Sources of uncertainty in future projections of the carbon cycle

This is the final version of the article. Available from the publisher via the DOI in this record.The inclusion of carbon cycle processes within CMIP5 Earth System Models provides the opportunity to explore the relative importance of differences in scenario and climate model representation to future land and ocean carbon fluxes. A two-way ANOVA approach was used to quantify the variability owing to differences between scenarios and between climate models at different lead times. For global ocean carbon fluxes, the variance attributed to differences between Representative Concentration Pathway scenarios exceeds the variance attributed to differences between climate models by around 2025, completely dominating by 2100. This contrasts with global land carbon fluxes, where the variance attributed to differences between climate models continues to dominate beyond 2100. This suggests that modelled processes that determine ocean fluxes are currently better constrained than those of land fluxes, thus we can be more confident in linking different future socio-economic pathways to consequences of ocean carbon uptake than for land carbon uptake. The apparent agreement in atmosphere-ocean carbon fluxes, globally, masks strong climate model differences at a regional level. The North Atlantic and Southern Ocean are key regions, where differences in modelled processes represent an important source of variability in projected regional fluxesMOHC authors were supported by the Joint DECC / Defra Met Office Hadley Centre Cli- mate Programme (GA01101). SY was supported by the Hong Kong Polytechnic University grant “Bayesian Modelling for Quantifying Uncertainty in Climate Predictions” (1-ZV9Z). We acknowl- edge use of R software package (R Core Team 2013). We acknowledge the World Climate Re- search Programme’s Working Group on Coupled Modelling, which is responsible for CMIP and we thank the climate modelling groups for providing their GCM output (listed in Table 1). Support of this dataset was provided by the Office of Science, U.S. Department of Energy

The relationship timeline: A method for the study of shared lived experiences in relational contexts

Lifeline methods—graphic illustrations of the pathways of lived experience traveled by individuals from birth to anticipated death—have been useful in the study of lived experience. Existing lifeline methods and research focus on the individual experience; absent from this literature are the collective experiences of those in intimate relationships. In this paper, based on our research with 120 same-sex couples, we present a method to allow for the joint creation of relationship timelines, which serve as the basis for eliciting dyadic data in multiple forms: graphic representations of relationship development through couples’ creation of a timeline of key events and periods; qualitative narratives of couples’ shared experiences; and quantitative ratings of significant events and periods in their lives together. Lessons learned from the application of this Relationship Timeline Method are discussed, as are implications for future study of shared lived experiences in relational contexts

Anthropometric indices of Gambian children after one or three annual rounds of mass drug administration with azithromycin for trachoma control.

BACKGROUND: Mass drug administration (MDA) with azithromycin, carried out for the control of blinding trachoma, has been linked to reduced mortality in children. While the mechanism behind this reduction is unclear, it may be due, in part, to improved nutritional status via a potential reduction in the community burden of infectious disease. To determine whether MDA with azithromycin improves anthropometric indices at the community level, we measured the heights and weights of children aged 1 to 4 years in communities where one (single MDA arm) or three annual rounds (annual MDA arm) of azithromycin had been distributed. METHODS: Data collection took place three years after treatment in the single MDA arm and one year after the final round of treatment in the annual MDA arm. Mean height-for-age, weight-for-age and weight-for-height z scores were compared between treatment arms. RESULTS: No significant differences in mean height-for-age, weight-for-age or weight-for-height z scores were found between the annual MDA and single MDA arms, nor was there a significant reduction in prevalence of stunting, wasting or underweight between arms. CONCLUSIONS: Our data do not provide evidence that community MDA with azithromycin improved anthropometric outcomes of children in The Gambia. This may suggest reductions in mortality associated with azithromycin MDA are due to a mechanism other than improved nutritional status

Congestive Heart Failure Leads to Prolongation of the PR Interval and Atrioventricular Junction Enlargement and Ion Channel Remodelling in the Rabbit.

Heart failure is a major killer worldwide. Atrioventricular conduction block is common in heart failure; it is associated with worse outcomes and can lead to syncope and bradycardic death. We examine the effect of heart failure on anatomical and ion channel remodelling in the rabbit atrioventricular junction (AVJ). Heart failure was induced in New Zealand rabbits by disruption of the aortic valve and banding of the abdominal aorta resulting in volume and pressure overload. Laser micro-dissection and real-time polymerase chain reaction (RT-PCR) were employed to investigate the effects of heart failure on ion channel remodelling in four regions of the rabbit AVJ and in septal tissues. Investigation of the AVJ anatomy was performed using micro-computed tomography (micro-CT). Heart failure animals developed first degree heart block. Heart failure caused ventricular myocardial volume increase with a 35% elongation of the AVJ. There was downregulation of HCN1 and Cx43 mRNA transcripts across all regions and downregulation of Cav1.3 in the transitional tissue. Cx40 mRNA was significantly downregulated in the atrial septum and AVJ tissues but not in the ventricular septum. mRNA abundance for ANP, CLCN2 and Navβ1 was increased with heart failure; Nav1.1 was increased in the inferior nodal extension/compact node area. Heart failure in the rabbit leads to prolongation of the PR interval and this is accompanied by downregulation of HCN1, Cav1.3, Cx40 and Cx43 mRNAs and anatomical enlargement of the entire heart and AVJ

Pharmacogenomic and structural analysis of constitutive G-protein coupled receptor activity

