'Word from the street' : when non-electoral representative claims meet electoral representation in the United Kingdom

Taking the specific case of street protests in the UK – the ‘word from the street’– this article examines recent (re)conceptualizations of political representation, most particularly Saward’s notion of ‘representative claim’. The specific example of nonelectoral claims articulated by protestors and demonstrators in the UK is used to illustrate: the processes of making, constituting, evaluating and accepting claims for and by constituencies and audiences; and the continuing distinctiveness of claims based upon electoral representation. Two basic questions structure the analysis: first, why would the political representative claims of elected representatives trump the nonelectoral claims of mass demonstrators and, second, in what ways does the ‘perceived legitimacy’ of the former differ from the latter

Italian Law 326/2003 for The Reimbursement of Orphan and Life Saving Drugs Awaiting Market Entry: Approvals, Rejections And Methods In Aifa's Evaluation Process Between January 2013 And May 2015

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The New Italian Health Care Reform: Introducing New Measures to Speed Up Market Access

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Cost-effectiveness analysis of Vaborem in Carbapenem-resistant Enterobacterales (CRE) -Klebsiella pneumoniae infections in Italy

Background: Vaborem is a fixed dose combination of vaborbactam and meropenem with potent activity against target Carbapenem-resistant Enterobacterales (CRE) pathogens, optimally developed for Klebsiella pneumoniae carbapenemase (KPC). The study aims to evaluate the cost-effectiveness of Vaborem versus best available therapy (BAT) for the treatment of patients with CRE-KPC associated infections in the Italian setting. Methods: A cost-effectiveness analysis was conducted based on a decision tree model that simulates the clinical pathway followed by physicians treating patients with a confirmed CRE-KPC infection in a 5-year time horizon. The Italian National Health System perspective was adopted with a 3% discount rate. The clinical inputs were mostly sourced from the phase 3, randomised, clinical trial (TANGO II). Unit costs were retrieved from the Italian official drug pricing list and legislation, while patient resource use was validated by a national expert. Model outcomes included life years (LYs) and quality adjusted life years (QALYs) gained, incremental costs, incremental cost- effectiveness ratio (ICER) and incremental cost-utility ratio (ICUR). Deterministic and probabilistic sensitivity analyses were also performed. Results: Vaborem is expected to decrease the burden associated with treatment failure and reduce the need for chronic renal replacement therapy while costs related to drug acquisition and long-term care (due to higher survival) may increase. Treatment with Vaborem versus BAT leads to a gain of 0.475 LYs, 0.384 QALYs, and incremental costs of €3549, resulting in an ICER and ICUR of €7473/LY and €9246/QALY, respectively. Sensitivity analyses proved the robustness of the model and also revealed that the probability of Vaborem being cost-effective reaches 90% when willingness to pay is €15,850/QALY. Conclusions: In the Italian setting, the introduction of Vaborem will lead to a substantial increase in the quality of life together with a minimal cost impact, therefore Vaborem is expected to be a cost-effective strategy compared to BAT

