Where Next for Co-Creating Public Services? Emerging Lessons and New Questions from CoSIE

Many models of innovation involve co-creation, which implies that people who use (or potentially use) public services work with providers to initiate, design, deliver and evaluate them (Voorberg et al. 2014, Torfing et al. 2019). The goal of the Co-Creation of Public Service Innovation in Europe project (CoSIE) is to contribute to democratic renewal and social inclusion through co-creating innovative public services by engaging diverse citizen groups and stakeholders in varied public services. CoSIE assumes that co-creation becomes innovative if it not only concerns the reduction of the public expenditure, but if it manages also to meet social needs, and to empower the beneficiaries of policies, by changing socio-political relations and redistributing socio-political responsibilities. More specifically, it aims to a) advance the active shaping of service priorities by end users and their informal support network and b) engage citizens, especially groups often called ’hard to reach’, in the collaborative design of public services. One way it does this is through the development of ten pilot cases, embedded in national contexts which strongly differ in socio-cultural, socio-political and socio-economical dimensions. The subsequent comparison permits an examination of the existence of common enabling or hindering factors. The CoSIE project builds on the idea that public sector innovations can be best achieved by creating collaborative partnerships between service providers (i.e. public sector agencies, third sector organisations, private companies) and citizens who benefit from services either directly or indirectly. Co-creation in CoSIE is an emerging, collaborative and power balancing activity that aims to enrich and enhance the value in public service offerings at any stage in the development of new service and during its implementation. It is manifested in a constructive exchange of different kinds of resources (ideas, competences, lived experience, etc.) that enhance the experienced value of public service. Individual and public value may be understood in terms of increased wellbeing, shared visions for the common good, policies, strategies, regulatory frameworks or new services. This paper draws together some of the ‘big ideas’ emerging from CoSIE in the form of a discussion paper aimed at European, national and regional policy-makers. The big ideas emerging from CoSIE can be grouped together as ideas associated with conceptualising co-creation, implementing co-creation and evidencing co-creation: Conceptualising co-creation • Strengths or asset-based approaches are key to co-creation • Co-creation is a moral endeavour Implementing co-creation • The role of technology in co-creation and innovation • The role of professionals in co-creating public services • Scaling up co-created innovations in public service reform Evidencing and evaluating co-creation in public service reform • Challenges for evaluators • Options for evaluating co-creation and strengths-based approache

Downregulation of organic cation transporters OCT1 (SLC22A1) and OCT3 (SLC22A3) in human hepatocellular carcinoma and their prognostic significance

<p>Abstract</p> <p>Background</p> <p>Organic cation transporters (OCT) are responsible for the uptake and intracellular inactivation of a broad spectrum of endogenous substrates and detoxification of xenobiotics and chemotherapeutics. The transporters became pharmaceutically interesting, because OCTs are determinants of the cytotoxicity of platin derivates and the transport activity has been shown to correlate with the sensitivity of tumors towards tyrosine kinase inhibitors. No data exist about the relevance of OCTs in hepatocellular carcinoma (HCC).</p> <p>Methods</p> <p>OCT1 (<it>SLC22A1</it>) and OCT3 (<it>SLC22A3</it>) mRNA expression was measured in primary human HCC and corresponding non neoplastic tumor surrounding tissue (TST) by real time PCR (n = 53). Protein expression was determined by western blot analysis and immunofluorescence. Data were correlated with the clinicopathological parameters of HCCs.</p> <p>Results</p> <p>Real time PCR showed a downregulation of <it>SLC22A1 </it>and <it>SLC22A3 </it>in HCC compared to TST (p ≤ 0.001). A low <it>SLC22A1 </it>expression was associated with a worse patient survival (p < 0.05). Downregulation was significantly associated with advanced HCC stages, indicated by a higher number of T3 tumors (p = 0.025) with a larger tumor diameter (p = 0.035), a worse differentiation (p = 0.001) and higher AFP-levels (p = 0.019). In accordance, <it>SLC22A1 </it>was less frequently downregulated in tumors with lower stages who underwent transarterial chemoembolization (p < 0.001) and liver transplantation (p = 0.001). Tumors with a low <it>SLC22A1 </it>expression (< median) showed a higher <it>SLC22A3 </it>expression compared to HCC with high <it>SLC22A1 </it>expression (p < 0.001). However, there was no significant difference in tumor characteristics according to the level of the <it>SLC22A3 </it>expression.</p> <p>In the western blot analysis we found a different protein expression pattern in tumor samples with a more diffuse staining in the immunofluorescence suggesting that especially OCT1 is not functional in advanced HCC.</p> <p>Conclusion</p> <p>The downregulation of OCT1 is associated with tumor progression and a worse patient survival.</p

