Data management strategies for multinational large-scale systems biology projects.

PubMed

Wruck, Wasco; Peuker, Martin; Regenbrecht, Christian R A

2014-01-01

Good accessibility of publicly funded research data is essential to secure an open scientific system and eventually becomes mandatory [Wellcome Trust will Penalise Scientists Who Don't Embrace Open Access. The Guardian 2012]. By the use of high-throughput methods in many research areas from physics to systems biology, large data collections are increasingly important as raw material for research. Here, we present strategies worked out by international and national institutions targeting open access to publicly funded research data via incentives or obligations to share data. Funding organizations such as the British Wellcome Trust therefore have developed data sharing policies and request commitment to data management and sharing in grant applications. Increased citation rates are a profound argument for sharing publication data. Pre-publication sharing might be rewarded by a data citation credit system via digital object identifiers (DOIs) which have initially been in use for data objects. Besides policies and incentives, good practice in data management is indispensable. However, appropriate systems for data management of large-scale projects for example in systems biology are hard to find. Here, we give an overview of a selection of open-source data management systems proved to be employed successfully in large-scale projects.

Data management strategies for multinational large-scale systems biology projects

PubMed Central

Peuker, Martin; Regenbrecht, Christian R.A.

2014-01-01

Good accessibility of publicly funded research data is essential to secure an open scientific system and eventually becomes mandatory [Wellcome Trust will Penalise Scientists Who Don’t Embrace Open Access. The Guardian 2012]. By the use of high-throughput methods in many research areas from physics to systems biology, large data collections are increasingly important as raw material for research. Here, we present strategies worked out by international and national institutions targeting open access to publicly funded research data via incentives or obligations to share data. Funding organizations such as the British Wellcome Trust therefore have developed data sharing policies and request commitment to data management and sharing in grant applications. Increased citation rates are a profound argument for sharing publication data. Pre-publication sharing might be rewarded by a data citation credit system via digital object identifiers (DOIs) which have initially been in use for data objects. Besides policies and incentives, good practice in data management is indispensable. However, appropriate systems for data management of large-scale projects for example in systems biology are hard to find. Here, we give an overview of a selection of open-source data management systems proved to be employed successfully in large-scale projects. PMID:23047157

Implementing a genomic data management system using iRODS in the Wellcome Trust Sanger Institute

PubMed Central

2011-01-01

Background Increasingly large amounts of DNA sequencing data are being generated within the Wellcome Trust Sanger Institute (WTSI). The traditional file system struggles to handle these increasing amounts of sequence data. A good data management system therefore needs to be implemented and integrated into the current WTSI infrastructure. Such a system enables good management of the IT infrastructure of the sequencing pipeline and allows biologists to track their data. Results We have chosen a data grid system, iRODS (Rule-Oriented Data management systems), to act as the data management system for the WTSI. iRODS provides a rule-based system management approach which makes data replication much easier and provides extra data protection. Unlike the metadata provided by traditional file systems, the metadata system of iRODS is comprehensive and allows users to customize their own application level metadata. Users and IT experts in the WTSI can then query the metadata to find and track data. The aim of this paper is to describe how we designed and used (from both system and user viewpoints) iRODS as a data management system. Details are given about the problems faced and the solutions found when iRODS was implemented. A simple use case describing how users within the WTSI use iRODS is also introduced. Conclusions iRODS has been implemented and works as the production system for the sequencing pipeline of the WTSI. Both biologists and IT experts can now track and manage data, which could not previously be achieved. This novel approach allows biologists to define their own metadata and query the genomic data using those metadata. PMID:21906284

The Francis Crick Institute.

PubMed

Peters, Keith; Smith, Jim

2017-04-01

The Francis Crick Institute Laboratory, opened in 2016, is supported by the Medical Research Council, Cancer Research UK, the Wellcome Trust, and University College London, King's College London and Imperial College London. The emphasis on research training and early independence of gifted scientists in a multidisciplinary environment provides unique opportunities for UK medical science, including clinical and translational research. © Royal College of Physicians 2017. All rights reserved.

Hunting for the Signatures of Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Giorgi, Elena Edi

2016-04-26

This prompts the ambitious question: can we find common mutations across individuals with the same cancer? And how many of these mutational patterns that are common across individuals can we attribute to particular exposures or biological processes? Distinguished postdoctoral researcher Ludmil Alexandrov, from the Los Alamos National Laboratory, has been working on this problem since his he was a PhD student at the Wellcome Trust Sanger Institute.

Sequencing Centers Panel at SFAF

ScienceCinema

Schilkey, Faye; Ali, Johar; Grafham, Darren; Muzny, Donna; Fulton, Bob; Fitzgerald, Mike; Hostetler, Jessica; Daum, Chris

2018-02-13

From left to right: Faye Schilkey of NCGR, Johar Ali of OICR, Darren Grafham of Wellcome Trust Sanger Institute, Donna Muzny of the Baylor College of Medicine, Bob Fulton of Washington University, Mike Fitzgerald of the Broad Institute, Jessica Hostetler of the J. Craig Venter Institute and Chris Daum of the DOE Joint Genome Institute discuss sequencing technologies, applications and pipelines on June 2, 2010 at the "Sequencing, Finishing, Analysis in the Future" meeting in Santa Fe, NM.

Sequencing Centers Panel at SFAF

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schilkey, Faye; Ali, Johar; Grafham, Darren

From left to right: Faye Schilkey of NCGR, Johar Ali of OICR, Darren Grafham of Wellcome Trust Sanger Institute, Donna Muzny of the Baylor College of Medicine, Bob Fulton of Washington University, Mike Fitzgerald of the Broad Institute, Jessica Hostetler of the J. Craig Venter Institute and Chris Daum of the DOE Joint Genome Institute discuss sequencing technologies, applications and pipelines on June 2, 2010 at the "Sequencing, Finishing, Analysis in the Future" meeting in Santa Fe, NM.

News

NASA Astrophysics Data System (ADS)

2002-05-01

Physics on Stage: Physics on the political stage Women in Physics: Allez les girls! Curriculum: Students want ethics debate in school science Physics on Stage: Buzzing around the tulips Events: GIREP 2002 Competition: Schumacher in the shower! Higher Education: Universities consider conceptual physics courses Resources: Evaluation of Advancing Physics Research Frontiers: Physics Teachers @ CERN 2002 UK Curriculum: Preparing useful citizens China: Changing the approach NSTA Annual Convention: Innovations and simplicity Europe: European Community Science and Society Action Plan Citizenship: ASE-Wellcome Trust citizenship education initiative

Using ancestry-informative markers to identify fine structure across 15 populations of European origin.

PubMed

Huckins, Laura M; Boraska, Vesna; Franklin, Christopher S; Floyd, James A B; Southam, Lorraine; Sullivan, Patrick F; Bulik, Cynthia M; Collier, David A; Tyler-Smith, Chris; Zeggini, Eleftheria; Tachmazidou, Ioanna

2014-10-01

The Wellcome Trust Case Control Consortium 3 anorexia nervosa genome-wide association scan includes 2907 cases from 15 different populations of European origin genotyped on the Illumina 670K chip. We compared methods for identifying population stratification, and suggest list of markers that may help to counter this problem. It is usual to identify population structure in such studies using only common variants with minor allele frequency (MAF) >5%; we find that this may result in highly informative SNPs being discarded, and suggest that instead all SNPs with MAF >1% may be used. We established informative axes of variation identified via principal component analysis and highlight important features of the genetic structure of diverse European-descent populations, some studied for the first time at this scale. Finally, we investigated the substructure within each of these 15 populations and identified SNPs that help capture hidden stratification. This work can provide information regarding the designing and interpretation of association results in the International Consortia.

The origins of the British Neuroscience Association.

PubMed

Reynolds, Edward H

2017-12-26

I describe the origins of the British Neuroscience Association (BNA) based on new documents which I have discovered. The foundation of the Brain Research Association (BRA) on February 23rd 1968 was influenced by IBRO, notably its two UK Council members, and by many UK neuroscientists, especially the London-based Black Horse Group. The BRA changed its name to the BNA in 1996. The documents are in the Wellcome Trust Archives. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Efficient phagocytosis and laccase activity affect the outcome of HIV-associated cryptococcosis

PubMed Central

Sabiiti, Wilber; Robertson, Emma; Beale, Mathew A.; Johnston, Simon A.; Brouwer, Annemarie E.; Loyse, Angela; Jarvis, Joseph N.; Gilbert, Andrew S.; Fisher, Matthew C.; Harrison, Thomas S.; May, Robin C.; Bicanic, Tihana

2014-01-01

Background. Cryptococcal meningitis (CM) is a leading cause of HIV-associated mortality globally. High fungal burden in cerebrospinal fluid (CSF) at diagnosis and poor fungal clearance during treatment are recognized adverse prognostic markers; however, the underlying pathogenic factors that drive these clinical manifestations are incompletely understood. We profiled a large set of clinical isolates for established cryptococcal virulence traits to evaluate the contribution of C. neoformans phenotypic diversity to clinical presentation and outcome in human cryptococcosis. Methods. Sixty-five C. neoformans isolates from clinical trial patients with matched clinical data were assayed in vitro to determine murine macrophage uptake, intracellular proliferation rate (IPR), capsule induction, and laccase activity. Analysis of the correlation between prognostic clinical and host immune parameters and fungal phenotypes was performed using Spearman’s r, while the fungal-dependent impact on long-term survival was determined by Cox regression analysis. Results. High levels of fungal uptake by macrophages in vitro, but not the IPR, were associated with CSF fungal burden (r = 0.38, P = 0.002) and long-term patient survival (hazard ratio [HR] 2.6, 95% CI 1.2–5.5, P = 0.012). High-uptake strains were hypocapsular (r = –0.28, P = 0.05) and exhibited enhanced laccase activity (r = 0.36, P = 0.003). Fungal isolates with greater laccase activity exhibited heightened survival ex vivo in purified CSF (r = 0.49, P < 0.0001) and resistance to clearance following patient antifungal treatment (r = 0.39, P = 0.003). Conclusion. These findings underscore the contribution of cryptococcal-phagocyte interactions and laccase-dependent melanin pathways to human clinical presentation and outcome. Furthermore, characterization of fungal-specific pathways that drive clinical manifestation provide potential targets for the development of therapeutics and the management of CM. Funding. This work was made possible by funding from the Wellcome Trust (WT088148MF), the Medical Research Council (MR/J008176/1), the NIHR Surgical Reconstruction and Microbiology Research Centre and the Lister Institute for Preventive Medicine (to R.C. May), and a Wellcome Trust Intermediate fellowship (089966, to T. Bicanic). The C. neoformans isolates were collected within clinical trials funded by the British Infection Society (fellowship to T. Bicanic), the Wellcome Trust (research training fellowships WT069991, to A.E. Brouwer and WT081794, to J.N. Jarvis), and the Medical Research Council, United Kingdom (76201). The funding sources had no role in the design or conduct of this study, nor in preparation of the manuscript. PMID:24743149

Beginning community engagement at a busy biomedical research programme: Experiences from the KEMRI CGMRC-Wellcome Trust Research Programme, Kilifi, Kenya

PubMed Central

Marsh, Vicki; Kamuya, Dorcas; Rowa, Yvonne; Gikonyo, Caroline; Molyneux, Sassy

2008-01-01

There is wide acknowledgement of the need for community engagement in biomedical research, particularly in international settings. Recent debates have described theoretical approaches to identifying situations where this is most critical and potential mechanisms to achieve it. However, there is relatively little published experience of community engagement in practice. A major component of the Kenya Medical Research Institute (KEMRI) Wellcome Trust Research Programme is centred on Kilifi District General Hospital and surrounding community of 240,000 local residents. Documented community perceptions of the research centre are generally positive, but many indicate a low understanding of research and therapeutic misconceptions of its activities. As in other settings, these misunderstandings have contributed to concerns and rumours, and potentially undermine ethical aspects of research and local trust in the institution. Through a series of consultative activities, a community engagement strategy has been developed in Kilifi to strengthen mutual understanding between community members and the Centre. One important component is the establishment of a representative local resident network in different geographic locations commonly involved in research, to supplement existing communication channels. Early implementation of the strategy has provided new and diverse opportunities for dialogue, interaction and partnership building. Through the complex social interactions inherent in the community engagement strategy, the centre aims to build context specific ethical relations with local residents and to strengthen understanding of how ethical principles can be applied in practice. Evaluations over time will assess the effectiveness and sustainability of these strategies, provide generalisable information for similar research settings, and contribute to debates on the universality of ethical principles for research. This paper aims to summarise the rationale for community engagement in research, drawing on published literature and local findings, to outline the process of community engagement in Kilifi and to describe issues emerging from its development and early implementation. PMID:18375028

GBOOST: a GPU-based tool for detecting gene-gene interactions in genome-wide case control studies.

PubMed

Yung, Ling Sing; Yang, Can; Wan, Xiang; Yu, Weichuan

2011-05-01

Collecting millions of genetic variations is feasible with the advanced genotyping technology. With a huge amount of genetic variations data in hand, developing efficient algorithms to carry out the gene-gene interaction analysis in a timely manner has become one of the key problems in genome-wide association studies (GWAS). Boolean operation-based screening and testing (BOOST), a recent work in GWAS, completes gene-gene interaction analysis in 2.5 days on a desktop computer. Compared with central processing units (CPUs), graphic processing units (GPUs) are highly parallel hardware and provide massive computing resources. We are, therefore, motivated to use GPUs to further speed up the analysis of gene-gene interactions. We implement the BOOST method based on a GPU framework and name it GBOOST. GBOOST achieves a 40-fold speedup compared with BOOST. It completes the analysis of Wellcome Trust Case Control Consortium Type 2 Diabetes (WTCCC T2D) genome data within 1.34 h on a desktop computer equipped with Nvidia GeForce GTX 285 display card. GBOOST code is available at http://bioinformatics.ust.hk/BOOST.html#GBOOST.

Genome-wide significant locus for Research Diagnostic Criteria Schizoaffective Disorder Bipolar type.

PubMed

Green, Elaine K; Di Florio, Arianna; Forty, Liz; Gordon-Smith, Katherine; Grozeva, Detelina; Fraser, Christine; Richards, Alexander L; Moran, Jennifer L; Purcell, Shaun; Sklar, Pamela; Kirov, George; Owen, Michael J; O'Donovan, Michael C; Craddock, Nick; Jones, Lisa; Jones, Ian R

2017-12-01

Studies have suggested that Research Diagnostic Criteria for Schizoaffective Disorder Bipolar type (RDC-SABP) might identify a more genetically homogenous subgroup of bipolar disorder. Aiming to identify loci associated with RDC-SABP, we have performed a replication study using independent RDC-SABP cases (n = 144) and controls (n = 6,559), focusing on the 10 loci that reached a p-value <10 -5 for RDC-SABP in the Wellcome Trust Case Control Consortium (WTCCC) bipolar disorder sample. Combining the WTCCC and replication datasets by meta-analysis (combined RDC-SABP, n = 423, controls, n = 9,494), we observed genome-wide significant association at one SNP, rs2352974, located within the intron of the gene TRAIP on chromosome 3p21.31 (p-value, 4.37 × 10 -8 ). This locus did not reach genome-wide significance in bipolar disorder or schizophrenia large Psychiatric Genomic Consortium datasets, suggesting that it may represent a relatively specific genetic risk for the bipolar subtype of schizoaffective disorder. © 2017 Wiley Periodicals, Inc.

Mutational Signature Mark Cancer’s Smoking Gun

DOE Office of Scientific and Technical Information (OSTI.GOV)

Alexandrov, Ludmil

A broad computational study of cancer genome sequences by Los Alamos National Laboratory with the UK’s Wellcome Trust Sanger Institute and other collaborators identifies telltale mutational signatures associated with smoking tobacco. The research demonstrates, for the first time, that smoking increases cancer risk by causing somatic mutations in tissues directly and indirectly exposed to tobacco smoke. The international study was published in the November 4 issue of Science. The analysis shows that tobacco smoking causes mutations leading to cancer by multiple distinct mechanisms, including by damaging DNA in organs and by speeding up a mutational cellular clock.

Mutational Signature Mark Cancer’s Smoking Gun

ScienceCinema

Alexandrov, Ludmil

2018-06-13

A broad computational study of cancer genome sequences by Los Alamos National Laboratory with the UK’s Wellcome Trust Sanger Institute and other collaborators identifies telltale mutational signatures associated with smoking tobacco. The research demonstrates, for the first time, that smoking increases cancer risk by causing somatic mutations in tissues directly and indirectly exposed to tobacco smoke. The international study was published in the November 4 issue of Science. The analysis shows that tobacco smoking causes mutations leading to cancer by multiple distinct mechanisms, including by damaging DNA in organs and by speeding up a mutational cellular clock.

Struggling to be Fit: Identity, Integrity, and the Law

PubMed Central

Harmon, Shawn HE; Brown, Abbe; Popat, Sita; Whatley, Sarah; O’Connor, Rory

2017-01-01

This interdisciplinary co-authored Analysis piece introduces identity and integrity, which are argued to sit at the core of the person. It analyses approaches taken to these concepts by legal regimes, particularly in the context of individuals using artificial limbs or digital avatars. The piece concludes that law engages with identity and integrity to a limited and incomplete extent; and that law is thus inadequate in its engagement with the person, and its meaning making in this respect. This piece draws on two interdisciplinary funded projects, funded by the Wellcome Trust and the Arts and Humanities Research Council. PMID:29271979

Significance of genome-wide association studies in molecular anthropology.

PubMed

Gupta, Vipin; Khadgawat, Rajesh; Sachdeva, Mohinder Pal

2009-12-01

The successful advent of a genome-wide approach in association studies raises the hopes of human geneticists for solving a genetic maze of complex traits especially the disorders. This approach, which is replete with the application of cutting-edge technology and supported by big science projects (like Human Genome Project; and even more importantly the International HapMap Project) and various important databases (SNP database, CNV database, etc.), has had unprecedented success in rapidly uncovering many of the genetic determinants of complex disorders. The magnitude of this approach in the genetics of classical anthropological variables like height, skin color, eye color, and other genome diversity projects has certainly expanded the horizons of molecular anthropology. Therefore, in this article we have proposed a genome-wide association approach in molecular anthropological studies by providing lessons from the exemplary study of the Wellcome Trust Case Control Consortium. We have also highlighted the importance and uniqueness of Indian population groups in facilitating the design and finding optimum solutions for other genome-wide association-related challenges.

Investigating Time Lags and Attribution in the Translation of Cancer Research: A Case Study Approach.

PubMed

Guthrie, Susan; Pollitt, Alexandra; Hanney, Stephen; Grant, Jonathan

2014-01-01

In 2012, RAND Europe and the Health Economics Research Group (Brunel University) were commissioned by the Wellcome Trust, Cancer Research UK, the National Institute for Health Research and the Academy of Medical Science to conduct a study of the returns to the public/charitable investment in cancer-related research. This study built on previous work published in the 2008 "What's it worth?" report that estimated the economic returns to medical research in terms of spillover benefits and health gain. The 2008 study was extensively quoted and cited as a clear justification for the economic importance of medical research and appears to have played a role in achieving the protection of the medical science budget in the recent public expenditure cuts. This cancer study used a similar approach to that used in the previous study, but with some methodological developments. One of the methodological developments was the inclusion of case studies to examine the validity and variability of the estimates on elapsed time between funding and health gains, and the amount of health gains that can be attributed to UK research. This study provides the full text of the five case studies conducted as well as some discussion of observations emerging across the case study set.

PBOOST: a GPU-based tool for parallel permutation tests in genome-wide association studies.

PubMed

Yang, Guangyuan; Jiang, Wei; Yang, Qiang; Yu, Weichuan

2015-05-01

The importance of testing associations allowing for interactions has been demonstrated by Marchini et al. (2005). A fast method detecting associations allowing for interactions has been proposed by Wan et al. (2010a). The method is based on likelihood ratio test with the assumption that the statistic follows the χ(2) distribution. Many single nucleotide polymorphism (SNP) pairs with significant associations allowing for interactions have been detected using their method. However, the assumption of χ(2) test requires the expected values in each cell of the contingency table to be at least five. This assumption is violated in some identified SNP pairs. In this case, likelihood ratio test may not be applicable any more. Permutation test is an ideal approach to checking the P-values calculated in likelihood ratio test because of its non-parametric nature. The P-values of SNP pairs having significant associations with disease are always extremely small. Thus, we need a huge number of permutations to achieve correspondingly high resolution for the P-values. In order to investigate whether the P-values from likelihood ratio tests are reliable, a fast permutation tool to accomplish large number of permutations is desirable. We developed a permutation tool named PBOOST. It is based on GPU with highly reliable P-value estimation. By using simulation data, we found that the P-values from likelihood ratio tests will have relative error of >100% when 50% cells in the contingency table have expected count less than five or when there is zero expected count in any of the contingency table cells. In terms of speed, PBOOST completed 10(7) permutations for a single SNP pair from the Wellcome Trust Case Control Consortium (WTCCC) genome data (Wellcome Trust Case Control Consortium, 2007) within 1 min on a single Nvidia Tesla M2090 device, while it took 60 min in a single CPU Intel Xeon E5-2650 to finish the same task. More importantly, when simultaneously testing 256 SNP pairs for 10(7) permutations, our tool took only 5 min, while the CPU program took 10 h. By permuting on a GPU cluster consisting of 40 nodes, we completed 10(12) permutations for all 280 SNP pairs reported with P-values smaller than 1.6 × 10⁻¹² in the WTCCC datasets in 1 week. The source code and sample data are available at http://bioinformatics.ust.hk/PBOOST.zip. gyang@ust.hk; eeyu@ust.hk Supplementary data are available at Bioinformatics online. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Establishing the UK DNA Bank for motor neuron disease (MND).

PubMed

Smith, Lucy; Cupid, B C; Dickie, B G M; Al-Chalabi, A; Morrison, K E; Shaw, C E; Shaw, P J

2015-07-14

In 2003 the Motor Neurone Disease (MND) Association, together with The Wellcome Trust, funded the creation of a national DNA Bank specific for MND. It was anticipated that the DNA Bank would constitute an important resource to researchers worldwide and significantly increase activity in MND genetic research. The DNA Bank houses over 3000 high quality DNA samples, all of which were donated by people living with MND, family members and non-related controls, accompanied by clinical phenotype data about the patients. Today the primary focus of the UK MND DNA Bank still remains to identify causative and disease modifying factors for this devastating disease.

CMDR based differential evolution identifies the epistatic interaction in genome-wide association studies.

PubMed

Yang, Cheng-Hong; Chuang, Li-Yeh; Lin, Yu-Da

2017-08-01

Detecting epistatic interactions in genome-wide association studies (GWAS) is a computational challenge. Such huge numbers of single-nucleotide polymorphism (SNP) combinations limit the some of the powerful algorithms to be applied to detect the potential epistasis in large-scale SNP datasets. We propose a new algorithm which combines the differential evolution (DE) algorithm with a classification based multifactor-dimensionality reduction (CMDR), termed DECMDR. DECMDR uses the CMDR as a fitness measure to evaluate values of solutions in DE process for scanning the potential statistical epistasis in GWAS. The results indicated that DECMDR outperforms the existing algorithms in terms of detection success rate by the large simulation and real data obtained from the Wellcome Trust Case Control Consortium. For running time comparison, DECMDR can efficient to apply the CMDR to detect the significant association between cases and controls amongst all possible SNP combinations in GWAS. DECMDR is freely available at https://goo.gl/p9sLuJ . chuang@isu.edu.tw or e0955767257@yahoo.com.tw. Supplementary data are available at Bioinformatics online. © The Author (2017). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Henry Solomon Wellcome: A philanthropist and a pioneer sponsor of medical research in the Sudan

PubMed Central

2013-01-01

Henry Solomon Wellcome, the famous drug manufacturer had a fascinating association with the Sudan. Besides supporting tropical medicine research in this country, he established an extensive project in the Sudan that aimed at combining archeological excavations, philanthropy and social reform. This article is an archives-based account on this side of Wellcome’s association with the Sudan. The article starts with Wellcome’s early years in the American Midwest and the evolution of his career and his rise as a world-renowned drug manufacturer. After the battle of Omdurman, Wellcome visited Sudan in 1900 – 1901 where he offered to support the establishment of the research laboratories which later came to be known as the Wellcome Tropical Research Laboratories in Khartoum. He then became directly involved in the planning and running of extensive archeological excavations in the central Sudan. This project served as a field in which Wellcome found an outlet for his philanthropy. More than 4000 labourers were employed in Jebel Moya. Professional archeologists and anatomists were recruited by Wellcome to supervise the work, and all the requirements in terms of equipment were catered for. Wellcome devised a Savings Bank System whereby part of the earnings of each labourer were saved to him till the end of the season. He also introduced one of his innovations: aerial photography using box kite which was used for the first time in archeology. Wellcome made it a rule that no applicant should be turned away. The Camp Commandant had to find suitable work for each applicant, including the handicapped who were assigned to appropriate jobs like mending baskets or cutting grass for building huts. Wellcome’s welfare work had a significant impact on the local inhabitants of Jebel Moya. Henry Solomon Wellcome, 1906. Oil painting by Hugh Goldwin Riviere. Credit: Wellcome Library PMID:27493379

Machine learning derived risk prediction of anorexia nervosa.

