421 research outputs found

    Community Building as a Philosophy, Not an Initiative

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    What happens when a foundation invests in community building for the long haul? The Ford Family Foundation, a rural embedded funder in southern Oregon, has made that transition over the past decade. The result is a transformed organization with a 10-year strategic plan focused on helping rural communities build the futures that they want to see — places where children and families can thrive. The foundation is pursuing community building not as a stand-alone strategy or “initiative,” but as a philosophy that guides local community development efforts based on capacity building and grantmaking based on partnerships. The shift to a community-based approach allows it to engage with rural communities on a nearly issue-agnostic basis and support them in developing the “Four Cs”: connections, capacity, community-led action, and a culture of community building. The approach is represented by the bilingual Community Building Approach Wheel, a framework and language created by convening a cross-section of rural leaders as working teams to describe communitybuilding principles and practices. The foundation developed partnerships with several communities to describe their communitybuilding work, and the wheel, now owned by dozens of communities, is not static: It continues to evolve as the work evolves, as new communities join, and as the foundation and its partners learn and change. This article shares learnings from The Ford Family Foundation’s experience of becoming a community-building organization and the difference it has made. It also discusses some of the pitfalls it has encountered along the way and how the foundation has responded to them. To be clear: This work is not done; it is ongoing. There is much more to do and much more to learn

    Resources management and effective co-operation fo organisations in Amazonia: a discussion on the social component of recycling in the city of Belém.

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    This paper alms to undstand the organisation process of recycling in Amazonia through the discussion of the social components of the sorting collection system mainly conducted by former farming families in the city fo Belém

    Using a realist approach to evaluate smoking cessation interventions targeting pregnant women and young people

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    Background This paper describes a study protocol designed to evaluate a programme of smoking cessation interventions targeting pregnant women and young people living in urban and rural locations in Northeast Scotland. The study design was developed on so-called 'realist' evaluation principles, which are concerned with the implementation of interventions as well as their outcomes. Methods/design A two-phased study was designed based on the Theory of Change (TOC) using mixed methods to assess both process and outcome factors. The study was designed with input from the relevant stakeholders. The mixed-methods approach consists of semi-structured interviews with planners, service providers, service users and non-users. These qualitative interviews will be analysed using a thematic framework approach. The quantitative element of the study will include the analysis of routinely collected data and specific project monitoring data, such as data on service engagement, service use, quit rates and changes in smoking status. Discussion The process of involving key stakeholders was conducted using logic modelling and TOC tools. Engaging stakeholders, including those responsible for funding, developing and delivering, and those intended to benefit from interventions aimed at them, in their evaluation design, are considered by many to increase the validity and rigour of the subsequent evidence generated. This study is intended to determine not only the components and processes, but also the possible effectiveness of this set of health interventions, and contribute to the evidence base about smoking cessation interventions aimed at priority groups in Scotland. It is also anticipated that this study will contribute to the ongoing debate about the role and challenges of 'realist' evaluation approaches in general, and the utility of logic modelling and TOC approaches in particular, for evaluation of complex health interventions

    Src Dependent Pancreatic Acinar Injury Can Be Initiated Independent of an Increase in Cytosolic Calcium

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    Several deleterious intra-acinar phenomena are simultaneously triggered on initiating acute pancreatitis. These culminate in acinar injury or inflammatory mediator generation in vitro and parenchymal damage in vivo. Supraphysiologic caerulein is one such initiator which simultaneously activates numerous signaling pathways including non-receptor tyrosine kinases such as of the Src family. It also causes a sustained increase in cytosolic calcium- a player thought to be crucial in regulating deleterious phenomena. We have shown Src to be involved in caerulein induced actin remodeling, and caerulein induced changes in the Golgi and post-Golgi trafficking to be involved in trypsinogen activation, which initiates acinar cell injury. However, it remains unclear whether an increase in cytosolic calcium is necessary to initiate acinar injury or if injury can be initiated at basal cytosolic calcium levels by an alternate pathway. To study the interplay between tyrosine kinase signaling and calcium, we treated mouse pancreatic acinar cells with the tyrosine phosphatase inhibitor pervanadate. We studied the effect of the clinically used Src inhibitor Dasatinib (BMS-354825) on pervanadate or caerulein induced changes in Src activation, trypsinogen activation, cell injury, upstream cytosolic calcium, actin and Golgi morphology. Pervanadate, like supraphysiologic caerulein, induced Src activation, redistribution of the F-actin from its normal location in the sub-apical area to the basolateral areas, and caused antegrade fragmentation of the Golgi. These changes, like those induced by supraphysiologic caerulein, were associated with trypsinogen activation and acinar injury, all of which were prevented by Dasatinib. Interestingly, however, pervanadate did not cause an increase in cytosolic calcium, and the caerulein induced increase in cytosolic calcium was not affected by Dasatinib. These findings suggest that intra-acinar deleterious phenomena may be initiated independent of an increase in cytosolic calcium. Other players resulting in acinar injury along with the Src family of tyrosine kinases remain to be explored. © 2013 Mishra et al

