Consent and recruitment: the reporting of paediatric trials published in 2012.

Objectives: We evaluated 300 paediatric trials to determine: the consent and recruitment strategies used, who trial information was targeted to, how incentives were used and if they achieved their recruitment targets. Methods: For this cross-sectional evaluation, we searched the Cochrane Central Register of Controlled Trials for paediatric trials published in 2012 and randomly selected 300 that reported on outcomes for participants aged ≤21 years. We collected data on consent and recruitment procedures for each trial and undertook descriptive analyses in SPSS statistics V.23. Results: All but one trial (99.7%) used a standard recruitment strategy. Most (92%) trials reported that consent was obtained but only 13% reported who obtained consent. Two-thirds (65%) of trials included school-aged participants, and of these 68% reported obtaining assent. Half (50%) of the trials reported who the trial information was targeted to. Most trials (75%) of school-aged participants targeted information towards children or children and their parents. Fourteen per cent of trials reported using incentives, half (50%) of which were in the form of compensation. Only 48% of trials reported sufficient data to determine if their recruitment targets were achieved. Of these, 70% achieved their targets. Conclusions: Notable reporting shortcomings included: how families were recruited into the trial, who obtained consent and/or assent and how, who trial information was directed to, whether incentives were used and sufficient data to determine if the recruitment target was achieved. Forthcoming paediatric-specific reporting standards may improve reporting in this priority area. Our data provide a baseline for ongoing monitoring of the state of the research

Reporting of data monitoring committees and adverse events in paediatric trials: a descriptive analysis.

Objectives:For 300 paediatric trials, we evaluated the reporting of: a data monitoring committee (DMC); interim analyses, stopping rules and early stopping; and adverse events and harm-related endpoints. Methods:For this cross-sectional evaluation, we randomly selected 300 paediatric trials published in 2012 from the Cochrane Central Register of Controlled Trials. We collected data on the reporting of a DMC; interim analyses, stopping rules and early stopping; and adverse events and harm-related endpoints. We reported the findings descriptively and stratified by trial characteristics. Results:Eighty-five (28%) of the trials investigated drugs, and 18% (n=55/300) reported a DMC. The reporting of a DMC was more common among multicentre than single centre trials (n=41/132, 31% vs n=14/139, 10%, p<0.001) and industry-sponsored trials compared with those sponsored by other sources (n=16/50, 32% vs n=39/250, 16%, p=0.009). Trials that reported a DMC enrolled more participants than those that did not (median [range]): 224 (10-60480) vs 91 (10-9528) (p<0.001). Only 25% of these trials reported interim analyses, and 42% reported stopping rules. Less than half (n=143/300, 48%) of trials reported on adverse events, and 72% (n=215/300) reported on harm-related endpoints. Trials that reported a DMC compared with those that did not were more likely to report adverse events (n=43/55, 78% vs 100/245, 41%, p<0.001) and harm-related endpoints (n=52/55, 95% vs. 163/245, 67%, p<0.001). Only 32% of drug trials reported a DMC; 18% and 19% did not report on adverse events or harm-related endpoints, respectively. Conclusions:The reporting of a DMC was infrequent, even among drug trials. Few trials reported stopping rules or interim analyses. Reporting of adverse events and harm-related endpoints was suboptimal

Reciprocity between narrative, questioning and imagination in the early and primary years: examining the role of narrative in possibility thinking

The concept of Possibility Thinking (PT) as a driving force of creativity has been investigated both conceptually and empirically for over a decade in early years settings and primary classrooms in England. In the first wave of qualitative empirical studies, play formed part of the enabling context. Criteria for episode selection for PT analysis were that episodes exhibited children immersed in sustained focused playful activity. During the second wave of PT studies, the research team’s attention was drawn to children’s imaginative storying in such playful contexts and it emerged that consideration of narrative in PT might prove fruitful. The current paper revisits key published work, and drawing on data previously analysed for features of PT, seeks to explore how narrative might relate to the current theorised framework. Fourteen published PT episodes are re-analysed in order to consider the role and construction of narrative in PT. The new analysis reveals that narrative plays a foundational role in PT, and that reciprocal relationships exist between questioning, imagination and narrative, layered between children and adults. Consequences for nurturing children’s creativity and for future PT research are explored

