Local political leadership and the modernisation of local government

Political leadership has been a key element of central government’s attempts to ‘modernise’ local government over the past decade, within a discourse that emphasised ‘strong’ and ‘visible’ leadership and the role of leaders and leadership in driving change within local authorities. In the context of such an approach, and also taking account of academic discourse, this article draws upon interviews with nearly thirty individuals in leadership positions in local authorities in England, Scotland and Wales to assess their experiences of leadership and their views of some aspects of the role and work of councils. It suggests that whilst there is broad convergence between the aspirations of government and the narratives that emerge from these leaders on some aspects of local political leadership, there are also differences, perhaps most notably over the relationship between changes to decision making structures and the loci of political power

microRNAs in nociceptive circuits as predictors of future clinical applications

Neuro-immune alterations in the peripheral and central nervous system play a role in the pathophysiology of chronic pain, and non-coding RNAs - and microRNAs (miRNAs) in particular - regulate both immune and neuronal processes. Specifically, miRNAs control macromolecular complexes in neurons, glia and immune cells and regulate signals used for neuro-immune communication in the pain pathway. Therefore, miRNAs may be hypothesized as critically important master switches modulating chronic pain. In particular, understanding the concerted function of miRNA in the regulation of nociception and endogenous analgesia and defining the importance of miRNAs in the circuitries and cognitive, emotional and behavioral components involved in pain is expected to shed new light on the enigmatic pathophysiology of neuropathic pain, migraine and complex regional pain syndrome. Specific miRNAs may evolve as new druggable molecular targets for pain prevention and relief. Furthermore, predisposing miRNA expression patterns and inter-individual variations and polymorphisms in miRNAs and/or their binding sites may serve as biomarkers for pain and help to predict individual risks for certain types of pain and responsiveness to analgesic drugs. miRNA-based diagnostics are expected to develop into hands-on tools that allow better patient stratification, improved mechanism-based treatment, and targeted prevention strategies for high risk individuals. \ua9 2013 Kress, H\ufcttenhofer, Landry, Kuner, Favereaux, Greenberg, Bednarik, Heppenstall, Kronenberg, Malcangio, Rittner, c\ue7eyler, Trajanoski, Mouritzen, Birklein, Sommer and Soreq

A Framework for city leadership in multilevel governance settings: the comparative contexts of Italy and the UK

This paper discusses the role of city leadership in the current multilevel governance settings and provides a conceptual framework for understanding the main elements of city leadership. Forms of political, managerial and civic leadership have been distinguished within city leadership and the main actors, structures, processes and followership patterns are examined using Italy and the UK as starting points of comparison. This comparative framework sheds a light on some common and different features in the city leadership patterns in Italy and the UK, such as the cross-cutting and multilayered administrative context for public service delivery; the common trend towards strengthening the executive side of political leadership rather than the representative one; the growing relevance of forms of civic leadership as a trigger for creating public and social value and for enhancing the resilience of the territories. Main differences deal instead with the role of central government in defining the role of city leaders, where Italy seems to experience a return towards greater centralization and controls, and the UK is experiencing an opposite trend towards the empowerment of local communities. Finally, the paper sets out some future directions for the research agenda on city leadership we are seeking to pursue

Nationwide Survival Benefit after Implementation of First-Line Immunotherapy for Patients with Advanced NSCLC—Real World Efficacy

SIMPLE SUMMARY: The expected change in overall survival (OS) in patients with advanced non-small cell lung cancer (NSCLC) after the clinical implementation of immune checkpoint inhibitor therapy (ICI) has not been substantially investigated in large real-world cohorts outside randomized controlled trials (RCTs). In this nationwide study, we compared OS before and after the implementation of ICI and found that 3-year OS tripled from 6% to 18%. Patients receiving ICI had a lower OS than demonstrated in RCTs, except for patients with performance status (PS) 0. More than a fifth of the patients progressed early within the first six ICI cycles. Adverse prognostic factors were PS ≥ 1 and metastases to the bone and liver. ABSTRACT: Background The selection of patients with non-small cell lung cancer (NSCLC) for immune checkpoint inhibitor (ICI) treatment remains challenging. This real-world study aimed to compare the overall survival (OS) before and after the implementation of ICIs, to identify OS prognostic factors, and to assess treatment data in first-line (1L) ICI-treated patients without epidermal growth factor receptor mutation or anaplastic lymphoma kinase translocation. Methods Data from the Danish NSCLC population initiated with 1L palliative antineoplastic treatment from 1 January 2013 to 1 October 2018, were extracted from the Danish Lung Cancer Registry (DLCR). Long-term survival and median OS pre- and post-approval of 1L ICI were compared. From electronic health records, additional clinical and treatment data were obtained for ICI-treated patients from 1 March 2017 to 1 October 2018. Results The OS was significantly improved in the DLCR post-approval cohort (n = 2055) compared to the pre-approval cohort (n = 1658). The 3-year OS rates were 18% (95% CI 15.6–20.0) and 6% (95% CI 5.1–7.4), respectively. On multivariable Cox regression, bone (HR = 1.63) and liver metastases (HR = 1.47), performance status (PS) 1 (HR = 1.86), and PS ≥ 2 (HR = 2.19) were significantly associated with poor OS in ICI-treated patients. Conclusion OS significantly improved in patients with advanced NSCLC after ICI implementation in Denmark. In ICI-treated patients, PS ≥ 1, and bone and liver metastases were associated with a worse prognosis

High-Throughput High-Resolution Class I HLA Genotyping in East Africa

HLA, the most genetically diverse loci in the human genome, play a crucial role in host-pathogen interaction by mediating innate and adaptive cellular immune responses. A vast number of infectious diseases affect East Africa, including HIV/AIDS, malaria, and tuberculosis, but the HLA genetic diversity in this region remains incompletely described. This is a major obstacle for the design and evaluation of preventive vaccines. Available HLA typing techniques, that provide the 4-digit level resolution needed to interpret immune responses, lack sufficient throughput for large immunoepidemiological studies. Here we present a novel HLA typing assay bridging the gap between high resolution and high throughput. The assay is based on real-time PCR using sequence-specific primers (SSP) and can genotype carriers of the 49 most common East African class I HLA-A, -B, and -C alleles, at the 4-digit level. Using a validation panel of 175 samples from Kampala, Uganda, previously defined by sequence-based typing, the new assay performed with 100% sensitivity and specificity. The assay was also implemented to define the HLA genetic complexity of a previously uncharacterized Tanzanian population, demonstrating its inclusion in the major East African genetic cluster. The availability of genotyping tools with this capacity will be extremely useful in the identification of correlates of immune protection and the evaluation of candidate vaccine efficacy

Leadership and systems of governance: The constraints on the scope for leadership of place-based development in sub-national territories

BENTLEY G., PUGALIS L. and SHUTT J. A triadic conceptualization of leadership, governance systems and central-local relations is constructed in order to aid understandings about the influence of systems of governance on the scope for place-based leadership. Deploying the dual concepts of ‘permissibility’ and ‘acceptability’ provides an innovative analytical device for deciphering the actually existing nature of place-based leadership. Recently initiated public-private-partnerships in one of the OECD’s most centralized countries are analysed to articulate characteristics of controlling mechanisms of the national system of governance which shape the degree of autonomy of leadership of city and regional development in sub-national terrains