PubMed

Guo, Yiran; Wei, Zhi; Keating, Brendan J; Hakonarson, Hakon

2016-01-20

Anorexia nervosa (AN) is a complex psychiatric disease with a moderate to strong genetic contribution. In addition to conventional genome wide association (GWA) studies, researchers have been using machine learning methods in conjunction with genomic data to predict risk of diseases in which genetics play an important role. In this study, we collected whole genome genotyping data on 3940 AN cases and 9266 controls from the Genetic Consortium for Anorexia Nervosa (GCAN), the Wellcome Trust Case Control Consortium 3 (WTCCC3), Price Foundation Collaborative Group and the Children's Hospital of Philadelphia (CHOP), and applied machine learning methods for predicting AN disease risk. The prediction performance is measured by area under the receiver operating characteristic curve (AUC), indicating how well the model distinguishes cases from unaffected control subjects. Logistic regression model with the lasso penalty technique generated an AUC of 0.693, while Support Vector Machines and Gradient Boosted Trees reached AUC's of 0.691 and 0.623, respectively. Using different sample sizes, our results suggest that larger datasets are required to optimize the machine learning models and achieve higher AUC values. To our knowledge, this is the first attempt to assess AN risk based on genome wide genotype level data. Future integration of genomic, environmental and family-based information is likely to improve the AN risk evaluation process, eventually benefitting AN patients and families in the clinical setting.

Toward an architecture of attachment disorganization: John Bowlby's published and unpublished reflections.

PubMed

Solomon, Judith; Duschinsky, Robbie; Bakkum, Lianne; Schuengel, Carlo

2017-10-01

This article examines the construct of disorganized attachment originally proposed by Main and Solomon, developing some new conjectures based on inspiration from a largely unknown source: John Bowlby's unpublished texts, housed at the Wellcome Trust Library Archive in London (with permission from the Bowlby family). We explore Bowlby's discussions of disorganized attachment, which he understood from the perspective of ethological theories of conflict behavior. Bowlby's reflections regarding differences among the behaviors used to code disorganized attachment will be used to explore distinctions that may underlie the structure of the current coding system. The article closes with an emphasis on the importance Bowlby placed on Popper's distinction between the context of discovery and the context of justification in developmental science.

Diverse Genome-wide Association Studies Associate the IL12/IL23 Pathway with Crohn Disease

PubMed Central

Wang, Kai; Zhang, Haitao; Kugathasan, Subra; Annese, Vito; Bradfield, Jonathan P.; Russell, Richard K.; Sleiman, Patrick M.A.; Imielinski, Marcin; Glessner, Joseph; Hou, Cuiping; Wilson, David C.; Walters, Thomas; Kim, Cecilia; Frackelton, Edward C.; Lionetti, Paolo; Barabino, Arrigo; Van Limbergen, Johan; Guthery, Stephen; Denson, Lee; Piccoli, David; Li, Mingyao; Dubinsky, Marla; Silverberg, Mark; Griffiths, Anne; Grant, Struan F.A.; Satsangi, Jack; Baldassano, Robert; Hakonarson, Hakon

2009-01-01

Previous genome-wide association (GWA) studies typically focus on single-locus analysis, which may not have the power to detect the majority of genuinely associated loci. Here, we applied pathway analysis using Affymetrix SNP genotype data from the Wellcome Trust Case Control Consortium (WTCCC) and uncovered significant association between Crohn Disease (CD) and the IL12/IL23 pathway, harboring 20 genes (p = 8 × 10−5). Interestingly, the pathway contains multiple genes (IL12B and JAK2) or homologs of genes (STAT3 and CCR6) that were recently identified as genuine susceptibility genes only through meta-analysis of several GWA studies. In addition, the pathway contains other susceptibility genes for CD, including IL18R1, JUN, IL12RB1, and TYK2, which do not reach genome-wide significance by single-marker association tests. The observed pathway-specific association signal was subsequently replicated in three additional GWA studies of European and African American ancestry generated on the Illumina HumanHap550 platform. Our study suggests that examination beyond individual SNP hits, by focusing on genetic networks and pathways, is important to unleashing the true power of GWA studies. PMID:19249008

Toward an architecture of attachment disorganization: John Bowlby’s published and unpublished reflections

PubMed Central

Solomon, Judith; Duschinsky, Robbie; Bakkum, Lianne; Schuengel, Carlo

2017-01-01

This article examines the construct of disorganized attachment originally proposed by Main and Solomon, developing some new conjectures based on inspiration from a largely unknown source: John Bowlby’s unpublished texts, housed at the Wellcome Trust Library Archive in London (with permission from the Bowlby family). We explore Bowlby’s discussions of disorganized attachment, which he understood from the perspective of ethological theories of conflict behavior. Bowlby’s reflections regarding differences among the behaviors used to code disorganized attachment will be used to explore distinctions that may underlie the structure of the current coding system. The article closes with an emphasis on the importance Bowlby placed on Popper’s distinction between the context of discovery and the context of justification in developmental science. PMID:28791871

Imaging as a biomarker in drug discovery for Alzheimer’s disease: is MRI a suitable technology?

PubMed Central

2014-01-01

This review provides perspectives on the utility of magnetic resonance imaging (MRI) as a neuroimaging approach in the development of novel treatments for Alzheimer’s disease. These considerations were generated in a roundtable at a recent Wellcome Trust meeting that included experts from academia and industry. It was agreed that MRI, either structural or functional, could be used as a diagnostic, for assessing worsening of disease status, for monitoring vascular pathology, and for stratifying clinical trial populations. It was agreed also that MRI implementation is in its infancy, requiring more evidence of association with the disease states, test-retest data, better standardization across multiple clinical sites, and application in multimodal approaches which include other imaging technologies, such as positron emission tomography, electroencephalography, and magnetoencephalography. PMID:25484927

Stochastic model search with binary outcomes for genome-wide association studies.

PubMed

Russu, Alberto; Malovini, Alberto; Puca, Annibale A; Bellazzi, Riccardo

2012-06-01

The spread of case-control genome-wide association studies (GWASs) has stimulated the development of new variable selection methods and predictive models. We introduce a novel Bayesian model search algorithm, Binary Outcome Stochastic Search (BOSS), which addresses the model selection problem when the number of predictors far exceeds the number of binary responses. Our method is based on a latent variable model that links the observed outcomes to the underlying genetic variables. A Markov Chain Monte Carlo approach is used for model search and to evaluate the posterior probability of each predictor. BOSS is compared with three established methods (stepwise regression, logistic lasso, and elastic net) in a simulated benchmark. Two real case studies are also investigated: a GWAS on the genetic bases of longevity, and the type 2 diabetes study from the Wellcome Trust Case Control Consortium. Simulations show that BOSS achieves higher precisions than the reference methods while preserving good recall rates. In both experimental studies, BOSS successfully detects genetic polymorphisms previously reported to be associated with the analyzed phenotypes. BOSS outperforms the other methods in terms of F-measure on simulated data. In the two real studies, BOSS successfully detects biologically relevant features, some of which are missed by univariate analysis and the three reference techniques. The proposed algorithm is an advance in the methodology for model selection with a large number of features. Our simulated and experimental results showed that BOSS proves effective in detecting relevant markers while providing a parsimonious model.

One Size Doesn’t Fit All: Measuring Individual Privacy in Aggregate Genomic Data

PubMed Central

Simmons, Sean; Berger, Bonnie

2017-01-01

Even in the aggregate, genomic data can reveal sensitive information about individuals. We present a new model-based measure, PrivMAF, that provides provable privacy guarantees for aggregate data (namely minor allele frequencies) obtained from genomic studies. Unlike many previous measures that have been designed to measure the total privacy lost by all participants in a study, PrivMAF gives an individual privacy measure for each participant in the study, not just an average measure. These individual measures can then be combined to measure the worst case privacy loss in the study. Our measure also allows us to quantify the privacy gains achieved by perturbing the data, either by adding noise or binning. Our findings demonstrate that both perturbation approaches offer significant privacy gains. Moreover, we see that these privacy gains can be achieved while minimizing perturbation (and thus maximizing the utility) relative to stricter notions of privacy, such as differential privacy. We test PrivMAF using genotype data from the Wellcome Trust Case Control Consortium, providing a more nuanced understanding of the privacy risks involved in an actual genome-wide association studies. Interestingly, our analysis demonstrates that the privacy implications of releasing MAFs from a study can differ greatly from individual to individual. An implementation of our method is available at http://privmaf.csail.mit.edu. PMID:29202050

Mental disorder ethics: theory and empirical investigation

PubMed Central

Eastman, N; Starling, B

2006-01-01

Mental disorders and their care present unusual problems within biomedical ethics. The disorders themselves invite an ethical critique, as does society's attitude to them; researching the diagnosis and treatment of mental disorders also presents special ethical issues. The current high profile of mental disorder ethics, emphasised by recent political and legal developments, makes this a field of research that is not only important but also highly topical. For these reasons, the Wellcome Trust's biomedical ethics programme convened a meeting, “Investigating Ethics and Mental Disorders”, in order to review some current research, and to stimulate topics and methods of future research in the field. The meeting was attended by policy makers, regulators, research funders, and researchers, including social scientists, psychiatrists, psychologists, lawyers, philosophers, criminologists, and others. As well as aiming to inspire a stronger research endeavour, the meeting also sought to stimulate an improved understanding of the methods and interactions that can contribute to “empirical ethics” generally. This paper reports on the meeting by describing contributions from individual speakers and discussion sections of the meeting. At the end we describe and discuss the conclusions of the meeting. As a result, the text is referenced less than would normally be expected in a review. Also, in summarising contributions from named presenters at the meeting it is possible that we have created inaccuracies; however, the definitive version of each paper, as provided directly by the presenter, is available at http://www.wellcome.ac.uk/doc.WTX025116.html. PMID:16446414

A relic of the Wellcome Tropical Research Laboratories in Khartoum (1903-34).

PubMed

Adeel, Ahmed Awad

2016-01-01

This article explores the origins of an old brass monocular microscope in the Central Laboratory in Khartoum, which used to be the Wellcome Tropical Research Laboratory in Khartoum (1903-1934). Examination of the microscope and review of published literature gave clues to the historical background of this microscope. Identical microscopes were first manufactured by R and J Beck in 1898, and continued to be advertised in 1899. The microscope was probably among the instruments provided by Wellcome for the initial establishment of the laboratories in 1902-1903. The article includes a brief review of the development of light microscopy. The need for preservation and proper restoration of old relics of the Wellcome laboratories in Khartoum is emphasized.

A relic of the Wellcome Tropical Research Laboratories in Khartoum (1903–34)

PubMed Central

2016-01-01

This article explores the origins of an old brass monocular microscope in the Central Laboratory in Khartoum, which used to be the Wellcome Tropical Research Laboratory in Khartoum (1903–1934). Examination of the microscope and review of published literature gave clues to the historical background of this microscope. Identical microscopes were first manufactured by R and J Beck in 1898, and continued to be advertised in 1899. The microscope was probably among the instruments provided by Wellcome for the initial establishment of the laboratories in 1902–1903. The article includes a brief review of the development of light microscopy. The need for preservation and proper restoration of old relics of the Wellcome laboratories in Khartoum is emphasized. PMID:27651557

Investigation of rheumatoid arthritis susceptibility loci in juvenile idiopathic arthritis confirms high degree of overlap.

PubMed

Hinks, Anne; Cobb, Joanna; Sudman, Marc; Eyre, Stephen; Martin, Paul; Flynn, Edward; Packham, Jonathon; Barton, Anne; Worthington, Jane; Langefeld, Carl D; Glass, David N; Thompson, Susan D; Thomson, Wendy

2012-07-01

Rheumatoid arthritis (RA) shares some similar clinical and pathological features with juvenile idiopathic arthritis (JIA); indeed, the strategy of investigating whether RA susceptibility loci also confer susceptibility to JIA has already proved highly successful in identifying novel JIA loci. A plethora of newly validated RA loci has been reported in the past year. Therefore, the aim of this study was to investigate these single nucleotide polymorphisms (SNP) to determine if they were also associated with JIA. Thirty-four SNP that showed validated association with RA and had not been investigated previously in the UK JIA cohort were genotyped in JIA cases (n=1242), healthy controls (n=4281), and data were extracted for approximately 5380 UK Caucasian controls from the Wellcome Trust Case-Control Consortium 2. Genotype and allele frequencies were compared between cases with JIA and controls using PLINK. A replication cohort of 813 JIA cases and 3058 controls from the USA was available for validation of any significant findings. Thirteen SNP showed significant association (p<0.05) with JIA and for all but one the direction of association was the same as in RA. Of the eight loci that were tested, three showed significant association in the US cohort. A novel JIA susceptibility locus was identified, CD247, which represents another JIA susceptibility gene whose protein product is important in T-cell activation and signalling. The authors have also confirmed association of the PTPN2 and IL2RA genes with JIA, both reaching genome-wide significance in the combined analysis.

A genome-wide association study of anorexia nervosa.

PubMed

Boraska, V; Franklin, C S; Floyd, J A B; Thornton, L M; Huckins, L M; Southam, L; Rayner, N W; Tachmazidou, I; Klump, K L; Treasure, J; Lewis, C M; Schmidt, U; Tozzi, F; Kiezebrink, K; Hebebrand, J; Gorwood, P; Adan, R A H; Kas, M J H; Favaro, A; Santonastaso, P; Fernández-Aranda, F; Gratacos, M; Rybakowski, F; Dmitrzak-Weglarz, M; Kaprio, J; Keski-Rahkonen, A; Raevuori, A; Van Furth, E F; Slof-Op 't Landt, M C T; Hudson, J I; Reichborn-Kjennerud, T; Knudsen, G P S; Monteleone, P; Kaplan, A S; Karwautz, A; Hakonarson, H; Berrettini, W H; Guo, Y; Li, D; Schork, N J; Komaki, G; Ando, T; Inoko, H; Esko, T; Fischer, K; Männik, K; Metspalu, A; Baker, J H; Cone, R D; Dackor, J; DeSocio, J E; Hilliard, C E; O'Toole, J K; Pantel, J; Szatkiewicz, J P; Taico, C; Zerwas, S; Trace, S E; Davis, O S P; Helder, S; Bühren, K; Burghardt, R; de Zwaan, M; Egberts, K; Ehrlich, S; Herpertz-Dahlmann, B; Herzog, W; Imgart, H; Scherag, A; Scherag, S; Zipfel, S; Boni, C; Ramoz, N; Versini, A; Brandys, M K; Danner, U N; de Kovel, C; Hendriks, J; Koeleman, B P C; Ophoff, R A; Strengman, E; van Elburg, A A; Bruson, A; Clementi, M; Degortes, D; Forzan, M; Tenconi, E; Docampo, E; Escaramís, G; Jiménez-Murcia, S; Lissowska, J; Rajewski, A; Szeszenia-Dabrowska, N; Slopien, A; Hauser, J; Karhunen, L; Meulenbelt, I; Slagboom, P E; Tortorella, A; Maj, M; Dedoussis, G; Dikeos, D; Gonidakis, F; Tziouvas, K; Tsitsika, A; Papezova, H; Slachtova, L; Martaskova, D; Kennedy, J L; Levitan, R D; Yilmaz, Z; Huemer, J; Koubek, D; Merl, E; Wagner, G; Lichtenstein, P; Breen, G; Cohen-Woods, S; Farmer, A; McGuffin, P; Cichon, S; Giegling, I; Herms, S; Rujescu, D; Schreiber, S; Wichmann, H-E; Dina, C; Sladek, R; Gambaro, G; Soranzo, N; Julia, A; Marsal, S; Rabionet, R; Gaborieau, V; Dick, D M; Palotie, A; Ripatti, S; Widén, E; Andreassen, O A; Espeseth, T; Lundervold, A; Reinvang, I; Steen, V M; Le Hellard, S; Mattingsdal, M; Ntalla, I; Bencko, V; Foretova, L; Janout, V; Navratilova, M; Gallinger, S; Pinto, D; Scherer, S W; Aschauer, H; Carlberg, L; Schosser, A; Alfredsson, L; Ding, B; Klareskog, L; Padyukov, L; Courtet, P; Guillaume, S; Jaussent, I; Finan, C; Kalsi, G; Roberts, M; Logan, D W; Peltonen, L; Ritchie, G R S; Barrett, J C; Estivill, X; Hinney, A; Sullivan, P F; Collier, D A; Zeggini, E; Bulik, C M

2014-10-01

Anorexia nervosa (AN) is a complex and heritable eating disorder characterized by dangerously low body weight. Neither candidate gene studies nor an initial genome-wide association study (GWAS) have yielded significant and replicated results. We performed a GWAS in 2907 cases with AN from 14 countries (15 sites) and 14 860 ancestrally matched controls as part of the Genetic Consortium for AN (GCAN) and the Wellcome Trust Case Control Consortium 3 (WTCCC3). Individual association analyses were conducted in each stratum and meta-analyzed across all 15 discovery data sets. Seventy-six (72 independent) single nucleotide polymorphisms were taken forward for in silico (two data sets) or de novo (13 data sets) replication genotyping in 2677 independent AN cases and 8629 European ancestry controls along with 458 AN cases and 421 controls from Japan. The final global meta-analysis across discovery and replication data sets comprised 5551 AN cases and 21 080 controls. AN subtype analyses (1606 AN restricting; 1445 AN binge-purge) were performed. No findings reached genome-wide significance. Two intronic variants were suggestively associated: rs9839776 (P=3.01 × 10(-7)) in SOX2OT and rs17030795 (P=5.84 × 10(-6)) in PPP3CA. Two additional signals were specific to Europeans: rs1523921 (P=5.76 × 10(-)(6)) between CUL3 and FAM124B and rs1886797 (P=8.05 × 10(-)(6)) near SPATA13. Comparing discovery with replication results, 76% of the effects were in the same direction, an observation highly unlikely to be due to chance (P=4 × 10(-6)), strongly suggesting that true findings exist but our sample, the largest yet reported, was underpowered for their detection. The accrual of large genotyped AN case-control samples should be an immediate priority for the field.

A genome-wide association study of anorexia nervosa

PubMed Central

Boraska, Vesna; Franklin, Christopher S; Floyd, James AB; Thornton, Laura M; Huckins, Laura M; Southam, Lorraine; Rayner, N William; Tachmazidou, Ioanna; Klump, Kelly L; Treasure, Janet; Lewis, Cathryn M; Schmidt, Ulrike; Tozzi, Federica; Kiezebrink, Kirsty; Hebebrand, Johannes; Gorwood, Philip; Adan, Roger AH; Kas, Martien JH; Favaro, Angela; Santonastaso, Paolo; Fernández-Aranda, Fernando; Gratacos, Monica; Rybakowski, Filip; Dmitrzak-Weglarz, Monika; Kaprio, Jaakko; Keski-Rahkonen, Anna; Raevuori, Anu; Van Furth, Eric F; Landt, Margarita CT Slof-Op t; Hudson, James I; Reichborn-Kjennerud, Ted; Knudsen, Gun Peggy S; Monteleone, Palmiero; Kaplan, Allan S; Karwautz, Andreas; Hakonarson, Hakon; Berrettini, Wade H; Guo, Yiran; Li, Dong; Schork, Nicholas J.; Komaki, Gen; Ando, Tetsuya; Inoko, Hidetoshi; Esko, Tõnu; Fischer, Krista; Männik, Katrin; Metspalu, Andres; Baker, Jessica H; Cone, Roger D; Dackor, Jennifer; DeSocio, Janiece E; Hilliard, Christopher E; O'Toole, Julie K; Pantel, Jacques; Szatkiewicz, Jin P; Taico, Chrysecolla; Zerwas, Stephanie; Trace, Sara E; Davis, Oliver SP; Helder, Sietske; Bühren, Katharina; Burghardt, Roland; de Zwaan, Martina; Egberts, Karin; Ehrlich, Stefan; Herpertz-Dahlmann, Beate; Herzog, Wolfgang; Imgart, Hartmut; Scherag, André; Scherag, Susann; Zipfel, Stephan; Boni, Claudette; Ramoz, Nicolas; Versini, Audrey; Brandys, Marek K; Danner, Unna N; de Kovel, Carolien; Hendriks, Judith; Koeleman, Bobby PC; Ophoff, Roel A; Strengman, Eric; van Elburg, Annemarie A; Bruson, Alice; Clementi, Maurizio; Degortes, Daniela; Forzan, Monica; Tenconi, Elena; Docampo, Elisa; Escaramís, Geòrgia; Jiménez-Murcia, Susana; Lissowska, Jolanta; Rajewski, Andrzej; Szeszenia-Dabrowska, Neonila; Slopien, Agnieszka; Hauser, Joanna; Karhunen, Leila; Meulenbelt, Ingrid; Slagboom, P Eline; Tortorella, Alfonso; Maj, Mario; Dedoussis, George; Dikeos, Dimitris; Gonidakis, Fragiskos; Tziouvas, Konstantinos; Tsitsika, Artemis; Papezova, Hana; Slachtova, Lenka; Martaskova, Debora; Kennedy, James L.; Levitan, Robert D.; Yilmaz, Zeynep; Huemer, Julia; Koubek, Doris; Merl, Elisabeth; Wagner, Gudrun; Lichtenstein, Paul; Breen, Gerome; Cohen-Woods, Sarah; Farmer, Anne; McGuffin, Peter; Cichon, Sven; Giegling, Ina; Herms, Stefan; Rujescu, Dan; Schreiber, Stefan; Wichmann, H-Erich; Dina, Christian; Sladek, Rob; Gambaro, Giovanni; Soranzo, Nicole; Julia, Antonio; Marsal, Sara; Rabionet, Raquel; Gaborieau, Valerie; Dick, Danielle M; Palotie, Aarno; Ripatti, Samuli; Widén, Elisabeth; Andreassen, Ole A; Espeseth, Thomas; Lundervold, Astri; Reinvang, Ivar; Steen, Vidar M; Le Hellard, Stephanie; Mattingsdal, Morten; Ntalla, Ioanna; Bencko, Vladimir; Foretova, Lenka; Janout, Vladimir; Navratilova, Marie; Gallinger, Steven; Pinto, Dalila; Scherer, Stephen; Aschauer, Harald; Carlberg, Laura; Schosser, Alexandra; Alfredsson, Lars; Ding, Bo; Klareskog, Lars; Padyukov, Leonid; Finan, Chris; Kalsi, Gursharan; Roberts, Marion; Logan, Darren W; Peltonen, Leena; Ritchie, Graham RS; Barrett, Jeffrey C; Estivill, Xavier; Hinney, Anke; Sullivan, Patrick F; Collier, David A; Zeggini, Eleftheria; Bulik, Cynthia M

2015-01-01

Anorexia nervosa (AN) is a complex and heritable eating disorder characterized by dangerously low body weight. Neither candidate gene studies nor an initial genome wide association study (GWAS) have yielded significant and replicated results. We performed a GWAS in 2,907 cases with AN from 14 countries (15 sites) and 14,860 ancestrally matched controls as part of the Genetic Consortium for AN (GCAN) and the Wellcome Trust Case Control Consortium 3 (WTCCC3). Individual association analyses were conducted in each stratum and meta-analyzed across all 15 discovery datasets. Seventy-six (72 independent) SNPs were taken forward for in silico (two datasets) or de novo (13 datasets) replication genotyping in 2,677 independent AN cases and 8,629 European ancestry controls along with 458 AN cases and 421 controls from Japan. The final global meta-analysis across discovery and replication datasets comprised 5,551 AN cases and 21,080 controls. AN subtype analyses (1,606 AN restricting; 1,445 AN binge-purge) were performed. No findings reached genome-wide significance. Two intronic variants were suggestively associated: rs9839776 (P=3.01×10-7) in SOX2OT and rs17030795 (P=5.84×10-6) in PPP3CA. Two additional signals were specific to Europeans: rs1523921 (P=5.76×10-6) between CUL3 and FAM124B and rs1886797 (P=8.05×10-6) near SPATA13. Comparing discovery to replication results, 76% of the effects were in the same direction, an observation highly unlikely to be due to chance (P=4×10-6), strongly suggesting that true findings exist but that our sample, the largest yet reported, was underpowered for their detection. The accrual of large genotyped AN case-control samples should be an immediate priority for the field. PMID:24514567

50 years of the International Committee on Taxonomy of Viruses: progress and prospects.

