Prognostic and predictive value of circulating tumor cells and CXCR4 expression as biomarkers for a CXCR4 peptide antagonist in combination with carboplatin-etoposide in small cell lung cancer: exploratory analysis of a phase II study.

Background Circulating tumor cells (CTCs) and chemokine (C-X-C motif) receptor 4 (CXCR4) expression in CTCs and tumor tissue were evaluated as prognostic or predictive markers of CXCR4 peptide antagonist LY2510924 plus carboplatin-etoposide (CE) versus CE in extensive-stage disease small cell lung cancer (ED-SCLC). Methods This exploratory analysis of a phase II study evaluated CXCR4 expression in baseline tumor tissue and peripheral blood CTCs and in post-treatment CTCs. Optimum cutoff values were determined for CTC counts and CXCR4 expression in tumors and CTCs as predictors of survival outcome. Kaplan-Meier estimates and hazard ratios were used to determine biomarker prognostic and predictive values. Results There was weak positive correlation at baseline between CXCR4 expression in tumor tissue and CTCs. Optimum cutoff values were H-score ≥ 210 for CXCR4+ tumor, ≥7% CTCs with CXCR4 expression (CXCR4+ CTCs), and ≥6 CTCs/7.5 mL blood. Baseline H-score for CXCR4+ tumor was not prognostic of progression-free survival (PFS) or overall survival (OS). Baseline CXCR4+ CTCs ≥7% was prognostic of shorter PFS. CTCs ≥6 at baseline and cycle 2, day 1 were prognostic of shorter PFS and OS. None of the biomarkers at their respective optimum cutoffs was predictive of treatment response of LY2510924 plus CE versus CE. Conclusions In patients with ED-SCLC, baseline CXCR4 expression in tumor tissue was not prognostic of survival or predictive of LY2510924 treatment response. Baseline CXCR4+ CTCs ≥7% was prognostic of shorter PFS. CTC count ≥6 at baseline and after 1 cycle of treatment were prognostic of shorter PFS and OS

A novel sub-seabed CO\u3csub\u3e2\u3c/sub\u3e release experiment informing monitoring and impact assessment for geological carbon storage

© 2014 The Authors. Carbon capture and storage is a mitigation strategy that can be used to aid the reduction of anthropogenic CO2 emissions. This process aims to capture CO2 from large point-source emitters and transport it to a long-term storage site. For much of Europe, these deep storage sites are anticipated to be sited below the sea bed on continental shelves. A key operational requirement is an understanding of best practice of monitoring for potential leakage and of the environmental impact that could result from a diffusive leak from a storage complex. Here we describe a controlled CO2 release experiment beneath the seabed, which overcomes the limitations of laboratory simulations and natural analogues. The complex processes involved in setting up the experimental facility and ensuring its successful operation are discussed, including site selection, permissions, communications and facility construction. The experimental design and observational strategy are reviewed with respect to scientific outcomes along with lessons learnt in order to facilitate any similar future

The iCanCope pain self-management application for adolescents with juvenile idiopathic arthritis: A pilot randomized controlled trial

Objectives: To evaluate the feasibility and preliminary effectiveness of iCanCope with Pain (iCanCope), a smartphone-based pain self-management program, in adolescents with JIA. iCanCope featured symptom tracking, goal-setting, pain coping skills and social support. Methods: A two-arm pilot randomized controlled trial was used to evaluate the iCanCope app compared with a version with symptom tracking only. Primary (feasibility) outcomes were: participant accrual/attrition rates, success of app deployment, acceptability and adherence. Secondary (preliminary effectiveness) outcomes were: pain intensity, pain-related activity limitations and health-related quality of life. Outcomes were assessed at baseline and 8 weeks. Adherence was defined as the proportion of completed symptom reports: \u27low\u27 (≤24%); \u27low-moderate\u27 (25-49%); \u27high-moderate\u27 (50-75%); or \u27high\u27 (76-100%). Linear mixed models were applied for preliminary effectiveness analyses as per intention-to-treat. Results: Adolescents (N = 60) were recruited from three paediatric rheumatology centres. Rates of accrual and attrition were 82 and 13%, respectively. Both apps were deployed with high success (over 85%) and were rated as highly acceptable. Adherence was similar for both groups, with most participants demonstrating moderate-to-high adherence. Both groups exhibited a clinically meaningful reduction in pain intensity (≥1 point) that did not statistically differ between groups. There were no significant changes in activity limitations or health-related quality of life. Conclusion: The iCanCope pilot randomized controlled trial was feasible to implement in a paediatric rheumatology setting. Both apps were deployed successfully, with high acceptability, and were associated with moderate-to-high adherence. Preliminary reductions in pain intensity warrant a future trial to evaluate effectiveness of iCanCope in improving health outcomes in adolescents with JIA

