Knowledge-based clinical pathway for medical quality improvement

Clinical pathways have been adopted for various diseases in clinical departments for quality improvement as a result of standardization of medical activities in treatment process. Using knowledge-based decision support on the basis of clinical pathways is a promising strategy to improve medical quality effectively. However, the clinical pathway knowledge has not been fully integrated into treatment process and thus cannot provide comprehensive support to the actual work practice. Therefore this paper proposes a knowledgebased clinical pathway management method which contributes to make use of clinical knowledge to support and optimize medical practice. We have developed a knowledgebased clinical pathway management system to demonstrate how the clinical pathway knowledge comprehensively supports the treatment process. The experiences from the use of this system show that the treatment quality can be effectively improved by the extracted and classified clinical pathway knowledge, seamless integration of patient-specific clinical pathway recommendations with medical tasks and the evaluating pathway deviations for optimization.

Integrated clinical pathway management for medical quality improvement-based on a semiotically inspired systems architecture

Clinical pathway is an approach to standardise care processes to support the implementations of clinical guidelines and protocols. It is designed to support the management of treatment processes including clinical and non-clinical activities, resources and also financial aspects. It provides detailed guidance for each stage in the management of a patient with the aim of improving the continuity and coordination of care across different disciplines and sectors. However, in the practical treatment process, the lack of knowledge sharing and information accuracy of paper-based clinical pathways burden health-care staff with a large amount of paper work. This will often result in medical errors, inefficient treatment process and thus poor quality medical services. This paper first presents a theoretical underpinning and a co-design research methodology for integrated pathway management by drawing input from organisational semiotics. An approach to integrated clinical pathway management is then proposed, which aims to embed pathway knowledge into treatment processes and existing hospital information systems. The capability of this approach has been demonstrated through the case study in one of the largest hospitals in China. The outcome reveals that medical quality can be improved significantly by the classified clinical pathway knowledge and seamless integration with hospital information systems.

Genetic association analysis of vitamin D pathway with obesity traits

Objective:Observational studies have examined the link between vitamin D deficiency and obesity traits. Some studies have reported associations between vitamin D pathway genes such as VDR, GC and CYP27B1 with body mass index (BMI) and waist circumference (WC); however, the findings have been inconsistent. Therefore, we investigated the involvement of vitamin D metabolic pathway genes in obesity-related traits in a large population-based study.Methods:We undertook a comprehensive analysis between 100 tagging single nucleotide polymorphisms (tagSNPs) in genes encoding for DHCR7, CYP2R1, VDBP, CYP27B1, CYP27A1, CYP24A1, VDR and RXRG, and obesity traits in 5224 participants (aged 45 years) in the 1958 British birth cohort (1958BC). We further extended our analyses to investigate the associations between SNPs and obesity traits using the summary statistics from the GIANT (Genetic Investigation of Anthropometric Traits) consortium (n=123 865).Results:In the 1958BC (n=5224), after Bonferroni correction, none of the tagSNPs were associated with obesity traits except for one tagSNP from CYP24A1 that was associated with waist-hip ratio (WHR) (rs2296239, P=0.001). However, the CYP24A1 SNP was not associated with BMI-adjusted WHR (WHRadj) in the 1958BC (rs2296239, P=1.00) and GIANT results (n=123 865, P=0.18). There was also no evidence for an interaction between the tagSNPs and obesity on BMI, WC, WHR and WHRadj in the 1958BC. In the GIANT consortium, none of the tagSNPs were associated with obesity traits.Conclusions:Despite a very large study, our findings suggest that the vitamin D pathway genes are unlikely to have a major role in obesity-related traits in the general population.

