Investigating market-based opportunities for the provision of nutritious and safe diets to prevent childhood stunting: a UKRI-GCRF action against stunting hub protocol paper.

BACKGROUND: Inadequate access to affordable, safe, desirable and convenient nutrient-dense food is one of the underlying causes of child stunting. While targeted nutrition-sensitive interventions (eg, backyard 'nutri-gardens') may increase dietary diversity within farming households, such interventions have limited scalability across the wider food system where markets remain underdeveloped. This research aims to develop and assess market-based interventions for key nutrient-dense foods to help improve the diets of women and children in the first 1000 days of life. METHODS: Data collection uses four parallel approaches in each of the three study countries (India, Indonesia and Senegal). (1) A novel food environment tool will be developed to characterise the accessibility and affordability of nutrient-dense foods in the study countries. The tool will be validated through pretesting using cognitive interviewing and piloting in purposively sampled households, 10 (cognitive interviewing) and 30 (piloting) households in each country; (2) stakeholder interviews (eg, with producers, intermediaries and retailers) will be conducted to map out nutrition-sensitive entry points of key value chains (eg, animal-sourced foods), before hotspots of potential food safety hazards will be identified from food samples collected along the chains; (3) the Optifood and Agrifood tools will be used to identify foods that can address food system nutrient gaps and engage key stakeholders to prioritise market interventions to improve nutrition outcomes. Optifood and Agrifood parameters will be informed by publicly available data, plus interviews and focus groups with value chain stakeholders; (4) informed by the previous three approaches and a campaign of participatory 'group model building', a novel system dynamics model will evaluate the impact of alternative market-based solutions on the availability and affordability of nutrient-dense foods over time. ETHICS AND DISSEMINATION: The study has received ethical approval in the United Kingdom, Senegal, Indonesia and India. Dissemination comprises peer-reviewed journals, international disciplinary conferences and multistakeholder dissemination workshops.

Identifying value chain trade-offs from fruit and vegetable aggregation services in Bangladesh using a system dynamics approach.

Significant progress has been made in cereal production in Bangladesh due to an agricultural policy environment that prioritizes the productivity of staple crops over fruit and vegetables (F&V). However, many smallholder farmers remain poorly connected to markets, which may lead to a limited supply response of F&V that can reduce opportunities for sufficient intake in neglected, consumer-facing, smaller retail markets. To address this issue, aggregation schemes have been conceived that collect and transport F&Vs on behalf of multiple farmers. Given the volume of horticultural produce produced and the reliance on developed transport infrastructure, aggregation schemes tend to supply wholesale and urban markets rather than underdeveloped rural and isolated markets. To this end, we investigated how a particular aggregation intervention ('Loop') could potentially improve the distribution of F&V to smaller markets whilst improving farmer benefits. We used an innovative system dynamics modeling approach based on Loop`s aggregation services in Jashore, Bangladesh, and to identify the potential trade-offs between consumer outcomes in retail markets and farmer benefits. We find that combining aggregation with a quota at the smaller market, transport subsidy, and current price growth does not result in trade-offs between consumer purchases and farmers`benefits. However, combining aggregation with current price growth can increase demand without losing farmers`benefits. The findings emphasize that standalone and multiple market-oriented interventions generate broader win-win benefits to promote inclusive food systems.

Understanding household and food system determinants of chicken and egg consumption in India.

Poultry is one of the fastest-growing agricultural sectors in India and its demand is said to be rising. There is a perception that higher incomes, growing population, urbanisation, and increased productivity in the industry have influenced Indian poultry consumption. However, consumer surveys have shown that the average poultry consumption in India has remained low. With this in mind, the paper analysed household determinants of chicken and egg consumption within the Indian population, using two rounds of National Sample Survey data (1993-1994 and 2011-2012). By conducting a spatiotemporal analysis of household consumption and expenditure survey and by using truncated Double Hurdle and Unconditional Quantile regressions (UQR) models, this study explored socio-economic and food system determinants of chicken and egg consumption in India. Key results highlight that while consumption has increased marginally over twenty years, supply-side determinants, such as price and poultry production concentration, influenced heterogenous consumption patterns in India. We also find evidence that historically marginalised groups consumed more chicken and eggs in comparison to non-marginalised groups and preliminary evidence suggests how household gender dynamics influence different consumption patterns. Adequate consumption of poultry is important to improve nutrient-deficient diets of vulnerable groups in India. Our findings on demand side determinants of poultry products are crucial to support consumer tailored actions to improve nutritional outcomes along with the Indian poultry sector policy planning.