PubMed

Adams, Michael J; Lefkowitz, Elliot J; King, Andrew M Q; Harrach, Balázs; Harrison, Robert L; Knowles, Nick J; Kropinski, Andrew M; Krupovic, Mart; Kuhn, Jens H; Mushegian, Arcady R; Nibert, Max L; Sabanadzovic, Sead; Sanfaçon, Hélène; Siddell, Stuart G; Simmonds, Peter; Varsani, Arvind; Zerbini, Francisco Murilo; Orton, Richard J; Smith, Donald B; Gorbalenya, Alexander E; Davison, Andrew J

2017-05-01

We mark the 50th anniversary of the International Committee on Taxonomy of Viruses (ICTV) by presenting a brief history of the organization since its foundation, showing how it has adapted to advancements in our knowledge of virus diversity and the methods used to characterize it. We also outline recent developments, supported by a grant from the Wellcome Trust (UK), that are facilitating substantial changes in the operations of the ICTV and promoting dialogue with the virology community. These developments will generate improved online resources, including a freely available and regularly updated ICTV Virus Taxonomy Report. They also include a series of meetings between the ICTV and the broader community focused on some of the major challenges facing virus taxonomy, with the outcomes helping to inform the future policy and practice of the ICTV.

A high HIV-1 strain variability in London, UK, revealed by full-genome analysis: Results from the ICONIC project.

PubMed

Yebra, Gonzalo; Frampton, Dan; Gallo Cassarino, Tiziano; Raffle, Jade; Hubb, Jonathan; Ferns, R Bridget; Waters, Laura; Tong, C Y William; Kozlakidis, Zisis; Hayward, Andrew; Kellam, Paul; Pillay, Deenan; Clark, Duncan; Nastouli, Eleni; Leigh Brown, Andrew J

2018-01-01

The ICONIC project has developed an automated high-throughput pipeline to generate HIV nearly full-length genomes (NFLG, i.e. from gag to nef) from next-generation sequencing (NGS) data. The pipeline was applied to 420 HIV samples collected at University College London Hospitals NHS Trust and Barts Health NHS Trust (London) and sequenced using an Illumina MiSeq at the Wellcome Trust Sanger Institute (Cambridge). Consensus genomes were generated and subtyped using COMET, and unique recombinants were studied with jpHMM and SimPlot. Maximum-likelihood phylogenetic trees were constructed using RAxML to identify transmission networks using the Cluster Picker. The pipeline generated sequences of at least 1Kb of length (median = 7.46Kb, IQR = 4.01Kb) for 375 out of the 420 samples (89%), with 174 (46.4%) being NFLG. A total of 365 sequences (169 of them NFLG) corresponded to unique subjects and were included in the down-stream analyses. The most frequent HIV subtypes were B (n = 149, 40.8%) and C (n = 77, 21.1%) and the circulating recombinant form CRF02_AG (n = 32, 8.8%). We found 14 different CRFs (n = 66, 18.1%) and multiple URFs (n = 32, 8.8%) that involved recombination between 12 different subtypes/CRFs. The most frequent URFs were B/CRF01_AE (4 cases) and A1/D, B/C, and B/CRF02_AG (3 cases each). Most URFs (19/26, 73%) lacked breakpoints in the PR+RT pol region, rendering them undetectable if only that was sequenced. Twelve (37.5%) of the URFs could have emerged within the UK, whereas the rest were probably imported from sub-Saharan Africa, South East Asia and South America. For 2 URFs we found highly similar pol sequences circulating in the UK. We detected 31 phylogenetic clusters using the full dataset: 25 pairs (mostly subtypes B and C), 4 triplets and 2 quadruplets. Some of these were not consistent across different genes due to inter- and intra-subtype recombination. Clusters involved 70 sequences, 19.2% of the dataset. The initial analysis of genome sequences detected substantial hidden variability in the London HIV epidemic. Analysing full genome sequences, as opposed to only PR+RT, identified previously undetected recombinants. It provided a more reliable description of CRFs (that would be otherwise misclassified) and transmission clusters.

Scalable privacy-preserving data sharing methodology for genome-wide association studies.

PubMed

Yu, Fei; Fienberg, Stephen E; Slavković, Aleksandra B; Uhler, Caroline

2014-08-01

The protection of privacy of individual-level information in genome-wide association study (GWAS) databases has been a major concern of researchers following the publication of "an attack" on GWAS data by Homer et al. (2008). Traditional statistical methods for confidentiality and privacy protection of statistical databases do not scale well to deal with GWAS data, especially in terms of guarantees regarding protection from linkage to external information. The more recent concept of differential privacy, introduced by the cryptographic community, is an approach that provides a rigorous definition of privacy with meaningful privacy guarantees in the presence of arbitrary external information, although the guarantees may come at a serious price in terms of data utility. Building on such notions, Uhler et al. (2013) proposed new methods to release aggregate GWAS data without compromising an individual's privacy. We extend the methods developed in Uhler et al. (2013) for releasing differentially-private χ(2)-statistics by allowing for arbitrary number of cases and controls, and for releasing differentially-private allelic test statistics. We also provide a new interpretation by assuming the controls' data are known, which is a realistic assumption because some GWAS use publicly available data as controls. We assess the performance of the proposed methods through a risk-utility analysis on a real data set consisting of DNA samples collected by the Wellcome Trust Case Control Consortium and compare the methods with the differentially-private release mechanism proposed by Johnson and Shmatikov (2013). Copyright © 2014 Elsevier Inc. All rights reserved.

Genetic liability for schizophrenia predicts risk of immune disorders.

PubMed

Stringer, Sven; Kahn, René S; de Witte, Lot D; Ophoff, Roel A; Derks, Eske M

2014-11-01

Schizophrenia patients and their parents have an increased risk of immune disorders compared to population controls and their parents. This may be explained by genetic overlap in the pathogenesis of both types of disorders. The purpose of this study was to investigate the genetic overlap between schizophrenia and three immune disorders and to compare with the overlap between schizophrenia and two disorders not primarily characterized by immune dysregulation: bipolar disorder and type 2 diabetes. We performed a polygenic risk score analysis using results from the schizophrenia Psychiatric GWAS consortium (PGC) (8922 cases and 9528 controls) and five Wellcome Trust Case Control Consortium (WTCCC) case samples as target cases: bipolar disorder (n=1998), type 1 diabetes (n=2000), Crohn's diseases (n=2005), rheumatoid arthritis (n=1999), and type 2 diabetes (n=1999). The WTCCC British Birth Cohort and National Blood Service samples (n=3004) were used as target controls. Additionally, we tested whether schizophrenia polygenic risk scores significantly differed between patients with immune disorder, bipolar disorder, and type 2 diabetes respectively. Polygenic risk scores for schizophrenia significantly predicted disease status in all three immune disorder samples (Nagelkerke-R(2) 1.1%-1.3%; p<0.05). The polygenic risk of schizophrenia in patients with immune disorders was significantly lower than in patients with bipolar disorder (Nagelkerke-R(2) 6.0%; p<0.05), but higher than in type 2 diabetes patients (Nagelkerke-R(2) 0.5%; p<0.05). Our results suggest that genetic factors are shared between schizophrenia and immune disorders. This contributes to an accumulating body of evidence that immune processes may play a role in the etiology of schizophrenia. Copyright © 2014 Elsevier B.V. All rights reserved.

Genome-wide genetic analyses highlight mitogen-activated protein kinase (MAPK) signaling in the pathogenesis of endometriosis.

PubMed

Uimari, Outi; Rahmioglu, Nilufer; Nyholt, Dale R; Vincent, Katy; Missmer, Stacey A; Becker, Christian; Morris, Andrew P; Montgomery, Grant W; Zondervan, Krina T

2017-04-01

Do genome-wide association study (GWAS) data for endometriosis provide insight into novel biological pathways associated with its pathogenesis? GWAS analysis uncovered multiple pathways that are statistically enriched for genetic association signals, analysis of Stage A disease highlighted a novel variant in MAP3K4, while top pathways significantly associated with all endometriosis and Stage A disease included several mitogen-activated protein kinase (MAPK)-related pathways. Endometriosis is a complex disease with an estimated heritability of 50%. To date, GWAS revealed 10 genomic regions associated with endometriosis, explaining <4% of heritability, while half of the heritability is estimated to be due to common risk variants. Pathway analyses combine the evidence of single variants into gene-based measures, leveraging the aggregate effect of variants in genes and uncovering biological pathways involved in disease pathogenesis. Pathway analysis was conducted utilizing the International Endogene Consortium GWAS data, comprising 3194 surgically confirmed endometriosis cases and 7060 controls of European ancestry with genotype data imputed up to 1000 Genomes Phase three reference panel. GWAS was performed for all endometriosis cases and for Stage A (revised American Fertility Society (rAFS) I/II, n = 1686) and B (rAFS III/IV, n = 1364) cases separately. The identified significant pathways were compared with pathways previously investigated in the literature through candidate association studies. The most comprehensive biological pathway databases, MSigDB (including BioCarta, KEGG, PID, SA, SIG, ST and GO) and PANTHER were utilized to test for enrichment of genetic variants associated with endometriosis. Statistical enrichment analysis was performed using the MAGENTA (Meta-Analysis Gene-set Enrichment of variaNT Associations) software. The first genome-wide association analysis for Stage A endometriosis revealed a novel locus, rs144240142 (P = 6.45 × 10-8, OR = 1.71, 95% CI = 1.23-2.37), an intronic single-nucleotide polymorphism (SNP) within MAP3K4. This SNP was not associated with Stage B disease (P = 0.086). MAP3K4 was also shown to be differentially expressed in eutopic endometrium between Stage A endometriosis cases and controls (P = 3.8 × 10-4), but not with Stage B disease (P = 0.26). A total of 14 pathways enriched with genetic endometriosis associations were identified (false discovery rate (FDR)-P < 0.05). The pathways associated with any endometriosis were Grb2-Sos provides linkage to MAPK signaling for integrins pathway (P = 2.8 × 10-5, FDR-P = 3.0 × 10-3), Wnt signaling (P = 0.026, FDR-P = 0.026) and p130Cas linkage to MAPK signaling for integrins pathway (P = 6.0 × 10-4, FDR-P = 0.029); with Stage A endometriosis: extracellular signal-regulated kinase (ERK)1 ERK2 MAPK (P = 5.0 × 10-4, FDR-P = 5.0 × 10-4) and with Stage B endometriosis: two overlapping pathways that related to extracellular matrix biology-Core matrisome (P = 1.4 × 10-3, FDR-P = 0.013) and ECM glycoproteins (P = 1.8 × 10-3, FDR-P = 7.1 × 10-3). Genes arising from endometriosis candidate gene studies performed to date were enriched for Interleukin signaling pathway (P = 2.3 × 10-12), Apoptosis signaling pathway (P = 9.7 × 10-9) and Gonadotropin releasing hormone receptor pathway (P = 1.2 × 10-6); however, these pathways did not feature in the results based on GWAS data. Not applicable. The analysis is restricted to (i) variants in/near genes that can be assigned to pathways, excluding intergenic variants; (ii) the gene-based pathway definition as registered in the databases; (iii) women of European ancestry. The top ranked pathways associated with overall and Stage A endometriosis in particular involve integrin-mediated MAPK activation and intracellular ERK/MAPK acting downstream in the MAPK cascade, both acting in the control of cell division, gene expression, cell movement and survival. Other top enriched pathways in Stage B disease include ECM glycoprotein pathways important for extracellular structure and biochemical support. The results highlight the need for increased efforts to understand the functional role of these pathways in endometriosis pathogenesis, including the investigation of the biological effects of the genetic variants on downstream molecular processes in tissue relevant to endometriosis. Additionally, our results offer further support for the hypothesis of at least partially distinct causal pathophysiology for minimal/mild (rAFS I/II) vs. moderate/severe (rAFS III/IV) endometriosis. The genome-wide association data and Wellcome Trust Case Control Consortium (WTCCC) were generated through funding from the Wellcome Trust (WT084766/Z/08/Z, 076113 and 085475) and the National Health and Medical Research Council (NHMRC) of Australia (241944, 339462, 389927, 389875, 389891, 389892, 389938, 443036, 442915, 442981, 496610, 496739, 552485 and 552498). N.R. was funded by a grant from the Medical Research Council UK (MR/K011480/1). A.P.M. is a Wellcome Trust Senior Fellow in Basic Biomedical Science (grant WT098017). All authors declare there are no conflicts of interest. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology.

Genome-wide genetic analyses highlight mitogen-activated protein kinase (MAPK) signaling in the pathogenesis of endometriosis

PubMed Central

Uimari, Outi; Rahmioglu, Nilufer; Nyholt, Dale R.; Vincent, Katy; Missmer, Stacey A.; Becker, Christian; Morris, Andrew P.; Montgomery, Grant W.

2017-01-01

Abstract STUDY QUESTION Do genome-wide association study (GWAS) data for endometriosis provide insight into novel biological pathways associated with its pathogenesis? SUMMARY ANSWER GWAS analysis uncovered multiple pathways that are statistically enriched for genetic association signals, analysis of Stage A disease highlighted a novel variant in MAP3K4, while top pathways significantly associated with all endometriosis and Stage A disease included several mitogen-activated protein kinase (MAPK)-related pathways. WHAT IS KNOWN ALREADY Endometriosis is a complex disease with an estimated heritability of 50%. To date, GWAS revealed 10 genomic regions associated with endometriosis, explaining <4% of heritability, while half of the heritability is estimated to be due to common risk variants. Pathway analyses combine the evidence of single variants into gene-based measures, leveraging the aggregate effect of variants in genes and uncovering biological pathways involved in disease pathogenesis. STUDY DESIGN, SIZE, DURATION Pathway analysis was conducted utilizing the International Endogene Consortium GWAS data, comprising 3194 surgically confirmed endometriosis cases and 7060 controls of European ancestry with genotype data imputed up to 1000 Genomes Phase three reference panel. GWAS was performed for all endometriosis cases and for Stage A (revised American Fertility Society (rAFS) I/II, n = 1686) and B (rAFS III/IV, n = 1364) cases separately. The identified significant pathways were compared with pathways previously investigated in the literature through candidate association studies. PARTICIPANTS/MATERIALS, SETTING, METHODS The most comprehensive biological pathway databases, MSigDB (including BioCarta, KEGG, PID, SA, SIG, ST and GO) and PANTHER were utilized to test for enrichment of genetic variants associated with endometriosis. Statistical enrichment analysis was performed using the MAGENTA (Meta-Analysis Gene-set Enrichment of variaNT Associations) software. MAIN RESULTS AND THE ROLE OF CHANCE The first genome-wide association analysis for Stage A endometriosis revealed a novel locus, rs144240142 (P = 6.45 × 10−8, OR = 1.71, 95% CI = 1.23–2.37), an intronic single-nucleotide polymorphism (SNP) within MAP3K4. This SNP was not associated with Stage B disease (P = 0.086). MAP3K4 was also shown to be differentially expressed in eutopic endometrium between Stage A endometriosis cases and controls (P = 3.8 × 10−4), but not with Stage B disease (P = 0.26). A total of 14 pathways enriched with genetic endometriosis associations were identified (false discovery rate (FDR)-P < 0.05). The pathways associated with any endometriosis were Grb2-Sos provides linkage to MAPK signaling for integrins pathway (P = 2.8 × 10−5, FDR-P = 3.0 × 10−3), Wnt signaling (P = 0.026, FDR-P = 0.026) and p130Cas linkage to MAPK signaling for integrins pathway (P = 6.0 × 10−4, FDR-P = 0.029); with Stage A endometriosis: extracellular signal-regulated kinase (ERK)1 ERK2 MAPK (P = 5.0 × 10−4, FDR-P = 5.0 × 10−4) and with Stage B endometriosis: two overlapping pathways that related to extracellular matrix biology—Core matrisome (P = 1.4 × 10−3, FDR-P = 0.013) and ECM glycoproteins (P = 1.8 × 10−3, FDR-P = 7.1 × 10−3). Genes arising from endometriosis candidate gene studies performed to date were enriched for Interleukin signaling pathway (P = 2.3 × 10−12), Apoptosis signaling pathway (P = 9.7 × 10−9) and Gonadotropin releasing hormone receptor pathway (P = 1.2 × 10−6); however, these pathways did not feature in the results based on GWAS data. LARGE SCALE DATA Not applicable. LIMITATIONS, REASONS FOR CAUTION The analysis is restricted to (i) variants in/near genes that can be assigned to pathways, excluding intergenic variants; (ii) the gene-based pathway definition as registered in the databases; (iii) women of European ancestry. WIDER IMPLICATIONS OF THE FINDINGS The top ranked pathways associated with overall and Stage A endometriosis in particular involve integrin-mediated MAPK activation and intracellular ERK/MAPK acting downstream in the MAPK cascade, both acting in the control of cell division, gene expression, cell movement and survival. Other top enriched pathways in Stage B disease include ECM glycoprotein pathways important for extracellular structure and biochemical support. The results highlight the need for increased efforts to understand the functional role of these pathways in endometriosis pathogenesis, including the investigation of the biological effects of the genetic variants on downstream molecular processes in tissue relevant to endometriosis. Additionally, our results offer further support for the hypothesis of at least partially distinct causal pathophysiology for minimal/mild (rAFS I/II) vs. moderate/severe (rAFS III/IV) endometriosis. STUDY FUNDING/COMPETING INTEREST(S) The genome-wide association data and Wellcome Trust Case Control Consortium (WTCCC) were generated through funding from the Wellcome Trust (WT084766/Z/08/Z, 076113 and 085475) and the National Health and Medical Research Council (NHMRC) of Australia (241944, 339462, 389927, 389875, 389891, 389892, 389938, 443036, 442915, 442981, 496610, 496739, 552485 and 552498). N.R. was funded by a grant from the Medical Research Council UK (MR/K011480/1). A.P.M. is a Wellcome Trust Senior Fellow in Basic Biomedical Science (grant WT098017). All authors declare there are no conflicts of interest. PMID:28333195

[The program of Founding Research Centers for Emerging and Reemerging Infectious Diseases: the present status and future prospects].

PubMed

Okamoto, Yoshiko; Nagai, Yoshiyuki

2007-12-01

The program of Founding Research Centers for Emerging and Reemerging Infectious Diseases was commenced in 2005 with an outline for Japanese universities and research institutions to establish bilateral collaboration research bases in countries where emerging and reemerging infections are breaking out or will likely break out. So far, six universities and two institutions are participating in the program and ten collaboration bases have been established in six countries (five in Asia and one in Africa). Each research base aims to contribute to the security and safety of the partner and own countries by facilitating better understanding of infectious diseases, technology innovation in diagnosis, therapy and prevention, and human resources development. The experiences of the Reseau International des Instituts Pasteur (RIIP), France, and the Wellcome Trust Southeast Asian Tropical Medicine Research Units (Oxford Network), United Kingdom, which appear to share similar missions, suggest that infectious diseases research that is based on overseas research bases can produce first-time results through the building of long-term mutual trust with the counterparts. By referring to these networks as models, Japan's program should be implemented over the long run but not be based on a short-time perspective. Thus, secure funding is a major issue.

Malaria research in Malawi from 1984 to 2016: a literature review and bibliometric analysis.

PubMed

Mwendera, Chikondi A; de Jager, Christiaan; Longwe, Herbert; Hongoro, Charles; Mutero, Clifford M; Phiri, Kamija S

2017-06-12

Malaria research can play a vital role in addressing the malaria burden in Malawi. An organized approach in addressing malaria in Malawi started in 1984 by the establishment of the first National Malaria Control Programme and research was recognized to be significant. This study aimed to assess the type and amount of malaria research conducted in Malawi from 1984 to 2016 and its related source of funding. A systematic literature search was conducted in the Medline/PubMed database for Malawian publications and approved malaria studies from two Ethical Committees were examined. Bibliometric analysis was utilized to capture the affiliations of first and senior/last authors, funding acknowledgements, while titles, abstracts and accessed full text were examined for research type. A total of 483 publications and 165 approved studies were analysed. Clinical and basic research in the fields of malaria in pregnancy 105 (21.5%), severe malaria 97 (20.1%) and vector and/or agent dynamics 69 (14.3%) dominated in the publications while morbidity 33 (20%), severe malaria 28 (17%) and Health Policy and Systems Research 24 (14.5%) dominated in the approved studies. In the publications, 146 (30%) first authors and 100 (21%) senior authors, and 88 (53.3%) principal investigators in approved studies were affiliated to Malawian-based institutions. Most researchers were affiliated to the Malawi-Liverpool Wellcome Trust, College of Medicine, Blantyre Malaria Project, Ministry of Health, and Malaria Alert Centre. The major malaria research funders were the National Institute for Health/USA, Wellcome Trust and the US Agency for International Development. Only three (2.5%) out of 118 journals publishing research on malaria in Malawi were from Africa and the Malaria Journal, with 76 (15.7%) publications, published most of the research from Malawi, followed by the American Journal of Tropical Medicine and Hygiene with 57 (11.8%) in comparison to only 13 (2.7%) published in the local Malawi Medical Journal. Clinical and basic research, which is mostly funded externally, in the fields of malaria in pregnancy, severe malaria and vector and/or agent dynamics dominated, while health policy and system research was least supported. The quantity may reflect scientific research activity but the initial primary impact is contribution to policy development.

The geography of imported malaria to non-endemic countries: a meta-analysis of nationally reported statistics.

PubMed

Tatem, Andrew J; Jia, Peng; Ordanovich, Dariya; Falkner, Michael; Huang, Zhuojie; Howes, Rosalind; Hay, Simon I; Gething, Peter W; Smith, David L

2017-01-01

Malaria remains a problem for many countries classified as malaria free through cases imported from endemic regions. Imported cases to non-endemic countries often result in delays in diagnosis, are expensive to treat, and can sometimes cause secondary local transmission. The movement of malaria in endemic countries has also contributed to the spread of drug resistance and threatens long-term eradication goals. Here we focused on quantifying the international movements of malaria to improve our understanding of these phenomena and facilitate the design of mitigation strategies. In this meta-analysis, we studied the database of publicly available nationally reported statistics on imported malaria in the past 10 years, covering more than 50 000 individual cases. We obtained data from 40 non-endemic countries and recorded the geographical variations. Infection movements were strongly skewed towards a small number of high-traffic routes between 2005 and 2015, with the west Africa region accounting for 56% (13 947/24 941) of all imported cases to non-endemic countries with a reported travel destination, and France and the UK receiving the highest number of cases, with more than 4000 reported cases per year on average. Countries strongly linked by movements of imported cases are grouped by historical, language, and travel ties. There is strong spatial clustering of plasmodium species types. The architecture of the air network, historical ties, demographics of travellers, and malaria endemicity contribute to highly heterogeneous patterns of numbers, routes, and species compositions of parasites transported. With global malaria eradication on the international agenda, malaria control altering local transmission, and the threat of drug resistance, understanding these patterns and their drivers is increasing in importance. Bill & Melinda Gates Foundation, National Institutes of Health, UK Medical Research Council, UK Department for International Development, Wellcome Trust. Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY license. Published by Elsevier Ltd.. All rights reserved.

Analyzing Genome-Wide Association Studies with an FDR Controlling Modification of the Bayesian Information Criterion

PubMed Central

Dolejsi, Erich; Bodenstorfer, Bernhard; Frommlet, Florian

2014-01-01

The prevailing method of analyzing GWAS data is still to test each marker individually, although from a statistical point of view it is quite obvious that in case of complex traits such single marker tests are not ideal. Recently several model selection approaches for GWAS have been suggested, most of them based on LASSO-type procedures. Here we will discuss an alternative model selection approach which is based on a modification of the Bayesian Information Criterion (mBIC2) which was previously shown to have certain asymptotic optimality properties in terms of minimizing the misclassification error. Heuristic search strategies are introduced which attempt to find the model which minimizes mBIC2, and which are efficient enough to allow the analysis of GWAS data. Our approach is implemented in a software package called MOSGWA. Its performance in case control GWAS is compared with the two algorithms HLASSO and d-GWASelect, as well as with single marker tests, where we performed a simulation study based on real SNP data from the POPRES sample. Our results show that MOSGWA performs slightly better than HLASSO, where specifically for more complex models MOSGWA is more powerful with only a slight increase in Type I error. On the other hand according to our simulations GWASelect does not at all control the type I error when used to automatically determine the number of important SNPs. We also reanalyze the GWAS data from the Wellcome Trust Case-Control Consortium and compare the findings of the different procedures, where MOSGWA detects for complex diseases a number of interesting SNPs which are not found by other methods. PMID:25061809

Design of the Coronary ARtery DIsease Genome-Wide Replication And Meta-Analysis (CARDIoGRAM) Study: A Genome-wide association meta-analysis involving more than 22 000 cases and 60 000 controls.