Genetic polymorphisms in the hypothalamic pathway in relation to subsequent weight change--the DiOGenes study

BACKGROUND: Single nucleotide polymorphisms (SNPs) in genes encoding the components involved in the hypothalamic pathway may influence weight gain and dietary factors may modify their effects. AIM: We conducted a case-cohort study to investigate the associations of SNPs in candidate genes with weight change during an average of 6.8 years of follow-up and to examine the potential effect modification by glycemic index (GI) and protein intake. METHODS AND FINDINGS: Participants, aged 20-60 years at baseline, came from five European countries. Cases ('weight gainers') were selected from the total eligible cohort (n = 50,293) as those with the greatest unexplained annual weight gain (n = 5,584). A random subcohort (n = 6,566) was drawn with the intention to obtain an equal number of cases and noncases (n = 5,507). We genotyped 134 SNPs that captured all common genetic variation across the 15 candidate genes; 123 met the quality control criteria. Each SNP was tested for association with the risk of being a 'weight gainer' (logistic regression models) in the case-noncase data and with weight gain (linear regression models) in the random subcohort data. After accounting for multiple testing, none of the SNPs was significantly associated with weight change. Furthermore, we observed no significant effect modification by dietary factors, except for SNP rs7180849 in the neuromedin β gene (NMB). Carriers of the minor allele had a more pronounced weight gain at a higher GI (P = 2 x 10⁻⁷). CONCLUSIONS: We found no evidence of association between SNPs in the studied hypothalamic genes with weight change. The interaction between GI and NMB SNP rs7180849 needs further confirmation.

A mathematical model of the sterol regulatory element binding protein 2 cholesterol biosynthesis pathway

Cholesterol is one of the key constituents for maintaining the cellular membrane and thus the integrity of the cell itself. In contrast high levels of cholesterol in the blood are known to be a major risk factor in the development of cardiovascular disease. We formulate a deterministic nonlinear ordinary differential equation model of the sterol regulatory element binding protein 2 (SREBP-2) cholesterol genetic regulatory pathway in an hepatocyte. The mathematical model includes a description of genetic transcription by SREBP-2 which is subsequently translated to mRNA leading to the formation of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), a main precursor of cholesterol synthesis. Cholesterol synthesis subsequently leads to the regulation of SREBP-2 via a negative feedback formulation. Parameterised with data from the literature, the model is used to understand how SREBP-2 transcription and regulation affects cellular cholesterol concentration. Model stability analysis shows that the only positive steady-state of the system exhibits purely oscillatory, damped oscillatory or monotic behaviour under certain parameter conditions. In light of our findings we postulate how cholesterol homestasis is maintained within the cell and the advantages of our model formulation are discussed with respect to other models of genetic regulation within the literature.

Fold-change detection in a whole-pathway model of Escherichia coli chemotaxis

There has been recent interest in sensory systems that are able to display a response which is proportional to a fold change in stimulus concentration, a feature referred to as fold-change detection (FCD). Here, we demonstrate FCD in a recent whole-pathway mathematical model of Escherichia coli chemotaxis. FCD is shown to hold for each protein in the signalling cascade and to be robust to kinetic rate and protein concentration variation. Using a sensitivity analysis, we find that only variations in the number of receptors within a signalling team lead to the model not exhibiting FCD. We also discuss the ability of a cell with multiple receptor types to display FCD and explain how a particular receptor configuration may be used to elucidate the two experimentally determined regimes of FCD behaviour. All findings are discussed in respect of the experimental literature.

The trafficking pathway of a wheat storage protein in transgenic rice endosperm

Background and Aims The trafficking of proteins in the endoplasmic reticulum (ER) of plant cells is a topic of considerable interest since this organelle serves as an entry point for proteins destined for other organelles, as well as for the ER itself. In the current work, transgenic rice was used to study the pattern and pathway of deposition of the wheat high molecular weight (HMW) glutenin sub-unit (GS) 1Dx5 within the rice endosperm using specific antibodies to determine whether it is deposited in the same or different protein bodies from the rice storage proteins, and whether it is located in the same or separate phases within these. Methods The protein distribution and the expression pattern of HMW sub-unit 1Dx5 in transgenic rice endosperm at different stages of development were determined using light and electron microscopy after labelling with antibodies. Key results The use of HMW-GS-specific antibodies showed that sub-unit 1Dx5 was expressed mainly in the sub-aleurone cells of the endosperm and that it was deposited in both types of protein body present in the rice endosperm: derived from the ER and containing prolamins, and derived from the vacuole and containing glutelins. In addition, new types of protein bodies were also formed within the endosperm cells. Conclusions The results suggest that the HMW 1Dx5 protein could be trafficked by either the ER or vacuolar pathway, possibly depending on the stage of development, and that its accumulation in the rice endosperm could compromise the structural integrity of protein bodies and their segregation into two distinct populations in the mature endosperm.

