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Abstract Recent biological surveys of ancient inselbergs in southern Malawi and northern Mozambique have led to the discovery and description of many species new to science, and overlapping centres of endemism across multiple taxa. Combining these endemic taxa with data on geology and climate, we propose the ‘South East Africa Montane Archipelago’ (SEAMA) as a distinct ecoregion of global biological importance. The ecoregion encompasses 30 granitic inselbergs reaching > 1000 m above sea level, hosting the largest (Mt Mabu) and smallest (Mt Lico) mid-elevation rainforests in southern Africa, as well as biologically unique montane grasslands. Endemic taxa include 127 plants, 45 vertebrates (amphibians, reptiles, birds, mammals) and 45 invertebrate species (butterflies, freshwater crabs), and two endemic genera of plants and reptiles. Existing dated phylogenies of endemic animal lineages suggests this endemism arose from divergence events coinciding with repeated isolation of these mountains from the pan-African forests, together with the mountains’ great age and relative climatic stability. Since 2000, the SEAMA has lost 18% of its primary humid forest cover (up to 43% in some sites)—one of the highest deforestation rates in Africa. Urgently rectifying this situation, while addressing the resource needs of local communities, is a global priority for biodiversity conservation.

Abstract The COVID-19 pandemic generated diverse impacts and responses in agricultural value chains worldwide. Cocoa is a key crop for Ecuadorian exports, and the analysis of effects the pandemic had on value chain actors contributes to the understanding of their individual capacities to coping with a major shock. The purpose of this study was to assess the number and severity of impacts and responses implemented by two links in the cocoa value chain to the pandemic, based on a survey of 158 cocoa farmers and 52 cocoa intermediaries from the main cocoa-producing provinces of the northern coast of Ecuador in 2021. Surveyed farmers and part of the intermediaries form part of the sustainability program of a large Swiss chocolate manufacturer. The impacts and responses reported were grouped into seven resources according to the Activity System Approach. Then, a comparison between groups was applied using the Wilcoxon rank sum test for nonparametric data, determining the most severe impacts and effective resilience responses among the actors. The results reveal that farmers and intermediaries were similarly affected by the pandemic, reporting 21 and 16 negative impacts, respectively. Farmers experienced a higher number and severity of impacts on financial and social resources, while intermediaries on human and material resources. The strongest impact was the loss of sales, reported by 65% of farmers and 58% of intermediaries. Farmers implemented more social responses that they judged highly effective, while intermediaries implemented more human responses that they judged highly effective. Public policy should enhance the social resources of farmers by strengthening their associativity and the capacities of their members, as mechanisms to mitigate their vulnerability to future health and climate crises. The financial resources of both actors should be protected through public credit and agricultural insurance.

Background: Osteoid osteoma accounts for 5% of bone tumours. Uncommon in the foot, although with predisposition for the talus. Methods: Retrospective review of four cases of osteoid osteoma in the foot and ankle with focus on investigation and management. Results: Equal male to female ratio. Mean age of 29.5 (±21.3). Nocturnal pain was present in 100% of cases. Three patients have had definitive treatment with resection. Mean time to diagnosis was 67 weeks (±65), and to treatment 46 weeks (±35). Diagnosis was established on imaging and histology, with sizes from 6mm to 15mm. The mean pre intervention Foot and Ankle Outcome Scores was 45%, improved to post intervention of 97%. Mean follow up time 17.6 months (±16). Conclusion: Osteoid osteomas are a challenging diagnosis. Remains an important differential in longstanding foot pain with minimal or no history of trauma. Treatment options include ablation or surgical resection. Level of evidence: IV.

A key strategy of chocolate manufacturers is the promotion of sustainable farming practices amongst their supplying cocoa producers. A growing body of micro-economic literature has analysed factors influencing the adoption of such practices, yet broadly disregarded value chain factors. Information on how factors within single value chains increase the adoption of sustainable farming practices can help direct chocolate companies’ investments and increase return of investments in sustainability. The objective of this study was to understand: (a) how important value chain factors are, relative to farmer and farm factors, for cocoa farmers’ implementation of sustainable farming practices and (b) through which mechanisms value chain factors influence sustainable farming practices implementation. By integrating the practice adoption with sustainable supply chain management literature, we contribute to closing an important research gap. We collected data from 394 cocoa farmers in Ecuador and Uganda and analysed the determinants of implementation sustainable farming practices, testing quantitatively whether value chain factors with variation within single value chains are significantly associated with practice implementation. These factors included information factors (farmers’ access to training; advisory service through the value chain) and structural factors (value chain organisation and persistence; farmers’ dependency on this value chain). We selected 11 sustainable farming practices or indicators across three sustainability dimensions, i.e., environmental, social, and economic. We found that value chain factors are comparable to farmer and farm factors in explaining the implementation of sustainable farming practices across dimensions. Both capacity building and stable relationships were significantly related with the implementation of certain sustainable farming practices. Yet these results were weaker than expected, indicating that their potential was not fully exploited within our case study value chains. Through their value chain sustainability initiatives, chocolate companies should disseminate knowledge, address inhibitors to sustainable farming practices implementation beyond knowledge, and align sustainability goals with all value chain actors.

