and given the power to influence strategic decisions before they become final. We also recommend that PLCs are provided with the authority to manage the direction and finances of their PL; and that ring-fenced funds are provided for the promotion of collaboration, coordination and staff training5. The way ahead In our view, having seen the ineffectiveness of much of the attempts [or lack of attempts] to harness synergies between multiple centres, and of the strength in few or sole centre partnerships, we believe that there is little to justify a full retention of the 8 legume species and 4 CGIAR centres in a CRP. TL I and II and PABRA have shown to be reasonably good cross-centre and single centre integrated programmes, but even they suffer from incomplete value chain approaches to increasing rural incomes while increasing food and nutritional security; they both need multi-faceted solutions which are not immediately forthcoming from Grain Legumes. It is important to embed Grain Legumes research within the agri-food systems these crops serve. Figure ES1 broadly shows the perceived current and potential degrees of synergy between centres, PLs and species, and is discussed more in the text. It is clear that the value chains for individual species from trait determination to nutritional impact have more cohesion than do the individual activities (e.g. trait deployment) across species. For this reason we believe that the future for research in Grain Legumes is best addressed by focusing on each of the species separately, and within an ecosystem framework; any synergy for research across species can be effected through communication and not necessarily through obligatory cooperative research. The ecosystem framework will allow for strengthening of agronomy type systems research, the arguments for benefits of inclusion of grain legumes in cropping systems, which is notable by its absence in much of what Grain Legumes currently undertakes. Figure ES1. Current and potential degrees of synergy between centres, PLs and crop species We therefore agree with the innovation in agri-food systems approach of the CG, and believe that Grain Legumes rightly belongs in the Dryland Cereals and Legumes Agri-food Systems. We believe that the option of combining the crops of dryland cereals and legumes in the cereal-legume-livestock systems of subsistence farming communities for whole-farm productivity is closest to the best way forward. Indeed the inclusion of grain legumes may not warrant even a CRP alone, rather the legume components should fit in with the major crops that determine the production systems. Legumes will always be subservient to the major cereals, as necessary adjuncts to the whole production system, providing both nutritional diversity and environmental services, neither achievable from cereals alone. Figure ES2. Most suitable option for integration of Grain Legumes and Dryland Cereals into an Agri-Food Systems CRP Most suitable option for integration of Grain Legumes and Dryland Cereals into an Agri-Food Systems CRP, which  Incorporates ex-Dryland Systems, Dryland Cereals, Grain Legumes, some HumidTropics, some ex-Livestock &Fisheries into a new CRP  Will cover full agri-food system VC for all 8 legumes in all ecologies, but must interact (dock) with the relevant AFS-CRPs for the dominant cereal in the relevant ecology  Hence, will need to negotiate with other Agrifood Systems-CRPs on who does what for legumes  In addition, responsible for sorghum and millet in the mixed dryland crop-livestock agro-ecologies For major game changers to be effected, we believe that the game has to change, and there is little evidence of this. The direction of CRPs is the correct route, but the journey has not yet come to its destination. A major change of game [such as the adoption of a Flagship Project approach as exemplified by the Australian CSIRO – where flagships contract services from centres of research excellence] would be painful to implant. The CGIAR system is going down the right pathway but it has not gone far enough.

