152 research outputs found

    Exiting From Large-Scale Initiatives: Lessons and Insights From a National Scan of Philanthropy

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    This article shares insights and lessons from a research project commissioned by The California Endowment in early 2016 to inform the planning for its transition out of Building Healthy Communities, a 10-year, place-based, policy- and systems-change initiative. The goal of the nationwide study, which included literature reviews and interviews with 30 executives and directors from 17 foundations, was to tap into philanthropic leaders’ accumulated wisdom about exiting out of similar initiatives. In generalizing the study’s findings for the broader philanthropic audience, this article presents a guiding framework for exit and sustainability planning in the form of a set of recommendations that relate to issues such as managing relationships between funder and grantee partners during the exit, using the initiative’s theory of change as a tool for decision-making, finding a balance between demonstrable success and equity, and managing the internal processes of the funding organization. The research shows that even though an exit is inherently difficult, it is possible to carry out in a way that does not undermine the accomplishments of the initiative and leaves the foundation and its grantee partners in strengthened positions

    Lessons From the Assessment for Learning Project: Strategies for Building an Authentic Learning Community

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    This article explores findings from an evaluation of the Assessment for Learning Project, a grantee engagement strategy led by the Center for Innovation in Education focused on creating a learning community founded in continuous reflection and safety for risk-taking. The article shares the project’s model and approach, grounded in the core design elements of a field-facing learning agenda, grantmaking that leads with learning, and collective leadership. This article highlights the Assessment for Learning Project’s practices, such as a Request for Learning rather than traditional Request for Proposals; a requirement that grantees provide formative feedback to each other; and public demonstrations of learning in lieu of traditional reporting. And it explores how the project’s design helps flip the script on expertise by encouraging grantees to draw on one another for support and how it promotes a culture of experimentation that deepens learning relationships. Finally, this article points to the role of the project’s leadership team in modeling reflection and vulnerability, co-designing with grantees to bolster their leadership, and expanding its network by strategically connecting grantees to the broader field via a common learning agenda

    Major flaws in conflict prevention policies towards Africa : the conceptual deficits of international actors’ approaches and how to overcome them

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    Current thinking on African conflicts suffers from misinterpretations oversimplification, lack of focus, lack of conceptual clarity, state-centrism and lack of vision). The paper analyses a variety of the dominant explanations of major international actors and donors, showing how these frequently do not distinguish with sufficient clarity between the ‘root causes’ of a conflict, its aggravating factors and its triggers. Specifically, a correct assessment of conflict prolonging (or sustaining) factors is of vital importance in Africa’s lingering confrontations. Broader approaches (e.g. “structural stability”) offer a better analytical framework than familiar one-dimensional explanations. Moreover, for explaining and dealing with violent conflicts a shift of attention from the nation-state towards the local and sub-regional level is needed.Aktuelle Analysen afrikanischer Gewaltkonflikte sind hĂ€ufig voller Fehlinterpretationen (Mangel an Differenzierung, Genauigkeit und konzeptioneller Klarheit, Staatszentriertheit, fehlende mittelfristige Zielvorstellungen). Breitere AnsĂ€tze (z. B. das Modell der Strukturellen StabilitĂ€t) könnten die Grundlage fĂŒr bessere Analyseraster und Politiken sein als eindimensionale ErklĂ€rungen. hĂ€ufig differenzieren ErklĂ€rungsansĂ€tze nicht mit ausreichender Klarheit zwischen Ursachen, verschĂ€rfenden und auslösenden Faktoren. Insbesondere die richtige Einordnung konfliktverlĂ€ngernder Faktoren ist in den jahrzehntelangen gewaltsamen Auseinandersetzungen in Afrika von zentraler Bedeutung. Das Diskussionspapier stellt die große Variationsbreite dominanter ErklĂ€rungsmuster der wichtigsten internationalen Geber und Akteure gegenĂŒber und fordert einen Perspektivenwechsel zum Einbezug der lokalen und der subregionalen Ebene fĂŒr die ErklĂ€rung und Bearbeitung gewaltsamer Konflikte

