Credibility and Agency Termination under Parliamentarism

We investigate the life span and risk of termination of 723 arm’s length agencies in the United Kingdom between 1985 and 2008, an under investigated question in parliamentary systems. We hypothesize that termination risk depends on three groups of factors: (1) factors relating to the rationales for initial delegation of responsibility to the arm’s length agency; (2) factors relating to the political and economic position of the government; and (3) factors relating to the institutional form of the agency. We find that agencies intended to generate credible commitments in regulation are less likely than others to be terminated in any given year. Agencies operating under right-wing governments and under heavily indebted governments are more likely to be terminated, although left-wing governments are more sensitive to the effects of debt. Agencies structured as executive non-departmental public bodies and non-ministerial departments are also longer lived than others. Contrary to expectations about arm’s length agencies in parliamentary systems with single-party government, partisan change does not affect the risk of termination

Beyond the Revolving Door:Long-Term Lived Experience of Eating Disorders and Specialist Service Provision

In this study, we undertook a narrative analysis of participants’ long-term lived experience of eating disorders and specialist service provision. Eight participants were recruited with service experience across five National Health Service (NHS) Trusts in the United Kingdom. All participants had a minimum of 10 years self-reported experience living with an eating disorder. The data are presented across different temporal stages that demonstrate the development of participants’ self-construct in relation to their first contact with specialist services, what had happened in their lives for this to become necessary, and their current relationships with services, before exploring what participants need from services to help them feel heard going forward. Findings suggest that current methods of service delivery result in delayed and inappropriate supports and a consequent “battling” against professionals, which can provide an obstacle to compassionate and collaborative working and promote “revolving door” experiences

Cannabinoid receptors in GtoPdb v.2023.1

Cannabinoid receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Cannabinoid Receptors [119]) are activated by endogenous ligands that include N-arachidonoylethanolamine (anandamide), N-homo-γ-linolenoylethanolamine, N-docosatetra-7,10,13,16-enoylethanolamine and 2-arachidonoylglycerol. Potency determinations of endogenous agonists at these receptors are complicated by the possibility of differential susceptibility of endogenous ligands to enzymatic conversion [5].There are currently three licenced cannabinoid medicines each of which contains a compound that can activate CB1 and CB2 receptors [111]. Two of these medicines were developed to suppress nausea and vomiting produced by chemotherapy. These are nabilone (Cesamet®), a synthetic CB1/CB2 receptor agonist, and synthetic Δ9-tetrahydrocannabinol (Marinol®; dronabinol), which can also be used as an appetite stimulant. The third medicine, Sativex®, contains mainly Δ9-tetrahydrocannabinol and cannabidiol, both extracted from cannabis, and is used to treat multiple sclerosis and cancer pain

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

Cabinet Governance and Political Stability in English Urban Councils

Policy-makers have long been concerned with the quality of local political leadership and have often resorted to institutional reform to try to improve political leadership. This paper looks at a specific and neglected facet of the political management reforms that have been implemented in English local government over the last decade: the tenure and turnover of cabinet members. The tenure of top politicians may be an important influence on the performance of local government particularly when political management is designed to favour individualised leadership. On the one hand, excessively short tenures for top politicians may damage the ability of governments to develop strategic plans and ensure they are implemented while on the other hand the risk of loss of office is central to political accountability and excessively long tenures may be indicative of an insulated and unresponsive elite. While some research attention has been paid to the tenures of leaders of councils in England there is little systematic information about the tenure of cabinet members. This paper discusses the relevance of cabinet stability and provides an overview of recent experience in England

The role of private sector actors in sub-national economic governance in England and the USA

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