Essays on health care reform, wealth inequality, and demography

This thesis contains three chapters. The first chapter uses a general equilibrium framework to simulate and compare the long run effects of the Patient Protection and Affordable Care Act (PPACA) and of health care costs reduction policies on macroeconomic variables, government budget, and welfare of individuals. We found that all policies were able to reduce uninsured population, with the PPACA being more effective than cost reductions. The PPACA increased public deficit mainly due to the Medicaid expansion, forcing tax hikes. On the other hand, cost reductions alleviated the fiscal burden of public insurance, reducing public deficit and taxes. Regarding welfare effects, the PPACA as a whole and cost reductions are welfare improving. High welfare gains would be achieved if the U.S. medical costs followed the same trend of OECD countries. Besides, feasible cost reductions are more welfare improving than most of the PPACA components, proving to be a good alternative. The second chapter documents that life cycle general equilibrium models with heterogeneous agents have a very hard time reproducing the American wealth distribution. A common assumption made in this literature is that all young adults enter the economy with no initial assets. In this chapter, we relax this assumption – not supported by the data – and evaluate the ability of an otherwise standard life cycle model to account for the U.S. wealth inequality. The new feature of the model is that agents enter the economy with assets drawn from an initial distribution of assets. We found that heterogeneity with respect to initial wealth is key for this class of models to replicate the data. According to our results, American inequality can be explained almost entirely by the fact that some individuals are lucky enough to be born into wealth, while others are born with few or no assets. The third chapter documents that a common assumption adopted in life cycle general equilibrium models is that the population is stable at steady state, that is, its relative age distribution becomes constant over time. An open question is whether the demographic assumptions commonly adopted in these models in fact imply that the population becomes stable. In this chapter we prove the existence of a stable population in a demographic environment where both the age-specific mortality rates and the population growth rate are constant over time, the setup commonly adopted in life cycle general equilibrium models. Hence, the stability of the population do not need to be taken as assumption in these models.

Capacidade de combinação em sete populações de melancia

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Quality characteristics and fertilizing ability of ram sperm subpopulations separated by partition in an aqueous two-phase system

Centrifugal countercurrent distribution (CCCD) in an aqueous two-phase system (TPS) is a resolute technique revealing sperm heterogeneity and for the estimation of the fertilizing potential of a given semen sample. However, separated sperm subpopulations have never been tested for their fertilizing ability yet. Here, we have compared sperm quality parameters and the fertilizing ability of sperm subpopulations separated by the CCCD process from ram semen samples maintained at 20 degrees C or cooled down to 5 degrees C. Total and progressive sperm motility was evaluated by computer-assisted analysis using a CASA system and membrane integrity was evaluated by flow cytometry by staining with CFDA/Pl. The capacitation state, staining with chlortetracycline, and apoptosis-related markers, such as phosphatidylserine (PS) translocation detected with Annexin V. and DNA damage detected by the TUNEL assay, were determined by fluorescence microscopy. Additionally, the fertilizing ability of the fractionated subpopulations was comparative assessed by zona binding assay (ZBA). CCCD analysis revealed that the number of spermatozoa displaying membrane and DNA alterations was higher in samples chilled at 5 degrees C than at 20 degrees C. which can be reflected in the displacement to the left of the CCCD profiles. The spermatozoa located in the central and right chambers (more hydrophobic) presented higher values (P<0.01) of membrane integrity, lower PS translocation (P<0.05) and DNA damage (P<0.001) than those in the left part of the profile, where apoptotic markers were significantly increased and the proportion of viable non-capacitated sperm was reduced. We have developed a new protocol to recover spermatozoa from the CCCD fractions and we proved that these differences were related with the fertilizing ability determined by ZBA, because we found that the number of spermatozoa attached per oocyte was significantly higher for spermatozoa recovered from the central and right chambers, in both types of samples. This is the first time, to our knowledge that sperm recovered from a two-phase partition procedure are used for fertilization assays. These results open up new possibilities for using specific subpopulations of sperm for artificial insemination or in vitro fertilization, not only regarding better sperm quality but also certain characteristics such as subpopulations enriched in spermatozoa bearing X or Y chromosome that we have already isolated or any other feature. (C) 2011 Elsevier B.V. All rights reserved.