    Drosophila KCNQ Channel Displays Evolutionarily Conserved Electrophysiology and Pharmacology with Mammalian KCNQ Channels

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    Of the five human KCNQ (Kv7) channels, KCNQ1 with auxiliary subunit KCNE1 mediates the native cardiac IKs current with mutations causing short and long QT cardiac arrhythmias. KCNQ4 mutations cause deafness. KCNQ2/3 channels form the native M-current controlling excitability of most neurons, with mutations causing benign neonatal febrile convulsions. Drosophila contains a single KCNQ (dKCNQ) that appears to serve alone the functions of all the duplicated mammalian neuronal and cardiac KCNQ channels sharing roughly 50–60% amino acid identity therefore offering a route to investigate these channels. Current information about the functional properties of dKCNQ is lacking therefore we have investigated these properties here. Using whole cell patch clamp electrophysiology we compare the biophysical and pharmacological properties of dKCNQ with the mammalian neuronal and cardiac KCNQ channels expressed in HEK cells. We show that Drosophila KCNQ (dKCNQ) is a slowly activating and slowly-deactivating K+ current open at sub-threshold potentials that has similar properties to neuronal KCNQ2/3 with some features of the cardiac KCNQ1/KCNE1 accompanied by conserved sensitivity to a number of clinically relevant KCNQ blockers (chromanol 293B, XE991, linopirdine) and opener (zinc pyrithione). We also investigate the molecular basis of the differential selectivity of KCNQ channels to the opener retigabine and show a single amino acid substitution (M217W) can confer sensitivity to dKCNQ. We show dKCNQ has similar electrophysiological and pharmacological properties as the mammalian KCNQ channels, allowing future study of physiological and pathological roles of KCNQ in Drosophila and whole organism screening for new modulators of KCNQ channelopathies

    ANK3 related neurodevelopmental disorders: expanding the spectrum of heterozygous loss-of-function variants

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    ANK3 encodes multiple isoforms of ankyrin-G, resulting in variegated tissue expression and function, especially regarding its role in neuronal development. Based on the zygosity, location, and type, ANK3 variants result in different neurodevelopmental phenotypes. Autism spectrum disorder has been associated with heterozygous missense variants in ANK3, whereas a more severe neurodevelopmental phenotype is caused by isoform-dependent, autosomal-dominant, or autosomal-recessive loss-of-function variants. Here, we present four individuals affected by a variable neurodevelopmental phenotype harboring a heterozygous frameshift or nonsense variant affecting all ANK3 transcripts. Thus, we provide further evidence of an isoform-based phenotypic continuum underlying ANK3-associated pathologies and expand its phenotypic spectrum.Genetics of disease, diagnosis and treatmen

    On the problem of supersonic gas flow in two-dimensional channel with the oscillating upper wall

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    In the present paper we solve the problem of supersonic gas flow in two-dimensional channel with the moving upper wall making oscillations according to the harmonic law. In order to get a numerical solution for gas dynamics equations we have implemented a difference scheme with space and time approximation of the first order and one with space approximation of the second order. Depending on a type of harmonic law and initial gas inflow conditions, the peculiarities of angle-shock wave propagation in moving curvilinear domains have been investigated. It has been determined that the increase of oscillation amplitude causes the increase of shock wave intensity. It has been shown that under particular oscillation amplitude the moving wall has practically no effect on the flow within the domain
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