An analysis of the City Challenge decision-making process : The Dearne Valley Partnership and Sheffield.

This study aims to explore the decision-making processes affecting urban change. It uses the City Challenge initiative to help illuminate the changing nature of Urban Policy in Britain and explores the decision-making process in some depth. City Challenge is an urban regeneration initiative introduced in 1991 by the Department of the Environment to improve selected areas of social, economic and environmental deprivation. It is an empirical study based upon thirty four face-to-face interviews with key actors in two case study areas in South Yorkshire - Sheffield and the Dearne Valley. Initially the study contextualises the City Challenge initiative within British Urban Policy. The thesis draws upon three themes that emerge from an examination of the processes of decision-making in the urban environment Firstly aspects of partnerships are considered applying a series of partnership models to the City Challenge decision-making process. Secondly relations between central and local government and the changing role of local government are explored using a series of appropriate models. Finally two American theories, growth coalition theory and regime theory, are applied to the City Challenge decision-making process to explore public/private alliances. The study concludes with some observations about the research findings and suggestions for further study

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

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

Examining the factor structures of the five facet mindfulness questionnaire and the self-compassion scale.

The five facet mindfulness questionnaire (FFMQ; Baer, Smith, Hopkins, Krietemeyer, and Toney, 2006) and the self-compassion scale (SCS; Neff, 2003) are widely used measures of mindfulness and self-compassion in mindfulness-based intervention research. The psychometric properties of the FFMQ and the SCS need to be independently replicated in community samples and relevant clinical samples to support their use. Our primary aim was to establish the factor structures of the FFMQ and SCS in individuals with recurrent depression in remission, since mindfulness-based cognitive therapy (MBCT) was developed as a treatment for preventing depressive relapse. In order to determine the consistency across populations, we examined the factor structures of the FFMQ and SCS in 3 samples: (1) a convenience sample of adults, (2) a sample of adults who practice meditation, and (3) a sample of adults who suffer from recurrent depression and were recruited to take part in a trial of MBCT. Confirmatory factor analyses (CFAs) showed that a 4-factor hierarchical model of the FFMQ best fits the community sample and the clinical sample but that a 5-factor hierarchical model of the FFMQ best fits the meditator sample. CFA did not endorse the SCS 6-factor hierarchical structure in any of the 3 samples. Clinicians and researchers should be aware of the psychometric properties of the FFMQ to measure mindfulness when comparing meditators and nonmeditators. Further research is needed to develop a more psychometrically robust measure of self-compassion

Examining the factor structures of the five facet mindfulness questionnaire and the self-compassion scale.

The five facet mindfulness questionnaire (FFMQ; Baer, Smith, Hopkins, Krietemeyer, and Toney, 2006) and the self-compassion scale (SCS; Neff, 2003) are widely used measures of mindfulness and self-compassion in mindfulness-based intervention research. The psychometric properties of the FFMQ and the SCS need to be independently replicated in community samples and relevant clinical samples to support their use. Our primary aim was to establish the factor structures of the FFMQ and SCS in individuals with recurrent depression in remission, since mindfulness-based cognitive therapy (MBCT) was developed as a treatment for preventing depressive relapse. In order to determine the consistency across populations, we examined the factor structures of the FFMQ and SCS in 3 samples: (1) a convenience sample of adults, (2) a sample of adults who practice meditation, and (3) a sample of adults who suffer from recurrent depression and were recruited to take part in a trial of MBCT. Confirmatory factor analyses (CFAs) showed that a 4-factor hierarchical model of the FFMQ best fits the community sample and the clinical sample but that a 5-factor hierarchical model of the FFMQ best fits the meditator sample. CFA did not endorse the SCS 6-factor hierarchical structure in any of the 3 samples. Clinicians and researchers should be aware of the psychometric properties of the FFMQ to measure mindfulness when comparing meditators and nonmeditators. Further research is needed to develop a more psychometrically robust measure of self-compassion