Context detection and abstraction in smart environments

Context-aware computing is currently considered the most promising approach to overcome information overload and to speed up access to relevant information and services. Context-awareness may be derived from many sources, including user profile and preferences, network information, sensor analysis; usually context-awareness relies on the ability of computing devices to interact with the physical world, i.e. with the natural and artificial objects hosted within the "environment”. Ideally, context-aware applications should not be intrusive and should be able to react according to user’s context, with minimum user effort. Context is an application dependent multidimensional space and the location is an important part of it since the very beginning. Location can be used to guide applications, in providing information or functions that are most appropriate for a specific position. Hence location systems play a crucial role. There are several technologies and systems for computing location to a vary degree of accuracy and tailored for specific space model, i.e. indoors or outdoors, structured spaces or unstructured spaces. The research challenge faced by this thesis is related to pedestrian positioning in heterogeneous environments. Particularly, the focus will be on pedestrian identification, localization, orientation and activity recognition. This research was mainly carried out within the “mobile and ambient systems” workgroup of EPOCH, a 6FP NoE on the application of ICT to Cultural Heritage. Therefore applications in Cultural Heritage sites were the main target of the context-aware services discussed. Cultural Heritage sites are considered significant test-beds in Context-aware computing for many reasons. For example building a smart environment in museums or in protected sites is a challenging task, because localization and tracking are usually based on technologies that are difficult to hide or harmonize within the environment. Therefore it is expected that the experience made with this research may be useful also in domains other than Cultural Heritage. This work presents three different approaches to the pedestrian identification, positioning and tracking: Pedestrian navigation by means of a wearable inertial sensing platform assisted by the vision based tracking system for initial settings an real-time calibration; Pedestrian navigation by means of a wearable inertial sensing platform augmented with GPS measurements; Pedestrian identification and tracking, combining the vision based tracking system with WiFi localization. The proposed localization systems have been mainly used to enhance Cultural Heritage applications in providing information and services depending on the user’s actual context, in particular depending on the user’s location.

De Novo Design of secondary structures: Synthesis and conformational studies

Chemists have long sought to extrapolate the power of biological catalysis and recognition to synthetic systems. These efforts have focused largely on low molecular weight catalysts and receptors; however, biological systems themselves rely almost exclusively on polymers, proteins and RNA, to perform complex chemical functions. Proteins and RNA are unique in their ability to adopt compact, well-ordered conformations, and specific folding provides precise spatial orientation of the functional groups that comprise the “active site”. These features suggest that identification of new polymer backbones with discrete and predictable folding propensities (“foldamers”) will provide a basis for design of molecular machines with unique capabilities. The foldamer approach complements current efforts to design unnatural properties into polypeptides and polynucleotides. The aim of this thesis is the synthesis and conformational studies of new classes of foldamers, using a peptidomimetic approach. Moreover their attitude to be utilized as ionophores, catalysts, and nanobiomaterials were analyzed in solution and in the solid state. This thesis is divided in thematically chapters that are reported below. It begins with a very general introduction (page 4) which is useful, but not strictly necessary, to the expert reader. It is worth mentioning that paragraph I.3 (page 22) is the starting point of this work and paragraph I.5 (page 32) isrequired to better understand the results of chapters 4 and 5. In chapter 1 (page 39) is reported the synthesis and conformational analysis of a novel class of foldamers containing (S)-β3-homophenylglycine [(S)-β3-hPhg] and D- 4-carboxy-oxazolidin-2-one (D-Oxd) residues in alternate order is reported. The experimental conformational analysis performed in solution by IR, 1HNMR, and CD spectroscopy unambiguously proved that these oligomers fold into ordered structures with increasing sequence length. Theoretical calculations employing ab initio MO theory suggest a helix with 11-membered hydrogenbonded rings as the preferred secondary structure type. The novel structures enrich the field of peptidic foldamers and might be useful in the mimicry of native peptides. In chapter 2 cyclo-(L-Ala-D-Oxd)3 and cyclo-(L-Ala-DOxd) 4 were prepared in the liquid phase with good overall yields and were utilized for bivalent ions chelation (Ca2+, Mg2+, Cu2+, Zn2+ and Hg2+); their chelation skill was analyzed with ESI-MS, CD and 1HNMR techniques and the best results were obtained with cyclo-(L-Ala-D-Oxd)3 and Mg2+ or Ca2+. Chapter 3 describes an application of oligopeptides as catalysts for aldol reactions. Paragraph 3.1 concerns the use of prolinamides as catalysts of the cross aldol addition of hydroxyacetone to aromatic aldeydes, whereas paragraphs 3.2 and 3.3 are about the catalyzed aldol addition of acetone to isatins. By means of DFT and AIM calculations, the steric and stereoelectronic effects that control the enantioselectivity in the cross-aldol addition of acetone to isatin catalysed by L-proline have been studied, also in the presence of small quantities of water. In chapter 4 is reported the synthesis and the analysis of a new fiber-like material, obtained from the selfaggregation of the dipeptide Boc-L-Phe-D-Oxd-OBn, which spontaneously forms uniform fibers consisting of parallel infinite linear chains arising from singleintermolecular N-H···O=C hydrogen bonds. This is the absolute borderline case of a parallel β-sheet structure. Longer oligomers of the same series with general formula Boc-(L-Phe-D-Oxd)n-OBn (where n = 2-5), are described in chapter 5. Their properties in solution and in the solid state were analyzed, in correlation with their attitude to form intramolecular hydrogen bond. In chapter 6 is reported the synthesis of imidazolidin-2- one-4-carboxylate and (tetrahydro)-pyrimidin-2-one-5- carboxylate, via an efficient modification of the Hofmann rearrangement. The reaction affords the desired compounds from protected asparagine or glutamine in good to high yield, using PhI(OAc)2 as source of iodine(III).