Specific biomarkers for stochastic division patterns and starvation-induced quiescence under limited glucose levels in fission yeast

Glucose as a source of energy is centrally important to our understanding of life. We investigated the cell division–quiescence behavior of the fission yeast Schizosaccharomyces pombe under a wide range of glucose concentrations (0–111 mm). The mode of S. pombe cell division under a microfluidic perfusion system was surprisingly normal under highly diluted glucose concentrations (5.6 mm, 1/20 of the standard medium, within human blood sugar levels). Division became stochastic, accompanied by a curious division-timing inheritance, in 2.2–4.4 mm glucose. A critical transition from division to quiescence occurred within a narrow range of concentrations (2.2–1.7 mm). Under starvation (1.1 mm) conditions, cells were mostly quiescent and only a small population of cells divided. Under fasting (0 mm) conditions, division was immediately arrested with a short chronological lifespan (16 h). When cells were first glucose starved prior to fasting, they possessed a substantially extended lifespan (∼14 days). We employed a quantitative metabolomic approach for S. pombe cell extracts, and identified specific metabolites (e.g. biotin, trehalose, ergothioneine, S-adenosyl methionine and CDP-choline), which increased or decreased at different glucose concentrations, whereas nucleotide triphosphates, such as ATP, maintained high concentrations even under starvation. Under starvation, the level of S-adenosyl methionine increased sharply, accompanied by an increase in methylated amino acids and nucleotides. Under fasting, cells rapidly lost antioxidant and energy compounds, such as glutathione and ATP, but, in fasting cells after starvation, these and other metabolites ensuring longevity remained abundant. Glucose-starved cells became resistant to 40 mm H2O2 as a result of the accumulation of antioxidant compounds

ISQUEMIA MESENTÉRICA AGUDA: QUADRO CLÍNICO, DIAGNÓSTICO E TRATAMENTO.