Arabinogalactan G1-4A isolated from Tinospora cordifolia induces PKC/mTOR mediated direct activation of natural killer cells and through dendritic cell cross-talk.

BACKGROUND: Tinospora cordifolia polysaccharide G1-4A activates antigen-presenting cells, but its effect on natural killer (NK) cells is not known. The objective of this study is to assess the effect of G1-4A on NK cells; direct effects as well as through dendritic cell (DC) cross-talk. METHODS: NK cell phenotype and function were assessed in spleen cells treated in vitro with G1-4A or isolated from mice administered with G1-4A. Following treatment with G1-4A in vitro or in cells isolated from G1-4A treated mice (in vivo), activated NK cell phenotype was characterized as CD3-NKp46+CD69+ cells by flow cytometry; NK cell function was evaluated by IFN-γ secretion (ELISA) and cytotoxicity assay (calcein release by target cells in effector: target cells co-culture assay). RESULTS: Both in vitro as well as in vivoG1-4A treatment increased phenotypic and functional activation of NK cells. So, we wanted to determine if this was through NK-DC crosstalk or direct activation of NK cells. There was increased NK cell activation following co-culture with bone marrow derived DC matured withG1-4A in vitro or splenic DC isolated from G1-4A administered mice indicating crosstalk. G1-4A also increased activation of NK cells in (a) CD11c depleted splenic cells that was contact dependent and (b) purified NKp46+ cells that was abrogated by PKC/mTOR inhibitors indicating direct effects on NK cells. CONCLUSION: In summary, treatment with G1-4A results in phenotypic and functional activation of NK cells directly as well as through NK-DC cross talk and has the potential to be used as an immunotherapeutic agent.

Processed foods purchase profiles in urban India in 2013 and 2016: a cluster and multivariate analysis.

OBJECTIVES: Sales of ultraprocessed foods (UPFs) and beverages are rising in low-income and middle-income countries. Such foods are often linked with weight gain, obesity, type 2 diabetes and hypertension-diseases that are on the rise in India. This paper analysed patterns in purchases of processed and UPF by urban Indian households. SETTING: Panel data from Kantar -Worldpanel Division, India for 2013 and 2016. PARTICIPANTS: 58 878 urban Indian households. METHODS: We used K-mean partition clustering and multivariate regression to analyse patterns in processed food (PF) and UPF purchase for urban India. RESULTS: Three-quarters of urban Indian households purchased over ten PF groups. Mean per person annual PF purchase was 150 kg. UPF purchase was low at 6.4 kg in 2016 but had grown by 6% since 2013. Cluster analysis identified three patterns of consumption, characterised by low (54% of the households in 2016), medium (36%) and high (10%) PF purchase quantities. High cluster households purchased over three times as much PFs and UPF as the low cluster households. Notably, salt purchases were persistently high across clusters in both years (>3.3 kg), while sweet snack and ready-to-eat food purchases grew consistently in all clusters between 2013 and 2016. A positive and significant association was found between household purchases of UPF and their socioeconomic status as well as ownership of durables, such as refrigerator, colour television and washing machine (all p<0.001). Spatial characteristics including size of town (p<0.05) in which the household is located were also positively associated with the purchase of UPF. CONCLUSION: Results suggest the need for tailored regional and city level interventions to curb the low but growing purchase of UPF. New data on obesity and rise of non-communicable diseases, the results are concerning given the links between lifestyle changes and the speed of urbanisation in Indian cities.