PubMed

Preuss, Michael; König, Inke R; Thompson, John R; Erdmann, Jeanette; Absher, Devin; Assimes, Themistocles L; Blankenberg, Stefan; Boerwinkle, Eric; Chen, Li; Cupples, L Adrienne; Hall, Alistair S; Halperin, Eran; Hengstenberg, Christian; Holm, Hilma; Laaksonen, Reijo; Li, Mingyao; März, Winfried; McPherson, Ruth; Musunuru, Kiran; Nelson, Christopher P; Burnett, Mary Susan; Epstein, Stephen E; O'Donnell, Christopher J; Quertermous, Thomas; Rader, Daniel J; Roberts, Robert; Schillert, Arne; Stefansson, Kari; Stewart, Alexandre F R; Thorleifsson, Gudmar; Voight, Benjamin F; Wells, George A; Ziegler, Andreas; Kathiresan, Sekar; Reilly, Muredach P; Samani, Nilesh J; Schunkert, Heribert

2010-10-01

Recent genome-wide association studies (GWAS) of myocardial infarction (MI) and other forms of coronary artery disease (CAD) have led to the discovery of at least 13 genetic loci. In addition to the effect size, power to detect associations is largely driven by sample size. Therefore, to maximize the chance of finding novel susceptibility loci for CAD and MI, the Coronary ARtery DIsease Genome-wide Replication And Meta-analysis (CARDIoGRAM) consortium was formed. CARDIoGRAM combines data from all published and several unpublished GWAS in individuals with European ancestry; includes >22 000 cases with CAD, MI, or both and >60 000 controls; and unifies samples from the Atherosclerotic Disease VAscular functioN and genetiC Epidemiology study, CADomics, Cohorts for Heart and Aging Research in Genomic Epidemiology, deCODE, the German Myocardial Infarction Family Studies I, II, and III, Ludwigshafen Risk and Cardiovascular Heath Study/AtheroRemo, MedStar, Myocardial Infarction Genetics Consortium, Ottawa Heart Genomics Study, PennCath, and the Wellcome Trust Case Control Consortium. Genotyping was carried out on Affymetrix or Illumina platforms followed by imputation of genotypes in most studies. On average, 2.2 million single nucleotide polymorphisms were generated per study. The results from each study are combined using meta-analysis. As proof of principle, we meta-analyzed risk variants at 9p21 and found that rs1333049 confers a 29% increase in risk for MI per copy (P=2×10⁻²⁰). CARDIoGRAM is poised to contribute to our understanding of the role of common genetic variation on risk for CAD and MI.

A high HIV-1 strain variability in London, UK, revealed by full-genome analysis: Results from the ICONIC project

PubMed Central

Frampton, Dan; Gallo Cassarino, Tiziano; Raffle, Jade; Hubb, Jonathan; Ferns, R. Bridget; Waters, Laura; Tong, C. Y. William; Kozlakidis, Zisis; Hayward, Andrew; Kellam, Paul; Pillay, Deenan; Clark, Duncan; Nastouli, Eleni; Leigh Brown, Andrew J.

2018-01-01

Background & methods The ICONIC project has developed an automated high-throughput pipeline to generate HIV nearly full-length genomes (NFLG, i.e. from gag to nef) from next-generation sequencing (NGS) data. The pipeline was applied to 420 HIV samples collected at University College London Hospitals NHS Trust and Barts Health NHS Trust (London) and sequenced using an Illumina MiSeq at the Wellcome Trust Sanger Institute (Cambridge). Consensus genomes were generated and subtyped using COMET, and unique recombinants were studied with jpHMM and SimPlot. Maximum-likelihood phylogenetic trees were constructed using RAxML to identify transmission networks using the Cluster Picker. Results The pipeline generated sequences of at least 1Kb of length (median = 7.46Kb, IQR = 4.01Kb) for 375 out of the 420 samples (89%), with 174 (46.4%) being NFLG. A total of 365 sequences (169 of them NFLG) corresponded to unique subjects and were included in the down-stream analyses. The most frequent HIV subtypes were B (n = 149, 40.8%) and C (n = 77, 21.1%) and the circulating recombinant form CRF02_AG (n = 32, 8.8%). We found 14 different CRFs (n = 66, 18.1%) and multiple URFs (n = 32, 8.8%) that involved recombination between 12 different subtypes/CRFs. The most frequent URFs were B/CRF01_AE (4 cases) and A1/D, B/C, and B/CRF02_AG (3 cases each). Most URFs (19/26, 73%) lacked breakpoints in the PR+RT pol region, rendering them undetectable if only that was sequenced. Twelve (37.5%) of the URFs could have emerged within the UK, whereas the rest were probably imported from sub-Saharan Africa, South East Asia and South America. For 2 URFs we found highly similar pol sequences circulating in the UK. We detected 31 phylogenetic clusters using the full dataset: 25 pairs (mostly subtypes B and C), 4 triplets and 2 quadruplets. Some of these were not consistent across different genes due to inter- and intra-subtype recombination. Clusters involved 70 sequences, 19.2% of the dataset. Conclusions The initial analysis of genome sequences detected substantial hidden variability in the London HIV epidemic. Analysing full genome sequences, as opposed to only PR+RT, identified previously undetected recombinants. It provided a more reliable description of CRFs (that would be otherwise misclassified) and transmission clusters. PMID:29389981

Stochastic model search with binary outcomes for genome-wide association studies

PubMed Central

Malovini, Alberto; Puca, Annibale A; Bellazzi, Riccardo

2012-01-01

Objective The spread of case–control genome-wide association studies (GWASs) has stimulated the development of new variable selection methods and predictive models. We introduce a novel Bayesian model search algorithm, Binary Outcome Stochastic Search (BOSS), which addresses the model selection problem when the number of predictors far exceeds the number of binary responses. Materials and methods Our method is based on a latent variable model that links the observed outcomes to the underlying genetic variables. A Markov Chain Monte Carlo approach is used for model search and to evaluate the posterior probability of each predictor. Results BOSS is compared with three established methods (stepwise regression, logistic lasso, and elastic net) in a simulated benchmark. Two real case studies are also investigated: a GWAS on the genetic bases of longevity, and the type 2 diabetes study from the Wellcome Trust Case Control Consortium. Simulations show that BOSS achieves higher precisions than the reference methods while preserving good recall rates. In both experimental studies, BOSS successfully detects genetic polymorphisms previously reported to be associated with the analyzed phenotypes. Discussion BOSS outperforms the other methods in terms of F-measure on simulated data. In the two real studies, BOSS successfully detects biologically relevant features, some of which are missed by univariate analysis and the three reference techniques. Conclusion The proposed algorithm is an advance in the methodology for model selection with a large number of features. Our simulated and experimental results showed that BOSS proves effective in detecting relevant markers while providing a parsimonious model. PMID:22534080

Gene-Gene and Gene-Environment Interactions in Ulcerative Colitis

PubMed Central

Wang, Ming-Hsi; Fiocchi, Claudio; Zhu, Xiaofeng; Ripke, Stephan; Kamboh, M. Ilyas; Rebert, Nancy; Duerr, Richard H.; Achkar, Jean-Paul

2014-01-01

Genome-wide association studies (GWAS) have identified at least 133 ulcerative colitis (UC) associated loci. The role of genetic factors in clinical practice is not clearly defined. The relevance of genetic variants to disease pathogenesis is still uncertain because of not characterized gene-gene and gene-environment interactions. We examined the predictive value of combining the 133 UC risk loci with genetic interactions in an ongoing inflammatory bowel disease (IBD) GWAS. The Wellcome Trust Case-Control Consortium (WTCCC) IBD GWAS was used as a replication cohort. We applied logic regression (LR), a novel adaptive regression methodology, to search for high order interactions. Exploratory genotype correlations with UC sub-phenotypes (extent of disease, need of surgery, age of onset, extra-intestinal manifestations and primary sclerosing cholangitis (PSC)) were conducted. The combination of 133 UC loci yielded good UC risk predictability (area under the curve [AUC] of 0.86). A higher cumulative allele score predicted higher UC risk. Through LR, several lines of evidence for genetic interactions were identified and successfully replicated in the WTCCC cohort. The genetic interactions combined with the gene-smoking interaction significantly improved predictability in the model (AUC, from 0.86 to 0.89, P=3.26E-05). Explained UC variance increased from 37% to 42% after adding the interaction terms. A within case analysis found suggested genetic association with PSC. Our study demonstrates that the LR methodology allows the identification and replication of high order genetic interactions in UC GWAS datasets. UC risk can be predicted by a 133 loci and improved by adding gene-gene and gene-environment interactions. PMID:24241240

Hierarchical Naive Bayes for genetic association studies.

PubMed

Malovini, Alberto; Barbarini, Nicola; Bellazzi, Riccardo; de Michelis, Francesca

2012-01-01

Genome Wide Association Studies represent powerful approaches that aim at disentangling the genetic and molecular mechanisms underlying complex traits. The usual "one-SNP-at-the-time" testing strategy cannot capture the multi-factorial nature of this kind of disorders. We propose a Hierarchical Naïve Bayes classification model for taking into account associations in SNPs data characterized by Linkage Disequilibrium. Validation shows that our model reaches classification performances superior to those obtained by the standard Naïve Bayes classifier for simulated and real datasets. In the Hierarchical Naïve Bayes implemented, the SNPs mapping to the same region of Linkage Disequilibrium are considered as "details" or "replicates" of the locus, each contributing to the overall effect of the region on the phenotype. A latent variable for each block, which models the "population" of correlated SNPs, can be then used to summarize the available information. The classification is thus performed relying on the latent variables conditional probability distributions and on the SNPs data available. The developed methodology has been tested on simulated datasets, each composed by 300 cases, 300 controls and a variable number of SNPs. Our approach has been also applied to two real datasets on the genetic bases of Type 1 Diabetes and Type 2 Diabetes generated by the Wellcome Trust Case Control Consortium. The approach proposed in this paper, called Hierarchical Naïve Bayes, allows dealing with classification of examples for which genetic information of structurally correlated SNPs are available. It improves the Naïve Bayes performances by properly handling the within-loci variability.

The HABP2 G534E Variant Is an Unlikely Cause of Familial Nonmedullary Thyroid Cancer

PubMed Central

Sahasrabudhe, Ruta; Stultz, Jacob; Williamson, John; Lott, Paul; Estrada, Ana; Bohorquez, Mabel; Palles, Claire; Polanco-Echeverry, Guadalupe; Jaeger, Emma; Martin, Lynn; Echeverry, Maria Magdalena; Tomlinson, Ian

2016-01-01

Context: A recent study reported the nonsynonymous G534E (rs7080536, allele A) variant in the HABP2 gene as causal in familial nonmedullary thyroid cancer (NMTC). Objective: The objective of this study was to evaluate the causality of HABP2 G534E in the TCUKIN study, a multicenter population-based study of NMTC cases from the British Isles. Design and Setting: A case-control analysis of rs7080536 genotypes was performed using 2105 TCUKIN cases and 5172 UK controls. Participants: Cases comprised 2105 NMTC cases. Patient subgroups with papillary (n = 1056), follicular (n = 691), and Hürthle cell (n = 86) thyroid cancer cases were studied separately. Controls comprised 5172 individuals from the 1958 Birth Cohort and the National Blood Donor Service study. The controls had previously been genotyped using genome-wide single nucleotide polymorphism arrays by the Wellcome Trust Case Control Consortium study. Outcome Measures: Association between HABP2 G534E (rs7080536A) and NMTC risk was evaluated using logistic regression. Results: The frequency of the HABP2 G534E was 4.2% in cases and 4.6% in controls. We did not detect an association between this variant and NMTC risk (odds ratio [OR] = 0.896; 95% confidence interval, 0.746–1.071; P = .233). We also failed to detect an association between the HABP2 G534E and cases with papillary (1056 cases; G534E frequency = 3.5%; OR = 0.74; P = .017), follicular (691 cases; G534E frequency = 4.7%; OR = 1.00; P = 1.000), or Hürthle cell (86 cases; G534E frequency = 6.3%; OR = 1.40; P = .279) histology. Conclusions: We found that HABP2 G534E is a low-to-moderate frequency variant in the British Isles and failed to detect an association with NMTC risk, independent of histological type. Hence, our study does not implicate HABP2 G534E or a correlated polymorphism in familial NMTC, and additional data are required before using this variant in NMTC risk assessment. PMID:26691890

The HABP2 G534E variant is an unlikely cause of familial non-medullary thyroid cancer.

PubMed

Sahasrabudhe, Ruta; Stultz, Jacob; Williamson, John; Lott, Paul; Estrada, Ana; Bohorquez, Mabel; Palles, Claire; Polanco-Echeverry, Guadalupe; Jaeger, Emma; Martin, Lynn; Magdalena Echeverry, Maria; Tomlinson, Ian; Carvajal-Carmona, Luis G

2016-03-01

A recent study reported the non-synonymous G534E (rs7080536, allele A) variant in the HABP2 gene as causal in familial non-medullary thyroid cancer (NMTC). The objective of this study was to evaluate the causality of HABP2 G534E in the TCUKIN study, a multi-center population based study of NMTC cases from the British Isles. A case-control analysis of rs7080536 genotypes was performed using 2,105 TCUKIN cases and 5,172 UK controls. Cases comprised 2,105 NMTC cases. Patients sub-groups with papillary (N=1,056), follicular (N=691) and Hurthle cell (N=86) TC cases were studied separately. Controls comprised 5,172 individuals from the 1958 Birth Cohort (58C) and the National Blood Donor Service (NBS) study. The controls had previously been genotyped using genome-wide SNP arrays by the Wellcome Trust Case Control Consortium study. Measures: Association between HABP2 G534E (rs7080536A) and NMTC risk was evaluated using logistic regression. The frequency of HABP2 G534E was 4.2% in cases and 4.6% in controls. We did not detect an association between this variant and NMTC risk (OR=0.896, 95% CI: 0.746-1.071, P=0.233). We also failed to detect an association between HABP2 G534E and cases with papillary (1056 cases, G534E frequency= 3.5%, OR=0.74, P=0.017), follicular (691 cases, G534E frequency= 4.7%, OR=1.00, P=1.000) or Hurthle cell (86 cases, G534E frequency= 6.3%, OR=1.40, P=0.279) histology. We found that HABP2 G534E is a low-to-moderate frequency variant in the British Isles and failed to detect an association with NMTC risk, independent of histological type. Hence, our study does not implicate HABP2 G534E or a correlated polymorphism in familial NMTC and additional data are required before using this variant in NMTC risk assessment.

CHEK2, MGMT, SULT1E1 and SULT1A1 polymorphisms and endometrial cancer risk.

PubMed

O'Mara, Tracy A; Ferguson, Kaltin; Fahey, Paul; Marquart, Louise; Yang, Hannah P; Lissowska, Jolanta; Chanock, Stephen; Garcia-Closas, Montserrat; Thompson, Deborah J; Healey, Catherine S; Dunning, Alison M; Easton, Douglas F; Webb, Penelope M; Spurdle, Amanda B

2011-08-01

Several single nucleotide polymorphisms (SNPs) in candidate genes of DNA repair and hormone pathways have been reported to be associated with endometrial cancer risk. We sought to confirm these associations in two endometrial cancer case-control sample sets and used additional data from an existing genome-wide association study to prioritize an additional SNP for further study. Five SNPs from the CHEK2, MGMT, SULT1E1 and SULT1A1 genes, genotyped in a total of 1597 cases and 1507 controls from two case-control studies, the Australian National Endometrial Cancer Study and the Polish Endometrial Cancer Study, were assessed for association with endometrial cancer risk using logistic regression analysis. Imputed data was drawn for CHEK2 rs8135424 for 666 cases from the Study of Epidemiology and Risk factors in Cancer Heredity study and 5190 controls from the Wellcome Trust Case Control Consortium. We observed no association between SNPs in the MGMT, SULT1E1 and SULT1A1 genes and endometrial cancer risk. The A allele of the rs8135424 CHEK2 SNP was associated with decreased risk of endometrial cancer (adjusted per-allele OR 0.83; 95%CI 0.70-0.98; p = .03) however this finding was opposite to that previously published. Imputed data for CHEK2 rs8135424 supported the direction of effect reported in this study (OR 0.85; 95% CI 0.65-1.10). Previously reported endometrial cancer risk associations with SNPs from in genes involved in estrogen metabolism and DNA repair were not replicated in our larger study population. This study highlights the need for replication of candidate gene SNP studies using large sample groups, to confirm risk associations and better prioritize downstream studies to assess the causal relationship between genetic variants and cancer risk. Our findings suggest that the CHEK2 SNP rs8135424 be prioritized for further study as a genetic factor associated with risk of endometrial cancer.

Back to the Future: Lessons Learned in Modern Target-based and Whole-Cell Lead Optimization of Antimalarials

PubMed Central

Chatterjee, Arnab K; Yeung, Bryan KS

2012-01-01

Antimalarial drug discovery has historically benefited from the whole-cell (phenotypic) screening approach to identify lead molecules in the search for new drugs. However over the past two decades there has been a shift in the pharmaceutical industry to move away from whole-cell screening to target-based approaches. As part of a Wellcome Trust and Medicines for Malaria Venture (MMV) funded consortium to discover new blood-stage antimalarials, we used both approaches to identify new antimalarial chemotypes, two of which have progressed beyond the lead optimization phase and display excellent in vivo efficacy in mice. These two advanced series were identified through a cell-based optimization devoid of target information and in this review we summarize the advantages of this approach versus a target-based optimization. Although the each lead optimization required slightly different medicinal chemistry strategies, we observed some common issues across the different the scaffolds which could be applied to other cell based lead optimization programs. PMID:22242845

Implementing a successful data-management framework: the UK10K managed access model

PubMed Central

2013-01-01

This paper outlines the history behind open access principles and describes the development of a managed access data-sharing process for the UK10K Project, currently Britain’s largest genomic sequencing consortium (2010 to 2013). Funded by the Wellcome Trust, the purpose of UK10K was two-fold: to investigate how low-frequency and rare genetic variants contribute to human disease, and to provide an enduring data resource for future research into human genetics. In this paper, we discuss the challenge of reconciling data-sharing principles with the practicalities of delivering a sequencing project of UK10K’s scope and magnitude. We describe the development of a sustainable, easy-to-use managed access system that allowed rapid access to UK10K data, while protecting the interests of participants and data generators alike. Specifically, we focus in depth on the three key issues that emerge in the data pipeline: study recruitment, data release and data access. PMID:24229443

Competence and Human Resource Development in Multinational Companies in Three European Union Member States: A Comparative Analysis between Austria, the Netherlands and the United Kingdom. CEDEFOP Panorama Series.

ERIC Educational Resources Information Center

Markowitsch, Jorg; Kollinger, Iris; Warmerdam, John; Moerel, Hans; Konrad, John; Burell, Catherine; Guile, David

A comparative analysis of human resources development and management in the subsidiaries of three multinational companies (Xerox, Glaxo Wellcome, and AXA Nordstern Colonia) was conducted in these three European Union (EU) member states: Austria, the United Kingdom, and the Netherlands. Case studies were used, focusing on competence needs and…

Epidemiological characteristics of hand-foot-and-mouth disease in China, 2008-2012

PubMed Central

Sun, Junling; Wu, Joseph T; Chang, Zhaorui; Liu, Fengfeng; Fang, Vicky J; Zheng, Yingdong; Cowling, Benjamin J; Varma, Jay K; Farrar, Jeremy J; Leung, Gabriel M; Yu, Hongjie

2014-01-01

Summary Background Hand–foot–and–mouth disease (HFMD) is a common childhood illness caused by enteroviruses. Increasingly it imposes a substantial disease burden throughout East and Southeast Asia. To better inform vaccine and other interventions, we characterized the epidemiology of HFMD in China based on enhanced surveillance. Methods We extracted epidemiological, clinical and laboratory data from reported HFMD cases during 2008–2012 and compiled climatic, geographic and demographic information. All analyses were stratified by age, disease severity, laboratory confirmation status and enterovirus subtype. Findings The surveillance registry captured 7,200,092 probable HFMD cases (annualized incidence, 1·2 per 1,000), of whom 3·7% were laboratory–confirmed and 0·03% died. Incidence and mortality were highest in children aged 12–23 months (in 2012: 38·2 cases per 1,000 and 1·5 death per 100,000). Median durations from onset to diagnosis and death were 1·5 days and 3·5 days respectively. The risk of cardiopulmonary or neurological complications was 1·1% and the severe-case fatality risk was 3·0%, with >90% of deaths associated with enterovirus 71. HFMD peaked annually in June in the North, whereas Southern China experienced semi-annual outbreaks in May and September/October. Geographic differences in seasonal patterns were weakly associated with climate and demographic factors (variance explained 8-23% and 3–19%, respectively). Interpretation This is the largest population-based study to date of the epidemiology of HFMD. Future mitigation policies should take full account of the heterogeneities of disease burden identified. Additional epidemiologic and serologic studies are warranted to elucidate local HFMD dynamics and immunity patterns and optimize interventions. Funding China–US Collaborative Program on Emerging and Re-emerging Infectious Diseases; World Health Organization; The Li Ka Shing Oxford Global Health Programme and Wellcome Trust; Harvard Center for Communicable Disease Dynamics; Health and Medical Research Fund, Government of the Hong Kong Special Administrative Region. PMID:24485991

Prevalence of infertility and help seeking among 15 000 women and men

PubMed Central

Datta, J.; Palmer, M.J.; Tanton, C.; Gibson, L.J.; Jones, K.G.; Macdowall, W.; Glasier, A.; Sonnenberg, P.; Field, N.; Mercer, C.H.; Johnson, A.M.; Wellings, K.

2016-01-01

STUDY QUESTION What is the prevalence of infertility and of help seeking among women and men in Britain? SUMMARY ANSWER One in eight women and one in ten men aged 16–74 years had experienced infertility, defined by unsuccessfully attempting pregnancy for a year or longer, and little more than half of these people sought medical or professional help. WHAT IS KNOWN ALREADY Estimates of infertility and help seeking in Britain vary widely and are not easily comparable because of different definitions and study populations. STUDY DESIGN, SIZE, DURATION A cross-sectional population survey was conducted between 2010 and 2012 with a sample of 15 162 women and men aged 16–74 years. PARTICIPANTS/MATERIALS, SETTING, METHODS Participants completed the Natsal-3 questionnaire, using computer-assisted personal interviewing (CAPI) and computer-assisted self-interview (CASI). MAIN RESULTS AND THE ROLE OF CHANCE The reported prevalence of infertility was 12.5% (CI 95% 11.7–13.3) among women and 10.1% (CI 95% 9.2–11.1) among men. Increased prevalence was associated with later cohabitation with a partner, higher socio-economic status and, for those who had a child, becoming parents at older ages. The reported prevalence of help seeking was 57.3% (CI 95% 53.6–61.0) among women and 53.2% (CI 95% 48.1–58.1) among men. Help seekers were more likely to be better educated and in higher status occupations and, among those who had a child, to have become parents later in life. LIMITATIONS, REASONS FOR CAUTION These data are cross-sectional so it is not possible to establish temporality or infer causality. Self-reported data may be subject to recall bias. WIDER IMPLICATIONS OF THE FINDINGS The study provides estimates of infertility and help seeking in Britain and the results indicate that the prevalence of infertility is higher among those delaying parenthood. Those with higher educational qualifications and occupational status are more likely to consult with medical professionals for fertility problems than others and these inequalities in help seeking should be considered by clinical practice and public health. STUDY FUNDING/COMPETING INTEREST(S) Funding was provided by grants from the Medical Research Council and the Wellcome Trust, with support from the Economic and Social Research Council and the Department of Health. AMJ is a Governor of the Wellcome Trust. Other authors have no competing interests. PMID:27365525

Prevalences of sexually transmitted infections in young adults and female sex workers in Peru: a national population-based survey.