Introduction: Acute Mesenteric Ischemia (AMI) is a rare pathology with a nonspecific clinical presentation, so that, in general, the diagnosis is late, a fact that compromises the implementation of adequate treatment. This pathology has several etiologies and commonly affects the elderly population, a fact that increases the concern of the health system, since in the current Brazilian scenario we have an inversion of the age pyramid and an increase in the senile population. Therefore, it is essential to understand the clinical nature of this medical emergency, as well as the diagnostic criteria and therapeutic basis, in order to ensure the best management of the case and the best prognosis for the patient. Thus, the main objective of this work is to carry out a review of the main clinical, diagnostic and therapeutic parameters of AMI. Methodology: This is a narrative review of the literature, which was carried out through a search on the PUBMED targeting platform using the descriptions joined by the AND operator: "Mesenteric Ischemia", "Diagnosis", "Therapeutics", “Surgical Procedures, Operative ”. We obtained 196 articles indexed in MEDLINE databases, which were submitted to the following inclusion criteria: published within 5 years, full text available in full and original study. After that, of the 14 articles found, 5 were excluded after reading the title and abstract because they did not fit the desired standards. The search and analysis of the articles was carried out in pairs, independently and blindly, there was no disagreement between the authors and after excluding duplicates, 7 articles were used in this review. Results and Discussion: For clinical suspicion, it is essential to be aware of the typical clinical features of the disease, with abdominal pain that is disproportionate to the physical examination. some specific etiologies bleeding. In general, laboratory tests have little value in terms of diagnostic criteria or exclusion of the disease, imaging tests being fundamental, with a main indication for tomography, in view of the limitations of ultrasound. The treatment consists of several parts, being essential to replace the volume, start empiric antibiotic therapy and revascularize the patient, as well as follow the treatment with drugs to prevent relapses. Conclusion: Understanding this pathology is essential to make an early diagnosis and determine the best intervention and ensure lower morbidity and mortality.Introdução: A Isquemia Mesentérica Aguda (IMA) consiste em uma patologia rara e com a clínica inespecífica, de modo que, em geral, o diagnóstico é tardio, fato que compromete a implantação do tratamento de modo adequado. Essa patologia apresenta diversas etiologias e acomete comumente a população idosa, fato que aumenta a preocupação do sistema de saúde, uma vez que contamos no cenário atual brasileiro com a inversão da pirâmide etária e aumento da população senil. Mediante isso, é fundamental compreender a clínica dessa emergência médica, bem como os critérios diagnósticos e a base terapêutica, de modo a garantir a melhor condução do caso e melhor prognóstico do paciente. Desse modo, o objetivo principal desse trabalho é realizar uma revisão dos principais parâmetros clínicos, diagnósticos e terapêuticos da IMA. Metodologia: Trata-se de uma revisão narrativa da literatura, a qual foi realizada mediante uma busca na plataforma de direcionamento PUBMED utilizando os descritos unidos pelo operador AND: "Mesenteric Ischemia", "Diagnosis", "Therapeutics", “Surgical Procedures, Operative”. Obteve-se 196 artigos indexado as bases MEDLINE, os quais foram submetidos aos seguintes critérios de inclusão: publicados dentro de 5 anos, texto completo disponível na íntegra e estudo original. Após isso, dos 14 artigos encontrados, 5 foram excluídos após leitura de título e resumo por não se enquadrarem nos padrões desejados. A busca e análise dos artigos foi feita aos pares, de modo independente e cega, não houve discordância entre os autores e após excluir duplicatas, 7 artigos foram usados nessa revisão.&nbsp; Resultados e Discussões: Para a suspeita clínica, é fundamental está atento a clínica típica da doença, cursando com dor abdominal desproporcional ao exame físico, além disso é comum o paciente apresentar alterações do trato gastrointestinal, tais como náuseas, vômitos, diarreia e, em algumas etiologias específicas sangramentos. Em geral, os exames laboratoriais tem pouco valor em critérios de diagnóstico ou exclusão da doença, sendo fundamental exames de imagem, com uma indicação principal para a tomografia, tendo em vista as limitações do ultrassom. O tratamento é composto por várias partes, sendo fundamental repor volume, iniciar antibioticoterapia empírica e revascularizar o paciente, bem como seguir tratamento com medicamentos para evitar recidivas. Conclusão: A compreensão dessa patologia é fundamental para fazer um diagnóstico precoce e determinar a melhor intervenção e garantir menor morbimortalidade

Evidence for the association of the SLC22A4 and SLC22A5 genes with Type 1 Diabetes: a case control study