Macrophage induced ERK-TGF-ß1 signaling in MCF7 breast cancer cells result in reversible cancer stem cell plasticity and epithelial mesenchymal transition.

BACKGROUND: Breast cancer is a heterogenous disease composed of multiple clonal populations and the mechanism by which the tumor microenvironment induces cancer stem cell plasticity is not fully understood. METHODS: MCF7 breast cancer cells were treated with macrophage conditioned medium (MɸCM). PD98059 and SB431542 were used for ERK and TGF-ßR inhibition respectively. Epithelial-mesenchymal transition (EMT) and cancer stem cell markers (CSC) were studied using qRT-PCR and flowcytometry. SCID mice were used for animal experiments. RESULTS: MɸCM- induced ERK/TGF-ß1 signaling led to enrichment of CSC and EMT in MCF7 cells and mammospheres. These effects were abrogated by both MEK inhibitor PD98059 (TGF-ß1 synthesis) and SB431542 (TGF-ß1 signaling). The increase in CSC was both hybrid (ALDH1+) and mesenchymal (CD44+ CD24- cells). Increase in hybrid E/M state was at a single cell level as confirmed by the increase in both claudin-1 (E) and vimentin (M). This did not have any growth advantage in SCID mice and monitoring of CSC and EMT markers before and after growth in SCID mice indicated reversal of these markers in tumor cells recovered from mice. Removal of MɸCM and neutralization of TNF-α, IL-6 and IL-1ß in MɸCM abrogated ERK phosphorylation, TGF-ß and CSC enrichment indicating the requirement of continuous signaling for maintenance. CONCLUSIONS: ERK signaling plays an important role in MɸCM- induced EMT and CSC plasticity which is completely reversible upon withdrawal of signals. GENERAL SIGNIFICANCE: Our experimental observations support the semi-independent nature of EMT-stemness connection which is very dynamic and reversible depending on the microenvironment.

A food systems approach and qualitative system dynamics model to reveal policy issues within the commercial broiler chicken system in South Africa.

Global broiler production and consumption levels continue to rise. South Africa's broiler system is dominated by commercial production and formal retail trade, with competition from cheap imports. Local broiler policies have narrow, production-driven, short-term aims for industry growth and national food security. However, these have unintended consequences that undermine the system's future sustainability. Using a food systems approach, this study developed a qualitative system dynamics model of the South African commercial broiler system and used it to engage stakeholders in policy discussions within the boundaries of health, nutrition, and environmental sustainability. A problem statement and key system elements were drawn from a previously published qualitative study and were validated by 15 stakeholders via an online questionnaire. From this, a seed model was developed, expanded into a larger model, and shared in a modular format with stakeholders in virtual meetings, on an individual or institutional basis, for feedback and validation, and for discussion of areas for policy consideration. Refinements were incorporated into the modules, policy considerations were summarised, and crosscutting issues were identified. The model demonstrated the system's complexity, interlinkages, feedbacks, reinforcing and balancing loops, and behaviour archetypes. The modular presentation format created a suitable platform for stakeholder engagement. Current policies focus on local commercial production, formal markets, and affordability without cognisance of the broader system represented by the model. Inequality pervades throughout the system. Commercial producers, linked to large supermarkets and fast-food chains, dominate the system, presenting barriers to entry. Affordability is unintentionally traded off against non-communicable disease risks through brining of most frozen products, and ultra-processing of fast-food items. Foodborne disease control is critical, given the proportion of vulnerable individuals, and greater coherence of food safety policy is urgently needed. The environmental footprint of broilers, whilst less than that of ruminants, deserves closer scrutiny based on its dependence on intensive cereal production for feed. This study's food systems approach provides a system-wide perspective and a foundation for policymakers to develop more integrated and transformative policies.

Identification of EPZ004777 and FG2216 as inhibitors of TGF-ß1 induced Treg cells by screening a library of epigenetic compounds.

