An ‘“Electric Telegraph” of the Heart’: a community of feeling in the Victorian language of flowers

The publishing craze of the language of flowers anthologies spanned the length of the nineteenth century. As a cultural fad and popular form allied to the gift annual and the gift book, the language of flowers anthologies were well-known and prolific. The floriography of the flower 'vocabularies' became diffused and disseminated throughout the cultural imagination, yet, the anthologies were initially marketed at a female, middle-class, 'genteel' readership, with the broad aim of advancing the romantic endeavours of the reader. In this article, I ask whether there was a community of meaning, authorship and readership of the language of flowers. Was a community of feeling established through the ‘gifting’ process inherent within this genre? Might the books have been meaningful to a wider range of relationships beyond the proposed remit of romantic entanglement? Looking to case studies of personalised inscriptions, together with the introductory and prefatory contents of the books, I will consider whether the language of flowers had a broader appeal than might be assumed, investigating just how far floral meanings became embedded in notions of feeling. Finally, I will speculate about how we might consider feeling through flowers now, in light of the many perceived foibles and failings of this nineteenth-century genre

Making Gothic mountains: Everest and the EcoGothic

An ecoGothic Everest is arguably a contemporary phenomenon, a lived experience, where human perceptions of the mountain as both monstrous and desirable are enacted through its commodified and environmentally unstable condition. Climate-changeinduced alterations on Everest are exacerbated by commercialism: melting glaciers, thickening air, and corrupted waters as corpses and human waste litter the mountainside. Meanwhile, there are accusations that Dark Tourism has found a home on the crowning peak of ‘the roof of the world,’ as would-be summiteers photograph bodies acting as route-markers, and droves of hopefuls pay large sums to swarm upon the slopes in their summit bids, regardless of numerous fatal tragedies fuelling the criticism of ‘bagging’ this most prestigious of peaks. Despite the contemporary nature of the ecoGothic on Everest, its manifestation is born out of a historical literary imagination which created the iconography of the Gothic mountain, alongside the rise of mountaineering and its accompanying literature. This article considers how the Gothic aesthetic has influenced mountaineering and in fact contributed to the creation and maintenance of an ecoGothic Everest. The Gothic terror of Everest today is not generated primarily through fictional reimaginings of the untameable wilderness, but through encountering the human-made degradation of the peak, consolidating the mountain as a site of lived ecoGothic in current times. By focalising Everest through the ecoGothic, George Mallory’s famous statement of intent to summit, ‘because it is there,’ no longer seems a legitimate motivation behind so-called human mastery of the mountain

Effects of weight loss interventions for adults who are obese on mortality, cardiovascular disease and cancer : a systematic review and meta-analysis

We thank Associate Professor Andrew Grey for helping to resolve discrepancies in data extraction and interpretation for cardiovascular events and cancer events. We thank trialists from 16 studies for clarifying or providing additional information for this review [Andrews 2011, Aveyard 2016, Bennett 2012, de Vos 2014, Finnish Diabetes Prevention Study 2009, Goodwin 2014, Green 2015, Horie 2016, Hunt (FFIT) 2014, Katula 2013, Li (Da Qing) 2014, Logue 2005, Ma 2013, O’Neil 2016, Rejeski (CLIP) 2011, Uusitupa 1993] and also others who provided information, but their trials were later found not to fulfil our inclusion criteria. Funding: The Health Services Research Unit is funded by the Chief Scientist Office of the Scottish Government Health and Social Care Directorate.Peer reviewedPublisher PD

Offset Banking in New Zealand: towards sustainable development, with insight from international models