PubMed

Cárcamo, César P; Campos, Pablo E; García, Patricia J; Hughes, James P; Garnett, Geoff P; Holmes, King K

2012-10-01

We assessed prevalences of seven sexually transmitted infections (STIs) in Peru, stratified by risk behaviours, to help to define care and prevention priorities. In a 2002 household-based survey of the general population, we enrolled randomly selected 18-29-year-old residents of 24 cities with populations greater than 50 000 people. We then surveyed female sex workers (FSWs) in these cities. We gathered data for sexual behaviour; vaginal specimens or urine for nucleic acid amplification tests for Neisseria gonorrhoeae, Chlamydia trachomatis, and Trichomonas vaginalis; and blood for serological tests for syphilis, HIV, and (in subsamples) herpes simplex virus 2 (HSV2) and human T-lymphotropic virus. This study is a registered component of the PREVEN trial, number ISRCTN43722548. 15 261 individuals from the general population and 4485 FSWs agreed to participate in our survey. Overall prevalence of infection with HSV2, weighted for city size, was 13·5% in men, 13·6% in women, and 60·6% in FSWs (all values in FSWs standardised to age composition of women in the general population). The prevalence of C trachomatis infection was 4·2% in men, 6·5% in women, and 16·4% in FSWs; of T vaginalis infection was 0·3% in men, 4·9% in women, and 7·9% in FSWs; and of syphilis was 0·5% in men, 0·4% in women, and 0·8% in FSWs. N gonorrhoeae infection had a prevalence of 0·1% in men and women, and of 1·6% in FSWs. Prevalence of HIV infection was 0·5% in men and FSWs, and 0·1% in women. Four (0·3%) of 1535 specimens were positive for human T-lymphotropic virus 1. In men, 65·0% of infections with HIV, 71·5% of N gonorrhoeae, and 41·4% of HSV2 and 60·9% of cases of syphilis were in the 13·3% who had sex with men or unprotected sex with FSWs in the past year. In women from the general population, 66·7% of infections with HIV and 16·7% of cases of syphilis were accounted for by the 4·4% who had been paid for sex by any of their past three partners. Defining of high-risk groups could guide targeting of interventions for communicable diseases-including STIs-in the general Peruvian population. Wellcome Trust-Burroughs Wellcome Fund Infectious Disease Initiative and US National Institutes of Health. Copyright © 2012 Elsevier Ltd. All rights reserved.

Evidence for somatic gene conversion and deletion in bipolar disorder, Crohn's disease, coronary artery disease, hypertension, rheumatoid arthritis, type-1 diabetes, and type-2 diabetes

PubMed Central

2011-01-01

Background During gene conversion, genetic information is transferred unidirectionally between highly homologous but non-allelic regions of DNA. While germ-line gene conversion has been implicated in the pathogenesis of some diseases, somatic gene conversion has remained technically difficult to investigate on a large scale. Methods A novel analysis technique is proposed for detecting the signature of somatic gene conversion from SNP microarray data. The Wellcome Trust Case Control Consortium has gathered SNP microarray data for two control populations and cohorts for bipolar disorder (BD), cardiovascular disease (CAD), Crohn's disease (CD), hypertension (HT), rheumatoid arthritis (RA), type-1 diabetes (T1D) and type-2 diabetes (T2D). Using the new analysis technique, the seven disease cohorts are analyzed to identify cohort-specific SNPs at which conversion is predicted. The quality of the predictions is assessed by identifying known disease associations for genes in the homologous duplicons, and comparing the frequency of such associations with background rates. Results Of 28 disease/locus pairs meeting stringent conditions, 22 show various degrees of disease association, compared with only 8 of 70 in a mock study designed to measure the background association rate (P < 10-9). Additional candidate genes are identified using less stringent filtering conditions. In some cases, somatic deletions appear likely. RA has a distinctive pattern of events relative to other diseases. Similarities in patterns are apparent between BD and HT. Conclusions The associations derived represent the first evidence that somatic gene conversion could be a significant causative factor in each of the seven diseases. The specific genes provide potential insights about disease mechanisms, and are strong candidates for further study. Please see Commentary: http://www.biomedcentral.com/1741-7015/9/13/abstract. PMID:21291537

Evidence for somatic gene conversion and deletion in bipolar disorder, Crohn's disease, coronary artery disease, hypertension, rheumatoid arthritis, type-1 diabetes, and type-2 diabetes.

PubMed

Ross, Kenneth Andrew

2011-02-03

During gene conversion, genetic information is transferred unidirectionally between highly homologous but non-allelic regions of DNA. While germ-line gene conversion has been implicated in the pathogenesis of some diseases, somatic gene conversion has remained technically difficult to investigate on a large scale. A novel analysis technique is proposed for detecting the signature of somatic gene conversion from SNP microarray data. The Wellcome Trust Case Control Consortium has gathered SNP microarray data for two control populations and cohorts for bipolar disorder (BD), cardiovascular disease (CAD), Crohn's disease (CD), hypertension (HT), rheumatoid arthritis (RA), type-1 diabetes (T1D) and type-2 diabetes (T2D). Using the new analysis technique, the seven disease cohorts are analyzed to identify cohort-specific SNPs at which conversion is predicted. The quality of the predictions is assessed by identifying known disease associations for genes in the homologous duplicons, and comparing the frequency of such associations with background rates. Of 28 disease/locus pairs meeting stringent conditions, 22 show various degrees of disease association, compared with only 8 of 70 in a mock study designed to measure the background association rate (P < 10-9). Additional candidate genes are identified using less stringent filtering conditions. In some cases, somatic deletions appear likely. RA has a distinctive pattern of events relative to other diseases. Similarities in patterns are apparent between BD and HT. The associations derived represent the first evidence that somatic gene conversion could be a significant causative factor in each of the seven diseases. The specific genes provide potential insights about disease mechanisms, and are strong candidates for further study.

Design of the Coronary ARtery DIsease Genome-Wide Replication And Meta-Analysis (CARDIoGRAM) Study

PubMed Central

Preuss, Michael; König, Inke R.; Thompson, John R.; Erdmann, Jeanette; Absher, Devin; Assimes, Themistocles L.; Blankenberg, Stefan; Boerwinkle, Eric; Chen, Li; Cupples, L. Adrienne; Hall, Alistair S.; Halperin, Eran; Hengstenberg, Christian; Holm, Hilma; Laaksonen, Reijo; Li, Mingyao; März, Winfried; McPherson, Ruth; Musunuru, Kiran; Nelson, Christopher P.; Burnett, Mary Susan; Epstein, Stephen E.; O’Donnell, Christopher J.; Quertermous, Thomas; Rader, Daniel J.; Roberts, Robert; Schillert, Arne; Stefansson, Kari; Stewart, Alexandre F.R.; Thorleifsson, Gudmar; Voight, Benjamin F.; Wells, George A.; Ziegler, Andreas; Kathiresan, Sekar; Reilly, Muredach P.; Samani, Nilesh J.; Schunkert, Heribert

2011-01-01

Background Recent genome-wide association studies (GWAS) of myocardial infarction (MI) and other forms of coronary artery disease (CAD) have led to the discovery of at least 13 genetic loci. In addition to the effect size, power to detect associations is largely driven by sample size. Therefore, to maximize the chance of finding novel susceptibility loci for CAD and MI, the Coronary ARtery DIsease Genome-wide Replication And Meta-analysis (CARDIoGRAM) consortium was formed. Methods and Results CARDIoGRAM combines data from all published and several unpublished GWAS in individuals with European ancestry; includes >22 000 cases with CAD, MI, or both and >60 000 controls; and unifies samples from the Atherosclerotic Disease VAscular functioN and genetiC Epidemiology study, CADomics, Cohorts for Heart and Aging Research in Genomic Epidemiology, deCODE, the German Myocardial Infarction Family Studies I, II, and III, Ludwigshafen Risk and Cardiovascular Heath Study/AtheroRemo, MedStar, Myocardial Infarction Genetics Consortium, Ottawa Heart Genomics Study, PennCath, and the Wellcome Trust Case Control Consortium. Genotyping was carried out on Affymetrix or Illumina platforms followed by imputation of genotypes in most studies. On average, 2.2 million single nucleotide polymorphisms were generated per study. The results from each study are combined using meta-analysis. As proof of principle, we meta-analyzed risk variants at 9p21 and found that rs1333049 confers a 29% increase in risk for MI per copy (P=2×10−20). Conclusion CARDIoGRAM is poised to contribute to our understanding of the role of common genetic variation on risk for CAD and MI. PMID:20923989

Poly-Omic Prediction of Complex Traits: OmicKriging

PubMed Central

Wheeler, Heather E.; Aquino-Michaels, Keston; Gamazon, Eric R.; Trubetskoy, Vassily V.; Dolan, M. Eileen; Huang, R. Stephanie; Cox, Nancy J.; Im, Hae Kyung

2014-01-01

High-confidence prediction of complex traits such as disease risk or drug response is an ultimate goal of personalized medicine. Although genome-wide association studies have discovered thousands of well-replicated polymorphisms associated with a broad spectrum of complex traits, the combined predictive power of these associations for any given trait is generally too low to be of clinical relevance. We propose a novel systems approach to complex trait prediction, which leverages and integrates similarity in genetic, transcriptomic, or other omics-level data. We translate the omic similarity into phenotypic similarity using a method called Kriging, commonly used in geostatistics and machine learning. Our method called OmicKriging emphasizes the use of a wide variety of systems-level data, such as those increasingly made available by comprehensive surveys of the genome, transcriptome, and epigenome, for complex trait prediction. Furthermore, our OmicKriging framework allows easy integration of prior information on the function of subsets of omics-level data from heterogeneous sources without the sometimes heavy computational burden of Bayesian approaches. Using seven disease datasets from the Wellcome Trust Case Control Consortium (WTCCC), we show that OmicKriging allows simple integration of sparse and highly polygenic components yielding comparable performance at a fraction of the computing time of a recently published Bayesian sparse linear mixed model method. Using a cellular growth phenotype, we show that integrating mRNA and microRNA expression data substantially increases performance over either dataset alone. Using clinical statin response, we show improved prediction over existing methods. PMID:24799323

The role of training in STD prevention and control.

PubMed

Barnes, C; Cathcart, S

1998-03-01

The World Health Organization (WHO) estimates that 340 million new cases of curable sexually transmitted diseases (STDs) (excluding HIV and herpes simplex virus) occurred in 1995. The level of infection with STDs is especially troubling in developing countries, where they cause considerable morbidity. The consequences of infection with STDs can be personal, social, and economic. STD control programs are based upon the principles of primary and secondary prevention. Primary prevention strategies involve preventing the occurrence of new infections, while secondary prevention strategies aim to improve the management of STDs, and thereby to reduce their transmission and subsequent associated morbidity and mortality. Both primary and secondary prevention strategies require the dissemination of information from health workers to the at-risk population at a grassroots level, usually in primary health care centers. Health workers must therefore have a comprehensive and up-to-date knowledge of the many aspects of STDs, and be confident in their ability to communicate that information to others. A study in Tanzania determined that improvement in primary health care, including the provision of worker training, resulted in a 40% reduction in the incidence of HIV. The Wellcome Trust's new Topics in International Health series provides information on STDs on an interactive CD-ROM covering the epidemiology, diagnosis, clinical features, and treatment of the major STDs, except HIV, which is the subject of a separate CD-ROM. The CD-ROM was designed to be used in training programs for medical students and health care workers.

MultiBLUP: improved SNP-based prediction for complex traits.

PubMed

Speed, Doug; Balding, David J

2014-09-01

BLUP (best linear unbiased prediction) is widely used to predict complex traits in plant and animal breeding, and increasingly in human genetics. The BLUP mathematical model, which consists of a single random effect term, was adequate when kinships were measured from pedigrees. However, when genome-wide SNPs are used to measure kinships, the BLUP model implicitly assumes that all SNPs have the same effect-size distribution, which is a severe and unnecessary limitation. We propose MultiBLUP, which extends the BLUP model to include multiple random effects, allowing greatly improved prediction when the random effects correspond to classes of SNPs with distinct effect-size variances. The SNP classes can be specified in advance, for example, based on SNP functional annotations, and we also provide an adaptive procedure for determining a suitable partition of SNPs. We apply MultiBLUP to genome-wide association data from the Wellcome Trust Case Control Consortium (seven diseases), and from much larger studies of celiac disease and inflammatory bowel disease, finding that it consistently provides better prediction than alternative methods. Moreover, MultiBLUP is computationally very efficient; for the largest data set, which includes 12,678 individuals and 1.5 M SNPs, the total analysis can be run on a single desktop PC in less than a day and can be parallelized to run even faster. Tools to perform MultiBLUP are freely available in our software LDAK. © 2014 Speed and Balding; Published by Cold Spring Harbor Laboratory Press.

Simultaneous Genotype Calling and Haplotype Phasing Improves Genotype Accuracy and Reduces False-Positive Associations for Genome-wide Association Studies

PubMed Central

Browning, Brian L.; Yu, Zhaoxia

2009-01-01

We present a novel method for simultaneous genotype calling and haplotype-phase inference. Our method employs the computationally efficient BEAGLE haplotype-frequency model, which can be applied to large-scale studies with millions of markers and thousands of samples. We compare genotype calls made with our method to genotype calls made with the BIRDSEED, CHIAMO, GenCall, and ILLUMINUS genotype-calling methods, using genotype data from the Illumina 550K and Affymetrix 500K arrays. We show that our method has higher genotype-call accuracy and yields fewer uncalled genotypes than competing methods. We perform single-marker analysis of data from the Wellcome Trust Case Control Consortium bipolar disorder and type 2 diabetes studies. For bipolar disorder, the genotype calls in the original study yield 25 markers with apparent false-positive association with bipolar disorder at a p < 10−7 significance level, whereas genotype calls made with our method yield no associated markers at this significance threshold. Conversely, for markers with replicated association with type 2 diabetes, there is good concordance between genotype calls used in the original study and calls made by our method. Results from single-marker and haplotypic analysis of our method's genotype calls for the bipolar disorder study indicate that our method is highly effective at eliminating genotyping artifacts that cause false-positive associations in genome-wide association studies. Our new genotype-calling methods are implemented in the BEAGLE and BEAGLECALL software packages. PMID:19931040

Genome-wide gene–gene interaction analysis for next-generation sequencing

PubMed Central

Zhao, Jinying; Zhu, Yun; Xiong, Momiao

2016-01-01

The critical barrier in interaction analysis for next-generation sequencing (NGS) data is that the traditional pairwise interaction analysis that is suitable for common variants is difficult to apply to rare variants because of their prohibitive computational time, large number of tests and low power. The great challenges for successful detection of interactions with NGS data are (1) the demands in the paradigm of changes in interaction analysis; (2) severe multiple testing; and (3) heavy computations. To meet these challenges, we shift the paradigm of interaction analysis between two SNPs to interaction analysis between two genomic regions. In other words, we take a gene as a unit of analysis and use functional data analysis techniques as dimensional reduction tools to develop a novel statistic to collectively test interaction between all possible pairs of SNPs within two genome regions. By intensive simulations, we demonstrate that the functional logistic regression for interaction analysis has the correct type 1 error rates and higher power to detect interaction than the currently used methods. The proposed method was applied to a coronary artery disease dataset from the Wellcome Trust Case Control Consortium (WTCCC) study and the Framingham Heart Study (FHS) dataset, and the early-onset myocardial infarction (EOMI) exome sequence datasets with European origin from the NHLBI's Exome Sequencing Project. We discovered that 6 of 27 pairs of significantly interacted genes in the FHS were replicated in the independent WTCCC study and 24 pairs of significantly interacted genes after applying Bonferroni correction in the EOMI study. PMID:26173972

An overview of the genetic dissection of complex traits.

PubMed

Rao, D C

2008-01-01

Thanks to the recent revolutionary genomic advances such as the International HapMap consortium, resolution of the genetic architecture of common complex traits is beginning to look hopeful. While demonstrating the feasibility of genome-wide association (GWA) studies, the pathbreaking Wellcome Trust Case Control Consortium (WTCCC) study also serves to underscore the critical importance of very large sample sizes and draws attention to potential problems, which need to be addressed as part of the study design. Even the large WTCCC study had vastly inadequate power for several of the associations reported (and confirmed) and, therefore, most of the regions harboring relevant associations may not be identified anytime soon. This chapter provides an overview of some of the key developments in the methodological approaches to genetic dissection of common complex traits. Constrained Bayesian networks are suggested as especially useful for analysis of pathway-based SNPs. Likewise, composite likelihood is suggested as a promising method for modeling complex systems. It discusses the key steps in a study design, with an emphasis on GWA studies. Potential limitations highlighted by the WTCCC GWA study are discussed, including problems associated with massive genotype imputation, analysis of pooled national samples, shared controls, and the critical role of interactions. GWA studies clearly need massive sample sizes that are only possible through genuine collaborations. After all, for common complex traits, the question is not whether we can find some pieces of the puzzle, but how large and what kind of a sample we need to (nearly) solve the genetic puzzle.

iLOCi: a SNP interaction prioritization technique for detecting epistasis in genome-wide association studies

PubMed Central

2012-01-01

Background Genome-wide association studies (GWAS) do not provide a full account of the heritability of genetic diseases since gene-gene interactions, also known as epistasis are not considered in single locus GWAS. To address this problem, a considerable number of methods have been developed for identifying disease-associated gene-gene interactions. However, these methods typically fail to identify interacting markers explaining more of the disease heritability over single locus GWAS, since many of the interactions significant for disease are obscured by uninformative marker interactions e.g., linkage disequilibrium (LD). Results In this study, we present a novel SNP interaction prioritization algorithm, named iLOCi (Interacting Loci). This algorithm accounts for marker dependencies separately in case and control groups. Disease-associated interactions are then prioritized according to a novel ranking score calculated from the difference in marker dependencies for every possible pair between case and control groups. The analysis of a typical GWAS dataset can be completed in less than a day on a standard workstation with parallel processing capability. The proposed framework was validated using simulated data and applied to real GWAS datasets using the Wellcome Trust Case Control Consortium (WTCCC) data. The results from simulated data showed the ability of iLOCi to identify various types of gene-gene interactions, especially for high-order interaction. From the WTCCC data, we found that among the top ranked interacting SNP pairs, several mapped to genes previously known to be associated with disease, and interestingly, other previously unreported genes with biologically related roles. Conclusion iLOCi is a powerful tool for uncovering true disease interacting markers and thus can provide a more complete understanding of the genetic basis underlying complex disease. The program is available for download at http://www4a.biotec.or.th/GI/tools/iloci. PMID:23281813

Greek Manuscripts at the Wellcome Library in London: A Descriptive Catalogue

PubMed Central

Bouras-Vallianatos, Petros

2015-01-01

This article presents a new, detailed catalogue of the Greek manuscripts at the Wellcome Library in London. It consists of an introduction to the history of the collection and its scholarly importance, followed by separate entries for each manuscript. Each entry identifies the text(s) found in the respective manuscript – including reference to existing printed edition(s) of such texts – and gives a physical description of the codex, details on its provenance and bibliographical references. PMID:25766544

Public engagement in Malawi through a health-talk radio programme ' Umoyo nkukambirana': A mixed-methods evaluation.

PubMed

Nyirenda, Deborah; Makawa, Tamara Chipasula; Chapita, Greyson; Mdalla, Chisomo; Nkolokosa, Mzati; O'byrne, Thomasena; Heyderman, Robert; Desmond, Nicola

2018-02-01

Radio is an effective source of health information in many resource poor countries. In Malawi, 53% of households own radios however few radio programmes in Malawi focus on health issues in the context of medical research. An interactive health-talk radio programme ' Umoyo nkukambirana' was introduced by Malawi-Liverpool-Wellcome Trust Clinical Research Programme on a national radio station. The aim was to increase awareness of health and medical research, and improve engagement between researchers, healthcare workers and the public. The content and presentation were developed through participatory community consultations. Focus Group Discussions were conducted with established Radio Listening Clubs whilst quantitative data was collected using toll free FrontlineSMS to explore national response. A total of 277 to 695 SMS (Median: 477) were received per theme. The majority of SMS were received from men (64%) and mainly from rural areas (54%). The programme improved knowledge of medical research, health and dispelled misconceptions. This study suggests that the radio may be an effective means of increasing the exposure of men to health information in resource poor settings.

Public engagement in Malawi through a health-talk radio programme ‘Umoyo nkukambirana’: A mixed-methods evaluation

PubMed Central

Nyirenda, Deborah; Makawa, Tamara Chipasula; Chapita, Greyson; Mdalla, Chisomo; Nkolokosa, Mzati; O’byrne, Thomasena; Heyderman, Robert; Desmond, Nicola

2016-01-01

Radio is an effective source of health information in many resource poor countries. In Malawi, 53% of households own radios however few radio programmes in Malawi focus on health issues in the context of medical research. An interactive health-talk radio programme ‘Umoyo nkukambirana’ was introduced by Malawi-Liverpool-Wellcome Trust Clinical Research Programme on a national radio station. The aim was to increase awareness of health and medical research, and improve engagement between researchers, healthcare workers and the public. The content and presentation were developed through participatory community consultations. Focus Group Discussions were conducted with established Radio Listening Clubs whilst quantitative data was collected using toll free FrontlineSMS to explore national response. A total of 277 to 695 SMS (Median: 477) were received per theme. The majority of SMS were received from men (64%) and mainly from rural areas (54%). The programme improved knowledge of medical research, health and dispelled misconceptions. This study suggests that the radio may be an effective means of increasing the exposure of men to health information in resource poor settings. PMID:27365364

Gene therapy coming of age in Latin America.

PubMed

Podhajcer, Osvaldo; Pitossi, Fernando; Agilar-Cordova, Estuardo

2002-08-01

"Gene Therapy in Latin America: From the Bench to the Clinic," a meeting sponsored by the Wellcome Trust and the United Nations University through the Biotechnology Program for Latin America and the Caribbean, took place in Buenos Aires, Argentina from May 20 to 22. This symposium, which was hosted by Osvaldo Podhajcer and Fernando Pitossi,had more than 150 basic scientists and physician-scientists from academia, government and industry in Latin America, similar to the first meeting of the Asociacion Iberoamericana de Terapia Génica (Iberoamerican Society of Gene Therapy, AITG) held in Guadalajara, México, two years ago. Participants represented Argentina, Mexico, Brazil, Chile, Uruguay, Costa Rica, Colombia, Venezuela, and Guatemala, with guests from the United States and Europe. All came together to discuss the latest developments in this field in the region. A primary objective of this gathering was to bring together Latin American scientists involved in gene therapy to strengthen continental collaborations and to further disseminate the scientific expertise available in Latin America. The symposium was followed by a 10-day practical course for 25 students from all over Latin America.

Understanding Teamwork in the Provision of Cancer Care: Highlighting the Role of Trust.

PubMed

Lazzara, Elizabeth H; Keebler, Joseph R; Day, Soosi; DiazGranados, Deborah; Pan, Minggui; King, Michael A; Tu, Shin-Ping

2016-11-01

Team science research has indicated that trust is a critical variable of teamwork, contributing greatly to a team's performance. Trust has long been examined in health care with research focusing on the development of trust by patients with their health care practitioners. Studies have indicated that trust is linked to patient satisfaction, adherence to treatment, continuity of care, and improved outcomes. We explore the construct of trust using a case example of a patient who received a surgical procedure for a precancerous polyp. We apply the principle of trust to the case as well as present the literature on trust and key definitions for understanding trust. Additionally, we apply the definitions presented to the specific case example by highlighting moments where trust is developed or violated. Lastly, we offer insights to health care practitioners on the development of trust in their own patient interactions to improve care.

Understanding Teamwork in the Provision of Cancer Care: Highlighting the Role of Trust

PubMed Central

Keebler, Joseph R.; Day, Soosi; DiazGranados, Deborah; Pan, Minggui; King, Michael A.; Tu, Shin-Ping

2016-01-01

Team science research has indicated that trust is a critical variable of teamwork, contributing greatly to a team’s performance. Trust has long been examined in health care with research focusing on the development of trust by patients with their health care practitioners. Studies have indicated that trust is linked to patient satisfaction, adherence to treatment, continuity of care, and improved outcomes. We explore the construct of trust using a case example of a patient who received a surgical procedure for a precancerous polyp. We apply the principle of trust to the case as well as present the literature on trust and key definitions for understanding trust. Additionally, we apply the definitions presented to the specific case example by highlighting moments where trust is developed or violated. Lastly, we offer insights to health care practitioners on the development of trust in their own patient interactions to improve care. PMID:27601505

Screen and clean: a tool for identifying interactions in genome-wide association studies.

PubMed

Wu, Jing; Devlin, Bernie; Ringquist, Steven; Trucco, Massimo; Roeder, Kathryn

2010-04-01

Epistasis could be an important source of risk for disease. How interacting loci might be discovered is an open question for genome-wide association studies (GWAS). Most researchers limit their statistical analyses to testing individual pairwise interactions (i.e., marginal tests for association). A more effective means of identifying important predictors is to fit models that include many predictors simultaneously (i.e., higher-dimensional models). We explore a procedure called screen and clean (SC) for identifying liability loci, including interactions, by using the lasso procedure, which is a model selection tool for high-dimensional regression. We approach the problem by using a varying dictionary consisting of terms to include in the model. In the first step the lasso dictionary includes only main effects. The most promising single-nucleotide polymorphisms (SNPs) are identified using a screening procedure. Next the lasso dictionary is adjusted to include these main effects and the corresponding interaction terms. Again, promising terms are identified using lasso screening. Then significant terms are identified through the cleaning process. Implementation of SC for GWAS requires algorithms to explore the complex model space induced by the many SNPs genotyped and their interactions. We propose and explore a set of algorithms and find that SC successfully controls Type I error while yielding good power to identify risk loci and their interactions. When the method is applied to data obtained from the Wellcome Trust Case Control Consortium study of Type 1 Diabetes it uncovers evidence supporting interaction within the HLA class II region as well as within Chromosome 12q24.