Premi a l'excel·lència investigadora. Àmbit de les Ciències de la Salut. 2008G-protein coupled receptors (GPCRs) respond to a chemically diverse plethora of signal transduction molecules. The notion that GPCRs also signal without an external chemical trigger, i.e. in a constitutive or spontaneous manner, resulted in a paradigm shift in the field of GPCR pharmacology. With the recognition of constitutive GPCR activity and the fact that GPCR binding and signaling can be strongly affected by a single point mutation, GPCR pharmacogenomics obtained a lot of attention. For a variety of GPCRs, point mutations have been convincingly linked to human disease. Mutations within conserved motifs, known to be involved in GPCR activation, might explain the properties of some naturally occurring constitutively active GPCR variants linked to disease. A brief history historical introduction to the present concept of constitutive receptor activity is given and the pharmacogenomic and the structural aspects of constitutive receptor activity are described

Quantitative transrectal shear wave elastography undergoing salvage extraperitoneal laparoscopic radical prostatectomy following failed radiotherapy

Background: To evaluate pre-surgical quantitative transrectal shear wave elastography (SWE) in the detection and characterisation of radioresistant prostate cancer.Methods: Twelve men with recurrent prostate cancer following external beam radiotherapy were included in a prospective protocol-driven study. All underwent MR imaging and quantitative shear wave elastographic assessment of recurrent disease prior to salvage laparoscopic radical prostatectomy procedures. Images were used to construct 3D mold printing and histopathological processing of surgical specimen. Statistical analyses including ROC were generated using software programmes.Results: There were 48 cancer foci identified on final histopathology using patient-specific mold-based approach in 12 patients. Mean number of lesion was 3.4 (range 2–4). Quantitative transrectal SWE showed a sensitivity and specificity 0.77 (95% CI 0.627–0.880) and 0.82 (95% CI 0.642–0.942), respectively. The diagnostic accuracy increased with increasing size of the lesions with overall AUC of 0.89.Conclusions: In our series, quantitative transrectal SWE showed a good diagnostic accuracy in the detection and characterisation of recurrent prostate cancer following failed radiotherapy treatment. These findings may help in targeting biopsies or future focal treatment options

Accounting Problems Under the Excess Profits Tax

DNA vaccines based on subunits from pathogens have several advantages over other vaccine strategies. DNA vaccines can easily be modified, they show good safety profiles, are stable and inexpensive to produce, and the immune response can be focused to the antigen of interest. However, the immunogenicity of DNA vaccines which is generally quite low needs to be improved. Electroporation and co-delivery of genetically encoded immune adjuvants are two strategies aiming at increasing the efficacy of DNA vaccines. Here, we have examined whether targeting to antigen-presenting cells (APC) could increase the immune response to surface envelope glycoprotein (Env) gp120 from Human Immunodeficiency Virus type 1 (HIV- 1). To target APC, we utilized a homodimeric vaccine format denoted vaccibody, which enables covalent fusion of gp120 to molecules that can target APC. Two molecules were tested for their efficiency as targeting units: the antibody-derived single chain Fragment variable (scFv) specific for the major histocompatilibility complex (MHC) class II I-E molecules, and the CC chemokine ligand 3 (CCL3). The vaccines were delivered as DNA into muscle of mice with or without electroporation. Targeting of gp120 to MHC class II molecules induced antibodies that neutralized HIV-1 and that persisted for more than a year after one single immunization with electroporation. Targeting by CCL3 significantly increased the number of HIV-1 gp120-reactive CD8(+) T cells compared to non-targeted vaccines and gp120 delivered alone in the absence of electroporation. The data suggest that chemokines are promising molecular adjuvants because small amounts can attract immune cells and promote immune responses without advanced equipment such as electroporation.Funding Agencies|Research Council of Norway; Odd Fellow</p

Asthma prescribing, ethnicity and risk of hospital admission: an analysis of 35,864 linked primary and secondary care records in East London

This work was partly supported by funding from the Asthma UK Centre for Applied Research

Best bang for your buck: Considerations for cost-efficiency in knowledge co-production

Knowledge co-production is a key strategy of collaborative engagement between research and management to achieve better outcomes. Whereas the principles of knowledge co-production in support of evidence-informed policy-making are increasingly understood, our understanding of its cost-efficiency - putting benefits in relation to its cost - is in its infancy. Here, we approach this gap by exploring the key considerations for ensuring that the benefits of co-production processes outweigh the significant direct and indirect costs they can incur. We conceptualise a relationship between the costs and benefits of co-production, consider preconditions that affect those costs and benefits, and outline options for improving the cost-benefit relationship. Specifically, we explore how to maximise co-production efficiency for key principles underpinning effective knowledge co-production (context-based, pluralistic, goal-oriented, interactive) and illustrate this with a hypothetical case study of co-production for the use and management of an emerging small-scale fishery. To this end, we conclude by providing a series of guiding questions that practitioners of co-production can use to help ensure that the benefits outweigh the costs. Our results provide researchers and practitioners with improved understanding of the costs and benefits of co-production and encourage the consideration of cost-efficiency in the planning of participatory research. Further, by considering the costs and benefits of co-production processes we provide critical insights into how to ensure effective and efficient science-policy engagement where expectations might exceed limited resources. This includes enabling more transparent and accountable funding and engagement decisions while engaging multiple context-specific streams of policy-relevant knowledge for evidence-informed policy