PENGEMBANGAN PROGRAM INTERVENSI DINI BERSUMBERDAYA KELUARGA PADA ANAK CEREBRAL PALSY DENGAN HAMBATAN KOMUNIKASI

Penelitian ini dilatarbelakangi oleh kurangnya pemahaman, penerimaan, dan sikap orang tua terhadap hambatan yang dihadapi anak. Hal ini berdampak pada kemampuan keluarga dalam memberikan layanan intervensi dini di rumah. Tujuan dari penelitian ini adalah untuk merumuskan program intervensi dini bersumber daya keluarga yang akan menjadi pedoman orang tua dalam melaksanakan intervensi. Penelitian ini menggunakan pendekatan kualitatif dengan metode deskriptif. Subjek dalam penelitian ini adalah satu keluarga yang memiliki anak Cerebral Palsy dengan hambatan komunikasi di Ciamis. Teknik pengumpulan data yang digunakan adalah observasi, wawancara, dan studi dokumentasi. Hasil penelitian menunjukkan bahwa: 1) anak memiliki hambatan komunikasi yang pencapaian perkembangan komunikasi verbalnya setara dengan anak usia 2-3 tahun dan usia kalender saat ini 5 tahun. 2) rendahnya tingkat pemahaman orangtua terhadap hambatan anak. 3). Rumusan program intervensi dini bersumber daya keluarga ini berdasarkan kondisi objektif serta kebutuhan keluarga dan anak. 4). tingkat pemahaman orang tua mengenai hambatan anak meningkat serta terjadi perubahan sikap dan perilaku orang tua kepada anak;--- The study was motivated by the lack of understanding, acceptance as well as the attitude of the parents toward their child’s obstacles. It somehow has an impact on family’s capacity to give early intervention support at home. This study was aimed at formulating an early intervention program to the child. The study used descriptive qualitative method involving a single family having a child suffering from Cerebral Palsy causing communication barrier at Ciamis. The techniques used in collecting the data were observations, interviews, and document analysis. The study revealed several findings as follows: 1) the child had communication barrier which made her communication verbal developmental stage was equal to 2-3 years old children. 2) The lack of understanding, acceptance and attitude of the parents toward their child’s communication barrier as well as the support in delivering early intervention at home. 3) The early intervention family-based program’s formulation was based on the objective condition as well as the needs’ of both the child and the parents. 4) The level understanding parents of the barriers to child increase and a change in attitudes and behavior of parents to child

The human ankyrin 1 promoter insulator sustains gene expression in a β-globin lentiviral vector in hematopoietic stem cells.

Lentiviral vectors designed for the treatment of the hemoglobinopathies require the inclusion of regulatory and strong enhancer elements to achieve sufficient expression of the β-globin transgene. Despite the inclusion of these elements, the efficacy of these vectors may be limited by transgene silencing due to the genomic environment surrounding the integration site. Barrier insulators can be used to give more consistent expression and resist silencing even with lower vector copies. Here, the barrier activity of an insulator element from the human ankyrin-1 gene was analyzed in a lentiviral vector carrying an antisickling human β-globin gene. Inclusion of a single copy of the Ankyrin insulator did not affect viral titer, and improved the consistency of expression from the vector in murine erythroleukemia cells. The presence of the Ankyrin insulator element did not change transgene expression in human hematopoietic cells in short-term erythroid culture or in vivo in primary murine transplants. However, analysis in secondary recipients showed that the lentiviral vector with the Ankyrin element preserved transgene expression, whereas expression from the vector lacking the Ankyrin insulator decreased in secondary recipients. These studies demonstrate that the Ankyrin insulator may improve long-term β-globin expression in hematopoietic stem cells for gene therapy of hemoglobinopathies

Cutting edge: extracellular high mobility group box-1 protein is a proangiogenic cytokine.

The chromosomal high mobility group box-1 (HMGB1) protein acts as a proinflammatory cytokine when released in the extracellular environment by necrotic and inflammatory cells. In the present study, we show that HMGB1 exerts proangiogenic effects by inducing MAPK ERK1/2 activation, cell proliferation, and chemotaxis in endothelial cells of different origin. Accordingly, HMGB1 stimulates membrane ruffling and repair of a mechanically wounded endothelial cell monolayer and causes endothelial cell sprouting in a three-dimensional fibrin gel. In keeping with its in vitro properties, HMGB1 stimulates neovascularization when applied in vivo on the top of the chicken embryo chorioallantoic membrane whose blood vessels express the HMGB1 receptor for advanced glycation end products (RAGE). Accordingly, RAGE blockade by neutralizing Abs inhibits HMGB1-induced neovascularization in vivo and endothelial cell proliferation and membrane ruffling in vitro. Taken together, the data identify HMGB1/RAGE interaction as a potent proangiogenic stimulus