BACKGROUND: Type 1 diabetes (T1D) is a chronic, autoimmune and multifactorial disease characterized by abnormal metabolism of carbohydrate and fat. Diminished carnitine plasma levels have been previously reported in T1D patients and carnitine increases the sensitivity of the cells to insulin. Polymorphisms in the carnitine transporters, encoded by the SLC22A4 and SLC22A5 genes, have been involved in susceptibility to two other autoimmune diseases, rheumatoid arthritis and Crohn's disease. For these reasons, we investigated for the first time the association with T1D of six single nucleotide polymorphisms (SNPs) mapping to these candidate genes: slc2F2, slc2F11, T306I, L503F, OCTN2-promoter and OCTN2-intron. METHODS: A case-control study was performed in the Spanish population with 295 T1D patients and 508 healthy control subjects. Maximum-likelihood haplotype frequencies were estimated by applying the Expectation-Maximization (EM) algorithm implemented by the Arlequin software. RESULTS: When independently analyzed, one of the tested polymorphisms in the SLC22A4 gene at 1672 showed significant association with T1D in our Spanish cohort. The overall comparison of the inferred haplotypes was significantly different between patients and controls (χ(2 )= 10.43; p = 0.034) with one of the haplotypes showing a protective effect for T1D (rs3792876/rs1050152/rs2631367/rs274559, CCGA: OR = 0.62 (0.41–0.93); p = 0.02). CONCLUSION: The haplotype distribution in the carnitine transporter locus seems to be significantly different between T1D patients and controls; however, additional studies in independent populations would allow to confirm the role of these genes in T1D risk

Nurses' perceptions and experiences of communication in the operating theatre: a focus group interview

UNLABELLED: Nurses' perceptions and experiences of communication in the operating theatre: a focus group interview BACKGROUND: Communication programmes are well established in nurse education. The focus of programmes is most often on communicating with patients with less attention paid to inter-professional communication or skills essential for working in specialised settings. Although there are many anecdotal reports of communication within the operating theatre, there are few empirical studies. This paper explores communication behaviours for effective practice in the operating theatre as perceived by nurses and serves as a basis for developing training. METHODS: A focus group interview was conducted with seven experienced theatre nurses from a large London teaching hospital. The interview explored their perceptions of the key as well as unique features of effective communication skills in the operating theatre. Data was transcribed and thematically analysed until agreement was achieved by the two authors. RESULTS: There was largely consensus on the skills deemed necessary for effective practice including listening, clarity of speech and being polite. Significant influences on the nature of communication included conflict in role perception and organisational issues. Nurses were often expected to work outside of their role which either directly or indirectly created barriers for effective communication. Perceptions of a lack of collaborative team effort also influenced communication. CONCLUSION: Although fundamental communication skills were identified for effective practice in the operating theatre, there were significant barriers to their use because of confusion over clarity of roles (especially nurses' roles) and the implications for teamwork. Nurses were dissatisfied with several aspects of communication. Future studies should explore the breadth and depth of this dissatisfaction in other operating theatres, its impact on morale and importantly on patient safety. Interprofessional communication training for operating theatre staff based in part on the key issues identified in this study may help to create clarity in roles and focus attention on effective teamwork and promote clinical safety

Dissociating Markers of Senescence and Protective Ability in Memory T Cells

No unique transcription factor or biomarker has been identified to reliably distinguish effector from memory T cells. Instead a set of surface markers including IL-7Rα and KLRG1 is commonly used to predict the potential of CD8 effector T cells to differentiate into memory cells. Similarly, these surface markers together with the tumor necrosis factor family member CD27 are frequently used to predict a memory T cell's ability to mount a recall response. Expression of these markers changes every time a memory cell is stimulated and repeated stimulation can lead to T cell senescence and loss of memory T cell responsiveness. This is a concern for prime–boost vaccine strategies which repeatedly stimulate T cells with the aim of increasing memory T cell frequency. The molecular cues that cause senescence are still unknown, but cell division history is likely to play a major role. We sought to dissect the roles of inflammation and cell division history in developing T cell senescence and their impact on the expression pattern of commonly used markers of senescence. We developed a system that allows priming of CD8 T cells with minimal inflammation and without acquisition of maximal effector function, such as granzyme expression, but a cell division history similar to priming with systemic inflammation. Memory cells derived from minimal effector T cells are fully functional upon rechallenge, have full access to non-lymphoid tissue and appear to be less senescent by phenotype upon rechallenge. However, we report here that these currently used biomarkers to measure senescence do not predict proliferative potential or protective ability, but merely reflect initial priming conditions