Effectiveness, safety and cost-effectiveness of homeopathy in general practice - summarized health technology assessment

Introduction: The Health Technology Assessment report on effectiveness, cost-effectiveness and appropriateness of homeopathy was compiled on behalf of the Swiss Federal Office for Public Health (BAG) within the framework of the 'Program of Evaluation of Complementary Medicine (PEK)'. Materials and Methods: Databases accessible by Internet were systematically searched, complemented by manual search and contacts with experts, and evaluated according to internal and external validity criteria. Results: Many high-quality investigations of pre-clinical basic research proved homeopathic high-potencies inducing regulative and specific changes in cells or living organisms. 20 of 22 systematic reviews detected at least a trend in favor of homeopathy. In our estimation 5 studies yielded results indicating clear evidence for homeopathic therapy. The evaluation of 29 studies in the domain 'Upper Respiratory Tract Infections/Allergic Reactions' showed a positive overall result in favor of homeopathy. 6 out of 7 controlled studies were at least equivalent to conventional medical interventions. 8 out of 16 placebocontrolled studies were significant in favor of homeopathy. Swiss regulations grant a high degree of safety due to product and training requirements for homeopathic physicians. Applied properly, classical homeopathy has few side-effects and the use of high-potencies is free of toxic effects. A general health-economic statement about homeopathy cannot be made from the available data. Conclusion: Taking internal and external validity criteria into account, effectiveness of homeopathy can be supported by clinical evidence and professional and adequate application be regarded as safe. Reliable statements of cost-effectiveness are not available at the moment. External and model validity will have to be taken more strongly into consideration in future studies.

Morphological and immunocytochemical analysis of Escherichia coli-specific surface antigens in wildtype strains and in recombinant Vibrio cholerae

Adhesion is the first step in the pathogenesis of enterotoxigenic Escherichia coli infections. The genes encoding the most prevalent adhesion factors CFA/I, CS3 and CS6 were cloned into Vibrio cholerae strain CVD 103-HgR and expression of fimbriae was investigated in wildtype and recombinant strains by transmission electron microscopy in conjunction with immunolabelling and negative staining. Negative staining was effective in revealing CFA/I and CS3, but not CS6. Although morphology of fimbriae differed between wildtype and recombinant strains, corresponding surface antigens were recognized by specific antibodies. The present study provides evidence that ETEC-specific fimbriae can adequately be expressed in an attenuated V. cholerae vaccine strain and that immunoelectron microscopy is a critical tool to validate the surface expression of antigens in view of their possible suitability for recombinant vaccines.

General distress, hopelessness—suicidal ideation and worrying in adolescence: Concurrent and predictive validity of a symptom-level bifactor model for clinical diagnoses