Biodiversity loss is an important issue for New Zealand: for the domestic environment, economy and society, but also for New Zealand as a member of the international community. Biodiversity offset banking is making an important contribution to addressing such issues in a number of countries around the world. Developing the ability to participate and take advantage of possible benefits requires comprehensively understanding both the fundamental principles and varying concepts, and supports the analysis necessary for New Zealand to progress towards offset banking. New Zealand can learn much from observing and investigating overseas models and use them as valuable templates. California and New South Wales provide examples of potential policies and frameworks (both economic and social) to establish and operate successful offset banking systems. Discussions of offset banking, both in theory and practice, frequently concern the potential failings of the system. These issues can be conceptualised as various forms of risk. Considering offset banking as sustainable development, this thesis addresses such risks to reflect the tripartite biological, financial and social framework of sustainable development. Biologically, risk is in the potential biodiversity outcomes are inadequate, unexpected or undesirable. Scientific uncertainty underlies this, both inherently and from the limits of current scientific disciplines. Through expanding scientific knowledge and experience, measures for reducing or accommodating the risk of uncertainty are emerging. Financial risk represents concerns that individual banks may lack the monetary support to achieve the specific biodiversity conservation required for the site. Also the system of interacting banks, bankers and traders may fail to produce financial outcomes that support effective and efficient biodiversity conservation over the breath of the scheme. Social risk lies in the potential that societies’ individuals conduct themselves in ways that conflict with achieving biodiversity conservation through malfeasance or negligence. Additionally, there is social risk that an offset banking system fails to respond appropriately to broader society and human, such as equity and intergenerational justice. Here, deliberating these risks is primary to appreciating how design elements and emergent properties minimize risks. Given comprehensive understanding, components of a system can be designed and allow informed policy, regulations and rules to offer successful risk mitigation. For this reason policy, rules and regulations observed within California and New South Wales helps to discuss this and establish guidance for New Zealand offset banking design to draw upon. Californian systems are achieving promising conservation and continued growth; New South Wales’ Biobanking scheme is robustly designed and in its early stages. Each contrasts in design and carries varying criticisms. California has been observed as potentially shortcoming biologically, whereas New South Wales Biobanking has been questioned based on the strength and character of its economic underpinnings. In addition to these considerations, New Zealand has significant societal perspectives to incorporate given current popular, socio-democratic conservation modus operandi. Identifying the three forms of risk present highlights the importance of allocating appropriate consideration and expertise to the biological, economic and social components of offset banking. Successful sustainable development, biodiversity conservation and risk mitigation may be achieved through designing mechanisms, regulations and governing policy for offset banking. New Zealand may therefore expand the success and application of current offsetting by taking guidance from examples and analysis presented here

School, peer and family relationships and adolescent substance use, subjective wellbeing and mental health symptoms in Wales: a cross sectional study

Positive relationships with family, friends and school staff are consistently linked with health and wellbeing during adolescence, though fewer studies explore how these micro-systems interact to influence adolescent health. This study tests the independent and interacting roles of family, peer and school relationships in predicting substance use, subjective wellbeing and mental health symptoms among 11–16 year olds in Wales. It presents cross-sectional analyses of the 2013 Health Behaviour in School-aged Children survey, completed by 9055 young people aged 11–16 years. Multilevel logistic regression analyses are used to test associations of family communication, family support, relationships with school staff, school peer connectedness, and support from friends, with tobacco use, cannabis use, alcohol use, subjective wellbeing and mental health symptoms. Positive relationships with family and school staff were consistently associated with better outcomes. Support from friends was associated with higher use of all substances, while higher school peer connectedness was associated with better subjective wellbeing and mental health. Better relationships with school staff were most strongly associated with positive subjective wellbeing, and fewer mental health symptoms where pupils reported less family support. Support from friends was associated with higher cannabis use and worse mental health among pupils with lower family support. Relationships with family and school staff may be important in protecting young people against substance use, and improving wellbeing and mental health. Interventions focused on student-staff relationships may be important for young people with less family support. Interventions based on peer support should be mindful of potential harmful effects for pupils with less support from family

Systematic review of reduced therapy regimens for children with low risk febrile neutropenia