Understanding diagnosis and management of dementia and guideline implementation in general practice: a qualitative study using the theoretical domains framework

Dementia is a growing problem, causing substantial burden for patients, their families, and society. General practitioners (GPs) play an important role in diagnosing and managing dementia; however, there are gaps between recommended and current practice. The aim of this study was to explore GPs' reported practice in diagnosing and managing dementia and to describe, in theoretical terms, the proposed explanations for practice that was and was not consistent with evidence-based guidelines

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

Temporal variability in aquatic carbon and GHG concentrations and fluxes in a peatland catchment

Here we present a complete 5-year dataset of all aquatic carbon and GHG species (POC, DOC, DIC, CO2, CH4, N2O) from Auchencorth Moss, an ombrotrophic Scottish peatland. The study aims to analyse and explain temporal variability in concentrations and fluxes (both downstream export and evasion) at weekly, seasonal and annual time scales. The aquatic pathway is increasingly being recognised as an important component of catchment carbon and greenhouse gas (GHG) budgets, particularly in peatland systems due to their large carbon store and strong hydrological connectivity. However, due to a lack of long-term measurements few studies have been able to adequately consider temporal variability in total concentrations and fluxes. We show that short-term within year variability in concentrations exists across all species and this is strongly linked to changes in discharge. Seasonal cyclicity was only evident for DOC, CH4 and N2O concentrations; however temperature correlated with monthly means in all species except DIC. Whilst the temperature dependence in monthly DOC and POC concentrations appeared to be related to biological productivity in the terrestrial system, we suggest the temperature correlation with CO2 and CH4 was primarily due to in-stream temperature-dependent solubility of the two gases. Interannual variability in total aquatic carbon concentration was strongly correlated with catchment gross primary production (GPP) indicating a strong linkage between the terrestrial and aquatic systems. DOC represented the largest aquatic carbon flux term (19.3 ± 4.59 g C m-2 yr-1), followed by CO2 evasion (10.0 g C m-2 yr -1). Despite an estimated contribution to the total aquatic carbon flux of between 8 - 48%, evasion estimates contained the greatest uncertainty and therefore represent an area which requires a significant future research effort. Interannual variability in total carbon export was low in comparison with variability in terrestrial fluxes, and could be explained primarily by temperature and precipitation. Hence changes in catchment carbon cycling resulting from climatic or land-use influences may be easier to identify in terms of aquatic C fluxes compared to land-atmosphere exchange flux terms such as GPP and net ecosystem exchange (NEE)

Five year record of aquatic carbon and greenhouse gas concentrations from Auchencorth Moss

Dataset contains concentrations of particulate and dissolved organic carbon, inorganic carbon, CO2, CH4 and N2O in the Black Burn stream which drains Auchencorth Moss peatland in South East Scotland. Auchencorth Moss is part of the Centre for Ecology & Hydrology's UK Carbon Catchment project. Concentrations have been measured approximately weekly from January 2007 to December 2011 and are published in Global Change Biology doi: 10.1111/gcb.1220

Direct and continuous measurement of dissolved carbon dioxide in freshwater aquatic systems — method and applications

Understanding of the processes that control CO2 concentrations in the aquatic environment has been hampered by the absence of a direct method to make continuous measurements over both short- and long-term time intervals. We describe an in situ method in which a non-dispersive infrared (NDIR) sensor is enclosed in a water impermeable, gas permeable polytetrafluoroethylene (PTFE) membrane and deployed in a freshwater environment. This allows measurements of CO2 concentration to be made directly at a specific depth in the water column without the need for pumps or reagents. We demonstrate the potential of the method using examples from different aquatic environments characterized by a range of CO2 concentrations (0.5–8.0 mg CO2-C L-1, equivalent to ca 40–650 μmol CO2 L-1). These comprise streams and ponds from tropical, temperate and boreal regions. Data derived from the sensor was compared with direct measurements of CO2 concentrations using headspace analysis. Sensor performance following long-term (>6 months) field deployment conformed to manufacturers’ specifications, with no drift detected. We conclude that the sensor-based method is a robust, accurate and responsive method, with a wide range of potential applications, particularly when combined with other in situ sensor-based measurements of related variables