OBJECTIVES/GOALS: Glioblastoma (GBM) is the most common and aggressive adult primary brain malignancy. Clinically, GBM is refractory to T cell immune checkpoint blockade (ICB), in part due to its dense immune suppressive myeloid stroma. Here we show that myeloid-targeting STING agonists can repolarize the GBM microenvironment to cure ICB-refractory GBM models. METHODS/STUDY POPULATION: Using the synthetic cyclic di-nucleotide STING agonist IACS-8803 (8803) we treated orthotopic ICB-refractory QPP8 orthotopic murine GBM tumors intratumorally. We then analyzed survival and performed high parameter flow cytometry profiling of the tumor immune microenvironment following STING agonist treatment. To assess the contribution of adaptive immunity to STING agonist therapeutic efficacy, we treated orthotopic QPP8 tumors implanted in RAG1 KO mice and monitored survival. RESULTS/ANTICIPATED RESULTS: We found that STING agonist therapy cured murine orthotopic QPP8 tumors, in contrast to ICB that showed no survival benefit. In RAG1-/- mice bearing QPP8 tumors STING agonist therapy extended survival, however, the curative effect observed in wild-type mice was lost in the absence of adaptive immunity. STING agonist-treated QPP8 tumors displayed increased counts of CD8 T cells and NK cells, and decreased CD8 T cell PD1 expression. Infiltration of STING-treated gliomas by Ly6C+ F4/80+ Mono-MDSC substantially increased; however, these cells expressed reduced CD206 and CD163, suggestive of reduced immuno-suppression. Finally, in the cervical LN of QPP8-treated mice the frequency and CD80/CD86 expression of cDC1 cells increased.​ DISCUSSION/SIGNIFICANCE: ICB has failed in GBM, and the suppressive myeloid stroma remains a major barrier to generating anti-GBM T cell responses. Our work shows that STING activation, which primarily targets innate immunity myeloid cells 'upstream' of T cells in the antitumor immunity cycle, can cure ICB-refractory GBM tumors in an adaptive immunity-dependent manner.

Osteopontin (OPN) is produced by tumor cells as well as by myeloid cells and is enriched in the tumor microenvironment (TME) of many cancers. Given the roles of OPN in tumor progression and immune suppression, we hypothesized that targeting OPN with aptamers that have high affinity and specificity could be a promising therapeutic strategy. Bi-specific aptamers targeting ligands for cellular internalization were conjugated to siRNAs to suppress OPN were created, and therapeutic leads were selected based on target engagement and in vivo activity. Aptamers as carriers for siRNA approaches were created including a cancer targeting nucleolin aptamer Ncl-OPN siRNA and a myeloid targeting CpG oligodeoxynucleotide (ODN)-OPN siRNA conjugate. These aptamers were selected as therapeutic leads based on 70–90% OPN inhibition in cancer (GL261, 344SQ, 4T1B2b) and myeloid (DC2.4) cells relative to scramble controls. In established immune competent 344SQ lung cancer and 4T1B2b breast cancer models, these aptamers, including in combination, demonstrate therapeutic activity by inhibiting tumor growth. The Ncl-OPN siRNA aptamer demonstrated efficacy in an immune competent orthotopic glioma model administered systemically secondary to the ability of the aptamer to access the glioma TME. Therapeutic activity was demonstrated using both aptamers in a breast cancer brain metastasis model. Targeted inhibition of OPN in tumor cells and myeloid cells using bifunctional aptamers that are internalized by specific cell types and suppress OPN expression once internalized may have clinical potential in cancer treatment.

This paper examines the nature of the taxation profession in Australia and its development over the past three decades and then suggests a framework to analyse important initiatives that have taken place during this period. Using secondary sources and the organizing principles of State, Market and Community (Puxty et al., 1987), we begin with the subject of tax policies and legislation introduced by the state and its impact on the tax profession in Australia. We follow this with a discussion relating to the recognition of Australian tax practice as a profession. The paper then focusses on two key areas of professional development during the last three decades, namely: tax law and tax administration. The paper finds interesting issues relating to professionalization of taxation in Australia. With the involvement of the state, market and the society over the last three decades, there is a requirement to recognise taxation practice as a profession in Australia. The paper suggests that the establishment of the Tax Practitioners Board , a statutory body to regulate the taxation profession in Australia, in conjunction with approved professional associations, may have enhanced the effective maintenance of the tax profession which has contributed to social, political and economic development in Australia.

SWEA-Dataveg is a vegetation-plot database collecting observations mainly in sub-Saharan Africa but also open to the rest of the African continent. To date this database contains more than 5,500 plot observations provided by 47 sources (projects, monographs, and articles). While the database is stored in PostgreSQL (including the PostGIS extension), the R-package “vegtable” implements a suitable exchange format. In this article we assess the current content of SWEA-Database and introduce its history and future as a repository of data for syntaxonomic assessments and macroecological research.

The general purpose of the primary and secondary data available in this article is to support an integrated assessment of scenarios of crop-livestock integration at the territorial level i.e. of exchanges between arable and livestock farms. The data is a result of a research collaboration between the scientist from INRAE, agricultural advisers from Chamber of Agriculture of Pays de la Loire (CRAPL) and a collective of five arable and two livestock farmers located in the district of Pays de Pouzauges (Vendée department, western France). All participants formed part of the DiverIMPACTS project (https://www.diverimpacts.net/) that aims to achieve the full potential of diversification of cropping systems for improved productivity, delivery of ecosystem services and resource-efficient and sustainable value chains in Europe. The first dataset corresponds to the inputs of MAELIA (http://maelia-platform.inra.fr/), a spatial agent-based simulation platform that was used to support an iterative design and assessment of scenarios to redesign cropping systems. The second dataset corresponds to the outputs of MAELIA simulations and the associated indicators at the farm, group and territory level. The data comprise multiple shape and csv files characterizing the edaphic-climatic heterogeneity of the territory and cropping systems, farmers’ crop management rules (IF-THEN rules) and general information about the farms (e.g. crops, agricultural equipment, average crop yields). Data is reported for the baseline situation and three exchange scenarios containing different innovative cropping systems co-designed by scientists, agricultural advisers and the farmers. The data presented here can be found in the Portail Data INRA repository (https://doi.org/10.15454/3ZTCF5) and were used in the research article “Fostering local crop-livestock integration via legume exchanges using an innovative integrated assessment and modelling approach: MAELIA” [1].

Abstract Background The Janus kinase (JAK) and signal transduction and activation of transcription (STAT) signaling pathway is an attractive target in multiple cancers. Activation of the JAK-STAT pathway is important in both tumorigenesis and activation of immune responses. In diffuse large B-cell lymphoma (DLBCL), the transcription factor STAT3 has been associated with aggressive disease phenotype and worse overall survival. While multiple therapies inhibit upstream signaling, there has been limited success in selectively targeting STAT3 in patients. Antisense oligonucleotides (ASOs) represent a compelling therapeutic approach to target difficult to drug proteins such as STAT3 through of mRNA targeting. We report the evaluation of a next generation STAT3 ASO (AZD9150) in a non-Hodgkin’s lymphoma population, primarily consisting of patients with DLBCL. Methods Patients with relapsed or treatment refractory lymphoma were enrolled in this expansion cohort. AZD9150 was administered at 2 mg/kg and the 3 mg/kg (MTD determined by escalation cohort) dose levels with initial loading doses in the first week on days 1, 3, and 5 followed by weekly dosing. Patients were eligible to remain on therapy until unacceptable toxicity or progression. Blood was collected pre- and post-treatment for analysis of peripheral immune cells. Results Thirty patients were enrolled, 10 at 2 mg/kg and 20 at 3 mg/kg dose levels. Twenty-seven patients had DLBCL. AZD9150 was safe and well tolerated at both doses. Common drug-related adverse events included transaminitis, fatigue, and thrombocytopenia. The 3 mg/kg dose level is the recommended phase 2 dose. All responses were seen among DLBCL patients, including 2 complete responses with median duration of response 10.7 months and 2 partial responses. Peripheral blood cell analysis of three patients without a clinical response to therapy revealed a relative increase in proportion of macrophages, CD4+, and CD8+ T cells; this trend did not reach statistical significance. Conclusions AZD9150 was well tolerated and demonstrated efficacy in a subset of heavily pretreated patients with DLBCL. Studies in combination with checkpoint immunotherapies are ongoing. Trial registration Registered at ClinicalTrials.gov: NCT01563302. First submitted 2/13/2012.

