Institutions, Incentives and Conflict in Coffee Forest Use and Conservation : the Case of Yayo Forest in Iluu Abba Bora Zone, Southwest Ethiopia

Ethiopia is home to many endemic plants and animals including the coffee growing ‘wild’ in the montane rainforests of the South and Southwest. The coffee forest is, however, threatened by fast rate of deforestation. The extraction of the resource by the local community for livilihood as well as the use by different stakes of coffee forest for different purposes and the absence of viable institutional arrangement for use and conservation are among factors aggravating deforestation. This research explores institutions from federal to local level, rules that act either as incentives or disincentives for local users and rules leading to conflicts in coffee forest use and conservation. Institutions at different level, policies and proclamations, property rights and formal rules and regulations imposing disincentives as exogenous variables influence the action arena and leads to interactions and different outcomes. The research deals with institutions both as “the rules of the game” and “players of the game”. Relevant information to the research has been collected in 2007 and 2008 at different times using qualitative and quantitative methods. Results of this research show that institutions working on coffee forest from federal to local level, mainly the rules governing the coffee forest protected area (PA) cannot sustainably manage the coffee forest and ensure farmer’s subsistence. Instead, they contribute to creating disincentives among the local community and fueling conflicts. The rules are imposed by force through government institutions and cannot sustainably halt loss of biodiversity. In this work, analysis of formal and informal institutions shows that there is a need either to modify existing instititions or establish new ones. This can be done through integration of institutions, both vertically and horizontally, with the objective towards coffee forest biodiversity conservation. There is also a need for revision and practical implementation of forest policies and proclamations in keeping with the interests and customary resource uses of the community. The research also identifies different rules of the protected area (PA) that act as disincentives and that need to be changed including guidelines that can serve as yardistik in future use and conservation process. The study also shows that there is conflict among government institutions and the local community. The main causes of conflicts in the coffee forest demarcated area are driven by the need to expand coffee farm areas, disagreement over property rights, local community’s dependence on products from the coffee forest for livelihoods and prohibition of harvesting the forest for NTFPs. There is a big gap in the distribution of rights, responsibilities and returns among stakeholders which indicates the marginalization of local communities and their institutions from coffee forest use and conservation process. Analysis of the protected area (PA) rules and the conflicts created in general show the incompatibility of the current zoning approach with the previous forest use and the peasant’s livelihood. Co-management is suggested as a way forward in resolving conflicts and institutional problems. In efforts to realize this, it is essential to make smooth transition from management of coffee forest by force under the auspices of guards to management by well-designed CFM or co-management system

Activating Energy Communities for Systemic Change

The speed of energy transition in the Netherlands is low, in contrast to its 2050 climate change target of net-zero emissions. The transition requires 7.5 million households with natural gas connections, to move to renewable energy sources. The main challenge is not technical, many viable options are already available, but social: people will need to be supported to decide and act. In this paper, we identify interventions that could activate change within energy communities, through 19 interviews conducted in March 2021 in Austerlitz, Zeist municipality, The Netherlands. Interview questions were guided by the Capability, Opportunity, Motivation, and Behavioural (COM-B) change model. The model explains factors that affect people’s behaviour. Results indicate that renovation and energy transition are viewed as two separate processes. Austerlitz homeowners are waiting for the government to lead the energy transition process, while they continue to renovate their homes to improve comfort, aesthetics, safety, and convenience. Also, current interventions towards activating households are piecemeal and more focused on creating external opportunities (such as financial support), and barely address the psychological capabilities and motivation factors (belief, attitude, social norm, and perceived behavioural control). To boost psychological capabilities and motivation, we recommend interventions that enhance homeowners’ belief that the energy transition is part of their long-term home renovation plans, for their own benefit, to motivate them to drive the energy transition process. Interventions may include ‘show’ or ‘display’ houses where energy transition was combined with renovations and highlighting inspirational energy transition stories on the municipality website