PURPOSE: Reduced intensity therapy for children with low-risk febrile neutropenia may provide benefits to both patients and the health service. We have explored the safety of these regimens and the effect of timing of discharge. METHODS: Multiple electronic databases, conference abstracts and reference lists were searched. Randomised controlled trials (RCT) and prospective observational cohorts examining the location of therapy and/or the route of administration of antibiotics in people younger than 18 years who developed low-risk febrile neutropenia following treatment for cancer were included. Meta-analysis using a random effects model was conducted. I (2) assessed statistical heterogeneity not due to chance. Registration: PROSPERO (CRD42014005817). RESULTS: Thirty-seven studies involving 3205 episodes of febrile neutropenia were included; 13 RCTs and 24 prospective observational cohorts. Four safety events (two deaths, two intensive care admissions) occurred. In the RCTs, the odds ratio for treatment failure (persistence, worsening or recurrence of fever/infecting organisms, antibiotic modification, new infections, re-admission, admission to critical care or death) with outpatient treatment was 0.98 (95% confidence interval (95%CI) 0.44-2.19, I (2) = 0 %) and with oral treatment was 1.05 (95%CI 0.74-1.48, I (2) = 0 %). The estimated risk of failure using outpatient therapy from all prospective data pooled was 11.2 % (95%CI 9.7-12.8 %, I (2) = 77.2 %) and using oral antibiotics was 10.5 % (95%CI 8.9-12.3 %, I (2) = 78.3 %). The risk of failure was higher when reduced intensity therapies were used immediately after assessment, with lower rates when these were introduced after 48 hours. CONCLUSIONS: Reduced intensity therapy for specified groups is safe with low rates of treatment failure. Services should consider how these can be acceptably implemented

Meta-ethnography of experiences of early discharge, with a focus on paediatric febrile neutropenia

PURPOSE (STATING THE MAIN PURPOSES AND RESEARCH QUESTION): Many children have no significant sequelae of febrile neutropenia. A systematic review of clinical studies demonstrated patients at low risk of septic complications can be safely treated as outpatients using oral antibiotics with low rates of treatment failure. Introducing earlier discharge may improve quality of life, reduce hospital acquired infection and reduce healthcare service pressures. However, the review raised concerns that this might not be acceptable to patients, families and healthcare professionals. METHODS: This qualitative synthesis explored experiences of early discharge in paediatric febrile neutropenia, including reports from studies of adult febrile neutropenia and from other paediatric conditions. Systematic literature searching preceded meta-ethnographic analysis, including reading the studies and determining relationships between studies, translation of studies and synthesis of these translations. RESULTS: Nine papers were included. The overarching experience of early discharge is that decision-making is complex and difficult and influenced by fear, timing and resources. From this background, we identified two distinct themes. First, participants struggled with practical consequences of treatment regimens, namely childcare, finances and follow-up. A second theme identified social and emotional issues, including isolation, relational and environmental challenges. Linking these, participants considered continuity of care and the need for information important. CONCLUSIONS: Trust and confidence appeared interdependent with resources available to families-both are required to manage early discharge. Socially informed resilience is relevant to facilitating successful discharge strategies. Interventions which foster resilience may mediate the ability and inclination of families to accept early discharge. Services have an important role in recognising and enhancing resilience

Prokineticin 1 signaling and gene regulation in early human pregnancy

Prokineticin 1 (PROK1) is a recently described protein with a wide range of functions including tissue-specific angiogenesis, modulation of inflammatory responses, and regulation of hematopoiesis. The objective of this study was to investigate the role of PROK1 and prokineticin receptor 1 (PROKR1) in human endometrium during early pregnancy. PROK1 and PROKR1 expression is significantly elevated in first-trimester decidua, compared with nonpregnant endometrium. Expression of PROK1 and PROKR1 was localized in glandular epithelial and various cellular compartments within the stroma. To investigate the signaling pathways and target genes activated by PROK1, we generated an endometrial epithelial cell line stably expressing PROKR1 (Ishikawa PROKR1 cells). PROK1-PROKR1 interaction induced inositol phosphate mobilization and sequential phosphorylation of c-Src, epidermal growth factor receptor, and ERK 1/2. Gene microarray analysis on RNA extracted from Ishikawa PROKR1 cells treated with 40 nm PROK1 for 8 h revealed 49 genes to be differentially regulated. A number of these genes, including cyclooxygenase (COX)-2, leukemia inhibitory factor, IL-6, IL-8, and IL-11 are regulated in the endometrium during implantation and early pregnancy. We subsequently investigated the effect of PROK1 on expression of COX-2 in Ishikawa PROKR1 cells and first-trimester decidua. COX-2 mRNA and protein expression, and prostaglandin synthesis, were elevated in response to treatment with PROK1. Moreover, expression of COX-2 by PROK1 was dependent on activation of the Gq-phospholipase C-β-cSrc-epidermal growth factor receptor-MAPK/ERK kinase pathway. These data demonstrate that PROK1 and PROKR1 expression is elevated in human decidua during early pregnancy and that PROK1-PROKR1 interaction regulates expression of a host of implantation-related genes