BACKGROUND: Clinical disorders often share common symptoms and aetiological factors. Bifactor models acknowledge the role of an underlying general distress component and more specific sub-domains of psychopathology which specify the unique components of disorders over and above a general factor. METHODS: A bifactor model jointly calibrated data on subjective distress from The Mood and Feelings Questionnaire and the Revised Children's Manifest Anxiety Scale. The bifactor model encompassed a general distress factor, and specific factors for (a) hopelessness-suicidal ideation, (b) generalised worrying and (c) restlessness-fatigue at age 14 which were related to lifetime clinical diagnoses established by interviews at ages 14 (concurrent validity) and current diagnoses at 17 years (predictive validity) in a British population sample of 1159 adolescents. RESULTS: Diagnostic interviews confirmed the validity of a symptom-level bifactor model. The underlying general distress factor was a powerful but non-specific predictor of affective, anxiety and behaviour disorders. The specific factors for hopelessness-suicidal ideation and generalised worrying contributed to predictive specificity. Hopelessness-suicidal ideation predicted concurrent and future affective disorder; generalised worrying predicted concurrent and future anxiety, specifically concurrent generalised anxiety disorders. Generalised worrying was negatively associated with behaviour disorders. LIMITATIONS: The analyses of gender differences and the prediction of specific disorders was limited due to a low frequency of disorders other than depression. CONCLUSIONS: The bifactor model was able to differentiate concurrent and predict future clinical diagnoses. This can inform the development of targeted as well as non-specific interventions for prevention and treatment of different disorders.

Predicting 5- and 10-year survival in older women with early-stage breast cancer: self-rated health and walking ability.

OBJECTIVES To determine life expectancy for older women with breast cancer. DESIGN Prospective longitudinal study with 10 years of follow-up data. SETTING Hospitals or collaborating tumor registries in four geographic regions (Los Angeles, California; Minnesota; North Carolina; Rhode Island). PARTICIPANTS Women aged 65 and older at time of breast cancer diagnosis with Stage I to IIIA disease with measures of self-rated health (SRH) and walking ability at baseline (N = 615; 17% aged ≥80, 52% Stage I, 58% with ≥2 comorbidities). MEASUREMENTS Baseline SRH, baseline self-reported walking ability, all-cause and breast cancer-specific estimated probability of 5- and 10-year survival. RESULTS At the time of breast cancer diagnosis, 39% of women reported poor SRH, and 28% reported limited ability to walk several blocks. The all-cause survival curves appear to separate after approximately 3 years, and the difference in survival probability between those with low SRH and limited walking ability and those with high SRH and no walking ability limitation was significant (0.708 vs 0.855 at 5 years, P ≤ .001; 0.300 vs 0.648 at 10 years, P < .001). There were no differences between the groups in breast cancer-specific survival at 5 and 10 years (P = .66 at 5 years, P = .16 at 10 years). CONCLUSION The combination of low SRH and limited ability to walk several blocks at diagnosis is an important predictor of worse all-cause survival at 5 and 10 years. These self-report measures easily assessed in clinical practice may be an effective strategy to improve treatment decision-making in older adults with cancer.

Post-conflict slowing after incongruent stimuli: From general to conflict-specific

Encountering a cognitive conflict not only slows current performance, but it can also affect subsequent performance, in particular when the conflict is induced with bivalent stimuli (i.e., stimuli with relevant features for two different tasks) or with incongruent trials (i.e., stimuli with relevant features for two response alternatives). The post-conflict slowing following bivalent stimuli, called “bivalency effect”, affects all subsequent stimuli, irrespective of whether the subsequent stimuli share relevant features with the conflict stimuli. To date, it is unknown whether the conflict induced by incongruent stimuli results in a similar post-conflict slowing. To investigate this, we performed six experiments in which participants switched between two tasks. In one task, incongruent stimuli appeared occasionally; in the other task, stimuli shared no feature with the incongruent trials. The results showed an initial performance slowing that affected all tasks after incongruent trials. On further trials, however, the slowing only affected the task sharing features with the conflict stimuli. Therefore, the post-conflict slowing following incongruent stimuli is first general and then becomes conflict-specific across trials. These findings are discussed within current task switching and cognitive control accounts.

Isotopic signature of specific biomarkers derived from anaerobic methanotrophic archaea (ANME groups) and sulphate-reducing bacteria (SRB) at different cold seep provinces