A bifurcated pathway to thiazoles and imidazoles using a modular flow microreactor

A scalable method for the preparation of 4,5-disubstituted thiazoles and imidazoles as distinct regioisomeric products using a modular flow microreactor has been devised. The process makes use of microfluidic reaction chips and packed immobilized-reagent columns to effect bifurcation of the reaction pathway.

Abrupt CO2 experiments as tools for predicting and understanding CMIP5 representative concentration pathway projections

A fast simple climate modelling approach is developed for predicting and helping to understand general circulation model (GCM) simulations. We show that the simple model reproduces the GCM results accurately, for global mean surface air temperature change and global-mean heat uptake projections from 9 GCMs in the fifth coupled model inter-comparison project (CMIP5). This implies that understanding gained from idealised CO2 step experiments is applicable to policy-relevant scenario projections. Our approach is conceptually simple. It works by using the climate response to a CO2 step change taken directly from a GCM experiment. With radiative forcing from non-CO2 constituents obtained by adapting the Forster and Taylor method, we use our method to estimate results for CMIP5 representative concentration pathway (RCP) experiments for cases not run by the GCMs. We estimate differences between pairs of RCPs rather than RCP anomalies relative to the pre-industrial state. This gives better results because it makes greater use of available GCM projections. The GCMs exhibit differences in radiative forcing, which we incorporate in the simple model. We analyse the thus-completed ensemble of RCP projections. The ensemble mean changes between 1986–2005 and 2080–2099 for global temperature (heat uptake) are, for RCP8.5: 3.8 K (2.3 × 1024 J); for RCP6.0: 2.3 K (1.6 × 1024 J); for RCP4.5: 2.0 K (1.6 × 1024 J); for RCP2.6: 1.1 K (1.3 × 1024 J). The relative spread (standard deviation/ensemble mean) for these scenarios is around 0.2 and 0.15 for temperature and heat uptake respectively. We quantify the relative effect of mitigation action, through reduced emissions, via the time-dependent ratios (change in RCPx)/(change in RCP8.5), using changes with respect to pre-industrial conditions. We find that the effects of mitigation on global-mean temperature change and heat uptake are very similar across these different GCMs.

Tityus discrepans scorpion venom activates platelets through GPVI and a novel Src-dependent signaling pathway

In humans and other mammals, Tityus discrepans (Td) scorpion envenomation produces a variety of systemic effects including respiratory distress, a generalized inflammatory reaction, modulation of blood pressure, fibrin formation, and platelet activation. For many of these effects, the venom components and underlying mechanisms are not known. In the present study, we demonstrate that Td venom (TdV) stimulates integrin αIIbβ3-dependent aggregation of washed human and mouse platelets downstream of Src kinase activation. The pattern of increase in tyrosine phosphorylation induced by TdV in human platelets is similar to that induced by the collagen receptor GPVI, and includes FcR γ-chain, Syk, and PLC γ 2. Confirmation of GPVI activation by TdV was achieved by expression of human GPVI in chicken DT40 B cells and use of a reporter assay. To our surprise, TdV was able to activate mouse platelets deficient in the GPVI-FcR γ-chain complex through a pathway that was also dependent on Src kinases. TdV therefore activates platelets through GPVI and a second, as yet unidentified Src kinase-dependent pathway.