Genomic correlates of glatiramer acetate adverse cardiovascular effects lead to a novel locus mediating coronary risk

Glatiramer acetate is used therapeutically in multiple sclerosis but also known for adverse effects including elevated coronary artery disease (CAD) risk. The mechanisms underlying the cardiovascular side effects of the medication are unclear. Here, we made use of the chromosomal variation in the genes that are known to be affected by glatiramer treatment. Focusing on genes and gene products reported by drug-gene interaction database to interact with glatiramer acetate we explored a large meta-analysis on CAD genome-wide association studies aiming firstly, to investigate whether variants in these genes also affect cardiovascular risk and secondly, to identify new CAD risk genes. We traced association signals in a 200-kb region around genomic positions of genes interacting with glatiramer in up to 60 801 CAD cases and 123 504 controls. We validated the identified association in additional 21 934 CAD cases and 76 087 controls. We identified three new CAD risk alleles within the TGFB1 region on chromosome 19 that independently affect CAD risk. The lead SNP rs12459996 was genome-wide significantly associated with CAD in the extended meta-analysis (odds ratio 1.09, p = 1.58×10-12). The other two SNPs at the locus were not in linkage disequilibrium with the lead SNP and by a conditional analysis showed p-values of 4.05 × 10-10 and 2.21 × 10-6. Thus, studying genes reported to interact with glatiramer acetate we identified genetic variants that concordantly with the drug increase the risk of CAD. Of these, TGFB1 displayed signal for association. Indeed, the gene has been associated with CAD previously in both in vivo and in vitro studies. Here we establish genome-wide significant association with CAD in large human samples.This work was supported by grants from the Fondation Leducq (CADgenomics: Understanding CAD Genes, 12CVD02), the German Federal Ministry of Education and Research (BMBF) within the framework of the e:Med research and funding concept (e:AtheroSysMed, grant 01ZX1313A-2014 and SysInflame, grant 01ZX1306A), and the European Union Seventh Framework Programme FP7/2007-2013 under grant agreement no HEALTH-F2-2013-601456 (CVgenes-at-target). Further grants were received from the DFG as part of the Sonderforschungsbereich CRC 1123 (B2). T.K. was supported by a DZHK Rotation Grant. I.B. was supported by the Deutsche Forschungsgemeinschaft (DFG) cluster of excellence ‘Inflammation at Interfaces’. F.W.A. is supported by a Dekker scholarship-Junior Staff Member 2014T001 - Netherlands Heart Foundation and UCL Hospitals NIHR Biomedical Research Centre

Association of the PHACTR1/EDN1 genetic locus with spontaneous coronary artery dissection

Background: Spontaneous coronary artery dissection (SCAD) is an increasingly recognized cause of acute coronary syndromes (ACS) afflicting predominantly younger to middle-aged women. Observational studies have reported a high prevalence of extracoronary vascular anomalies, especially fibromuscular dysplasia (FMD) and a low prevalence of coincidental cases of atherosclerosis. PHACTR1/EDN1 is a genetic risk locus for several vascular diseases, including FMD and coronary artery disease, with the putative causal noncoding variant at the rs9349379 locus acting as a potential enhancer for the endothelin-1 (EDN1) gene. Objectives: This study sought to test the association between the rs9349379 genotype and SCAD. Methods: Results from case control studies from France, United Kingdom, United States, and Australia were analyzed to test the association with SCAD risk, including age at first event, pregnancy-associated SCAD (P-SCAD), and recurrent SCAD. Results: The previously reported risk allele for FMD (rs9349379-A) was associated with a higher risk of SCAD in all studies. In a meta-analysis of 1,055 SCAD patients and 7,190 controls, the odds ratio (OR) was 1.67 (95% confidence interval [CI]: 1.50 to 1.86) per copy of rs9349379-A. In a subset of 491 SCAD patients, the OR estimate was found to be higher for the association with SCAD in patients without FMD (OR: 1.89; 95% CI: 1.53 to 2.33) than in SCAD cases with FMD (OR: 1.60; 95% CI: 1.28 to 1.99). There was no effect of genotype on age at first event, P-SCAD, or recurrence. Conclusions: The first genetic risk factor for SCAD was identified in the largest study conducted to date for this condition. This genetic link may contribute to the clinical overlap between SCAD and FMD