Long-Term, Self-Dosing CBD Users: Indications, Dosage, and Self-Perceptions on General Health/Symptoms and Drug Use

Introduction: Self-dosing of off-the-shelf cannabidiol (CBD) for a myriad of health conditions is common in the USA. These CBD products are often mislabeled, suggesting that much less or much more CBD is being consumed than indicated on the label. This study examined the relationship between long-term self-dosing of CBD and (a) indications and, when a verified concentration of CBD is being consumed, (b) the daily CBD dosage, (c) the impact on general health and symptoms, and (d) over-the-counter (OTC) and prescription (Rx) drug usage. Methods: US adults 18–75 years of age who had used unverified CBD products for >1 month were recruited to participate in this decentralized, observational, IRB-approved study and provided a concentration-verified CBD product of their choice from 15 different vendors for 4 weeks. Prior to receiving product, they were queried on their primary reason for use (PRfU), primary symptom for use (PSfU), general health score (GHS), symptom score (SS), OTC and Rx drug use, and daily CBD dose. Individuals were queried daily on OTC and Rx drug use and CBD dose and weekly on SS and GHS prior to (pre-CBD) and after (post-CBD) ingestion of CBD on that day. Results: The PRfU included chronic pain, mental health, general health and wellness, sleep disorders, the central nervous system, digestive health, and others, while the PSfU included anxiety, back and/or joint pain, sleep, inflammation, and others. The mean daily dose was normally distributed, with a mean, median, and range of 53.1, 40.8, 8–390 mg/day, respectively. For both GHS and SS, the post-CBD was significantly higher than the pre-CBD score for each category of PRfU. The GHS scores did not change over the study, but pre- and post-CBD SS improved over time, with pre-improving more than post-CBD SS. The percentage of individuals decreasing or completely stopping OTC drugs or Rx drugs over the 4 weeks was 31.2% and 19.2%, respectively, with those taking CBD for chronic pain, decreasing drug use the most. OTC and Rx drug usage decreased when the CBD dose was changed and when GHS and SS improved. Conclusion: Pain, mental health (primarily anxiety/stress), and sleep are the most common reasons for CBD use. Self-administration of CBD reduced OTC and Rx drug usage at daily doses less than those reported in controlled studies. CBD self-administration significantly improves self-perception of general health and decreases symptom severity, and as these improve, fewer OTC and Rx drugs are used

Enabling equitable collective action and policy change for poverty reduction and improved natural resource management in the Eastern African highlands:

"The role of local and external institutions in natural resource management (NRM) is gaining attention in the literature, fostering greater understanding of the relationship between collective action and poverty, collective action and equity, and the conditions under which collective action institutions take root. It has also led to increased understanding of how uncritical practices by external development institutions can propagate social inequities in NRM. Yet little research has been conducted to understand how to foster local collective action institutions where they are absent, or to improve institutional practice. This research integrates empirical and action research in an effort to generate ‘working solutions' to problems facing rural communities in their efforts to manage their natural resources in the highlands of Ethiopia and Uganda. Following a brief introduction to the literature and the research, findings are presented according to two distinct phases of research. Data are first presented on existing forms of collective action, the influence of local and external institutions on economic development, and NRM problems that persist despite their negative livelihood consequences. Action research themes selected from a list of identified problems are then presented in greater detail, with lessons learnt thus far in attempting to overcome institutional barriers to improved NRM. The paper concludes with a discussion of the implications of findings for research, institutional practice, and policy." authors' abstractNatural resource management, Collective action, Equity, Livelihoods, East African highlands, Gender, Environmental management,

