Paper Session III-B - Space Exploration Initiative Logistics Support - Lessons from the DoD

A mission as complex as the Space Exploration Initiative (SEI) cannot succeed without adhering to sound principles in the planning, development, and execution of logistics support for the exploration crews and their mission equipment. While much attention will focus upon the development of reliable, robust, heavy lift launch vehicles, and scientific, technological breakthroughs for SEI, of equal concern is the supportability and sustainability of systems designed for mission operations and crew life support on the lunar and Martian surfaces

De novo assembly of red clover transcriptome based on RNA-Seq data provides insight into drought response, gene discovery and marker identification

Background Red clover (Trifolium pratense L.) is a versatile forage crop legume, which can tolerate a variety of soils and is suitable for silage production for winter feed and for grazing. It is one of the most important forage legumes in temperate livestock agriculture. Its beneficial attributes include ability to fix nitrogen, improve soil and provide protein rich animal feed. It is however, a short-lived perennial providing good biomass yield for two or three years. Improved persistency is thus a major breeding target. Better water-stress tolerance is one of the key factors influencing persistency, but little is known about how red clover tolerates water stress. Results Plants from a full sib mapping family were used in a drought experiment, in which the growth rate and relative water content (RWC) identified two pools of ten plants contrasting in their tolerance to drought. Key metabolites were measured and RNA-Seq analysis was carried out on four bulked samples: the two pools sampled before and after drought. Massively parallel sequencing was used to analyse the bulked RNA samples. A de novo transcriptome reconstruction based on the RNA-Seq data was made, resulting in 45181 contigs, representing ‘transcript tags’. These transcript tags were annotated with gene ontology (GO) terms. One of the most striking results from the expression analysis was that the drought sensitive plants were characterised by having approximately twice the number of differentially expressed transcript tags than the tolerant plants after drought. This difference was evident in most of the major GO terms. Before onset of drought the sensitive plants overexpressed a number of genes annotated as senescence-related. Furthermore, the concentration of three metabolites, particularly pinitol, but also proline and malate increased in leaves after drought stress. Conclusions This de novo assembly of a red clover transcriptome from leaf material of droughted and non-droughted plants provides a rich source for gene identification, single nucleotide polymorphisms (SNP) and short sequence repeats (SSR). Comparison of gene expression levels between pools and treatments identified candidate genes for further analysis of the genetic basis of drought tolerance in red clover

Identification of novel loci associated with hip shape:a meta-analysis of genome-wide association studies