AIMS: Regulatory T cells play an essential role in immune tolerance and homeostasis. Their long-term stability depends on epigenetic modifications and identification of small molecule modulators of Treg differentiation therefore has many applications. In this study, we performed a novel functional screen of an epigenetic compound library to identify compounds that can modulate generation of TGF-ß1 induced T regulatory cells. MAIN METHODS: A screening strategy based on IFN-γ ELISA was designed to screen epigenetic compound library. Effect of hit compounds on Treg phenotype and function was assessed by RT-PCR, flow cytometry and suppression assays. TGF-ß signalling proteins were assayed by western blotting. Chromatin Immunoprecipitation (ChIP) assay was used to assess epigenetic modifications at Foxp3 gene locus. KEY FINDINGS: We screened 160 compounds to identify hits capable of reversing TGF-ß induced inhibition of IFN-γ production in activated spleen cells and CD4+ T cells. Two compounds EPZ004777 and FG-2216 consistently reversed TGF-ß1 iTregs in terms of (a) differentiation of naïve T cells into CD4+CD25+Foxp3+Treg cells, (b) Foxp3 target gene expression and (c) Treg suppressive function without affecting TGF-ß downstream signalling. ChIP assay revealed that the compounds were able to reverse - TGF- ß mediated decrease in epigenetic marks H3K27me3 and 5-mC and an increase in epigenetic marks H3K4me3 and H3K27Ac in the promoter and conserved non coding sequence (CNS1) regions of the Foxp3 gene. SIGNIFICANCE: EPZ004777 and FG-2216 have been identified as potent epigenetic modulators that can reverse TGF-ß1 induced T regulatory cells and may be used to treat diverse immune disorders.

Effects of prolonged treatment of TGF-ßR inhibitor SB431542 on radiation-induced signaling in breast cancer cells.

PURPOSE: We have earlier characterized increased TGF-ß signaling in radioresistant breast cancer cells. In this study, we wanted to determine the effect of prolonged treatment of TGF-ßR inhibitor SB431542 on radiation-induced signaling, viz., genes regulating apoptosis, EMT, anti and pro-inflammatory cytokines. MATERIALS AND METHODS: Breast cancer cells were pretreated with TGF-ßR inhibitor (SB 431542) followed by exposure to 6 Gy and recovery period of 7 days (D7-6G). We assessed cell survival by MTT assay, cytokines by ELISA and expression analysis by RT-PCR, flow cytometry, and western blot. We carried out migration assays using trans well inserts. We performed bioinformatics analyses of human cancer database through cBioportal. RESULTS: There was an upregulation of TGF-ß1 and 3 and downregulation of TGF-ß2, TGF-ßR1, and TGF-ßR2 in invasive breast carcinoma samples compared to normal tissue. TGF-ß1 and TNF-α was higher in radioresistant D7-6G cells with upregulation of pSMAD3, pNF-kB, and ERK signaling. Pretreatment of D7-6G cells with TGF-ßR inhibitor SB431542 abrogated pSMAD3, increased proliferation, and migration along with an increase in apoptosis and pro-apoptotic genes. This was associated with hybrid E/M phenotype and downregulation of TGF-ß downstream genes, HMGA2 and Snail. There was complete agreement in the expression of mRNA and protein data in genes like vimentin, Snail and HMGA2 in different treatment groups. However, there was disagreement in expression of mRNA and protein in genes like Bax, Bcl-2, E-cadherin, Zeb-1 among the different treatment groups indicating post-transcriptional and post-translational processing of these proteins. Treatment of cells with only SB431542 also increased expression of some E/M genes indicating TGF-ß independent effects. Increased IL-6 and IL-10 secretion by SB431542 along with increase in pSTAT3 and pCREB1 could probably explain these TGF-ß/Smad3 independent effects. CONCLUSION: These results highlight that TGF-ß-pSMAD3 and TNF-α-pNF-kB are the predominant signaling pathways in radioresistant cells and possibility of some TGF-ß/Smad3 independent effects on prolonged treatment with the drug SB431542.

Economic inequality in malnutrition: a global systematic review and meta-analysis.