A "candidate-interactome" aggregate analysis of genome-wide association data in multiple sclerosis.

PubMed

Mechelli, Rosella; Umeton, Renato; Policano, Claudia; Annibali, Viviana; Coarelli, Giulia; Ricigliano, Vito A G; Vittori, Danila; Fornasiero, Arianna; Buscarinu, Maria Chiara; Romano, Silvia; Salvetti, Marco; Ristori, Giovanni

2013-01-01

Though difficult, the study of gene-environment interactions in multifactorial diseases is crucial for interpreting the relevance of non-heritable factors and prevents from overlooking genetic associations with small but measurable effects. We propose a "candidate interactome" (i.e. a group of genes whose products are known to physically interact with environmental factors that may be relevant for disease pathogenesis) analysis of genome-wide association data in multiple sclerosis. We looked for statistical enrichment of associations among interactomes that, at the current state of knowledge, may be representative of gene-environment interactions of potential, uncertain or unlikely relevance for multiple sclerosis pathogenesis: Epstein-Barr virus, human immunodeficiency virus, hepatitis B virus, hepatitis C virus, cytomegalovirus, HHV8-Kaposi sarcoma, H1N1-influenza, JC virus, human innate immunity interactome for type I interferon, autoimmune regulator, vitamin D receptor, aryl hydrocarbon receptor and a panel of proteins targeted by 70 innate immune-modulating viral open reading frames from 30 viral species. Interactomes were either obtained from the literature or were manually curated. The P values of all single nucleotide polymorphism mapping to a given interactome were obtained from the last genome-wide association study of the International Multiple Sclerosis Genetics Consortium & the Wellcome Trust Case Control Consortium, 2. The interaction between genotype and Epstein Barr virus emerges as relevant for multiple sclerosis etiology. However, in line with recent data on the coexistence of common and unique strategies used by viruses to perturb the human molecular system, also other viruses have a similar potential, though probably less relevant in epidemiological terms.

Identifying and exploiting trait-relevant tissues with multiple functional annotations in genome-wide association studies

PubMed Central

Zhang, Shujun

2018-01-01

Genome-wide association studies (GWASs) have identified many disease associated loci, the majority of which have unknown biological functions. Understanding the mechanism underlying trait associations requires identifying trait-relevant tissues and investigating associations in a trait-specific fashion. Here, we extend the widely used linear mixed model to incorporate multiple SNP functional annotations from omics studies with GWAS summary statistics to facilitate the identification of trait-relevant tissues, with which to further construct powerful association tests. Specifically, we rely on a generalized estimating equation based algorithm for parameter inference, a mixture modeling framework for trait-tissue relevance classification, and a weighted sequence kernel association test constructed based on the identified trait-relevant tissues for powerful association analysis. We refer to our analytic procedure as the Scalable Multiple Annotation integration for trait-Relevant Tissue identification and usage (SMART). With extensive simulations, we show how our method can make use of multiple complementary annotations to improve the accuracy for identifying trait-relevant tissues. In addition, our procedure allows us to make use of the inferred trait-relevant tissues, for the first time, to construct more powerful SNP set tests. We apply our method for an in-depth analysis of 43 traits from 28 GWASs using tissue-specific annotations in 105 tissues derived from ENCODE and Roadmap. Our results reveal new trait-tissue relevance, pinpoint important annotations that are informative of trait-tissue relationship, and illustrate how we can use the inferred trait-relevant tissues to construct more powerful association tests in the Wellcome trust case control consortium study. PMID:29377896

Global extent of chloroquine-resistant Plasmodium vivax: a systematic review and meta-analysis

PubMed Central

Price, Ric N; von Seidlein, Lorenz; Valecha, Neena; Nosten, Francois; Baird, J Kevin; White, Nicholas J

2014-01-01

Summary Background Chloroquine is the first-line treatment for Plasmodium vivax malaria in most endemic countries, but resistance is increasing. Monitoring of antimalarial efficacy is essential, but in P vivax infections the assessment of treatment efficacy is confounded by relapse from the dormant liver stages. We systematically reviewed P vivax malaria treatment efficacy studies to establish the global extent of chloroquine resistance. Methods We searched Medline, Web of Science, Embase, and the Cochrane Database of Systematic Reviews to identify studies published in English between Jan 1, 1960, and April 30, 2014, which investigated antimalarial treatment efficacy in P vivax malaria. We excluded studies that did not include supervised schizonticidal treatment without primaquine. We determined rates of chloroquine resistance according to P vivax malaria recurrence rates by day 28 whole-blood chloroquine concentrations at the time of recurrence and study enrolment criteria. Findings We identified 129 eligible clinical trials involving 21 694 patients at 179 study sites and 26 case reports describing 54 patients. Chloroquine resistance was present in 58 (53%) of 113 assessable study sites, spread across most countries that are endemic for P vivax. Clearance of parasitaemia assessed by microscopy in 95% of patients by day 2, or all patients by day 3, was 100% predictive of chloroquine sensitivity. Interpretation Heterogeneity of study design and analysis has confounded global surveillance of chloroquine-resistant P vivax, which is now present across most countries endemic for P vivax. Improved methods for monitoring of drug resistance are needed to inform antimalarial policy in these regions. Funding Wellcome Trust (UK). PMID:25213732

Brain swelling and death in children with cerebral malaria.

PubMed

Seydel, Karl B; Kampondeni, Samuel D; Valim, Clarissa; Potchen, Michael J; Milner, Danny A; Muwalo, Francis W; Birbeck, Gretchen L; Bradley, William G; Fox, Lindsay L; Glover, Simon J; Hammond, Colleen A; Heyderman, Robert S; Chilingulo, Cowles A; Molyneux, Malcolm E; Taylor, Terrie E

2015-03-19

Case fatality rates among African children with cerebral malaria remain in the range of 15 to 25%. The key pathogenetic processes and causes of death are unknown, but a combination of clinical observations and pathological findings suggests that increased brain volume leading to raised intracranial pressure may play a role. Magnetic resonance imaging (MRI) became available in Malawi in 2009, and we used it to investigate the role of brain swelling in the pathogenesis of fatal cerebral malaria in African children. We enrolled children who met a stringent definition of cerebral malaria (one that included the presence of retinopathy), characterized them in detail clinically, and obtained MRI scans on admission and daily thereafter while coma persisted. Of 348 children admitted with cerebral malaria (as defined by the World Health Organization), 168 met the inclusion criteria, underwent all investigations, and were included in the analysis. A total of 25 children (15%) died, 21 of whom (84%) had evidence of severe brain swelling on MRI at admission. In contrast, evidence of severe brain swelling was seen on MRI in 39 of 143 survivors (27%). Serial MRI scans showed evidence of decreasing brain volume in the survivors who had had brain swelling initially. Increased brain volume was seen in children who died from cerebral malaria but was uncommon in those who did not die from the disease, a finding that suggests that raised intracranial pressure may contribute to a fatal outcome. The natural history indicates that increased intracranial pressure is transient in survivors. (Funded by the National Institutes of Health and Wellcome Trust U.K.).

A “Candidate-Interactome” Aggregate Analysis of Genome-Wide Association Data in Multiple Sclerosis

PubMed Central

Policano, Claudia; Annibali, Viviana; Coarelli, Giulia; Ricigliano, Vito A. G.; Vittori, Danila; Fornasiero, Arianna; Buscarinu, Maria Chiara; Romano, Silvia; Salvetti, Marco; Ristori, Giovanni

2013-01-01

Though difficult, the study of gene-environment interactions in multifactorial diseases is crucial for interpreting the relevance of non-heritable factors and prevents from overlooking genetic associations with small but measurable effects. We propose a “candidate interactome” (i.e. a group of genes whose products are known to physically interact with environmental factors that may be relevant for disease pathogenesis) analysis of genome-wide association data in multiple sclerosis. We looked for statistical enrichment of associations among interactomes that, at the current state of knowledge, may be representative of gene-environment interactions of potential, uncertain or unlikely relevance for multiple sclerosis pathogenesis: Epstein-Barr virus, human immunodeficiency virus, hepatitis B virus, hepatitis C virus, cytomegalovirus, HHV8-Kaposi sarcoma, H1N1-influenza, JC virus, human innate immunity interactome for type I interferon, autoimmune regulator, vitamin D receptor, aryl hydrocarbon receptor and a panel of proteins targeted by 70 innate immune-modulating viral open reading frames from 30 viral species. Interactomes were either obtained from the literature or were manually curated. The P values of all single nucleotide polymorphism mapping to a given interactome were obtained from the last genome-wide association study of the International Multiple Sclerosis Genetics Consortium & the Wellcome Trust Case Control Consortium, 2. The interaction between genotype and Epstein Barr virus emerges as relevant for multiple sclerosis etiology. However, in line with recent data on the coexistence of common and unique strategies used by viruses to perturb the human molecular system, also other viruses have a similar potential, though probably less relevant in epidemiological terms. PMID:23696811

Genetic variants of FTO influence adiposity, insulin sensitivity, leptin levels, and resting metabolic rate in the Quebec Family Study.

PubMed

Do, Ron; Bailey, Swneke D; Desbiens, Katia; Belisle, Alexandre; Montpetit, Alexandre; Bouchard, Claude; Pérusse, Louis; Vohl, Marie-Claude; Engert, James C

2008-04-01

A genome-wide association study conducted by the Wellcome Trust Case Control Consortium recently associated single nucleotide polymorphisms (SNPs) in the FTO (fatso/fat mass and obesity associated) gene with type 2 diabetes. These associations were shown to be mediated by obesity. Other research groups found similar results in Europeans and Hispanics but not African Americans. The mechanism by which FTO influences obesity and type 2 diabetes is currently unknown. The present study investigated the role of two FTO SNPs (rs17817449 and rs1421085) in adiposity, insulin sensitivity, and body weight regulation, including energy intake and expenditure. We genotyped 908 individuals from the Quebec City metropolitan area that participated in the Quebec Family Study, a long-term study of extensively phenotyped individuals designed to investigate factors involved in adiposity. We found significant associations for both SNPs with several obesity-related phenotypes. In particular, rs17817449 was associated with BMI (P = 0.0014), weight (P = 0.0059), and waist circumference (P = 0.0021) under an additive model. In addition, this FTO SNP influenced fasting insulin (P = 0.011), homeostasis model assessment of insulin resistance (P = 0.038), and an insulin sensitivity index derived from an oral glucose tolerance test (P = 0.0091). Associations were also found with resting metabolic rate (RMR) (P = 0.042) and plasma leptin levels (P = 0.036). Adjustment for BMI abolished the associations with insulin sensitivity, RMR, and plasma leptin levels. These results confirm that genetic variation at the FTO locus contributes to the etiology of obesity, insulin resistance, and increased plasma leptin levels.

Cross-Tissue and Tissue-Specific eQTLs: Partitioning the Heritability of a Complex Trait

PubMed Central

Torres, Jason M.; Gamazon, Eric R.; Parra, Esteban J.; Below, Jennifer E.; Valladares-Salgado, Adan; Wacher, Niels; Cruz, Miguel; Hanis, Craig L.; Cox, Nancy J.

2014-01-01

Top signals from genome-wide association studies (GWASs) of type 2 diabetes (T2D) are enriched with expression quantitative trait loci (eQTLs) identified in skeletal muscle and adipose tissue. We therefore hypothesized that such eQTLs might account for a disproportionate share of the heritability estimated from all SNPs interrogated through GWASs. To test this hypothesis, we applied linear mixed models to the Wellcome Trust Case Control Consortium (WTCCC) T2D data set and to data sets representing Mexican Americans from Starr County, TX, and Mexicans from Mexico City. We estimated the proportion of phenotypic variance attributable to the additive effect of all variants interrogated in these GWASs, as well as a much smaller set of variants identified as eQTLs in human adipose tissue, skeletal muscle, and lymphoblastoid cell lines. The narrow-sense heritability explained by all interrogated SNPs in each of these data sets was substantially greater than the heritability accounted for by genome-wide-significant SNPs (∼10%); GWAS SNPs explained over 50% of phenotypic variance in the WTCCC, Starr County, and Mexico City data sets. The estimate of heritability attributable to cross-tissue eQTLs was greater in the WTCCC data set and among lean Hispanics, whereas adipose eQTLs significantly explained heritability among Hispanics with a body mass index ≥ 30. These results support an important role for regulatory variants in the genetic component of T2D susceptibility, particularly for eQTLs that elicit effects across insulin-responsive peripheral tissues. PMID:25439722

Role of genetic variation in insulin-like growth factor 1 receptor on insulin resistance and arterial hypertension.

PubMed

Sookoian, Silvia; Gianotti, Tomas Fernandez; Gemma, Carolina; Burgueño, Adriana L; Pirola, Carlos J

2010-06-01

To perform a two-stage study to explore the role of gene variants in the risk of insulin resistance and arterial hypertension. The selection of variants was performed by a first stage of in-silico analysis of the original genome-wide association data sets on genes involved in metabolic syndrome components, granted by the Diabetes Genetics Initiative and the Wellcome Trust Case-Control Consortium. We started by identifying single-nucleotide polymorphisms with a cutoff for association (P < 0.05) in both data sets after the application of a computational algorithm of gene prioritization. Among the more promising variants, six single-nucleotide polymorphisms in IGF1R (rs11247362, rs10902606, rs1317459, rs11854132, rs2684761, and rs2715416) were selected for further evaluation in our population. Altogether, 1094 men, aged 34.4 +/- 8.6 years, were included in a population-based study. Genotypes of rs2684761 showed significant association with insulin resistance (as a discrete trait, odds ratio per G allele 1.27, 95% confidence interval 1.03-1.56, P = 0.026; and homeostasis model assessment-insulin resistance as a continuous trait, P = 0.01). A significant association of rs2684761 with arterial hypertension was also observed (odds ratio per G allele 1.29, 95% confidence interval 1.02-1.64, P = 0.037) after adjusting for age and homeostasis model assessment-insulin resistance. Our study suggests for the first time a putative role of IGF1R variants in individual susceptibility to metabolic syndrome-related phenotypes, in particular on the risk of having insulin resistance and arterial hypertension.

The national bowel cancer audit project: the impact of organisational structure on outcome in operative bowel cancer within the United Kingdom.

PubMed

Cornish, J A; Tekkis, P P; Tan, E; Tilney, H S; Thompson, M R; Smith, J J

2011-06-01

To investigate the relationship between organisational structure, process and surgical outcomes for bowel cancer surgery. An e-survey was sent to the members of the Association of Coloproctology of Great Britain and Ireland to determine the organisational structure of their Trusts. Responses were combined with the National Bowel Cancer Audit (NBOCAP) data. Items investigated included; number of consultants, nurse specialists, volume of cases and intensive care facilities. Main outcome measures included: 30-day risk-adjusted mortality, length of stay (LOS), lymph node yield and circumferential margin involvement (CRM). One hundred and seventeen Trusts responded (65.8%), matched to 7666 patient episodes (NBOCAP data) from 54 (62.8%)Trusts who submitted data to the audit. Trusts treating <190 cases/annum (p > 0.001), <4 colorectal consultants (p > 0.001), <4 HDU beds (p > 0001) and <8 ITU beds (p > 0001) were more likely to have a 30-day-risk-adjusted mortality twice that of the national mean. Sixty five percent (n = 1603) of Trusts treating ≥ 190 cases/annum harvested ≥ 12 lymph nodes vs. 58.3% (n = 1435) in Trusts <190 cases/annum (p < 0.001). Trusts with ≥ 2 pathologists with an interest in bowel cancer harvested ≥ 12 lymph nodes more frequently (p=<0.001) and were more likely to identify extramural vascular invasion in the specimen (p = 0.015). Negative CRM was achieved in 81.4% (n = 81.4) of patients in Trusts treating ≥ 190 cases vs. 66.5% (n = 569) in Trusts<190 cases/annum (p < 0.001). Trusts offering fast track discharge were more likely to have a LOS < 15 days (p = 0.006). Surgeons treating ≤ 35 cases/annum had increased major post-operative complications (<35 cases = 70.2% vs. ≥ 35 cases = 21.9%; p < 0.001), however 30 day risk adjusted mortality was not increased in surgeons treating <35 cases/annum. This study shows that the organisational infrastructure of hospitals appears to have as great an impact on patient outcomes as the volume of cases performed by hospital Trusts. Crown Copyright © 2010. Published by Elsevier Ltd. All rights reserved.

Ischemic Stroke Is Associated with the ABO Locus: The EuroCLOT Study

PubMed Central

Williams, Frances M K; Carter, Angela M; Hysi, Pirro G; Surdulescu, Gabriela; Hodgkiss, Dylan; Soranzo, Nicole; Traylor, Matthew; Bevan, Steve; Dichgans, Martin; Rothwell, Peter M W; Sudlow, Cathie; Farrall, Martin; Silander, Kaisa; Kaunisto, Mari; Wagner, Peter; Saarela, Olli; Kuulasmaa, Kari; Virtamo, Jarmo; Salomaa, Veikko; Amouyel, Philippe; Arveiler, Dominique; Ferrieres, Jean; Wiklund, Per-Gunnar; Arfan Ikram, M; Hofman, Albert; Boncoraglio, Giorgio B; Parati, Eugenio A; Helgadottir, Anna; Gretarsdottir, Solveig; Thorsteinsdottir, Unnur; Thorleifsson, Gudmar; Stefansson, Kari; Seshadri, Sudha; DeStefano, Anita; Gschwendtner, Andreas; Psaty, Bruce; Longstreth, Will; Mitchell, Braxton D; Cheng, Yu-Ching; Clarke, Robert; Ferrario, Marco; Bis, Joshua C; Levi, Christopher; Attia, John; Holliday, Elizabeth G; Scott, Rodney J; Fornage, Myriam; Sharma, Pankaj; Furie, Karen L; Rosand, Jonathan; Nalls, Mike; Meschia, James; Mosely, Thomas H; Evans, Alun; Palotie, Aarno; Markus, Hugh S; Grant, Peter J; Spector, Tim D

2013-01-01

Objective End-stage coagulation and the structure/function of fibrin are implicated in the pathogenesis of ischemic stroke. We explored whether genetic variants associated with end-stage coagulation in healthy REFVIDunteers account for the genetic predisposition to ischemic stroke and examined their influence on stroke subtype. Methods Common genetic variants identified through genome-wide association studies of coagulation factors and fibrin structure/function in healthy twins (n = 2,100, Stage 1) were examined in ischemic stroke (n = 4,200 cases) using 2 independent samples of European ancestry (Stage 2). A third clinical collection having stroke subtyping (total 8,900 cases, 55,000 controls) was used for replication (Stage 3). Results Stage 1 identified 524 single nucleotide polymorphisms (SNPs) from 23 linkage disequilibrium blocks having significant association (p < 5 × 10–8) with 1 or more coagulation/fibrin phenotypes. The most striking associations included SNP rs5985 with factor XIII activity (p = 2.6 × 10–186), rs10665 with FVII (p = 2.4 × 10–47), and rs505922 in the ABO gene with both von Willebrand factor (p = 4.7 × 10–57) and factor VIII (p = 1.2 × 10–36). In Stage 2, the 23 independent SNPs were examined in stroke cases/noncases using MOnica Risk, Genetics, Archiving and Monograph (MORGAM) and Wellcome Trust Case Control Consortium 2 collections. SNP rs505922 was nominally associated with ischemic stroke (odds ratio = 0.94, 95% confidence interval = 0.88–0.99, p = 0.023). Independent replication in Meta-Stroke confirmed the rs505922 association with stroke, beta (standard error, SE) = 0.066 (0.02), p = 0.001, a finding specific to large-vessel and cardioembolic stroke (p = 0.001 and p = < 0.001, respectively) but not seen with small-vessel stroke (p = 0.811). Interpretation ABO gene variants are associated with large-vessel and cardioembolic stroke but not small-vessel disease. This work sheds light on the different pathogenic mechanisms underpinning stroke subtype. Ann Neurol 2013 PMID:23381943

Medical supplies for the expeditions of the heroic age of Antarctic exploration: introduction.

PubMed

Guly, H R

2012-06-01

During the heroic age of Antarctic exploration (1895-1922) there were at least 18 expeditions to the Antarctic lasting between 18 and 30 months. This is an introduction to a series of articles about the drugs taken and used in the Antarctic at this time. Most of the information relates to the expeditions of Robert Scott and Ernest Shackleton and the main supplier of medical equipment was Burroughs Wellcome and Co. This article also describes the medical cases that were taken to the Antarctic.

WGE: a CRISPR database for genome engineering.

PubMed

Hodgkins, Alex; Farne, Anna; Perera, Sajith; Grego, Tiago; Parry-Smith, David J; Skarnes, William C; Iyer, Vivek

2015-09-15

The rapid development of CRISPR-Cas9 mediated genome editing techniques has given rise to a number of online and stand-alone tools to find and score CRISPR sites for whole genomes. Here we describe the Wellcome Trust Sanger Institute Genome Editing database (WGE), which uses novel methods to compute, visualize and select optimal CRISPR sites in a genome browser environment. The WGE database currently stores single and paired CRISPR sites and pre-calculated off-target information for CRISPRs located in the mouse and human exomes. Scoring and display of off-target sites is simple, and intuitive, and filters can be applied to identify high-quality CRISPR sites rapidly. WGE also provides a tool for the design and display of gene targeting vectors in the same genome browser, along with gene models, protein translation and variation tracks. WGE is open, extensible and can be set up to compute and present CRISPR sites for any genome. The WGE database is freely available at www.sanger.ac.uk/htgt/wge : vvi@sanger.ac.uk or skarnes@sanger.ac.uk Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press.

Fish from Head to Tail: The 9th European Zebrafish Meeting in Oslo.

PubMed

Griffiths, Gareth; Müller, Ferenc; Ledin, Johan; Patton, E Elizabeth; Gjøen, Tor; Lobert, Viola Hélène; Winther-Larsen, Hanne Cecilie; Mullins, Mary; Joly, Jean-Stephane; Weltzien, Finn-Arne; Press, Charles McLean; Aleström, Peter

2016-04-01

The 9th European Zebrafish Meeting took place recently in Oslo (June 28-July 2, 2015). A total of 650 participants came to hear the latest research news focused on the zebrafish, Danio rerio, and to its distant evolutionary relative medaka, Oryzias latipes. The packed program included keynote and plenary talks, short oral presentations and poster sessions, workshops, and strategic discussions. The meeting was a great success and revealed dramatically how important the zebrafish in particular has become as a model system for topics, such as developmental biology, functional genomics, biomedicine, toxicology, and drug development. A new emphasis was given to its potential as a model for aquaculture, a topic of great economic interest to the host country Norway and for the future global food supply in general. Zebrafish husbandry as well as its use in teaching were also covered in separate workshops. As has become a tradition in these meetings, there was a well-attended Wellcome Trust Sanger Institute and ZFIN workshop focused on Zebrafish Genome Resources on the first day. The full EZM 2015 program with abstracts can be read and downloaded from the EZM 2015 Web site zebrafish2015.org .

Thinking ethically about genetic inheritance: liberal rights, communitarianism and the right to privacy for parents of donor insemination children.

PubMed

Burr, J; Reynolds, P

2008-04-01

The issue of genetic inheritance, and particularly the contradictory rights of donors, recipients and donor offspring as to the disclosure of donor identities, is ethically complicated. Donors, donor offspring and parents of donor offspring may appeal to individual rights for confidentiality or disclosure within legal systems based on liberal rights discourse. This paper explores the ethical issues of non-disclosure of genetic inheritance by contrasting two principle models used to articulate the problem--liberal and communitarian ethical models. It argues that whilst the latter provides a more constructive avenue to providing an ethics for donation than the competing and contradictory positions represented in a liberal rights approach, it raises issues of ethical judgement and authority that remain problematic. This ethical discussion is supported by a field study, funded by the Wellcome Trust, exploring the perceptions and experiences of recipients of donor sperm and their partners towards donor anonymity. The field study provides the empirical basis of an argument for making ethical judgements on the grounds of the community good rather than individual rights, that nevertheless recognises that both are inherently problematic.

Managing healthcare information: analyzing trust.