The agricultural sector faces serious environmental, social and economic challenges. In response, there has been a proliferation of labels and certifications aiming to ensure minimum farm sustainability performance. Organic agriculture (OA) a prominent example, having received substantial research attention relating to agronomic and environmental performance. While international OA movements are evolving to include broader sustainability aspirations, limited research exists on the social and economic performance of OA. To address this, we conducted a representative farm-based assessment of the Swiss organic sector to evaluate its contribution to sustainability across a wide range of themes based on the FAO Sustainability of Agriculture and Food Assessment (SAFA) Guidelines. We assessed 185 farms using the Sustainability Assessment and Monitoring RouTine (SMART) Farm Tool, chosen through stratified random sampling by farm type and agricultural zone. The results indicate that the Swiss organic sector makes a substantially positive contribution to sustainability, with average scores for theme goal achievement of 62% (Good Governance), 77% (Environmental Integrity), 70% (Economic Resilience), and 87% (Social Well-being). A set of 45 influential indicators (28 for plant production/mix farms and 30 for livestock farms) were selected based on the ability to explain variance (using Principal Component Analysis) and importance for goal achievement. The indicator sets explained a large amount of variation (ca. 70% for both farm types) and revealed a snapshot of management topics relevant to sustainability performance across the sector. These covered socio-political engagement, emissions to air and water, biodiversity, animal welfare, profitability, vulnerability, product quality, local economy, capacity building, and workplace risks. The spread of results across the sample, and comparisons to secondary data (literature and official statistics), revealed the importance of both well-studied issues (e.g., wide spread of energy consumption, variable yield levels/stability, local value chain dynamics) and more novel insights (e.g., strong political engagement, variable price premiums, lacking social security of farming families, insecure land tenure). We propose these topics as a basis for deeper analysis, designing improvement measures and conducting comparative research. This would bring much-needed breadth into the typically narrow debate surrounding the relative merits of OA.

Increasing consumer awareness on sustainability issues has led to the growing adoption of voluntary sustainability standards in agriculture. This study assesses the sustainability performance of typical conventional and certified coffee production systems in Brazil and Ethiopia based on expert judgements. We apply the SMART-Farm Tool, which represents an operationalization of the SAFA (Sustainability Assessment of Food and Agriculture systems) framework of FAO. Data were collected through expert interviews and uncertainties were estimated using Monte-Carlo simulations. A higher sustainability performance of the certified systems was observed regarding product information (+37%) and transparency (+39%) in Ethiopia. In Brazil, the certified system showed a higher overall sustainability performance compared to the conventional system in the environmental dimension and in some social and governance aspects, e.g., gender equality (+49%) and public health (+36%). Geographical or political conditions and farm type also had a strong influence on the observed sustainability performance. Typical smallholder production systems in Ethiopian coffee production performed comparable in the environmental dimension since all were low-input systems due to economic constraints. The conventional Brazilian system showed a better performance concerning employment relations (+14%) and profitability (+13%), as compared to the certified Brazilian systems, because larger farms were more likely to employ permanent staff and benefit from economies of scale.

Restoration of degraded ecosystems is known to enhance biodiversity and vegetation structure. Using a global meta-analysis, Crouzeilles et al. identify the drivers of restoration success in forest ecosystems at both the local and landscape scales.

The tumor microenvironment is the cellular and molecular environment in which the tumor exists and with which it continuously interacts. In B-cell lymphomas, this microenvironment is intriguing in that it plays critical roles in the regulation of tumor cell survival and proliferation, fostering immune escape as well as the development of treatment resistance. The purpose of this review is to summarize the proceedings of the Second Annual Summit on the Immune Microenvironment in Hematologic Malignancies that took place on September 11–12, 2014 in Dublin, Ireland. We provide a timely overview of the composition and biological relevance of the cellular and molecular microenvironment interface and discuss the role of interactions between the microenvironment and neoplastic cells in a variety of B-cell lymphomas. In addition, we focus on various novel therapeutic strategies that target the tumor microenvironment, including agents that modulate B-cell receptor pathways and immune-checkpoints, chimeric antigen receptor T cells and immunomodulatory agents.

We propose a Traffic Light approach to backtesting Expected Shortfall which is completely consistent with, and analogous to, the Traffic Light approach to backtesting VaR (Value at Risk) initially proposed by the Basel Committee on Banking Supervision in their 1996 consultative document Basle Committee on Banking Supervision (1996). The approach relies on the generalized coverage test for Expected Shortfall developed in Costanzino and Curran (2015).