Anaerobic methane-oxidizing microbial communities in sediments at cold methane seeps are important factors in controlling methane emission to the ocean and atmosphere. Here, we investigated the distribution and carbon isotopic signature of specific biomarkers derived from anaerobic methanotrophic archaea (ANME groups) and sulphate-reducing bacteria (SRB) responsible for the anaerobic oxidation of methane (AOM) at different cold seep provinces of Hydrate Ridge, Cascadia margin. The special focus was on their relation to in situ cell abundances and methane turnover. In general, maxima in biomarker abundances and minima in carbon isotope signatures correlated with maxima in AOM and sulphate reduction as well as with consortium biomass. We found ANME-2a/DSS aggregates associated with high abundances of sn-2,3-di-O-isoprenoidal glycerol ethers (archaeol, sn-2-hydroxyarchaeol) and specific bacterial fatty acids (C16:1omega5c, cyC17:0omega5,6) as well as with high methane fluxes (Beggiatoa site). The low to medium flux site (Calyptogena field) was dominated by ANME-2c/DSS aggregates and contained less of both compound classes but more of AOM-related glycerol dialkyl glycerol tetraethers (GDGTs). ANME-1 archaea dominated deeper sediment horizons at the Calyptogena field where sn-1,2-di-O-alkyl glycerol ethers (DAGEs), archaeol, methyl-branched fatty acids (ai-C15:0, i-C16:0, ai-C17:0), and diagnostic GDGTs were prevailing. AOM-specific bacterial and archaeal biomarkers in these sediment strata generally revealed very similar d13C-values of around -100 per mill. In ANME-2-dominated sediment sections, archaeal biomarkers were even more 13C-depleted (down to -120 per mill), whereas bacterial biomarkers were found to be likewise 13C-depleted as in ANME-1-dominated sediment layers (d13C: -100 per mill). The zero flux site (Acharax field), containing only a few numbers of ANME-2/DSS aggregates, however, provided no specific biomarker pattern. Deeper sediment sections (below 20 cm sediment depth) from Beggiatoa covered areas which included solid layers of methane gas hydrates contained ANME-2/DSS typical biomarkers showing subsurface peaks combined with negative shifts in carbon isotopic compositions. The maxima were detected just above the hydrate layers, indicating that methane stored in the hydrates may be available for the microbial community. The observed variations in biomarker abundances and 13C-depletions are indicative of multiple environmental and physiological factors selecting for different AOM consortia (ANME-2a/DSS, ANME-2c/DSS, ANME-1) along horizontal and vertical gradients of cold seep settings.

Policy processes and collective action in water reforms: the cases of Nicaragua and Suriname