This study was funded by Arthritis Research UK project grant 20244, which also provided salary funding for DB and CVG. LP works in the MRC Integrative Epidemiology Unit, a UK MRC‐funded unit (MC_ UU_ 12013/4 & MC_UU_12013/5). ALSPAC: We are extremely grateful to all the families who took part in this study, the midwives for their help in recruiting them, and the whole ALSPAC team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists, and nurses. ALSPAC data collection was supported by the Wellcome Trust (grants WT092830M; WT088806; WT102215/2/13/2), UK Medical Research Council (G1001357), and University of Bristol. The UK Medical Research Council and the Wellcome Trust (102215/2/13/2) and the University of Bristol provide core support for ALSPAC. Framingham Heart Study: The Framingham Osteoporosis Study is supported by grants from the National Institute of Arthritis, Musculoskeletal, and Skin Diseases and the National Institute on Aging (R01 AR41398, R01 AR 061162, R01 AR050066, and R01 AR061445). The analyses reflect intellectual input and resource development from the Framingham Heart Study investigators participating in the SNP Health Association Resource project. The Framingham Heart Study of the National Heart, Lung, and Blood Institute of the National Institutes of Health and Boston University School of Medicine were supported by the National Heart, Lung, and Blood Institute's Framingham Heart Study (N01‐HC‐25195) and its contract with Affymetrix, Inc., for genotyping services (N02‐HL‐6‐4278). Analyses reflect intellectual input and resource development from the Framingham Heart Study investigators participating in the SNP Health Association Resource (SHARe) project. A portion of this research was conducted using the Linux Cluster for Genetic Analysis (LinGA‐II) funded by the Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center. DK was also supported by Israel Science Foundation grant #1283/14. TDC and DR thank Dr Claire Reardon and the entire Harvard University Bauer Core facility for assistance with ATAC‐seq next generation sequencing. This work was funded in part by the Harvard University Milton Fund, NSF (BCS‐1518596), and NIH NIAMS (1R01AR070139‐01A1) to TDC. MrOS: The Osteoporotic Fractures in Men (MrOS) Study is supported by National Institutes of Health funding. The following institutes provide support: the National Institute on Aging (NIA), the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the National Center for Advancing Translational Sciences (NCATS), and NIH Roadmap for Medical Research under the following grant numbers: U01 AG027810, U01 AG042124, U01 AG042139, U01 AG042140, U01 AG042143, U01 AG042145, U01 AG042168, U01 AR066160, and UL1 TR000128. The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) provides funding for the MrOS ancillary study “Replication of candidate gene associations and bone strength phenotype in MrOS” under the grant number R01 AR051124. The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) provides funding for the MrOS ancillary study “GWAS in MrOS and SOF” under the grant number RC2 AR058973. SOF: The Study of Osteoporotic Fractures (SOF) is supported by National Institutes of Health funding. The National Institute on Aging (NIA) provides support under the following grant numbers: R01 AG005407, R01 AR35582, R01 AR35583, R01 AR35584, R01 AG005394, R01 AG027574, and R01 AG027576. TwinsUK: The study was funded by the Wellcome Trust; European Community's Seventh Framework Programme (FP7/2007‐2013). The study also receives support from the National Institute for Health Research (NIHR)‐funded BioResource, Clinical Research Facility, and Biomedical Research Centre based at Guy's and St Thomas’ NHS Foundation Trust in partnership with King's College London. SNP genotyping was performed by The Wellcome Trust Sanger Institute and National Eye Institute via NIH/CIDR. This study was also supported by the Australian National Health and Medical Research Council (project grants 1048216 and 1127156), the Sir Charles Gairdner Hospital RAC (SGW), and the iVEC/Pawsey Supercomputing Centre (project grants Pawsey0162 and Director2025 [SGW]). The salary of BHM was supported by a Raine Medical Research Foundation Priming Grant. The Umeå Fracture and Osteoporosis Study (UFO) is supported by the Swedish Research Council (K20006‐72X‐20155013), the Swedish Sports Research Council (87/06), the Swedish Society of Medicine, the Kempe‐Foundation (JCK‐1021), and by grants from the Medical Faculty of Umeå Unviersity (ALFVLL:968:22‐2005, ALFVL:‐937‐2006, ALFVLL:223:11‐2007, and ALFVLL:78151‐2009) and from the county council of Västerbotten (Spjutspetsanslag VLL:159:33‐2007). This publication is the work of the authors and does not necessarily reflect the views of any funders. None of the funders had any influence on data collection, analysis, interpretation of the results, or writing of the paper. DB will serve as the guarantor of the paper. Authors’ roles: Study conception and design: DAB, JSG, RMA, LP, DK, and JHT. Data collection: DJ, DPK, ESO, SRC, NEL, BHM, FMKW, JBR, SGW, TDC, BGF, DAL, CO, and UP‐L. Data analysis: DAB, DSE, FKK, JSG, FRS, CVG, RJB, RMA, SGW, EG, TDC, DR, and TB. Data interpretation: JSG, RMA, TDC, DR, DME, LP, DK, and JHT. Drafting manuscript: DAB and JHT. Revising manuscript content: JHT. All authors approved the final version of manuscript. DAB takes responsibility for the integrity of the data analysis.Peer reviewedPublisher PD

Narrative theology in Religious Education

This is an Author's Accepted Manuscript of an article published in British Journal of Religious Education, 20 March 2013. Copyright © 2013 Taylor & Francis. Available online at: http://www.tandfonline.com/10.1080/01416200.2013.785931This article advocates a pedagogy of Religious Education (RE) based upon a narratival framework informed by both narrative theology and narrative philosophy. Drawing on the work of narrative theologians including Stanley Hauerwas, the article outlines the nature of the framework, describes the four phases of learning that comprise the pedagogy, and explains how such an approach can overcome existing difficulties in how biblical texts are handled within RE. Working from the narrative assumption that individuals and communities are formed by reading, sharing and living within stories, it suggests that the pedagogy might encourage pupils to think about how the lives of Christians are shaped by their interpretations of biblical narratives, to offer their own interpretations of biblical and other texts, and to consider the stories – religious, non-religious or both – which shape their own lives. In so doing, the article moves away from a ‘proof-texting’ approach to the Bible towards one in which pupils are enabled to think about the significance of biblical narratives for both Christians and themselves

Prevalence of chronic cough, its risk factors and population attributable risk in the Burden of Obstructive Lung Disease (BOLD) study: a multinational cross-sectional study

