Public engagement with marine climate change issues: (Re)framings, understandings and responses

Climate change impacts on marine environments have been somewhat neglected in climate change research, particularly with regard to their social dimensions and implications. This paper contributes to addressing this gap through presenting a UK focused mixed-method study of how publics frame, understand and respond to marine climate change-related issues. It draws on data from a large national survey of UK publics (N = 1,001), undertaken in January 2011 as part of a wider European survey, in conjunction with in-depth qualitative insights from a citizens’ panel with participants from the East Anglia region, UK. This reveals that discrete marine climate change impacts, as often framed in technical or institutional terms, were not the most immediate or significant issues for most respondents. Study participants tended to view these climate impacts ‘in context’, in situated ways, and as entangled with other issues relating to marine environments and their everyday lives. Whilst making connections with scientific knowledge on the subject, public understandings of marine climate impacts were mainly shaped by personal experience, the visibility and proximity of impacts, sense of personal risk and moral or equity-based arguments. In terms of responses, study participants prioritised climate change mitigation measures over adaptation, even in high-risk areas. We consider the implications of these insights for research and practices of public engagement on marine climate impacts specifically, and climate change more generally

Analyse bodemdaling op de Bovenrijn

Sinds de mens in staat is de natuur naar zijnhand te zetten, heeft hij dit naar hartelust gedaan. Hoe minder hij in staat was de gevolgen op langere termijn te overzien, hoe méer de directe gevolgen op de voorgrond traden. Dit geldt op vele gebieden, ook op het gebied van de waterbouwkunde. De Rijn is een fraai voorbeeld van dergelijk handelen. Door de eeuwen heen is er aan de Rijn gewerkt, maar vooral sinds men in de vorige eeuw de beschikking heeft gekregen over geavanceerde werktuigen, zijn de werken zeer ingrijpend geworden. Het doel van deze werken was de verbetering van de bevaarbaarheid en bescherming tegen verstroming. De werken bestonden hoofdzakelijk uit bochtafsnijdingen, stuwen, kaden, dijken en baggerwerken. Behalve het beoogde doel werd echter ook een verdieping van de rivier bereikt. Dit was niet de bedoeling maar werd in het begin als onvermijdelijk geaccepteerd. De doelstelling van dit onderzoek zijn: 1) bepaling van de oorzaken van de bodemdaling van de Rijn. 2) wat zal in de toekomst gebeuren met deze oorzaken. 3) analyseren van factoren die van belang zijn voor een numerieke berekening van de toekomstige bodemdaling.Hydraulic EngineeringCivil Engineering and Geoscience

Household vulnerability to climate change: examining perceptions of households of flood risks in Georgetown and Paramaribo

The article examines household perceptions of flooding as part of climate change in two low elevation coastal zone cities in the Caribbean. The research examines differences in vulnerability of households as the combined results of socio-economic inequalities in entitlements and exposure to natural hazards - flooding and extreme rainfall. Case studies of Paramaribo and Georgetown show that household exposure to floods is increasing, with lower-income groups suffering longer from exposure and with more damaging effects. Such effects are time lost in work and education, damages to assets, and stress. Households in lower-income areas take more measures to prevent flooding than higher-income households. During floods social capital leads to mutual help among neighbors, but this is not carried through to collective organization in preventive strategies. Links with local government are also found to be lacking. Results show a lack of city-wide organization and participative measures for the households concerned, with possible detrimental effects on lower-income households

Colorectal cancer heterogeneity and targeted therapy: a case for molecular disease subtypes

Personalized cancer medicine is becoming increasingly important in colorectal cancer treatment. Especially for targeted therapies, large variations between individual treatment responses exist. Predicting therapy response is of utmost significance, as it prevents overtreatment and adverse effects in patients. For EGFR-targeted therapy, many mechanisms of resistance have been uncovered, for example, mutations in KRAS and BRAF, and upregulation of alternative receptors. Currently, routine testing for all known modifiers of response is unpractical, and as a result, decision-making for anti-EGFR therapy is still largely based on assessing the mutation status of an individual gene (KRAS). Recently, comprehensive classifications of colorectal cancer have been presented that integrate many of the (epi-)genetic and microenvironmental factors that contribute to colorectal cancer heterogeneity. These classification systems are not only of prognostic value but also predict therapy efficacy, including the response to anti-EGFR agents. Therefore, molecular subtype-based stratification to guide therapeutic decisions is a promising new strategy that might overcome the shortcomings of single gene testing in colorectal cancer as well as in other malignancies. Furthermore, the development of new agents in a disease subtype-specific fashion has the potential to transform drug-discovery studies and generate novel, more effective therapie