Las reformas de agua en países en desarrollo suelen llevarse a cabo junto con cambios institucionales más profundos o, incluso, acompañadas de cambios constitucionales o de régimen político. Por lo tanto, los marcos institucionales adaptados a países gobernados sujetos al estado de derecho pueden no ser apropiados para contextos gobernados fundamentalmente, al menos en sus inicios, por instituciones informales o poco maduras. Esta tesis toma las reformas de agua como punto de partida y pretende contribuir a la literatura mediante una serie de análisis empíricos tanto del ámbito general como del plano individual o sujeto personal de la política del agua. En el ámbito general, el foco se pone en los factores que explican el fallo de la acción colectiva en dos contextos diferentes: 1) en la implementación de la nueva Ley de Aguas de Nicaragua y 2) en el mantenimiento y revitalización de las instituciones de riego en Surinam. En el plano del individuo, la investigación se centra en las decisiones de los usuarios de los recursos y analiza el papel crítico de las variables sociales para la gestión de los recursos comunes. Para ello, el método de investigación utilizado es mixto, combinando el análisis de entrevistas, encuestas y experimentos. En el ámbito general, los resultados muestran que las principales barreras para la implementación de la nueva Ley de Aguas de Nicaragua podrían tener su reflejo en el lenguaje de la Ley y, por tanto, en la forma en la que se definen y configuran las instituciones incluidas en dicha Ley. Así, la investigación demuestra que la implementación de políticas no puede ser estudiada o entendida sin tener en cuenta tanto el diseño de la propia política como el marco socio-ecológico en el que se enmarca. El contexto específico de Nicaragua remarca la importancia de considerar tanto las instituciones formales como informales en los procesos de transición política. A pesar de que las reformas de agua requieren plazos largos para su implementación, el hecho de que exista una diferencia entre las reglas tal cual se definen formalmente y las reglas que operan en la realidad merece una mayor consideración en el diseño de políticas basadas fundamentalmente en instituciones formales. En el ámbito de la conducta individual, el análisis de la acción colectiva ofrece una serie de observaciones empíricas interesantes. En el caso de Nicaragua, los resultados indican que la intensidad de las relaciones sociales, el tipo de agentes dispuestos a proporcionar apoyo social y el nivel de confianza en la comunidad son factores que explican de manera significativa la participación en la comunidad. Sin embargo, el hecho de que la gestión colectiva de riego se produzca, en la mayoría de casos, en torno a lazos familiares sugiere que las variables de capital social críticas se definen en gran medida en la esfera familiar, siendo difícil que se extiendan fuera de estos nexos. El análisis experimental de los resultados de un juego de uso de recurso común y contribución al bien público muestra que las preferencias pro-sociales de los individuos y la heterogeneidad del grupo en términos de composición por sexo son factores que explican significativamente los resultados y las decisiones de apropiación a lo largo del juego. En términos del diseño de las políticas, es fundamental tener en cuenta las dinámicas de participación y uso de los recursos comunes de manera que los niveles de cooperación puedan mantenerse en el largo plazo, lo cual, como se observa en el caso de Surinam, no es siempre posible. Finalmente, el caso de Surinam es un ejemplo ilustrativo de los procesos de acción colectiva en economías en transición. El análisis del fallo de la acción colectiva en Surinam muestra que los procesos políticos vinculados al período colonial y de independencia explican en gran medida la falta de claridad en las reglas operacionales y colectivas que gobiernan la gestión de los sistemas de riego y drenaje. Los resultados empíricos sugieren que a pesar de que la acción colectiva para la provisión de los servicios de riego y drenaje estaba bien establecida bajo el régimen colonial, la auto-organización no prosperó en un contexto dependiente del apoyo externo y regido fundamentalmente por reglas diseñadas al nivel competencial del gobierno central. El sistema socio-ecológico que se desarrolló durante la transición post-colonial favoreció, así, la emergencia de comportamientos oportunistas, y posteriormente la inoperancia de los Water Boards (WBs) creados en la época colonial. En este sentido, cualquier intento por revitalizar los WBs y fomentar el desarrollo de la auto-organización de los usuarios necesitará abordar los problemas relacionados con los patrones demográficos, incluyendo la distribución de la tierra, el diseño de instituciones y la falta de confianza en el gobierno, además de las inversiones típicas en infraestructura y sistemas de información hidrológicos. El liderazgo del gobierno, aportando empuje de arriba-abajo, es, además, otro elemento imprescindible en Surinam. ABSTRACT Water reforms in developing countries take place along deeper institutional and even constitutional. Therefore, institutional frameworks that might result in positive outcomes in countries governed by the rule of law might not fit in contexts governed mainly by informal or immature institutions. This thesis takes water reforms as the starting point and aims to contribute to the literature by presenting several conceptual and empirical analyses at both general and individual levels. At the general national level, the focus is on the factors explaining failure of collective action in two different settings: 1) in the implementation of the new Nicaraguan Water Law and 2) in sustaining and revitalizing irrigation institutions in Suriname. At the individual level, the research focuses on the actions of resource users and analyzes the critical role of social variables for common pool resources management. For this purpose, the research presented in this thesis makes use of a mixed-method approach, combining interviews, surveys and experimental methods. Overall, the results show that major barriers for the implementation of the new Nicaraguan Water Law have its reflection on the language of the Law and, therefore, on the way institutions are defined and configured. In this sense, our study shows that implementation cannot fruitfully be studied and understood without taking into account both the policy design and the social-ecological context in which it is framed. The specific setting of Nicaragua highlights the relevance of considering both formal and informal institutions when promoting policy transitions. Despite the unquestionable fact that water reforms implementation needs long periods of time, there is still a gap between the rules on paper and the rules on the ground that deserves further attention when proposing policy changes on the basis of formal institutions. At the level of the individual agent, the analysis of collective action provides a number of interesting empirical insights. In the case of Nicaragua, I found that the intensity of social networks, the type of agents willing to provide social support and the level of trust in the community are all significant factors in explaining collective action at community level. However, the fact that most collective irrigation relies on family ties suggests that critical social capital variables might be defined within the family sphere and making it difficult to go beyond it. Experimental research combining a common pool resource and a public good game in Nicaragua shows that individuals’ pro-social traits and group heterogeneity in terms of sex composition are significant variables in explaining efficiency outcomes and effort decisions along the game. Thus, with regard to policy design, it is fundamental to consider carefully the dynamics of agents' participation and use of common pool resources, for sustaining cooperation in the long term, which, as seen in the case and Surinam, is not always possible. The case of Suriname provides a rich setting for the analysis of collective action in transition economies. The analysis of decay of collective irrigation in Suriname shows that the lack of clear operational and collective choice rules appear to be rooted in deeper political processes that date back to the colonial period. The empirical findings suggest that despite collective action for the provision of irrigation and drainage services was well established during the colonial period, self-organization did not flourish in a context governed by colonial state-crafted rules and mostly dependent on external support. The social-ecological system developed during the post-colonial transition process favored the emergence of opportunistic behavior. In this respect, any attempt to revitalize WBs and support self-organization will need to tackle the problems derived from demographic patterns, including land allocation, institutions design and government distrust, in addition to the typical investments in both physical infrastructure and hydrological information systems. The leadership role of the government, acting as a top-down trigger, is another essential element in Suriname.