OBJECTIVE: To describe the evidence on global and regional economic inequality in malnutrition, and the associations between economic inequality and malnutrition. METHODS: We conducted a systematic review and meta-analysis. Between 1 November 2020 and 22 January 2021, we searched Medline, Embase, Global Health, Eldis, Web of Science and EBSCO Discovery Service. We contacted 39 experts and tracked citations. We included any study reporting a concentration index (CIX) relating economic status and nutritional status and any multilevel study reporting an association between economic inequality and nutritional status. Nutritional status was measured as stunting, wasting, anaemia, or overweight in children (<5 years), or underweight, overweight or obesity, or anaemia in adults (15-49 years). We had no study date or language restriction. Quality was assessed using the Appraisal Tool for Cross-Sectional Studies (AXIS tool). We mapped estimates and pooled them using multilevel random-effects meta-analyses. RESULTS: From 6185 results, 91 studies provided 426 CIX (>2.9 million people) and 47 associations (~3.9 million people). Stunting (CIX -0.15 (95% CI -0.19 to -0.11)) and wasting (-0.03 (95% CI -0.05 to -0.02)) are concentrated among poor households. Adult overweight and obesity is concentrated in wealthier households (0.08 (95% CI -0.00 to 0.17)), particularly in South Asia (0.26 (95% CI 0.19 to 0.34)), but not in Europe and Central Asia (-0.02 (95% CI -0.08 to 0.05)) or North America (-0.04 (95% CI -0.10 to 0.03)). We found no association between 0.1 increase in Gini coefficient and adult underweight (OR 1.03 (95% CI 0.94 to 1.12)) or overweight and obesity (0.92 (95% CI 0.80 to 1.05)). CONCLUSIONS: There is good evidence that the prevalence of malnutrition varies by levels of absolute economic status. Undernutrition is concentrated in poor households, whereas concentration of overweight and obesity by economic status depends on region, and we lack information on economic inequalities in anaemia and child overweight. In contrast, links between malnutrition and relative economic status are less clear and should not be assumed; robust evidence on causal pathways is needed. PROSPERO REGISTRATION NUMBER: CRD42020201572.

Caste-Based Inequality in Fruit and Vegetable Consumption in India.

OBJECTIVE: Fruit and vegetable (F&V) consumption is of central importance to many diet-related health outcomes. In India, caste is a major basis of socioeconomic inequality. Recent analysis shows that more disadvantaged "lower" castes consume less F&V than the rest. This article explores whether this consumption gap arises due to differential distribution of drivers of consumption such as income and education across castes, or whether behavioral differences or discrimination may be at play. DESIGN: The Oaxaca-Blinder regression decomposition is applied to explain the gap in F&V consumption between "upper" castes and "lower" castes, using data from the 68th (2011-2012) round of the National Sample Survey Organization household survey. RESULTS: Differences in the distribution of F&V drivers account for all of the 50 grams/person/day consumption gap between upper and lower castes. In particular, much of the gap is explained by income differential across castes. CONCLUSIONS: In the long run, India's positive discrimination policies in education and employment that seek to equalize income across castes are also likely to help close the F&V consumption gap, leading to health benefits. In the medium run, interventions acting to boost lower caste income, such as cash transfers targeting lower castes, may be effective.

Economic evaluation of nutrition interventions: Does one size fit all?

BACKGROUND: Nutrition interventions have specific features that might warrant modifications to the methods used for economic evaluations of healthcare interventions. AIM: The aim of the article is to identify these features and when they challenge the use of cost-utility analysis (CUA). METHODS: A critical review of the literature is conducted and a 2 by 2 classification matrix for nutrition interventions is proposed based on 1) who the main party responsible for the implementation and funding of the intervention is; and 2) who the target recipient of the intervention is. The challenges of conducting economic evaluations for each group of nutrition interventions are then analysed according to four main aspects: attribution of effects, measuring and valuing outcomes, inter-sectorial costs and consequences and equity considerations. RESULTS AND CONCLUSIONS: CUA is appropriate for nutrition interventions when they are funded from the healthcare sector, have no (or modest) spill-overs to other sectors of the economy and have only (or mainly) health consequences. For other interventions, typically involving different government agencies, with cost implications for the private sector, with important wellbeing consequences outside health and with heterogeneous welfare effects across socio-economic groups, other economic evaluation methods need to be developed in order to offer valid guidance to policy making. For these interventions, checklists for critical appraisal of economic evaluations may require some substantial changes.

