The Cooperative Participatory Evaluation of Renewable Technologies on Ecosystem Services (CORPORATES)

Publisher PD

The bottom mixed layer depth as an indicator of subsurface Chlorophyll a distribution

Acknowledgements The authors thank Marine Scotland Science for providing the CTD data. Financial support This research has been supported by a MarCRF (Marine Collaboration Research Forum, jointly sponsored by the University of Aberdeen and Marine Scotland Science) PhD grant awarded to Arianna Zampollo.Peer reviewedPublisher PD

Femininity, Childhood and the Non-Making of a Sporting Celebrity: The Beth Tweddle Case

Gymnastics is regularly classified as a feminine-appropriate sport, embodying grace and elegance and is an Olympic sport which has regularly produced female sporting celebrities. Beth Tweddle is the most successful British gymnast of all time and the first to achieve international success, culminating in a medal at London 2012, yet she has received relatively little media coverage and few corporate endorsements. Employing a 'negative case' methodology, this athlete's relative lack of celebrity is investigated. The article suggests that it can be explained by (a) contradictions underpinning the gender-designation of gymnastics, and (b) the social invisibility of a core audience for the sport: young girls. An implication is that the achievement of celebrity within 'feminine' sport may be increasingly unattainable, especially for female athletes. The article uses mixed methods, including primary analysis of print and social media and secondary analysis of a national survey of young people in the UK

A Randomized, Placebo-controlled Trial of Preemptive Antifungal Therapy for the Prevention of Invasive Candidiasis Following Gastrointestinal Surgery for Intra-abdominal Infections.

BACKGROUND: Patients undergoing emergency gastrointestinal surgery for intra-abdominal infection are at risk of invasive candidiasis (IC) and candidates for preemptive antifungal therapy. METHODS: This exploratory, randomized, double-blind, placebo-controlled trial assessed a preemptive antifungal approach with micafungin (100 mg/d) in intensive care unit patients requiring surgery for intra-abdominal infection. Coprimary efficacy variables were the incidence of IC and the time from baseline to first IC in the full analysis set; an independent data review board confirmed IC. An exploratory biomarker analysis was performed using logistic regression. RESULTS: The full analysis set comprised 124 placebo- and 117 micafungin-treated patients. The incidence of IC was 8.9% for placebo and 11.1% for micafungin (difference, 2.24%; [95% confidence interval, -5.52 to 10.20]). There was no difference between the arms in median time to IC. The estimated odds ratio showed that patients with a positive (1,3)-β-d-glucan (ßDG) result were 3.66 (95% confidence interval, 1.01-13.29) times more likely to have confirmed IC than those with a negative result. CONCLUSIONS: This study was unable to provide evidence that preemptive administration of an echinocandin was effective in preventing IC in high-risk surgical intensive care unit patients with intra-abdominal infections. This may have been because the drug was administered too late to prevent IC coupled with an overall low number of IC events. It does provide some support for using ßDG to identify patients at high risk of IC. CLINICAL TRIALS REGISTRATION: NCT01122368

Schedule-dependent response of neuroblastoma cell lines to combinations of etoposide and cisplatin

The growth inhibitory effects of cisplatin and etoposide on neuroblastoma cell lines were investigated in several scheduled combinations. Results were analyzed using median effect and combination index analyses. In all schedules in which cisplatin was administered prior to etoposide a synergistic effect was observed. Conversely, an antagonistic effect was seen in all schedules where etoposide was administered before cisplatin

The p53 Codon 72 Pro/Pro Genotype Identifies Poor-Prognosis Neuroblastoma Patients: Correlation with Reduced Apoptosis and Enhanced Senescence by the p53-72P Isoform.

The p53 gene is rarely mutated in neuroblastoma, but codon 72 polymorphism that modulates its proapoptotic activity might influence cancer risk and clinical outcome. We investigated whether this polymorphism affects neuroblastoma risk and disease outcome and assessed the biologic effects of the p53-72R and p53-72P isoforms in p53-null cells. Comparison of 288 healthy subjects and 286 neuroblastoma patients revealed that the p53-72 polymorphism had no significant impact on the risk of developing neuroblastoma; however, patients with the Pro/Pro genotype had a shorter survival than those with the Arg/Arg or the Arg/Pro genotypes even in the stage 3 and 4 subgroup without MYCN amplification. By Cox regression analysis, the p53 Pro/Pro genotype seems to be an independent marker of poor prognosis (hazard ratio = 2.74; 95% confidence interval = 1.14\u20136.55, P = .014) together with clinical stage, MYCN status, and age at diagnosis. In vitro, p53-72P was less effective than p53-72R in inducing apoptosis and inhibiting survival of p53-null LAN-1 cells treated with etoposide, topotecan, or ionizing radiation but not taxol. By contrast, p53-72P was more effective in promoting p21-dependent accelerated senescence, alone or in the presence of etoposide. Thus, the p53-72 Pro/Pro genotype might be a marker of poor outcome independent of MYCN amplification, possibly improving risk stratification. Moreover, the lower apoptosis and the enhanced accelerated senescence by the p53-72P isoform in response to DNA damage suggest that patients with neuroblastoma with the p53-72 Pro/Pro genotype may benefit from therapeutic protocols that do not rely only on cytotoxic drugs that function, in part, through p53 activation

Influence of segmental chromosome abnormalities on survival in children over the age of 12 months with unresectable localised peripheral neuroblastic tumours without MYCN amplification.