Identification and characterization of a liver stage-specific promoter region of the malaria parasite Plasmodium.

During the blood meal of a Plasmodium-infected mosquito, 10 to 100 parasites are inoculated into the skin and a proportion of these migrate via the bloodstream to the liver where they infect hepatocytes. The Plasmodium liver stage, despite its clinical silence, represents a highly promising target for antimalarial drug and vaccine approaches. Successfully invaded parasites undergo a massive proliferation in hepatocytes, producing thousands of merozoites that are transported into a blood vessel to infect red blood cells. To successfully develop from the liver stage into infective merozoites, a tight regulation of gene expression is needed. Although this is a very interesting aspect in the biology of Plasmodium, little is known about gene regulation in Plasmodium parasites in general and in the liver stage in particular. We have functionally analyzed a novel promoter region of the rodent parasite Plasmodium berghei that is exclusively active during the liver stage of the parasite. To prove stage-specific activity of the promoter, GFP and luciferase reporter assays have been successfully established, allowing both qualitative and accurate quantitative analysis. To further characterize the promoter region, the transcription start site was mapped by rapid amplification of cDNA ends (5'-RACE). Using promoter truncation experiments and site-directed mutagenesis within potential transcription factor binding sites, we suggest that the minimal promoter contains more than one binding site for the recently identified parasite-specific ApiAP2 transcription factors. The identification of a liver stage-specific promoter in P. berghei confirms that the parasite is able to tightly regulate gene expression during its life cycle. The identified promoter region might now be used to study the biology of the Plasmodium liver stage, which has thus far proven problematic on a molecular level. Stage-specific expression of dominant-negative mutant proteins and overexpression of proteins normally active in other life cycle stages will help to understand the function of the proteins investigated.

A genetic investigation of the covariation among Inspection Time, Choice Reaction Time, and IQ subtest scores

Information processing speed, as measured by elementary cognitive tasks, is correlated with higher order cognitive ability so that increased speed relates to improved cognitive performance. The question of whether the genetic variation in Inspection Time (IT) and Choice Reaction Time (CRT) is associated with IQ through a unitary factor was addressed in this multivariate genetic study of IT, CRT, and IQ subtest scores. The sample included 184 MZ and 206 DZ twin pairs with a mean age of 16.2 years (range 15-18 years). They were administered a visual (pi-figure) IT task, a two-choice RT task, five computerized subtests of the Multidimensional Aptitude Battery, and the digit symbol substitution subtest from the WAIS-R. The data supported a factor model comprising a general, three group (verbal ability, visuospatial ability, broad speediness), and specific genetic factor structure, a shared environmental factor influencing all tests but IT, plus unique environmental factors that were largely specific to individual measures. The general genetic factor displayed factor loadings ranging between 0.35 and 0.66 for the IQ subtests, with IT and CRT loadings of -0.47 and -0.24, respectively. Results indicate that a unitary factor is insufficient to describe the entire relationship between cognitive speed measures and all IQ subtests, with independent genetic effects explaining further covariation between processing speed (especially CRT) and Digit Symbol.