DNA methylation based biomarkers in colorectal cancer: A systematic review

Since genetic and epigenetic alterations influence the development of colorectal cancer (CRC), huge potential lies in the use of DNA methylation as biomarkers to improve the current diagnosis, screening, prognosis and treatment prediction. Here we performed a systematic review on DNA methylation-based biomarkers published in CRC, and discussed the current state of findings and future challenges. Based on the findings, we then provide a perspective on future studies. Genome-wide studies on DNA methylation revealed novel biomarkers as well as distinct subgroups that exist in CRC. For diagnostic purposes, the most independently validated genes to study further are VIM, SEPT9, ITGA4, OSM4, GATA4 and NDRG4. These hypermethylated biomarkers can even be combined with LINE1 hypomethylation and the performance of markers should be examined in comparison to FIT further to find sensitive combinations. In terms of prognostic markers, myopodin, KISS1, TMEFF2, HLTF, hMLH1, APAF1, BCL2 and p53 are independently validated. Most prognostic markers published lack both a multivariate analysis in comparison to clinical risk factors and the appropriate patient group who will benefit by adjuvant chemotherapy. Methylation of IGFBP3, mir148a and PTEN are found to be predictive markers for 5-FU and EGFR therapy respectively. For therapy prediction, more studies should focus on finding markers for chemotherapeutic drugs as majority of the patients would benefit. Translation of these biomarkers into clinical utility would require large-scale prospective cohorts and randomized clinical trials in future. Based on these findings and consideration we propose an avenue to introduce methylation markers into clinical practice in near future. For future studies, multi-omics profiling on matched tissue and non-invasive cohorts along with matched cohorts of adenoma to carcinoma is indispensable to concurrently stratify CRC and find novel, robust biomarkers. Moreover, future studies should examine the timing and heterogeneity of methylation as well as the difference in methylation levels between epithelial and stromal tissue

Clinical and biological effects of demethylating agents on solid tumours - A systematic review

Background: It is assumed that DNA methylation plays a key role in both tumour development and therapy resistance. Demethylating agents have been shown to be effective in the treatment of haematological malignancies. Based on encouraging preclinical results, demethylating agents may also be effective in solid tumours. This systematic review summarizes the evidence of the effect of demethylating agents on clinical response, methylation and the immune system in solid tumours. Methods: We conducted a systematic literature search from 1949 to December 2016, according to the PRISMA guidelines. Studies which evaluated treatment with azacitidine, decitabine, guadecitabine, hydralazine, procaine, MG98 and/or zebularine in patients with solid tumours were included. Data on clinical response, effects on methylation and immune response were extracted. Results: Fifty-eight studies were included: in 13 studies complete responses (CR) were observed, 35 studies showed partial responses (PR), 47 studies stable disease (SD) and all studies except two showed progressive disease (PD). Effects on global methylation were observed in 11/15 studies and demethylation/ re-expression of tumour specific genes was seen in 15/17 studies. No clear correlation between (de) methylation and clinical response was observed. In 14 studies immune-related responses were reported, such as re-expression of cancer-testis antigens and upregulation of interferon genes. Conclusion: Demethylating agents are able to improve clinical outcome and alter methylation status in patients with solid tumours. Although beneficial effect has been shown in individual patients, overall response is limited. Further research on biomarker predicting therapy efficacy is indicated, particularly in earlier stage and highly methylated tumours. (C) 2017 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY licens

Capturing colorectal cancer inter-tumor heterogeneity in patient-derived xenograft (PDX) models

Patient-derived xenograft (PDX) models have become an important asset in translational cancer research. However, to provide a robust preclinical platform, PDXs need to accommodate the tumor heterogeneity that is observed in patients. Colorectal cancer (CRC) can be stratified into four consensus molecular subtypes (CMS) with distinct biological and clinical features. Surprisingly, using a set of CRC patients, we revealed the partial representation of tumor heterogeneity in PDX models. The epithelial subtypes, the largest subgroups of CRC subtype, were very ineffective in establishing PDXs, indicating the need for further optimization to develop an effective personalized therapeutic approach to CRC. Moreover, we showed that tumor cell proliferation was associated with successful PDX establishment and able to distinguish patient with poor clinical outcomes within CMS2 group