    Association analysis of ACE and ACTN3 in Elite Caucasian and East Asian Swimmers

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    PURPOSE: Polymorphic variation in the angiotensin-converting enzyme (ACE) and alpha-actinin-3 (ACTN3) genes has been reported to be associated with endurance and/or power-related human performance. Our aim was to investigate whether polymorphisms in ACE and ACTN3 are associated with elite swimmer status in Caucasian and East Asian populations. METHODS: ACE I/D and ACTN3 R577X genotyping was carried out for 200 elite Caucasian swimmers from European, Commonwealth, Russian and American cohorts (short and middle distance, SMD ≤ 400 m, n = 130; long distance, LD greater than 400 m, n = 70) and 326 elite Japanese and Taiwanese swimmers (short distance, SD ≤ 100 m, n = 166; middle distance, MD: 200 - 400 m, n = 160). Genetic associations were evaluated by logistic regression and other tests accommodating multiple testing adjustment. RESULTS: ACE I/D was associated with swimmer status in Caucasians, with the D-allele being overrepresented in SMD swimmers under both additive and I-allele dominant models (permutation test p = 0.003 and p = 0.0005, respectively). ACE I/D was also associated with swimmer status in East Asians. In this group, however, the I-allele was overrepresented in the SD swimmer group (permutation test p = 0.041 and p = 0.0098 under the additive and the D-allele-dominant models, respectively). ACTN3 R577X was not significantly associated with swimmer status in either Caucasians or East Asians. CONCLUSIONS: ACE I/D associations were observed in these elite swimmer cohorts, with different risk alleles responsible for the associations in swimmers of different ethnicities. The functional ACTN3 R577X polymorphism did not show any significant association with elite swimmer status, despite numerous previous reports of associations with 'power/sprint' performance in other sports.Additional co-authors: Jason Gulbin, Viktor A. Rogozkin, Ildus I. Ahmetov, Nan Yang, Kathryn N. North, Saraslanidis Ploutarhos, Hugh E. Montgomery, Mark E.S. Bailey, and Yannis P. Pitsiladi

    Modulation of the rod outer segment aerobic metabolism diminishes the production of radicals due to light absorption

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    Oxidative stress is a primary risk factor for both inflammatory and degenerative retinopathies. Our previous data on blue light-irradiated retinas demonstrated an oxidative stress higher in the rod outer segment (OS) than in the inner limb, leading to impairment of the rod OS extra-mitochondrial aerobic metabolism. Here the oxidative metabolism and Reactive Oxygen Intermediates (ROI) production was evaluated in purified bovine rod OS in function of exposure to different illumination conditions. A dose response was observed to varying light intensities and duration in terms of both ROI production and ATP synthesis. Pretreatment with resveratrol, inhibitor of F1Fo-ATP synthase, or metformin, inhibitor of the respiratory complex I, significantly diminished the ROI production. Metformin also diminished the rod OS Complex I activity and reduced the maximal OS response to light in ATP production. Data show for the first time the relationship existing in the rod OS between its -aerobic- metabolism, light absorption, and ROI production. A beneficial effect was exerted by metformin and resveratrol, in modulating the ROI production in the illuminated rod OS, suggestive of their beneficial action also in vivo. Data shed new light on preventative interventions for cone loss secondary to rod damage due to oxidative stress

    The N–Terminal Tail of hERG Contains an Amphipathic α–Helix That Regulates Channel Deactivation

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    The cytoplasmic N–terminal domain of the human ether–a–go–go related gene (hERG) K+ channel is critical for the slow deactivation kinetics of the channel. However, the mechanism(s) by which the N–terminal domain regulates deactivation remains to be determined. Here we show that the solution NMR structure of the N–terminal 135 residues of hERG contains a previously described Per–Arnt–Sim (PAS) domain (residues 26–135) as well as an amphipathic α–helix (residues 13–23) and an initial unstructured segment (residues 2–9). Deletion of residues 2–25, only the unstructured segment (residues 2–9) or replacement of the α–helix with a flexible linker all result in enhanced rates of deactivation. Thus, both the initial flexible segment and the α–helix are required but neither is sufficient to confer slow deactivation kinetics. Alanine scanning mutagenesis identified R5 and G6 in the initial flexible segment as critical for slow deactivation. Alanine mutants in the helical region had less dramatic phenotypes. We propose that the PAS domain is bound close to the central core of the channel and that the N–terminal α–helix ensures that the flexible tail is correctly orientated for interaction with the activation gating machinery to stabilize the open state of the channel

    Extracellular Tau Oligomers Produce An Immediate Impairment of LTP and Memory

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    Non-fibrillar soluble oligomeric forms of amyloid-\u3b2 peptide (oA\u3b2) and tau proteins are likely to play a major role in Alzheimer's disease (AD). The prevailing hypothesis on the disease etiopathogenesis is that oA\u3b2 initiates tau pathology that slowly spreads throughout the medial temporal cortex and neocortices independently of A\u3b2, eventually leading to memory loss. Here we show that a brief exposure to extracellular recombinant human tau oligomers (oTau), but not monomers, produces an impairment of long-term potentiation (LTP) and memory, independent of the presence of high oA\u3b2 levels. The impairment is immediate as it raises as soon as 20\u2009min after exposure to the oligomers. These effects are reproduced either by oTau extracted from AD human specimens, or naturally produced in mice overexpressing human tau. Finally, we found that oTau could also act in combination with oA\u3b2 to produce these effects, as sub-toxic doses of the two peptides combined lead to LTP and memory impairment. These findings provide a novel view of the effects of tau and A\u3b2 on memory loss, offering new therapeutic opportunities in the therapy of AD and other neurodegenerative diseases associated with A\u3b2 and tau pathology
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