Experimental evidence for proposed transformation pathway from the inverse hexagonal to inverse diamond cubic phase from oriented lipid samples

A macroscopically oriented inverse hexagonal phase (HII) of the lipid phytantriol in water is converted to an oriented inverse double diamond bicontinuous cubic phase (QIID). The initial HII phase is uniaxially oriented about the long axis of a capillary with the cylinders parallel to the capillary axis. The HII phase is converted by cooling to a QII D phase which is also highly oriented, where the cylindrical axis of the former phase has been converted to a ⟨110⟩ axis in the latter, as demonstrated by small-angle X-ray scattering. This epitaxial relationship allows us to discriminate between two competing proposed geometric pathways to convert HII to QIID. Our findings also suggest a new route to highly oriented cubic phase coatings, with applications as nanomaterial templates.

Stimulation of the p38 mitogen-activated protein kinase pathway in neonatal rat ventricular myocytes by the G protein-coupled receptor agonists, endothelin-1 and phenylephrine: a role in cardiac myocyte hypertrophy?

We examined the activation of the p38 mitogen-activated protein kinase (p38-MAPK) pathway by the G protein-coupled receptor agonists, endothelin-1 and phenylephrine in primary cultures of cardiac myocytes from neonatal rat hearts. Both agonists increased the phosphorylation (activation) of p38-MAPK by approximately 12-fold. A p38-MAPK substrate, MAPK-activated protein kinase 2 (MAPKAPK2), was activated approximately fourfold and 10 microM SB203580, a p38-MAPK inhibitor, abolished this activation. Phosphorylation of the MAPKAPK2 substrate, heat shock protein 25/27, was also increased. Using selective inhibitors, activation of the p38-MAPK pathway by endothelin-1 was shown to involve protein kinase C but not Gi/Go nor the extracellularly responsive kinase (ERK) pathway. SB203580 failed to inhibit the morphological changes associated with cardiac myocyte hypertrophy induced by endothelin-1 or phenylephrine between 4 and 24 h. However, it decreased the myofibrillar organization and cell profile at 48 h. In contrast, inhibition of the ERK cascade with PD98059 prevented the increase in myofibrillar organization but not cell profile. These data are not consistent with a role for the p38-MAPK pathway in the immediate induction of the morphological changes of hypertrophy but suggest that it may be necessary over a longer period to maintain the response.

Intake of total and subgroups of fat minimally affect the associations between selected single nucleotide polymorphisms in the PPARγ pathway and changes in anthropometry among European adults from cohorts of the DiOGenes study

BACKGROUND: Although the peroxisome proliferator-activated receptor γ (PPARγ) pathway is central in adipogenesis, it remains unknown whether it influences change in body weight (BW) and whether dietary fat has a modifying effect on the association. OBJECTIVES: We examined whether 27 single nucleotide polymorphisms (SNPs) within 4 genes in the PPARγ pathway are associated with the OR of being a BW gainer or with annual changes in anthropometry and whether intake of total fat, monounsaturated fat, polyunsaturated fat, or saturated fat has a modifying effect on these associations. METHODS: A case-noncase study included 11,048 men and women from cohorts in the European Diet, Obesity and Genes study; 5552 were cases, defined as individuals with the greatest BW gain during follow-up, and 6548 were randomly selected, including 5496 noncases. We selected 4 genes [CCAAT/enhancer binding protein β (CEBPB), phosphoenolpyruvate carboxykinase 2, PPARγ gene (PPARG), and sterol regulatory element binding transcription factor 1] according to evidence about biologic plausibility for interactions with dietary fat in weight regulation. Diet was assessed at baseline, and anthropometry was followed for 7 y. RESULTS: The ORs for being a BW gainer for the 27 genetic variants ranged from 0.87 (95% CI: 0.79, 1.03) to 1.12 (95% CI: 0.96, 1.22) per additional minor allele. Uncorrected, CEBPB rs4253449 had a significant interaction with the intake of total fat and subgroups of fat. The OR for being a BW gainer for each additional rs4253449 minor allele per 100 kcal higher total fat intake was 1.07 (95% CI: 1.02, 1.12; P = 0.008), and similar associations were found for subgroups of fat. CONCLUSIONS: Among European men and women, the influence of dietary fat on associations between SNPs in the PPARγ pathway and anthropometry is likely to be absent or marginal. The observed interaction between rs4253449 and dietary fat needs confirmation.

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.