Evaluation of a ferrozine based autonomous in situ lab-on-chip analyzer for dissolved iron species in coastal waters

The trace metal iron (Fe) is an essential micronutrient for phytoplankton growth and limits, or co-limits primary production across much of the world's surface ocean. Iron is a redox sensitive element, with Fe(II) and Fe(III) co-existing in natural waters. Whilst Fe(II) is the most soluble form, it is also transient with rapid oxidation rates in oxic seawater. Measurements of Fe(II) are therefore preferably undertaken in situ. For this purpose an autonomous wet chemical analyzer based on lab-on-chip technology was developed for the in situ determination of the concentration of dissolved (<0.45 μm) Fe species (Fe(II) and labile Fe) suitable for deployments in a wide range of aquatic environments. The spectrophotometric approach utilizes a buffered ferrozine solution and a ferrozine/ascorbic acid mixture for Fe(II) and labile Fe(III) analyses, respectively. Diffusive mixing, color development and spectrophotometric detection take place in three separate flow cells with different lengths such that the analyzer can measure a broad concentration range from low nM to several μM of Fe, depending on the desired application. A detection limit of 1.9 nM Fe was found. The microfluidic analyzer was tested in situ for nine days in shallow waters in the Kiel Fjord (Germany) along with other sensors as a part of the SenseOCEAN EU-project. The analyzer's performance under natural conditions was assessed with discrete samples collected and processed according to GEOTRACES protocol [acidified to pH < 2 and analyzed via inductively coupled plasma mass spectrometry (ICP-MS)]. The mechanical performance of the analyzer over the nine day period was good (consistent high precision of Fe(II) and Fe(III) standards with a standard deviation of 2.7% (n = 214) and 1.9% (n = 217), respectively, and successful completion of every programmed data point). However, total dissolved Fe was consistently low compared to ICP-MS data. Recoveries between 16 and 75% were observed, indicating that the analyzer does not measure a significant fraction of natural dissolved Fe species in coastal seawater. It is suggested that an acidification step would be necessary in order to ensure that the analyzer derived total dissolved Fe concentration is reproducible and consistent with discrete values

Can big data solve a big problem? Reporting the obesity data landscape in line with the Foresight obesity system map.

BACKGROUND: Obesity research at a population level is multifaceted and complex. This has been characterised in the UK by the Foresight obesity systems map, identifying over 100 variables, across seven domain areas which are thought to influence energy balance, and subsequent obesity. Availability of data to consider the whole obesity system is traditionally lacking. However, in an era of big data, new possibilities are emerging. Understanding what data are available can be the first challenge, followed by an inconsistency in data reporting to enable adequate use in the obesity context. In this study we map data sources against the Foresight obesity system map domains and nodes and develop a framework to report big data for obesity research. Opportunities and challenges associated with this new data approach to whole systems obesity research are discussed. METHODS: Expert opinion from the ESRC Strategic Network for Obesity was harnessed in order to develop a data source reporting framework for obesity research. The framework was then tested on a range of data sources. In order to assess availability of data sources relevant to obesity research, a data mapping exercise against the Foresight obesity systems map domains and nodes was carried out. RESULTS: A reporting framework was developed to recommend the reporting of key information in line with these headings: Background; Elements; Exemplars; Content; Ownership; Aggregation; Sharing; Temporality (BEE-COAST). The new BEE-COAST framework was successfully applied to eight exemplar data sources from the UK. 80% coverage of the Foresight obesity systems map is possible using a wide range of big data sources. The remaining 20% were primarily biological measurements often captured by more traditional laboratory based research. CONCLUSIONS: Big data offer great potential across many domains of obesity research and need to be leveraged in conjunction with traditional data for societal benefit and health promotion