Somatic mutations and clonal hematopoiesis in congenital neutropenia

© 2018 by The American Society of Hematology. Severe congenital neutropenia (SCN) and Shwachman-Diamond syndrome (SDS) are congenital neutropenia syndromes with a high rate of leukemic transformation. Hematopoietic stressors may contribute to leukemic transformation by increasing the mutation rate in hematopoietic stem/progenitor cells (HSPCs) and/or by promoting clonal hematopoiesis. We sequenced the exome of individual hematopoietic colonies derived from 13 patients with congenital neutropenia to measure total mutation burden and performed error-corrected sequencing on a panel of 46 genes on 80 patients with congenital neutropenia to assess for clonal hematopoiesis. An average of 3.6 ± 1.2 somatic mutations per exome was identified in HSPCs from patients with SCN compared with 3.960.4 for healthy controls (P = NS). Clonal hematopoiesis due to mutations in TP53 was present in 48% (13/ 27) of patients with SDS but was not seen in healthy controls (0/17, P \u3c .001) or patients with SCN (0/40, P \u3c .001). Our SDS cohort was young (median age 6.3 years), and many of the patients had multiple TP53 mutations. Conversely, clonal hematopoiesis due to mutations of CSF3R was present in patients with SCN but was not detected in healthy controls or patients with SDS. These data show that hematopoietic stress, including granulocyte colony-stimulating factor, do not increase the mutation burden in HSPCs in congenital neutropenia. Rather, distinct hematopoietic stressors result in the selective expansion of HSPCs carrying specific gene mutations. In particular, in SDS there is enormous selective pressure to expand TP53-mutated HSPCs, suggesting that acquisition of TP53 mutations is an early, likely initiating event, in the transformation to myelodysplastic syndrome/acute myeloid leukemia in patients with SDS

Leveraging Tensions in Systemic Design

Complex systems do not lend themselves to simplification. Systemic designers have no choice but to embrace complexity, and in doing so, embrace opposing concepts and the resulting paradoxes. It is at the interplay of these ideas that they find the most fruitful regions of exploration. Within the field of systemic design, we find tensions between the positions that different practitioners and scholars take and the methods, practices and ideas they promote. Rather than viewing these differences as problems that need resolving, we see those tensions and differences in perspectives and ideas as opportunities to develop the field. Examples of tensions are: - Humanizing systems versus technical systems solutions - The do-ers/ entrepreneurs versus the thinkers/ philosophers in systemic design - Bottom-up system innovation versus top-down system innovation - The need for predictability and structure versus the need for surprise and emergence - Western ways of systems thinking versus indigenous, Eastern and other ways of systems thinking The goal of this workshop is to explore the tensions that exist in the field of systemic design and the ways they can be leveraged to develop the field

43P MRTX-500: Phase II trial of sitravatinib (sitra) + nivolumab (nivo) in patients (pts) with non-squamous (NSQ) non-small cell lung cancer (NSCLC) progressing on or after prior checkpoint inhibitor (CPI) therapy