Changes in take-home aerated soft drink purchases in urban India after the implementation of Goods and Services Tax (GST): An interrupted time series analysis.

OBJECTIVES: Taxes on sugar-sweetened beverages (SSB) are increasingly being implemented as public health interventions to limit the consumption of sugar and reduce associated health risks. In July 2017, India imposed a new tax rate on aerated (carbonated) drinks as part of the Goods and Services Tax (GST) reform. This study investigates the post-GST changes in the purchase of aerated drinks in urban India. METHODS: An interrupted time series analysis was conducted on state-level monthly take-home purchases of aerated drinks in urban India from January 2013 to June 2018. We assessed changes in the year-on-year growth rate (i.e. percentage change) in aerated drink purchases with controls for contextual variables. RESULTS: We found no evidence of a reduction in state-level monthly take-home aerated drink purchases in urban India following the implementation of GST. Further analysis showed that the year-on-year growth rate in aerated drink purchases increased slightly (0.1 percentage point per month, 95%CI = 0.018, 0.181) after the implementation of GST; however, this trend was temporary and decreased over time (0.008 percentage point per month, 95%CI = -0.015, -0.001). CONCLUSIONS: In India, a country currently with low aerated drink consumption, the implementation of GST was not associated with a reduction in aerated drink purchase in urban settings. Due to the lack of accurate and sufficiently detailed price data, it is not possible to say whether this finding is driven by prices not changing sufficiently. Furthermore, the impact of GST reform on industry practice (reformulation, marketing) and individual behaviour choices (substitution) is unknown and warrants further investigation to understand how such taxes could be implemented to deliver public health benefits.

Identifying 'win-win-win' futures from inequitable value chain trade-offs: A system dynamics approach.

CONTEXT: There is growing recognition that food systems must adapt to become more sustainable and equitable. Consequently, in developing country contexts, there is increasing momentum away from traditional producer-facing value chain upgrades towards efforts to increase both the availability and affordability of nutritious foods at the consumer level. However, such goals must navigate the inherent complexities of agricultural value chains, which involve multiple interactions, feedbacks and unintended consequences, including important but often surprising trade-offs between producers and consumers. OBJECTIVE AND METHODS: Based around the 'Loop' horticultural aggregation scheme of Digital Green in Bihar, India, we develop a system dynamics modelling framework to survey the value chain trade-offs emerging from upgrades that aim to improve the availability of fruits and vegetables in small retail-oriented markets. We model the processes of horticultural production, aggregation, marketing, and retailing - searching for futures that are 'win-win-win' for: (i) the availability of fruits and vegetables in small retail markets, (ii) the profits of farmers participating in aggregation, and (iii) the sustainability of the initial scheme for Digital Green as an organisation. We simulate two internal upgrades to aggregation and two upgrades to the wider enabling environment through a series of 5000 Monte Carlo trajectories - designed to explore the plausible future dynamics of the three outcome dimensions relative to the baseline. RESULTS: We find that 'win-win-win' futures cannot be achieved by internal changes to the aggregation scheme alone, emerging under a narrow range of scenarios that boost supplies to the small retail market whilst simultaneously supporting the financial takeaways of farmers. In contrast, undesirable producer versus consumer trade-offs emerge as unintended consequences of scaling-up aggregation and the introduction of market-based cold storage. SIGNIFICANCE: This approach furthers ongoing efforts to capture complex value chain processes, outcomes and upgrades within system dynamics modelling frameworks, before scanning the horizon of plausible external scenarios, internal dynamics and unintended trade-offs to identify 'win-win-win' futures for all.

Moving towards sustainable food systems: A review of Indian food policy budgets.