PubMed

Söderström, Eva; Eriksson, Nomie; Åhlfeldt, Rose-Mharie

2016-08-08

Purpose - The purpose of this paper is to analyze two case studies with a trust matrix tool, to identify trust issues related to electronic health records. Design/methodology/approach - A qualitative research approach is applied using two case studies. The data analysis of these studies generated a problem list, which was mapped to a trust matrix. Findings - Results demonstrate flaws in current practices and point to achieving balance between organizational, person and technology trust perspectives. The analysis revealed three challenge areas, to: achieve higher trust in patient-focussed healthcare; improve communication between patients and healthcare professionals; and establish clear terminology. By taking trust into account, a more holistic perspective on healthcare can be achieved, where trust can be obtained and optimized. Research limitations/implications - A trust matrix is tested and shown to identify trust problems on different levels and relating to trusting beliefs. Future research should elaborate and more fully address issues within three identified challenge areas. Practical implications - The trust matrix's usefulness as a tool for organizations to analyze trust problems and issues is demonstrated. Originality/value - Healthcare trust issues are captured to a greater extent and from previously unchartered perspectives.

Blood transcriptomic diagnosis of pulmonary and extrapulmonary tuberculosis

PubMed Central

Roe, Jennifer K; Thomas, Niclas; Gil, Eliza; Best, Katharine; Tsaliki, Evdokia; Morris‑Jones, Stephen; Stafford, Sian; Simpson, Nandi; Witt, Karolina D; Chain, Benjamin; Miller, Robert F; Martineau, Adrian

2016-01-01

BACKGROUND. Novel rapid diagnostics for active tuberculosis (TB) are required to overcome the time delays and inadequate sensitivity of current microbiological tests that are critically dependent on sampling the site of disease. Multiparametric blood transcriptomic signatures of TB have been described as potential diagnostic tests. We sought to identify the best transcript candidates as host biomarkers for active TB, extend the evaluation of their specificity by comparison with other infectious diseases, and to test their performance in both pulmonary and extrapulmonary TB. METHODS. Support vector machine learning, combined with feature selection, was applied to new and previously published blood transcriptional profiles in order to identify the minimal TB‑specific transcriptional signature shared by multiple patient cohorts including pulmonary and extrapulmonary TB, and individuals with and without HIV-1 coinfection. RESULTS. We identified and validated elevated blood basic leucine zipper transcription factor 2 (BATF2) transcript levels as a single sensitive biomarker that discriminated active pulmonary and extrapulmonary TB from healthy individuals, with receiver operating characteristic (ROC) area under the curve (AUC) scores of 0.93 to 0.99 in multiple cohorts of HIV-1–negative individuals, and 0.85 in HIV-1–infected individuals. In addition, we identified and validated a potentially novel 4-gene signature comprising CD177, haptoglobin, immunoglobin J chain, and galectin 10 that discriminated active pulmonary and extrapulmonary TB from other febrile infections, giving ROC AUCs of 0.94 to 1. CONCLUSIONS. Elevated blood BATF2 transcript levels provide a sensitive biomarker that discriminates active TB from healthy individuals, and a potentially novel 4-gene transcriptional signature differentiates between active TB and other infectious diseases in individuals presenting with fever. FUNDING. MRC, Wellcome Trust, Rosetrees Trust, British Lung Foundation, NIHR. PMID:27734027

Blood transcriptomic diagnosis of pulmonary and extrapulmonary tuberculosis.

PubMed

Roe, Jennifer K; Thomas, Niclas; Gil, Eliza; Best, Katharine; Tsaliki, Evdokia; Morris-Jones, Stephen; Stafford, Sian; Simpson, Nandi; Witt, Karolina D; Chain, Benjamin; Miller, Robert F; Martineau, Adrian; Noursadeghi, Mahdad

2016-10-06

BACKGROUND. Novel rapid diagnostics for active tuberculosis (TB) are required to overcome the time delays and inadequate sensitivity of current microbiological tests that are critically dependent on sampling the site of disease. Multiparametric blood transcriptomic signatures of TB have been described as potential diagnostic tests. We sought to identify the best transcript candidates as host biomarkers for active TB, extend the evaluation of their specificity by comparison with other infectious diseases, and to test their performance in both pulmonary and extrapulmonary TB. METHODS. Support vector machine learning, combined with feature selection, was applied to new and previously published blood transcriptional profiles in order to identify the minimal TB‑specific transcriptional signature shared by multiple patient cohorts including pulmonary and extrapulmonary TB, and individuals with and without HIV-1 coinfection. RESULTS. We identified and validated elevated blood basic leucine zipper transcription factor 2 ( BATF2 ) transcript levels as a single sensitive biomarker that discriminated active pulmonary and extrapulmonary TB from healthy individuals, with receiver operating characteristic (ROC) area under the curve (AUC) scores of 0.93 to 0.99 in multiple cohorts of HIV-1-negative individuals, and 0.85 in HIV-1-infected individuals. In addition, we identified and validated a potentially novel 4-gene signature comprising CD177, haptoglobin, immunoglobin J chain, and galectin 10 that discriminated active pulmonary and extrapulmonary TB from other febrile infections, giving ROC AUCs of 0.94 to 1. CONCLUSIONS. Elevated blood BATF2 transcript levels provide a sensitive biomarker that discriminates active TB from healthy individuals, and a potentially novel 4-gene transcriptional signature differentiates between active TB and other infectious diseases in individuals presenting with fever. FUNDING. MRC, Wellcome Trust, Rosetrees Trust, British Lung Foundation, NIHR.

Sir Henry Solomon Wellcome and Dr Andrew Balfour: an enterprise on the Nile and the early foundation of public health and medical research in the Sudan (1899-1935).

PubMed

Elhadd, T A

2015-01-01

In Sudan, modern medical practice and medical research began soon after the creation of Anglo-Egyptian Sudan at the turn of the 20th century. The benevolent involvement of Sir Henry Solomon Wellcome, and the ingenious feat of his protégé Sir Andrew Balfour, was crucial to the strong foundation of that establishment. Sir Henry Wellcome provided the financial sponsorship plus influential, logistical and moral support. Dr Balfour put great energy into making the enterprise one of the most amazing medical achievements in colonial medicine. Improvement in the public health of the capital Khartoum was emulated by other doctors working in this vast country. Research was not restricted to tropical medicine; it also encompassed agricultural and chemical research. This helped with the establishment of the first modern medical school in the country in 1924 and resulted in the medical service in Sudan being described as one of the best in the world. Many British doctors flocked to Sudan to make a fortune and to set a path for their career back in Britain.

Atrial Fibrillation Genetic Risk and Ischemic Stroke Mechanisms.

PubMed

Lubitz, Steven A; Parsons, Owen E; Anderson, Christopher D; Benjamin, Emelia J; Malik, Rainer; Weng, Lu-Chen; Dichgans, Martin; Sudlow, Cathie L; Rothwell, Peter M; Rosand, Jonathan; Ellinor, Patrick T; Markus, Hugh S; Traylor, Matthew

2017-06-01

Atrial fibrillation (AF) is a leading cause of cardioembolic stroke, but the relationship between AF and noncardioembolic stroke subtypes are unclear. Because AF may be unrecognized, and because AF has a substantial genetic basis, we assessed for predisposition to AF across ischemic stroke subtypes. We examined associations between AF genetic risk and Trial of Org 10172 in Acute Stroke Treatment stroke subtypes in 2374 ambulatory individuals with ischemic stroke and 5175 without from the Wellcome Trust Case-Control Consortium 2 using logistic regression. We calculated AF genetic risk scores using single-nucleotide polymorphisms associated with AF in a previous independent analysis across a range of preselected significance thresholds. There were 460 (19.4%) individuals with cardioembolic stroke, 498 (21.0%) with large vessel, 474 (20.0%) with small vessel, and 814 (32.3%) individuals with strokes of undetermined cause. Most AF genetic risk scores were associated with stroke, with the strongest association ( P =6×10 - 4 ) attributed to scores of 944 single-nucleotide polymorphisms (each associated with AF at P <1×10 - 3 in a previous analysis). Associations between AF genetic risk and stroke were enriched in the cardioembolic stroke subset (strongest P =1.2×10 - 9 , 944 single-nucleotide polymorphism score). In contrast, AF genetic risk was not significantly associated with noncardioembolic stroke subtypes. Comprehensive AF genetic risk scores were specific for cardioembolic stroke. Incomplete workups and subtype misclassification may have limited the power to detect associations with strokes of undetermined pathogenesis. Future studies are warranted to determine whether AF genetic risk is a useful biomarker to enhance clinical discrimination of stroke pathogeneses. © 2017 American Heart Association, Inc.

Rapid and Accurate Multiple Testing Correction and Power Estimation for Millions of Correlated Markers

PubMed Central

Han, Buhm; Kang, Hyun Min; Eskin, Eleazar

2009-01-01

With the development of high-throughput sequencing and genotyping technologies, the number of markers collected in genetic association studies is growing rapidly, increasing the importance of methods for correcting for multiple hypothesis testing. The permutation test is widely considered the gold standard for accurate multiple testing correction, but it is often computationally impractical for these large datasets. Recently, several studies proposed efficient alternative approaches to the permutation test based on the multivariate normal distribution (MVN). However, they cannot accurately correct for multiple testing in genome-wide association studies for two reasons. First, these methods require partitioning of the genome into many disjoint blocks and ignore all correlations between markers from different blocks. Second, the true null distribution of the test statistic often fails to follow the asymptotic distribution at the tails of the distribution. We propose an accurate and efficient method for multiple testing correction in genome-wide association studies—SLIDE. Our method accounts for all correlation within a sliding window and corrects for the departure of the true null distribution of the statistic from the asymptotic distribution. In simulations using the Wellcome Trust Case Control Consortium data, the error rate of SLIDE's corrected p-values is more than 20 times smaller than the error rate of the previous MVN-based methods' corrected p-values, while SLIDE is orders of magnitude faster than the permutation test and other competing methods. We also extend the MVN framework to the problem of estimating the statistical power of an association study with correlated markers and propose an efficient and accurate power estimation method SLIP. SLIP and SLIDE are available at http://slide.cs.ucla.edu. PMID:19381255

Genome-wide association study of suicide attempts in mood disorder patients.

PubMed

Perlis, Roy H; Huang, Jie; Purcell, Shaun; Fava, Maurizio; Rush, A John; Sullivan, Patrick F; Hamilton, Steven P; McMahon, Francis J; Schulze, Thomas G; Schulze, Thomas; Potash, James B; Zandi, Peter P; Willour, Virginia L; Penninx, Brenda W; Boomsma, Dorret I; Vogelzangs, Nicole; Middeldorp, Christel M; Rietschel, Marcella; Nöthen, Markus; Cichon, Sven; Gurling, Hugh; Bass, Nick; McQuillin, Andrew; Hamshere, Marian; Craddock, Nick; Sklar, Pamela; Smoller, Jordan W

2010-12-01

Family and twin studies suggest that liability for suicide attempts is heritable and distinct from mood disorder susceptibility. The authors therefore examined the association between common genomewide variation and lifetime suicide attempts. The authors analyzed data on lifetime suicide attempts from genomewide association studies of bipolar I and II disorder as well as major depressive disorder. Bipolar disorder subjects were drawn from the Systematic Treatment Enhancement Program for Bipolar Disorder cohort, the Wellcome Trust Case Control Consortium bipolar cohort, and the University College London cohort. Replication was pursued in the NIMH Genetic Association Information Network bipolar disorder project and a German clinical cohort. Depression subjects were drawn from the Sequential Treatment Alternatives to Relieve Depression cohort, with replication in the Netherlands Study of Depression and Anxiety/Netherlands Twin Register depression cohort. Strongest evidence of association for suicide attempt in bipolar disorder was observed in a region without identified genes (rs1466846); five loci also showed suggestive evidence of association. In major depression, strongest evidence of association was observed for a single nucleotide polymorphism in ABI3BP, with six loci also showing suggestive association. Replication cohorts did not provide further support for these loci. However, meta-analysis incorporating approximately 8,700 mood disorder subjects identified four additional regions that met the threshold for suggestive association, including the locus containing the gene coding for protein kinase C-epsilon, previously implicated in models of mood and anxiety. The results suggest that inherited risk for suicide among mood disorder patients is unlikely to be the result of individual common variants of large effect. They nonetheless provide suggestive evidence for multiple loci, which merit further investigation.

Genome-Wide Association Study of Suicide Attempts in Mood Disorder Patients

PubMed Central

Perlis, Roy H.; Huang, Jie; Purcell, Shaun; Fava, Maurizio; Rush, A. John; Sullivan, Patrick F.; Hamilton, Steven P.; McMahon, Francis J.; Schulze, Thomas; Potash, James B.; Zandi, Peter P.; Willour, Virginia L.; Penninx, Brenda W.; Boomsma, Dorret I.; Vogelzangs, Nicole; Middeldorp, Christel M.; Rietschel, Marcella; Nöthen, Markus; Cichon, Sven; Gurling, Hugh; Bass, Nick; McQuillin, Andrew; Hamshere, Marian; Craddock, Nick; Sklar, Pamela; Smoller, Jordan W.

2013-01-01

Objective Family and twin studies suggest that liability for suicide attempts is heritable and distinct from mood disorder susceptibility. The authors therefore examined the association between common genomewide variation and lifetime suicide attempts. Method The authors analyzed data on lifetime suicide attempts from genomewide association studies of bipolar I and II disorder as well as major depressive disorder. Bipolar disorder subjects were drawn from the Systematic Treatment Enhancement Program for Bipolar Disorder cohort, the Wellcome Trust Case Control Consortium bipolar cohort, and the University College London cohort. Replication was pursued in the NIMH Genetic Association Information Network bipolar disorder project and a German clinical cohort. Depression subjects were drawn from the Sequential Treatment Alternatives to Relieve Depression cohort, with replication in the Netherlands Study of Depression and Anxiety/Netherlands Twin Register depression cohort. Results Strongest evidence of association for suicide attempt in bipolar disorder was observed in a region without identified genes (rs1466846); five loci also showed suggestive evidence of association. In major depression, strongest evidence of association was observed for a single nucleotide polymorphism in ABI3BP, with six loci also showing suggestive association. Replication cohorts did not provide further support for these loci. However, meta-analysis incorporating approximately 8,700 mood disorder subjects identified four additional regions that met the threshold for suggestive association, including the locus containing the gene coding for protein kinase C-epsilon, previously implicated in models of mood and anxiety. Conclusions The results suggest that inherited risk for suicide among mood disorder patients is unlikely to be the result of individual common variants of large effect. They nonetheless provide suggestive evidence for multiple loci, which merit further investigation. PMID:21041247

26 CFR 1.682(a)-1 - Income of trust in case of divorce, etc.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 26 Internal Revenue 8 2010-04-01 2010-04-01 false Income of trust in case of divorce, etc. 1.682(a... (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Miscellaneous § 1.682(a)-1 Income of trust in case of divorce... of the obligor spouse's minor children in the divorce or separate maintenance decree, the separation...

A score to predict and stratify risk of tuberculosis in adult contacts of tuberculosis index cases: a prospective derivation and external validation cohort study.

PubMed

Saunders, Matthew J; Wingfield, Tom; Tovar, Marco A; Baldwin, Matthew R; Datta, Sumona; Zevallos, Karine; Montoya, Rosario; Valencia, Teresa R; Friedland, Jon S; Moulton, Larry H; Gilman, Robert H; Evans, Carlton A

2017-11-01

Contacts of tuberculosis index cases are at increased risk of developing tuberculosis. Screening, preventive therapy, and surveillance for tuberculosis are underused interventions in contacts, particularly adults. We developed a score to predict risk of tuberculosis in adult contacts of tuberculosis index cases. In 2002-06, we recruited contacts aged 15 years or older of index cases with pulmonary tuberculosis who lived in desert shanty towns in Ventanilla, Peru. We followed up contacts for tuberculosis until February, 2016. We used a Cox proportional hazards model to identify index case, contact, and household risk factors for tuberculosis from which to derive a score and classify contacts as low, medium, or high risk. We validated the score in an urban community recruited in Callao, Peru, in 2014-15. In the derivation cohort, we identified 2017 contacts of 715 index cases, and median follow-up was 10·7 years (IQR 9·5-11·8). 178 (9%) of 2017 contacts developed tuberculosis during 19 147 person-years of follow-up (incidence 0·93 per 100 person-years, 95% CI 0·80-1·08). Risk factors for tuberculosis were body-mass index, previous tuberculosis, age, sustained exposure to the index case, the index case being in a male patient, lower community household socioeconomic position, indoor air pollution, previous tuberculosis among household members, and living in a household with a low number of windows per room. The 10-year risks of tuberculosis in the low-risk, medium-risk, and high-risk groups were, respectively, 2·8% (95% CI 1·7-4·4), 6·2% (4·8-8·1), and 20·6% (17·3-24·4). The 535 (27%) contacts classified as high risk accounted for 60% of the tuberculosis identified during follow-up. The score predicted tuberculosis independently of tuberculin skin test and index-case drug sensitivity results. In the external validation cohort, 65 (3%) of 1910 contacts developed tuberculosis during 3771 person-years of follow-up (incidence 1·7 per 100 person-years, 95% CI 1·4-2·2). The 2·5-year risks of tuberculosis in the low-risk, medium-risk, and high-risk groups were, respectively, 1·4% (95% CI 0·7-2·8), 3·9% (2·5-5·9), and 8·6%· (5·9-12·6). Our externally validated risk score could predict and stratify 10-year risk of developing tuberculosis in adult contacts, and could be used to prioritise tuberculosis control interventions for people most likely to benefit. Wellcome Trust, Department for International Development Civil Society Challenge Fund, Joint Global Health Trials consortium, Bill & Melinda Gates Foundation, Imperial College National Institutes of Health Research Biomedical Research Centre, Foundation for Innovative New Diagnostics, Sir Halley Stewart Trust, WHO, TB REACH, and Innovation for Health and Development. Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

Replication of Associations of Genetic Loci Outside the HLA Region With Susceptibility to Anti–Cyclic Citrullinated Peptide–Negative Rheumatoid Arthritis

PubMed Central

Viatte, Sebastien; Massey, Jonathan; Bowes, John; Duffus, Kate; Eyre, Stephen; Barton, Anne; Loughlin, John; Arden, Nigel; Birrell, Fraser; Carr, Andrew; Deloukas, Panos; Doherty, Michael; McCaskie, Andrew W.; Ollier, William E. R.; Rai, Ashok; Ralston, Stuart H.; Spector, Tim D.; Valdes, Ana M.; Wallis, Gillian A.; Wilkinson, J. Mark; Zeggini, Eleftheria

2016-01-01

Objective Genetic polymorphisms within the HLA region explain only a modest proportion of anti–cyclic citrullinated peptide (anti‐CCP)–negative rheumatoid arthritis (RA) heritability. However, few non‐HLA markers have been identified so far. This study was undertaken to replicate the associations of anti‐CCP–negative RA with non‐HLA genetic polymorphisms demonstrated in a previous study. Methods The Rheumatoid Arthritis Consortium International densely genotyped 186 autoimmune‐related regions in 3,339 anti‐CCP–negative RA patients and 15,870 controls across 6 different populations using the Illumina ImmunoChip array. We performed a case–control replication study of the anti‐CCP–negative markers with the strongest associations in that discovery study, in an independent cohort of anti‐CCP–negative UK RA patients. Individuals from the arcOGEN Consortium and Wellcome Trust Case Control Consortium were used as controls. Genotyping in cases was performed using Sequenom MassArray technology. Genome‐wide data from controls were imputed using the 1000 Genomes Phase I integrated variant call set release version 3 as a reference panel. Results After genotyping and imputation quality control procedures, data were available for 15 non‐HLA single‐nucleotide polymorphisms in 1,024 cases and 6,348 controls. We confirmed the known markers ANKRD55 (meta‐analysis odds ratio [OR] 0.80; P = 2.8 × 10−13) and BLK (OR 1.13; P = 7.0 × 10−6) and identified new and specific markers of anti‐CCP–negative RA (prolactin [PRL] [OR 1.13; P = 2.1 × 10−6] and NFIA [OR 0.85; P = 2.5 × 10−6]). Neither of these loci is associated with other common, complex autoimmune diseases. Conclusion Anti‐CCP–negative RA and anti‐CCP–positive RA are genetically different disease subsets that only partially share susceptibility factors. Genetic polymorphisms located near the PRL and NFIA genes represent examples of genetic susceptibility factors specific for anti‐CCP–negative RA. PMID:26895230

CASE Planned Giving Ideas. The Best of CASE CURRENTS.

ERIC Educational Resources Information Center

Carter, Virginia L., Ed.; Garigan, Catherine S., Ed.

Collected are articles by planned giving (deferred giving) experts on institutional commitment, policies, and programs to encourage various types of gifts to higher education institutions: bequests, unitrusts, annuity trusts, charitable income trusts (lead trusts), pooled income funds, gifts of land and so on. A major article covers how to hire…

Revealing Preconditions for Trustful Collaboration in CSCL

ERIC Educational Resources Information Center

Gerdes, Anne

2010-01-01

This paper analyses preconditions for trust in virtual learning environments. The concept of trust is discussed with reference to cases reporting trust in cyberspace and through a philosophical clarification holding that trust in the form of self-surrender is a common characteristic of all human co-existence. In virtual learning environments,…

26 CFR 1.50B-5 - Limitations with respect to certain persons.

Code of Federal Regulations, 2014 CFR

2014-04-01

... paragraph. (b) Regulated investment companies and real estate investment trusts. (1) In the case of a regulated investment company or a real estate investment trust subject to taxation under subchapter M... real estate investment trust taxable income, as the case may be. For purposes of the preceding sentence...

26 CFR 1.50B-5 - Limitations with respect to certain persons.

Code of Federal Regulations, 2011 CFR

2011-04-01

... paragraph. (b) Regulated investment companies and real estate investment trusts. (1) In the case of a regulated investment company or a real estate investment trust subject to taxation under subchapter M... real estate investment trust taxable income, as the case may be. For purposes of the preceding sentence...

26 CFR 1.50B-5 - Limitations with respect to certain persons.

Code of Federal Regulations, 2012 CFR

2012-04-01

... paragraph. (b) Regulated investment companies and real estate investment trusts. (1) In the case of a regulated investment company or a real estate investment trust subject to taxation under subchapter M... real estate investment trust taxable income, as the case may be. For purposes of the preceding sentence...

26 CFR 1.50B-5 - Limitations with respect to certain persons.

Code of Federal Regulations, 2013 CFR

2013-04-01

... paragraph. (b) Regulated investment companies and real estate investment trusts. (1) In the case of a regulated investment company or a real estate investment trust subject to taxation under subchapter M... real estate investment trust taxable income, as the case may be. For purposes of the preceding sentence...

26 CFR 1.50B-5 - Limitations with respect to certain persons.

Code of Federal Regulations, 2010 CFR

2010-04-01

... paragraph. (b) Regulated investment companies and real estate investment trusts. (1) In the case of a regulated investment company or a real estate investment trust subject to taxation under subchapter M... real estate investment trust taxable income, as the case may be. For purposes of the preceding sentence...

26 CFR 1.643(a)-6 - Income of foreign trust.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 26 Internal Revenue 8 2010-04-01 2010-04-01 false Income of foreign trust. 1.643(a)-6 Section 1... (CONTINUED) INCOME TAXES Estates, Trusts, and Beneficiaries § 1.643(a)-6 Income of foreign trust. (a) Distributable net income of a foreign trust. In the case of a foreign trust (see section 7701(a)(31)), the...

Trust-Guided Behavior Adaptation Using Case-Based Reasoning

DTIC Science & Technology

2015-08-01

the same behaviors were evaluated in each set. To account for this, the similarity function looks at the overlap between the two sets and ignores...interruptions would reduce the cost of case genera- tion. 6 Related Work Existing approaches for measuring inverse trust differ from our own in that...where a case- based reasoning system considers the reliability of a case’s source, also takes trust into account . Our work also has sim- ilarities

26 CFR 8.1 - Charitable remainder trusts.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 26 Internal Revenue 14 2010-04-01 2010-04-01 false Charitable remainder trusts. 8.1 Section 8.1... Charitable remainder trusts. (a) Certain wills and trusts in existence on September 21, 1974. In the case of a will executed before September 21, 1974, or a trust created (within the meaning of applicable...

Inter-Organizational Trust in EDI Adoption: The Case of Ford Motor Company and PBR Limited in Australia.