Background: Chronic cough is a common respiratory symptom with an impact on daily activities and quality of life. Global prevalence data are scarce and derive mainly from European and Asian countries and studies with outcomes other than chronic cough. In this study, we aimed to estimate the prevalence of chronic cough across a large number of study sites as well as to identify its main risk factors using a standardized protocol and definition. Methods: We analyzed cross-sectional data from 33,983 adults (≥40 years), recruited between Jan 2, 2003 and Dec 26, 2016, in 41 sites (34 countries) from the Burden of Obstructive Lung Disease (BOLD) study. We estimated the prevalence of chronic cough for each site accounting for sampling design. To identify risk factors, we conducted multivariable logistic regression analysis within each site and then pooled estimates using random-effects meta-analysis. We also calculated the population-attributable risk (PAR) associated with each of the identified risk factors. Findings: The prevalence of chronic cough varied from 3% in India (rural Pune) to 24% in the United States of America (Lexington, KY). Chronic cough was more common among females, both current and passive smokers, those working in a dusty job, those with a history of tuberculosis, those who were obese, those with a low level of education, and those with hypertension or airflow limitation. The most influential risk factors were current smoking and working in a dusty job. Interpretation: Our findings suggested that the prevalence of chronic cough varies widely across sites in different world regions. Cigarette smoking and exposure to dust in the workplace are its major risk factors.info:eu-repo/semantics/publishedVersio

Association of respiratory symptoms and lung function with occupation in the multinational Burden of Obstructive Lung Disease (BOLD) study

Background Chronic obstructive pulmonary disease has been associated with exposures in the workplace. We aimed to assess the association of respiratory symptoms and lung function with occupation in the Burden of Obstructive Lung Disease study. Methods We analysed cross-sectional data from 28 823 adults (≥40 years) in 34 countries. We considered 11 occupations and grouped them by likelihood of exposure to organic dusts, inorganic dusts and fumes. The association of chronic cough, chronic phlegm, wheeze, dyspnoea, forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1)/FVC with occupation was assessed, per study site, using multivariable regression. These estimates were then meta-analysed. Sensitivity analyses explored differences between sexes and gross national income. Results Overall, working in settings with potentially high exposure to dusts or fumes was associated with respiratory symptoms but not lung function differences. The most common occupation was farming. Compared to people not working in any of the 11 considered occupations, those who were farmers for ≥20 years were more likely to have chronic cough (OR 1.52, 95% CI 1.19–1.94), wheeze (OR 1.37, 95% CI 1.16–1.63) and dyspnoea (OR 1.83, 95% CI 1.53–2.20), but not lower FVC (β=0.02 L, 95% CI −0.02–0.06 L) or lower FEV1/FVC (β=0.04%, 95% CI −0.49–0.58%). Some findings differed by sex and gross national income. Conclusion At a population level, the occupational exposures considered in this study do not appear to be major determinants of differences in lung function, although they are associated with more respiratory symptoms. Because not all work settings were included in this study, respiratory surveillance should still be encouraged among high-risk dusty and fume job workers, especially in low- and middle-income countries.publishedVersio

Prevalence of chronic cough, its risk factors and population attributable risk in the Burden of Obstructive Lung Disease (BOLD) study: a multinational cross-sectional study

© 2024 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)Background: Chronic cough is a common respiratory symptom with an impact on daily activities and quality of life. Global prevalence data are scarce and derive mainly from European and Asian countries and studies with outcomes other than chronic cough. In this study, we aimed to estimate the prevalence of chronic cough across a large number of study sites as well as to identify its main risk factors using a standardised protocol and definition. Methods: We analysed cross-sectional data from 33,983 adults (≥40 years), recruited between Jan 2, 2003 and Dec 26, 2016, in 41 sites (34 countries) from the Burden of Obstructive Lung Disease (BOLD) study. We estimated the prevalence of chronic cough for each site accounting for sampling design. To identify risk factors, we conducted multivariable logistic regression analysis within each site and then pooled estimates using random-effects meta-analysis. We also calculated the population attributable risk (PAR) associated with each of the identifed risk factors. Findings: The prevalence of chronic cough varied from 3% in India (rural Pune) to 24% in the United States of America (Lexington,KY). Chronic cough was more common among females, both current and passive smokers, those working in a dusty job, those with a history of tuberculosis, those who were obese, those with a low level of education and those with hypertension or airflow limitation. The most influential risk factors were current smoking and working in a dusty job. Interpretation: Our findings suggested that the prevalence of chronic cough varies widely across sites in different world regions. Cigarette smoking and exposure to dust in the workplace are its major risk factors.info:eu-repo/semantics/publishedVersio

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes