36 research outputs found
Does the Composition of Dissolved Organic Carbon (DOC) in Peatland Streams Reflect the DOC Leached from Vegetation, Litter and Soil?
No abstract available
Retrofit information challenges and potential solutions: Perspectives of households, retrofit professionals and local policy makers in the United Kingdom
Rapidly scaling up energy retrofit for existing buildings is critical to help meet climate targets. Information is frequently identified as a key barrier to residential retrofit. This paper explores the role of information sharing in accelerating retrofit market transformation, through interviews and photo elicitation with homeowners (N = 9) and two workshops with stakeholders (N = 33) in a local authority retrofit project in Gloucestershire (UK). Findings are thematically analysed and suggestions for future local and national policy action are identified. The research finds that even for engaged, knowledgeable homeowners, accessing appropriate information is still a significant retrofit barrier. Two themes around the nature of information and information delivery are identified and key issues include information overload, a lack of context-specific information and in-person engagement, and a need for trustworthy, local information sources. Local authorities have potential to act as trusted intermediaries for structured, relevant retrofit information but require support from national governments to increase capacity and resources at local levels. National governments also have a critical role in providing clear and consistent messaging and leadership on the importance and benefits of retrofit. Policies around financial incentives are not sufficient alone and must be accompanied by strategies to overcome informational and other barriers if retrofit is to be accelerated in this decisive decade for climate action
Does the Composition of Dissolved Organic Carbon (DOC) in Peatland Streams Reflect the DOC Leached from Vegetation, Litter and Soil?
No abstract available
Circulating biomarkers during treatment in patients with advanced biliary tract cancer receiving cediranib in the UK ABC-03 trial
BACKGROUND: Advanced biliary tract cancer (ABC) has a poor prognosis. Cediranib, in addition to cisplatin/gemcitabine [CisGem], improved the response rate, but did not improve the progression-free survival (PFS) in the ABC-03 study. Minimally invasive biomarkers predictive of cediranib benefit may improve patient outcomes.
METHODS: Changes in 15 circulating plasma angiogenesis or inflammatory-related proteins and cytokeratin-18 (CK18), measured at baseline and during therapy until disease progression, were correlated with overall survival (OS) using time-varying covariate Cox models (TVC).
RESULTS: Samples were available from n=117/124 (94%) patients. Circulating Ang1&2, FGFb, PDGFbb, VEGFC, VEGFR1 and CK18 decreased as a result of the therapy, independent of treatment with cediranib. Circulating VEGFR2 and Tie2 were preferentially reduced by cediranib. Patients with increasing levels of VEGFA at any time had a worse PFS and OS; this detrimental effect was attenuated in patients receiving cediranib. TVC analysis revealed CK18 and VEGFR2 increases correlated with poorer OS in all patients (P< 0.001 and P=0.02, respectively).
CONCLUSIONS: Rising circulating VEGFA levels in patients with ABC, treated with CisGem, are associated with worse PFS and OS, not seen in patients receiving cediranib. Rising levels of markers of tumour burden (CK18) and potential resistance (VEGFR2) are associated with worse outcomes and warrant validation
Mental Health Through Movement
Children’s mental health: ‘has become an issue of real concern, in the media and to both politicians and NHS leaders, over the last five years in particular. It has prompted numerous inquiries, reports, recommendations and pledges by politicians and NHS leaders to improve the situation’: https://www.theguardian.com/society/2018/nov/22/what-is-happening-withchildrens-mental-health On July 1st 2019, the Local Government Association released statistics to show that: ‘There were 205,720 cases where a child was identified as having a mental health issue in 2017/18, compared with 133,600 in 2014/15- up 54%’: https://www.local.gov.uk/about/news/councils-seeing-more-560-child-mentalhealth-cases-every-day It is within this context that the All-Party Parliamentary Group on A Fit and Healthy Childhood presents its 14th Report: ‘Positive Mental Health Through Movement’. With 1 in 10 children now having a mental health diagnosis and 1 in 4 an undiagnosed mental health issue, this, our third Report on the issue of child mental health, addresses the link between positive mental health and physical activity and movement experiences at a time when, paradoxically, today’s children and young people are more inactive and play less than ever before. The growing recognition of a link between mental health and movement is fortuitous because from September 2019, health education in English schools will be statutory alongside the expectation that they will offer their pupils at least 30 ‘active minutes’ per day. The APPG on A Fit and Healthy Childhood welcomes the change whilst recognising that those responsible for implementing the new strategy (including practitioners and families) will need guidance as they help children to develop individual strategies to address future adverse events and foster the positive sense of self that will enable them to lead fulfilled, healthy lives. This Report is therefore presented as a practical contribution to an essential debate. It offers new strategies against the persistence of historical and traditional ways of thinking; examines and collates best practice in the devolved Home Countries as well as the wider world and discusses exactly what is required to ensure that future child mental health strategy is holistic. It is respectful of equalities and is aware that the successful outcome of policies is entirely dependent upon the expertise and confidence of those tasked with the responsibility of delivering them. As the 21st century advances, we consider the effects of the digital age and its impact on children and young people’s mental health and wellbeing and the crucial role of parents and carers who want the best for their children in a societal climate where, all too often, fears of ‘nanny state’ meddling serve to isolate families who suffer in silence – until a disaster that may have been all too predictable and preventable overtakes them, making a private grief a public concern. The trajectory of progress in mental health policy has been ‘stop start’ rather than linear, with legislative change in 1959 and 1983, an increase in spending from 1997- 2010 and radical changes to child and adolescent mental health services (CAMHS) in 2000. The Wessely Independent Review of the Mental Health Act is another such milestone: https://www.gov.uk/government/groups/independent-review-of-the-mentalhealth-act The APPG on A Fit and Healthy Childhood anticipates that the Government will fulfil its pledge to parents, children and practitioners by introducing much needed mental health legislation - and that our trio of Reports and the holistic theme of this one will help to inform a strategy that works for 21st century children
Reply to Comment on "The UK consensus position on the treatment of pancreatic cancer during the COVID-19 pandemic".
Funder: DH | National Institute for Health Research (NIHR); doi: https://doi.org/10.13039/501100000272Funder: Cancer Research UK (CRUK); doi: https://doi.org/10.13039/50110000028
Vandetanib plus gemcitabine versus placebo plus gemcitabine in locally advanced or metastatic pancreatic carcinoma (ViP): a prospective, randomised, double-blind, multicentre phase 2 trial.
BACKGROUND: Erlotinib is an EGFR tyrosine kinase inhibitor that has shown a significant but only marginally improved median overall survival when combined with gemcitabine in patients with locally advanced and metastatic pancreatic cancer. Vandetanib is a novel tyrosine kinase inhibitor of VEGFR2, RET, and EGFR, all of which are in involved in the pathogenesis of pancreatic cancer. We investigated the clinical efficacy of vandetanib when used in combination with gemcitabine in patients with advanced pancreatic cancer. METHODS: The Vandetanib in Pancreatic Cancer (ViP) trial was a phase 2 double-blind, multicentre, randomised placebo-controlled trial in previously untreated adult patients (aged ≥18 years) diagnosed with locally advanced or metastatic carcinoma of the pancreas confirmed by cytology or histology. Patients had to have an Eastern Cooperative Oncology Group (ECOG) score of 0-2 and a documented life expectancy of at least 3 months. Patients were randomly assigned 1:1 to receive vandetanib plus gemcitabine (vandetanib group) or placebo plus gemcitabine (placebo group) according to pre-generated sequences produced on the principle of randomly permuted blocks with variable block sizes of two and four. Patients were stratified at randomisation by disease stage and ECOG performance status. All patients received gemcitabine 1000 mg/m(2) as a 30-min intravenous infusion, weekly, for 7 weeks followed by a 1-week break, followed by a cycle of 3 weeks of treatment with a 1-week break, until disease progression, and either oral vandetanib 300 mg per day once daily or matching placebo. Patients and investigators were masked to treatment assignment. The primary outcome measure was overall survival (defined as the difference in time between randomisation and death from any cause or the censor date) in the intention-to-treat population. This trial has been completed and the final results are reported. The study is registered at EudraCT, number 2007-004299-38, and ISRCTN, number ISRCTN96397434. FINDINGS: Patients were screened and enrolled between Oct 24, 2011, and Oct 7, 2013. Of 381 patients screened, 142 eligible patients were randomly assigned to treatment (72 to the vandetanib group and 70 to the placebo group). At database lock on July 15, 2015, at a median follow-up of 24·9 months (IQR 24·3 to not attainable), 131 patients had died: 70 (97%) of 72 in the vandetanib group and 61 (87%) of 70 in the placebo group. The median overall survival was 8·83 months (95% CI 7·11-11·58) in the vandetanib group and 8·95 months (6·55-11·74) in the placebo group (hazard ratio 1·21, 80·8% CI 0·95-1·53; log rank χ(2)1df 1·1, p=0·303). The most common grade 3-4 adverse events were neutropenia (35 [49%] of 72 patients in the vandetanib group vs 22 [31%] of 70 in the placebo group), thrombocytopenia (20 [28%] vs 16 [23%]), hypertension (nine [13%] vs 11 [16%]), leucopenia (12 [17%] vs 13 [19%]), and fatigue (17 [24%] vs 15 [21%]). No treatment-related deaths occurred during the study. INTERPRETATION: The addition of vandetanib to gemcitabine monotherapy did not improve overall survival in advanced pancreatic cancer. Tyrosine kinase inhibitors might still have potential in the treatment of pancreatic cancer but further development requires the identification of biomarkers to specifically identify responsive cancer subtypes. FUNDING: Cancer Research UK and AstraZeneca
Female Representation but Male Rule? Party Competition and the Political Glass Ceiling
A large literature has studied the context that affects womens numerical representation, but few have moved beyond numbers to study the drivers of a gender gap in political influence among elected politicians. Using panel data for the careers of 35.000 Swedish municipal politicians over six election cycles we first document the said gender gap. Women are substantially less likely to be re-elected for office, which is the most important pre-condition for obtaining influential appointments. Turing to the determinants we find that supply factors, primarily family responsibilities, explain some of this gap. Meanwhile, demand factors such as experience, age, education and income do not. Finding that competition between political parties closes the gap, we argue that a negative bias against women among party selectors thrives in contexts where meritocracy is not enforced. Positive correlations between competition and measures of competence for elected politicians of both genders further support this conclusion
Identification of common genetic risk variants for autism spectrum disorder
Autism spectrum disorder (ASD) is a highly heritable and heterogeneous group of neurodevelopmental phenotypes diagnosed in more than 1% of children. Common genetic variants contribute substantially to ASD susceptibility, but to date no individual variants have been robustly associated with ASD. With a marked sample-size increase from a unique Danish population resource, we report a genome-wide association meta-analysis of 18,381 individuals with ASD and 27,969 controls that identified five genome-wide-significant loci. Leveraging GWAS results from three phenotypes with significantly overlapping genetic architectures (schizophrenia, major depression, and educational attainment), we identified seven additional loci shared with other traits at equally strict significance levels. Dissecting the polygenic architecture, we found both quantitative and qualitative polygenic heterogeneity across ASD subtypes. These results highlight biological insights, particularly relating to neuronal function and corticogenesis, and establish that GWAS performed at scale will be much more productive in the near term in ASD
Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders
Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.Peer reviewe