Lessons About Evaluating Health-Coverage Advocacy Across Multiple Campaigns and Foundations

This article draws on a dozen years’ experience in evaluating major consumerhealth advocacy initiatives to build the knowledge base about advocacy evaluation. The authors explain how their evaluations were strengthened by articulating a detailed theory of change and emphasizing assessment of interim outcomes from many perspectives and methods. Even with comprehensive data and integrated analysis, however, some ambiguity in the results is inevitable; there is no completely objective way to determine the effectiveness of an advocacy initiative. Moreover, sometimes solid or even exceptional advocacy efforts do not lead to desired policy outcomes. Advocacy initiatives that fail initially may be groundwork for future opportunities. Evaluators must tell a compelling story about what advocates hope to achieve, how they tried to achieve it, and the extent to which external factors helped or hindered progress. The narrative about why advocates did what they did must describe context and its influence on all aspects of advocacy campaigns, from goal setting to strategy development to implementation

Inhibition of platelet-derived growth factor signaling attenuates pulmonary fibrosis

Pulmonary fibrosis is the consequence of a variety of diseases with no satisfying treatment option. Therapy-induced fibrosis also limits the efficacy of chemotherapy and radiotherapy in numerous cancers. Here, we studied the potential of platelet-derived growth factor (PDGF) receptor tyrosine kinase inhibitors (RTKIs) to attenuate radiation-induced pulmonary fibrosis. Thoraces of C57BL/6 mice were irradiated (20 Gy), and mice were treated with three distinct PDGF RTKIs (SU9518, SU11657, or Imatinib). Irradiation was found to induce severe lung fibrosis resulting in dramatically reduced mouse survival. Treatment with PDGF RTKIs markedly attenuated the development of pulmonary fibrosis in excellent correlation with clinical, histological, and computed tomography results. Importantly, RTKIs also prolonged the life span of irradiated mice. We found that radiation up-regulated expression of PDGF (A–D) isoforms leading to phosphorylation of PDGF receptor, which was strongly inhibited by RTKIs. Our findings suggest a pivotal role of PDGF signaling in the pathogenesis of pulmonary fibrosis and indicate that inhibition of fibrogenesis, rather than inflammation, is critical to antifibrotic treatment. This study points the way to a potential new approach for treating idiopathic or therapy-related forms of lung fibrosis

A Pragmatic Assessment of Government Support for Organic Agriculture in Ireland

Drawing on a pragmatic approach, this paper provides an analysis of governmental support for organic farming in Ireland. There are varying levels of encouragement and programmes provided to farmers in their conversion from conventional to organic production, and in their maintenance of organic production. Support policies vary across regions and are linked to European Union legislation, thus it is challenging to document the many types of support in place. This research investigates relevant technical, financial, and policy support available to organic farmers in Ireland. This exploratory study develops an assessment of Ireland within eight key categories of organic agricultural support: leadership, policy, research, technical support, financial support, marketing and promotion, education and information, and future developments. Information and data from the Irish Department of Agriculture, Fisheries and Food (DAFF), the Irish Agriculture and Food Development Authority (Teagasc), and other governmental and semi-governmental agencies were utilized to assess the level of support in each category. Following the pragmatic approach, this assessment provides key findings which allow policymakers, organizations and citizens to better understand the current situation and set a path for the future development of organic farming in Ireland

Archaeogenomic distinctiveness of the Isthmo-Colombian area

The recently enriched genomic history of Indigenous groups in the Americas is still meager concerning continental Central America. Here, we report ten pre-Hispanic (plus two early colonial) genomes and 84 genome-wide profiles from seven groups presently living in Panama. Our analyses reveal that pre-Hispanic demographic events contributed to the extensive genetic structure currently seen in the area, which is also characterized by a distinctive Isthmo-Colombian Indigenous component. This component drives these populations on a specific variability axis and derives from the local admixture of different ancestries of northern North American origin(s). Two of these ancestries were differentially associated to Pleistocene Indigenous groups that also moved into South America, leaving heterogenous genetic footprints. An additional Pleistocene ancestry was brought by a still unsampled population of the Isthmus (UPopI) that remained restricted to the Isthmian area, expanded locally during the early Holocene, and left genomic traces up to the present day.Universidad del NorteUniversità degli Studi di Pavi

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

The Democratic Civilization

251 hal.;12 c

Le système des partis politiques en Suisse

Lipson Leslie. Le système des partis politiques en Suisse. In: Revue française de science politique, 6ᵉ année, n°4, 1956. pp. 813-832

Văn minh dân chủ

268 tr. ; 24 cm