Background: Therapy with CPI has improved OS in a subset of pts with NSCLC. Mechanisms of CPI resistance, however, have been described, including an immunosuppressive tumor microenvironment (TME), which may recruit immunosuppressive myeloid-derived suppressor cells (MDSCs), regulatory T cells (Tregs), and M2-polarized macrophages in the TME. Sitra, a spectrum-selective TKI targeting TAM (Tyro3/Axl/MerTK) receptors and VEGFR2, reduces the number of MDSCs and Tregs and increases the M1/M2-polarized macrophage ratio. It is hypothesized to overcome an immunosuppressive TME and augment antitumor immune responses. Methods: MRTX-500 (NCT02954991) is a phase II study evaluating sitra (120 mg QD) + nivo (Q2W or Q4W) in pts with NSQ NSCLC who have progressed on or after treatment, with a CPI-based regimen (anti-PD1/PD-L1) and/or platinum doublet chemotherapy. The primary endpoint is ORR per RECIST 1.1. Secondary endpoints include OS, PFS, and safety. We report updated efficacy data for pts with NSCLC with PCB (prior clinical benefit; CR, PR, or SD ≥12 weeks) from a CPI who were treated with sitra + nivo as either 2L or 3L therapy. Results: As of 17 October 2020, 68 pts with PCB (57% female; median age, 66 years; ECOG PS 0/1/2, 27%/66%/7%) were treated. Median follow-up was 28 months, median OS was 15 months (95% CI 9.3, 21.1),1- and 2-year OS rates were 56% and 32%, respectively. Median PFS was 6 months, and ORR was 16% (11/68), including 2 CRs. Median duration of response was 13 months. In all CPI-experienced pts evaluable for safety (n=124), treatment related adverse events (TRAEs) occurred in 91% of pts, with Gr 3/4 TRAEs occurring in 60% of pts. The most common (≥10%) Gr 3/4 TRAEs were hypertension and diarrhea. There were no Gr 5 TRAEs. Discontinuation rates for sitra and nivo due to any AE were 30% and 27%, respectively. Conclusions: Sitra + nivo demonstrated antitumor activity and encouraging OS compared to historical controls and no new safety signals were observed in pts with NSQ NSCLC who progressed on prior CPI. This combination is being evaluated in the phase III SAPPHIRE study. Previously presented at ESMO 2021, FPN (Final Publication Number): 1191O, Ticiana Leal et al. - Reused with permission. Clinical trial identification: NCT02954991

1191O MRTX-500: Phase II trial of sitravatinib (sitra) + nivolumab (nivo) in patients (pts) with non-squamous (NSQ) non-small cell lung cancer (NSCLC) progressing on or after prior checkpoint inhibitor (CPI) therapy

Background: Therapy with CPI has improved OS across many tumor types, including in a subset of pts with NSCLC. Mechanisms of CPI resistance, however, have been described, including an immunosuppressive TME, which may include recruitment of immunosuppressive myeloid-derived suppressor cells (MDSCs), regulatory T cells (Tregs), and M2-polarized macrophages within the TME. Sitra, a spectrum-selective TKI targeting TAM (Tyro3/Axl/MerTK) receptors and VEGFR2, reduces the number of MDSCs and Tregs while increasing the ratio of M1/M2-polarized macrophages, and thus is hypothesized to overcome an immunosuppressive TME and augment antitumor immune responses. Methods: MRTX-500 (NCT02954991) is a phase II study evaluating sitra (120 mg QD) + nivo (Q2W or Q4W) in pts with NSQ NSCLC who have progressed on or after treatment, with a CPI-based regimen (anti-PD1/PD-L1) and/or platinum doublet chemotherapy. The primary endpoint is ORR per RECIST 1.1. Secondary endpoints include OS, PFS, and safety. We report updated efficacy data for pts with NSCLC with PCB (prior clinical benefit; CR, PR, or SD ≥12 weeks) from a CPI who were treated with sitra + nivo as either 2L or 3L therapy. Results: As of 17 October 2020, 68 pts with PCB (57% female; median age, 66 years; ECOG PS 0/1/2, 27%/66%/7%) were treated. Median follow-up was 28 months, median OS was 15 months (95% CI 9.3, 21.1),1- and 2-year OS rates were 56% and 32%, respectively. Median PFS was 6 months, and ORR was 16% (11/68), including 2 CRs. Median duration of response was 13 months. In all CPI-experienced pts evaluable for safety (n=124), treatment related adverse events (TRAEs) occurred in 91% of pts, with Gr 3/4 TRAEs occurring in 60% of pts. The most common (≥10%) Gr 3/4 TRAEs were hypertension and diarrhea. There were no Gr 5 TRAEs. Discontinuation rates for sitra and nivo due to any AE were 30% and 27%, respectively. Conclusions: Sitra + nivo demonstrated antitumor activity and encouraging OS compared to historical controls and no new safety signals were observed in pts with NSQ NSCLC who progressed on prior CPI. This combination is being evaluated in the phase III SAPPHIRE study