Moving towards sustainable food systems is a complex problem, which requires high level co-ordination, coherence, and integration of national food policy. The aim of this study is to explore where environmental sustainability is integrated into national food policy in India. A scoping review of food policies was conducted, and findings mapped to ministerial responsibility, estimated budget allocation, and relevant Sustainable Development Goals. Fifty-two policies were identified, under the responsibility of 10 ministries, and with relevance to six Sustainable Development Goals. Content analysis identified references to environmental sustainability were concentrated in policies with the smallest budgetary allocation. Resources together with political will are required to integrate environmental sustainability into food policies and avoid conflicts with more well-established health, societal, and economic priorities.

TGF-ßR inhibitor SB431542 restores immune suppression induced by regulatory B-T cell axis and decreases tumour burden in murine fibrosarcoma.

The contribution of immune cells in soft tissue sarcomas (STS) is not completely known and understanding their role is very essential for employing immunotherapy strategies. Here, we show that murine fibrosarcoma-conditioned medium promoted total spleen cell proliferation but inhibited T cell responses to mitogenic and allo-antigen-mediated stimulation. This increased proliferation was found to be in B cells resulting in generation of Breg further leading to Treg population. This was found to be the same in vitro and in vivo. The phenotype of these B cells was CD19+CD81+CD27+CD25+PD-L1hi and they secreted both IL-10 and TGF-ß. These tumor evoked Bregs (tBreg), when co-cultured with B depleted T cells, suppressed their proliferation in response to anti-CD3/CD28 stimulation. tBreg-induced suppression of T cell responses was not abrogated by the inhibition or neutralization of IL-10 but by the small molecule inhibitor of TGFß Receptor type I, SB431542. While SB531542 per se was not cytotoxic to tumor cells, administration of SB431542 in tumor-bearing mice (TBM) significantly reduced the tumor burden. In addition, the treatment significantly reduced Treg cells and rescued proliferation of T cells in response to mitogen and allo-antigen. Collectively, our results identify that tumor evoked Breg cells mediate T cell immune suppression through TGFß-mediated pathway and that targeting the Breg-Treg axis can be potentially used as an immunotherapy agent.

Using Qualitative System Dynamics Analysis to Promote Inclusive Livestock Value Chains: A Case Study of the South African Broiler Value Chain.

Livestock value chains globally are increasingly dualistic, with integrated market-leaders co-existing with comparatively disadvantaged small producers who, nevertheless, support rural livelihoods and food access, and can also contribute to more resilient supply chains. The South African broiler value chain provides a highly illustrative case study. The purpose of this study is to identify potential leverage points for policy intervention to support small and emerging producers in the South African broiler value chain, and to discuss the strengths and limitations of system dynamics approaches to promote inclusive food value chains. This study develops a causal loop diagram (CLD) based on semi-structured stakeholder interviews and policy documents. The main challenges, key variables and causal relationships between them are systematically identified. Variables are coded, generalised and graphically represented, and entry points for intervention and their links to existing policies are mapped. The challenges faced by smallholders in the context of our study can be characterised, using a CLD, as a set of interlinked and reinforcing dynamics which perpetuate existing disadvantages and reinforce duality in the value chain. Key policy entry points have been identified that could be targeted by a coordinated policy package, including: Direct support for infrastructure investment and input access through grants, subsidies or other policies; credit and liquidity provision for day-to-day expenses; creation of aggregation mechanisms for both inputs and outputs; regulations or initiatives that directly target the relationship of farmers with the commercial segment to improve access to day-old-chicks and, finally, training in business and technical skills. Although most of these interventions have been addressed at some point, implementation has been fragmented, failing to fully consider their complementary nature, thus undermining effectiveness. Existing approaches to consensus building and stakeholder participation in system dynamics research can present challenges when it comes to engaging with complex policy processes and issues of conflict of interest that are relevant in the context of smallholder promotion and equitable food systems, but there are promising avenues for addressing. Despite some methodological challenges, we find that there is considerable scope for system dynamics approaches to inform policy for smallholder promotion, even in contexts characterised by complex policy processes.