Disability in young adults following major trauma: 5 year follow up of survivors

BACKGROUND: Injuries are a major cause of mortality and morbidity in young people. Despite this, the long-term consequences for young survivors of severe injury are relatively unexplored. METHODS: Population based cohort study involving 5 year post injury structured interview of all cases of major trauma (Injury Severity Score > 15) identified retrospectively for 12 month period (1988 to 1989) within former Yorkshire Health Authority area of the United Kingdom. RESULTS: 125 individuals aged 11–24 years at time of injury were identified. Of these, 109 (87%) were interviewed. Only 20% (95% CI 14–29%) of those interviewed reported no disability. Mean Office of Population Census and Surveys (OPCS) disability score of the remainder was 7.5 (median 5.8, range 0.5 to 19.4). The most commonly encountered areas of disability were behaviour (54%, 95% CI 45–63%), intellectual functioning (39%, 95% CI 31–49%) and locomotion (29%, 95% CI 22–39%). Many respondents reported that their daily lives were adversely affected by their health problems for example, causing problems with work, 54% (95% CI 45–63%), or looking after the home, 28% (95% CI 21–38%). Higher OPCS scores were usually but not always associated with greater impact on daily activities. The burden of caring responsibilities fell largely on informal carers. 51% (95% CI 42–61%) of those interviewed would have liked additional help to cope with their injury and disability. CONCLUSION: The study has revealed significant disability amongst a cohort of young people 5 years post severe injury. Whilst many of these young people were coping well with the consequences of their injuries, others reported continuing problems with the activities of daily life. The factors underpinning the young people's differing experiences and social outcome should be explored

Mitigation Effectiveness for Improving Nesting Success of Greater Sage-Grouse Influenced by Energy Development

Sagebrush Artemisia spp. habitats being developed for oil and gas reserves are inhabited by sagebrush obligate species--including the greater sage-grouse Centrocercus urophasianus (sage-grouse) that is currently being considered for protection under the U.S. Endangered Species Act. Numerous studies suggest increasing oil and gas development may exacerbate species extinction risks. Therefore, there is a great need for effective on-site mitigation to reduce impacts to co-occurring wildlife such as sage-grouse. Nesting success is a primary factor in avian productivity and declines in nesting success are also thought to be an important contributor to population declines in sage-grouse. From 2008 to 2011 we monitored 296 nests of radio-marked female sage-grouse in a natural gas (NG) field in the Powder River Basin, Wyoming, USA, and compared nest survival in mitigated and non-mitigated development areas and relatively unaltered areas to determine if specific mitigation practices were enhancing nest survival. Nest survival was highest in relatively unaltered habitats followed by mitigated, and then non-mitigated NG areas. Reservoirs used for holding NG discharge water had the greatest support as having a direct relationship to nest survival. Within a 5-km2 area surrounding a nest, the probability of nest failure increased by about 15% for every 1.5 km increase in reservoir water edge. Reducing reservoirs was a mitigation focus and sage-grouse nesting in mitigated areas were exposed to almost half of the amount of water edge compared to those in non-mitigated areas. Further, we found that an increase in sagebrush cover was positively related to nest survival. Consequently, mitigation efforts focused on reducing reservoir construction and reducing surface disturbance, especially when the surface disturbance results in sagebrush removal, are important to enhancing sage-grouse nesting success