BACKGROUND: The prognostic impact of segmental chromosome alterations (SCAs) in children older than 1 year, diagnosed with localised unresectable neuroblastoma (NB) without MYCN amplification enrolled in the European Unresectable Neuroblastoma (EUNB) protocol is still to be clarified, while, for other group of patients, the presence of SCAs is associated with poor prognosis. METHODS: To understand the role of SCAs we performed multilocus/pangenomic analysis of 98 tumour samples from patients enrolled in the EUNB protocol. RESULTS: Age at diagnosis was categorised into two groups using 18 months as the age cutoff. Significant difference in the presence of SCAs was seen in tumours of patients between 12 and 18 months and over 18 months of age at diagnosis, respectively (P=0.04). A significant correlation (P=0.03) was observed between number of SCAs per tumour and age. Event-free (EFS) and overall survival (OS) were calculated in both age groups, according to both the presence and number of SCAs. In older patients, a poorer survival was associated with the presence of SCAs (EFS=46% vs 75%, P=0.023; OS=66.8% vs 100%, P=0.003). Moreover, OS of older patients inversely correlated with number of SCAs (P=0.002). Finally, SCAs provided additional prognostic information beyond histoprognosis, as their presence was associated with poorer OS in patients over 18 months with unfavourable International Neuroblastoma Pathology Classification (INPC) histopathology (P=0.018). CONCLUSIONS: The presence of SCAs is a negative prognostic marker that impairs outcome of patients over the age of 18 months with localised unresectable NB without MYCN amplification, especially when more than one SCA is present. Moreover, in older patients with unfavourable INPC tumour histoprognosis, the presence of SCAs significantly affects OS

Combination Therapies Targeting Alk-Aberrant Neuroblastoma in Preclinical Models.

BACKGROUND: ALK activating mutations are identified in approximately 10% of newly diagnosed neuroblastomas and ALK amplifications in a further 1-2% of cases. Lorlatinib, a third generation ALK inhibitor, will soon be given alongside induction chemotherapy for children with ALK-aberrant neuroblastoma. However, resistance to single agent treatment has been reported and therapies that improve the response duration are urgently required. We studied the preclinical combination of lorlatinib with chemotherapy, or with the MDM2 inhibitor, idasanutlin, as recent data has suggested that ALK inhibitor resistance can be overcome through activation of the p53-MDM2 pathway. AIMS: To study the preclinical activity of ALK inhibitors alone and combined with chemotherapy or idasanutlin. METHODS: We compared different ALK inhibitors in preclinical models prior to evaluating lorlatinib in combination with chemotherapy or idasanutlin. We developed a triple chemotherapy (CAV: cyclophosphamide, doxorubicin and vincristine) in vivo dosing schedule and applied this to both neuroblastoma genetically engineered mouse models (GEMM) and patient derived xenografts (PDX). RESULTS: Lorlatinib in combination with chemotherapy was synergistic in immunocompetent neuroblastoma GEMM. Significant growth inhibition in response to lorlatinib was only observed in the ALK-amplified PDX model with high ALK expression. In this PDX lorlatinib combined with idasanutlin resulted in complete tumor regression and significantly delayed tumor regrowth. CONCLUSION: In our preclinical neuroblastoma models, high ALK expression was associated with lorlatinib response alone or in combination with either chemotherapy or idasanutlin. The synergy between MDM2 and ALK inhibition warrants further evaluation of this combination as a potential clinical approach for children with neuroblastoma

Age-dependency of the prognostic impact of tumor genomics in localized resectable MYCN non-amplified neuroblastomas Report from the SIOPEN Biology Group on the LNESG Trials

BACKGROUND: Biology based treatment reduction, i.e. surgery alone also in case of not totally resected tumors, was advised in neuroblastoma patients with localized resectable disease without MYCN amplification. However, whether the genomic background of these tumors may influence outcome was unknown and therefore scrutinized in a meta-analysis comprising two prospective therapy studies and a ‘validation’ cohort. PATIENTS AND METHODS: Diagnostic samples were derived from 406 INSS stages 1/2A/2B tumors from three cohorts: LNESGI/II and COG. Genomic data were analyzed in two age groups (cut-off: 18 months) and quality controlled by the SIOPEN Biology Group. RESULTS: In both patient age groups stage 2 tumors led to similarly reduced event-free survival (5y-EFS: 83+3% versus 80+4%), but overall survival was only decreased in patients >18m (5y-OS: 97+1% versus 87+4%; p=0.001). In the latter age subgroup, only tumors with SCA led to relapses, with 11q loss as the strongest marker (5y-EFS: 40+15% versus 89+5%; p18m but not <18m. CONCLUSION: The tumor genomic make-up of resectable non-MYCN amplified stage 2 neuroblastomas has a distinct age-dependent prognostic impact in neuroblastoma patients. While in the younger age group tumors with unfavourable (SCA) and favorable genetics showed relapses, both without worsening OS, in the older age group only tumors with unfavorable genetics led to relapses and decreased OS.N/

Contributions to conservation outcomes by natural history museum-led citizen science: Examining evidence and next steps

publisher: Elsevier articletitle: Contributions to conservation outcomes by natural history museum-led citizen science: Examining evidence and next steps journaltitle: Biological Conservation articlelink: http://dx.doi.org/10.1016/j.biocon.2016.08.040 content_type: article copyright: © 2016 The Authors. Published by Elsevier Ltd.The file attached is the published version of the article