ERIC Educational Resources Information Center

Ratnasingam, Pauline

2001-01-01

This study examines behavioral dimensions of trading partner trust in EDI (electronic data interchange) adoption via a qualitative interpretative case study conducted between an automotive manufacturer (Ford Motor Company) in Australia and their first tier supplier, PBR Limited. Findings suggest that trust is important for cooperative long-term…

26 CFR 1.665(a)-0A - Excess distributions by trusts; scope of subpart D.

Code of Federal Regulations, 2010 CFR

2010-04-01

...” for the preceding year is also deemed distributed. To prevent double taxation, however, the...., an accumulation trust), in most cases, as if the income had been currently distributed to the...” of the trust, which, in the case of distributions made for a taxable year beginning after December 31...

Impact of case-mix on comparisons of patient-reported experience in NHS acute hospital trusts in England.

PubMed

Raleigh, Veena; Sizmur, Steve; Tian, Yang; Thompson, James

2015-04-01

To examine the impact of patient-mix on National Health Service (NHS) acute hospital trust scores in two national NHS patient surveys. Secondary analysis of 2012 patient survey data for 57,915 adult inpatients at 142 NHS acute hospital trusts and 45,263 adult emergency department attendees at 146 NHS acute hospital trusts in England. Changes in trust scores for selected questions, ranks, inter-trust variance and score-based performance bands were examined using three methods: no adjustment for case-mix; the current standardization method with weighting for age, sex and, for inpatients only, admission method; and a regression model adjusting in addition for ethnicity, presence of a long-term condition, proxy response (inpatients only) and previous emergency attendances (emergency department survey only). For both surveys, all the variables examined were associated with patients' responses and affected inter-trust variance in scores, although the direction and strength of impact differed between variables. Inter-trust variance was generally greatest for the unadjusted scores and lowest for scores derived from the full regression model. Although trust scores derived from the three methods were highly correlated (Kendall's tau coefficients 0.70-0.94), up to 14% of trusts had discordant ranks of when the standardization and regression methods were compared. Depending on the survey and question, up to 14 trusts changed performance bands when the regression model with its fuller case-mix adjustment was used rather than the current standardization method. More comprehensive case-mix adjustment of patient survey data than the current limited adjustment reduces performance variation between NHS acute hospital trusts and alters the comparative performance bands of some trusts. Given the use of these data for high-impact purposes such as performance assessment, regulation, commissioning, quality improvement and patient choice, a review of the long-standing method for analysing patient survey data would be timely, and could improve rigour and comparability across the NHS. Performance comparisons need to be perceived as fair and scientifically robust to maintain confidence in publicly reported data, and to support their use by both the public and the NHS. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Virtual Trust in US-India Global Outsource Teams: A Qualitative Exploratory Case Study

ERIC Educational Resources Information Center

Gugliotti, Domenic

2017-01-01

The purpose of this qualitative exploratory case study was to identify and analyze, trust behaviors used by members of an outsourced virtual team in an on and offshore engagement. The inability to build trust in outsourced engagements can cause serious damage to the collaboration within the virtual team causing it to fail. This study provides…

Clostridium difficile multidisciplinary team root cause analysis: impact on clinical care and circumvention of financial penalties posed by clinical commissioning groups, but at what cost?

PubMed

Saeed, Kordo; Petridou, Christina; Gray, Hazel; Dryden, Matthew; Davis-Blues, Karen; Lucero, Sheryl; Parker, Natalie; Keyser, Taryn; Matthews, Tanya; Cortes, Nick; Kidd, Stephen; Thomas, Claire; Peacock, Heather; Hornzee, Joanna; Wake, Bruce

2018-03-01

In Hampshire Hospitals NHS Foundation Trust, in addition to an on-the-spot investigation into hospital-onset Clostridium difficile infection (CDI) by the infection prevention team, a multidisciplinary team root cause analysis (MDT-RCA) forum has been developed. The MDT-RCA aims to deliver a more thorough investigation into individual cases and the recommendation of cases to the clinical commissioning groups (CCG) appeals panel against potential financial penalties (£10,000 per breached case). We mainly aimed to investigate the financial impact of MDT-RCAs to the Trust. Over two years, 84 cases of hospital-onset CDI cases were reviewed by the MDT-RCA forum. Among this cohort, no additional learning outcomes were identified by the MDT-RCAs over those that were found by on-the-spot investigations. In total, 543 staff members attended the MDT-RCAs at a potential cost to the Trust of £23,795.74-£51,670.10. The Trust appealed against financial penalties for 27 cases and 14 were successful, i.e. £140,000 would have been avoided had targets been breached by 14 cases. However, targets were only breached by two cases, meaning only £20,000 in fines was avoided. Deducting this from the total costs of the MDT-RCA meant the Trust lost £3,795.74-£31,670.10. Over the two years reviewed, the MDT-RCA proved to be costly to the Trust, with no additional learning or quality improvement measures identified.

Artemis and ACT: viewing, annotating and comparing sequences stored in a relational database.

PubMed

Carver, Tim; Berriman, Matthew; Tivey, Adrian; Patel, Chinmay; Böhme, Ulrike; Barrell, Barclay G; Parkhill, Julian; Rajandream, Marie-Adèle

2008-12-01

Artemis and Artemis Comparison Tool (ACT) have become mainstream tools for viewing and annotating sequence data, particularly for microbial genomes. Since its first release, Artemis has been continuously developed and supported with additional functionality for editing and analysing sequences based on feedback from an active user community of laboratory biologists and professional annotators. Nevertheless, its utility has been somewhat restricted by its limitation to reading and writing from flat files. Therefore, a new version of Artemis has been developed, which reads from and writes to a relational database schema, and allows users to annotate more complex, often large and fragmented, genome sequences. Artemis and ACT have now been extended to read and write directly to the Generic Model Organism Database (GMOD, http://www.gmod.org) Chado relational database schema. In addition, a Gene Builder tool has been developed to provide structured forms and tables to edit coordinates of gene models and edit functional annotation, based on standard ontologies, controlled vocabularies and free text. Artemis and ACT are freely available (under a GPL licence) for download (for MacOSX, UNIX and Windows) at the Wellcome Trust Sanger Institute web sites: http://www.sanger.ac.uk/Software/Artemis/ http://www.sanger.ac.uk/Software/ACT/

The Sheffield RNAi Screening Facility (SRSF): portfolio growth and technology development.

PubMed

Brown, Stephen

2014-05-01

The Sheffield RNAi Screening Facility (SRSF) (www.rnai.group.shef.ac.uk) was established in 2008 with Wellcome Trust and University of Sheffield funding, with the task to provide the first UK RNAi screening resource for academic groups interested in identifying genes required in a diverse range of biological processes using Drosophila cell culture. The SRSF has carried out a wide range of screens varying in sizes from bespoke small-scale libraries, targeting a few hundred genes, to high-throughput, genome-wide studies. The SRSF has grown and improved with a dedicated partnership of its academic customers based mainly in the UK. We are part of the UK Academics Functional Genomics Network, participating in organizing an annual meeting in London and are part of the University of Sheffield's D3N (www.d3n.org.uk), connecting academics, biotech and pharmaceutical companies with a multidisciplinary network in Drug Discovery and Development. Recently, the SRSF has been funded by the Yorkshire Cancer Research Fund to perform genome-wide RNAi screens using human cells as part of a core facility for regional Yorkshire Universities and screens are now underway. Overall the SRSF has carried out more than 40 screens from Drosophila and human cell culture experiments.

The under-representation of minority ethnic groups in UK medical research.

PubMed

Smart, Andrew; Harrison, Eric

2017-02-01

Objectives . The paper investigates differences in engagement with medical research between White British and Black, Asian and Minority Ethnic (BAME) groups in the UK, using data from the Wellcome Trust Monitor (WTM). The study used two waves of the WTM (n = 2575) to examine associations between ethnic group and participation in medical research, and willingness to participate (WP) in medical research. Logistic regression models controlled for socio-economic and demographic factors, and relevant outlooks and experiences that are assumed to be markers of engagement. Respondents from the BAME group were less likely to have participated in medical research compared to those from the White British group, but there was only patchy evidence of small ethnic group differences in WP. Influences on engagement with medical research varied somewhat between the White British and BAME groups, in particular in relation to occupation, education, health, attitudes to medical science and belief. These findings consolidate previously context-specific evidence of BAME group under-representation in the UK, and highlight heterogeneity in that group. Efforts to address the under-representation of those from BAME groups might benefit from targeted strategies for recruitment and advocacy, although improved data sets are required to fully understand ethnic differences in engagement with medical research.

Restoring trust in the pharmaceutical sector on the basis of the SSRI case.

PubMed

Hernandez, Juan Francisco; van Thiel, Ghislaine J M W; Mantel-Teeuwisse, Aukje K; Raaijmakers, Jan A M; Pieters, Toine

2014-05-01

The lack of public trust in the pharmaceutical sector (i.e. industry, authorities and doctors) could compromise the future of drug development and the regulatory system. Public trust integrates two important components, namely the vulnerability of the truster and the competence of the trustee. Because trust appears to have eroded as a result of drug safety controversies, this paper analyzes the role of public trust during the selective serotonin reuptake inhibitor (SSRI) and suicidality controversy focusing on the aforementioned trust components. Because the competence component of trust is argued to be paramount in determining and maintaining public trust, the SSRI case shows that this component is a part of public trust where these institutions can build on, and might therefore be better used to substantiate and reinforce, public trust. Efforts to build trust should rely on the ethical, professional (competence) and societal commitment of institutions and individuals to protect the vulnerability of the public during controversies. Because shared values can create trust or increase its levels within a specific environment, industry, authorities and physicians ought to develop novel and cooperative strategies to highlight their shared values and motivations. Rules, regulations and settlements are indispensable tools but undue regulation is costly and can backfire on the rather sensitive trust relationships in the pharmaceutical sector. Copyright © 2013 Elsevier Ltd. All rights reserved.

Trust of Population within Social Relations System of the Population: A Case Study of Nasleg Administration in the Republic of Sakha (Yakutia)

ERIC Educational Resources Information Center

Mikhaylova, Anna; Popova, Liudmila

2016-01-01

The research consists in studying the level of population's trust in nasleg administration (in the administrative-territorial unit) of MS "Khatyryksky nasleg" of Namsky ulus using the case study. The leading research methods for the problem are empirical methods that allow revealing the level of population's trust in administration. The…

26 CFR 1.56A-4 - Certain taxpayers.

Code of Federal Regulations, 2014 CFR

2014-04-01

... of the minimum tax in the case of estates and trusts, electing small business corporations, common trust funds, regulated investment companies, real estate investment trusts, and partnerships, see §§ 1...

26 CFR 1.56A-4 - Certain taxpayers.

Code of Federal Regulations, 2012 CFR

2012-04-01

... of the minimum tax in the case of estates and trusts, electing small business corporations, common trust funds, regulated investment companies, real estate investment trusts, and partnerships, see §§ 1...

26 CFR 1.56A-4 - Certain taxpayers.

Code of Federal Regulations, 2013 CFR

2013-04-01

... of the minimum tax in the case of estates and trusts, electing small business corporations, common trust funds, regulated investment companies, real estate investment trusts, and partnerships, see §§ 1...

26 CFR 1.56A-4 - Certain taxpayers.

Code of Federal Regulations, 2011 CFR

2011-04-01

... of the minimum tax in the case of estates and trusts, electing small business corporations, common trust funds, regulated investment companies, real estate investment trusts, and partnerships, see §§ 1...

36 CFR 1011.11 - How will the Presidio Trust use tax refund offset to collect a debt?

Code of Federal Regulations, 2010 CFR

2010-07-01

... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false How will the Presidio Trust... PRESIDIO TRUST DEBT COLLECTION Procedures To Collect Presidio Trust Debts § 1011.11 How will the Presidio Trust use tax refund offset to collect a debt? (a) Tax refund offset. In most cases, the FMS uses the...

An omnibus permutation test on ensembles of two-locus analyses can detect pure epistasis and genetic heterogeneity in genome-wide association studies.

PubMed

Setsirichok, Damrongrit; Tienboon, Phuwadej; Jaroonruang, Nattapong; Kittichaijaroen, Somkit; Wongseree, Waranyu; Piroonratana, Theera; Usavanarong, Touchpong; Limwongse, Chanin; Aporntewan, Chatchawit; Phadoongsidhi, Marong; Chaiyaratana, Nachol

2013-01-01

This article presents the ability of an omnibus permutation test on ensembles of two-locus analyses (2LOmb) to detect pure epistasis in the presence of genetic heterogeneity. The performance of 2LOmb is evaluated in various simulation scenarios covering two independent causes of complex disease where each cause is governed by a purely epistatic interaction. Different scenarios are set up by varying the number of available single nucleotide polymorphisms (SNPs) in data, number of causative SNPs and ratio of case samples from two affected groups. The simulation results indicate that 2LOmb outperforms multifactor dimensionality reduction (MDR) and random forest (RF) techniques in terms of a low number of output SNPs and a high number of correctly-identified causative SNPs. Moreover, 2LOmb is capable of identifying the number of independent interactions in tractable computational time and can be used in genome-wide association studies. 2LOmb is subsequently applied to a type 1 diabetes mellitus (T1D) data set, which is collected from a UK population by the Wellcome Trust Case Control Consortium (WTCCC). After screening for SNPs that locate within or near genes and exhibit no marginal single-locus effects, the T1D data set is reduced to 95,991 SNPs from 12,146 genes. The 2LOmb search in the reduced T1D data set reveals that 12 SNPs, which can be divided into two independent sets, are associated with the disease. The first SNP set consists of three SNPs from MUC21 (mucin 21, cell surface associated), three SNPs from MUC22 (mucin 22), two SNPs from PSORS1C1 (psoriasis susceptibility 1 candidate 1) and one SNP from TCF19 (transcription factor 19). A four-locus interaction between these four genes is also detected. The second SNP set consists of three SNPs from ATAD1 (ATPase family, AAA domain containing 1). Overall, the findings indicate the detection of pure epistasis in the presence of genetic heterogeneity and provide an alternative explanation for the aetiology of T1D in the UK population.

26 CFR 1.665(a)-1A - Undistributed net income.

Code of Federal Regulations, 2010 CFR

2010-04-01

... (CONTINUED) INCOME TAXES Treatment of Excess Distributions of Trusts Applicable to Taxable Years Beginning on Or After January 1, 1969 § 1.665(a)-1A Undistributed net income. (a) Domestic trusts. The term undistributed net income, in the case of a trust (other than a foreign trust created by a U.S. person) means...

26 CFR 1.665(a)-0 - Excess distributions by trusts; scope of subpart D.

Code of Federal Regulations, 2010 CFR

2010-04-01

... generally to prevent a shift of tax burden to a trust from a beneficiary or beneficiaries. In the case of a foreign trust created by a U.S. person, subpart D is designed to prevent certain other tax avoidance... TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Treatment of Excess Distributions of Trusts...

How Much Do You Trust Me? Learning a Case-Based Model of Inverse Trust

DTIC Science & Technology

2014-10-01

155–156 5. Jian, J.Y., Bisantz, A.M., Drury , C.G.: Foundations for an empirically determined scale of trust in automated systems. International...517–527 8. Carlson, M.S., Desai, M., Drury , J.L., Kwak, H., Yanco, H.A.: Identifying factors that influence trust in automated cars and medical

26 CFR 1.682(a)-1 - Income of trust in case of divorce, etc.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 26 Internal Revenue 8 2012-04-01 2012-04-01 false Income of trust in case of divorce, etc. 1.682(a... case of divorce, etc. (a) In general. (1) Section 682(a) provides rules in certain cases for... specified to be for the support of the obligor spouse's minor children in the divorce or separate...

26 CFR 1.682(a)-1 - Income of trust in case of divorce, etc.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 26 Internal Revenue 8 2011-04-01 2011-04-01 false Income of trust in case of divorce, etc. 1.682(a... case of divorce, etc. (a) In general. (1) Section 682(a) provides rules in certain cases for... specified to be for the support of the obligor spouse's minor children in the divorce or separate...

26 CFR 1.682(a)-1 - Income of trust in case of divorce, etc.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 26 Internal Revenue 8 2014-04-01 2014-04-01 false Income of trust in case of divorce, etc. 1.682(a... case of divorce, etc. (a) In general. (1) Section 682(a) provides rules in certain cases for... specified to be for the support of the obligor spouse's minor children in the divorce or separate...

26 CFR 1.682(a)-1 - Income of trust in case of divorce, etc.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 26 Internal Revenue 8 2013-04-01 2013-04-01 false Income of trust in case of divorce, etc. 1.682(a... case of divorce, etc. (a) In general. (1) Section 682(a) provides rules in certain cases for... specified to be for the support of the obligor spouse's minor children in the divorce or separate...

Why we need easy access to all data from all clinical trials and how to accomplish it

PubMed Central

2011-01-01

International calls for registering all trials involving humans and for sharing the results, and sometimes also the raw data and the trial protocols, have increased in recent years. Such calls have come, for example, from the Organization for Economic Cooperation and Development (OECD), the World Health Organization (WHO), the US National Institutes of Heath, the US Congress, the European Commission, the European ombudsman, journal editors, The Cochrane Collaboration, and several funders, for example the UK Medical Research Council, the Wellcome Trust, the Bill and Melinda Gates Foundation and the Hewlett Foundation. Calls for data sharing have mostly been restricted to publicly-funded research, but I argue that the distinction between publicly-funded and industry-funded research is an artificial and irrelevant one, as the interests of the patients must override commercial interests. I also argue why it is a moral imperative to render all results from all trials involving humans, also healthy volunteers, publicly available. Respect for trial participants who often run a personal and unknown risk by participating in trials requires that they - and therefore also the society at large that they represent - be seen as the ultimate owners of trial data. Data sharing would lead to tremendous benefits for patients, progress in science, and rational use of healthcare resources based on evidence we can trust. The harmful consequences are minor compared to the benefits. It has been amply documented that the current situation, with selective reporting of favorable research and biased data analyses being the norm rather than the exception, is harmful to patients and has led to the death of tens of thousands of patients that could have been avoided. National and supranational legislation is needed to make data sharing happen as guidelines and other voluntary agreements do not work. I propose the contents of such legislation and of appropriate sanctions to hold accountable those who refuse to share their data. PMID:22112900

Mergers and Anti-trust Issues in Recent CAB Cases

NASA Technical Reports Server (NTRS)

Andrews, A. M.

1972-01-01

The airline industry is surveyed-particularly domestic trunklines-in relation to collective approaches to industry concerns. These actions are classified by the apparent degree of anti-trust issue present. Recent route merger cases are considered from the CAB staff viewpoint.

National Audubon Society v. Superior Court: a watershed case integrating the public trust doctrine and California water law

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gaylord, R.K.

Audobon v. Superior Court is a ''watershed'' case in its integration of the public trust doctrine within traditional water law. The public trust doctrine requires the state to exercise a duty of continued supervision over the taking and use of appropriated water. As a result, the state must periodically balance the economic interests served by the water appropriations with the ecological and recreational interests protected under the public trust. The state can best meet this burden by adopting a balancing procedure that includes comprehensive, long-term planning of the economic effects and ecological interests in water appropriation. 78 references.

A qualitative study of the role of workplace and interpersonal trust in shaping service quality and responsiveness in Zambian primary health centres

PubMed Central

Topp, Stephanie M; Chipukuma, Julien M

2016-01-01

Background: Human decisions, actions and relationships that invoke trust are at the core of functional and productive health systems. Although widely studied in high-income settings, comparatively few studies have explored the influence of trust on health system performance in low- and middle-income countries. This study examines how workplace and inter-personal trust impact service quality and responsiveness in primary health services in Zambia. Methods: This multi-case study included four health centres selected for urban, peri-urban and rural characteristics. Case data included provider interviews (60); patient interviews (180); direct observation of facility operations (two weeks/centre) and key informant interviews (14) that were recorded and transcribed verbatim. Case-based thematic analysis incorporated inductive and deductive coding. Results: Findings demonstrated that providers had weak workplace trust influenced by a combination of poor working conditions, perceptions of low pay and experiences of inequitable or inefficient health centre management. Weak trust in health centre managers’ organizational capacity and fairness contributed to resentment amongst many providers and promoted a culture of blame-shifting and one-upmanship that undermined teamwork and enabled disrespectful treatment of patients. Although patients expressed a high degree of trust in health workers’ clinical capacity, repeated experiences of disrespectful or unresponsive care undermined patients’ trust in health workers’ service values and professionalism. Lack of patient–provider trust prompted some patients to circumvent clinic systems in an attempt to secure better or more timely care. Conclusion: Lack of resourcing and poor leadership were key factors leading to providers’ weak workplace trust and contributed to often-poor quality services, driving a perverse cycle of negative patient–provider relations across the four sites. Findings highlight the importance of investing in both structural factors and organizational management to strengthen providers’ trust in their employer(s) and colleagues, as an entry-point for developing both the capacity and a work culture oriented towards respectful and patient-centred care. PMID:25999586

Dysfunction of NaV1.4, a skeletal muscle voltage-gated sodium channel, in sudden infant death syndrome: a case-control study.

PubMed

Männikkö, Roope; Wong, Leonie; Tester, David J; Thor, Michael G; Sud, Richa; Kullmann, Dimitri M; Sweeney, Mary G; Leu, Costin; Sisodiya, Sanjay M; FitzPatrick, David R; Evans, Margaret J; Jeffrey, Iona J M; Tfelt-Hansen, Jacob; Cohen, Marta C; Fleming, Peter J; Jaye, Amie; Simpson, Michael A; Ackerman, Michael J; Hanna, Michael G; Behr, Elijah R; Matthews, Emma

2018-04-14

Sudden infant death syndrome (SIDS) is the leading cause of post-neonatal infant death in high-income countries. Central respiratory system dysfunction seems to contribute to these deaths. Excitation that drives contraction of skeletal respiratory muscles is controlled by the sodium channel NaV1.4, which is encoded by the gene SCN4A. Variants in NaV1.4 that directly alter skeletal muscle excitability can cause myotonia, periodic paralysis, congenital myopathy, and myasthenic syndrome. SCN4A variants have also been found in infants with life-threatening apnoea and laryngospasm. We therefore hypothesised that rare, functionally disruptive SCN4A variants might be over-represented in infants who died from SIDS. We did a case-control study, including two consecutive cohorts that included 278 SIDS cases of European ancestry and 729 ethnically matched controls without a history of cardiovascular, respiratory, or neurological disease. We compared the frequency of rare variants in SCN4A between groups (minor allele frequency <0·00005 in the Exome Aggregation Consortium). We assessed biophysical characterisation of the variant channels using a heterologous expression system. Four (1·4%) of the 278 infants in the SIDS cohort had a rare functionally disruptive SCN4A variant compared with none (0%) of 729 ethnically matched controls (p=0·0057). Rare SCN4A variants that directly alter NaV1.4 function occur in infants who had died from SIDS. These variants are predicted to significantly alter muscle membrane excitability and compromise respiratory and laryngeal function. These findings indicate that dysfunction of muscle sodium channels is a potentially modifiable risk factor in a subset of infant sudden deaths. UK Medical Research Council, the Wellcome Trust, National Institute for Health Research, the British Heart Foundation, Biotronik, Cardiac Risk in the Young, Higher Education Funding Council for England, Dravet Syndrome UK, the Epilepsy Society, the Eunice Kennedy Shriver National Institute of Child Health & Human Development of the National Institutes of Health, and the Mayo Clinic Windland Smith Rice Comprehensive Sudden Cardiac Death Program. Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

Technique Selectively Represses Immune System

MedlinePlus

... from attacking myelin in a mouse model of multiple sclerosis. Dr David Furness, Wellcome Images. All rights reserved ... devised a way to successfully treat symptoms resembling multiple sclerosis in a mouse model. With further development, the ...

Case Study Analysis of Trust and Commitment Between the Civil Engineering Commodity Council and the Civil Engineering Career Field

DTIC Science & Technology

2013-03-01

Factors influencing success ..................................................................................... 61 Antecedents of Trust ...were organized in a network that proposed which factors influence trust development between organizations. A sample list of codes and associated...perspective of trust as having a positive influence on commitment and cooperation towards an organization. Examples of factors that may influence the

26 CFR 1.691(c)-2 - Estates and trusts.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 26 Internal Revenue 8 2010-04-01 2010-04-01 false Estates and trusts. 1.691(c)-2 Section 1.691(c... (CONTINUED) INCOME TAXES Income in Respect of Decedents § 1.691(c)-2 Estates and trusts. (a) In the case of an estate or trust, the deduction prescribed in section 691(c) is determined in the same manner as...

26 CFR 1.48-6 - Estates and trusts.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 26 Internal Revenue 1 2010-04-01 2010-04-01 true Estates and trusts. 1.48-6 Section 1.48-6... Computing Credit for Investment in Certain Depreciable Property § 1.48-6 Estates and trusts. (a) In general. (1) In the case of an estate or trust, the basis of “new section 38 property” and the cost of “used...

A management approach that drives actions strategically: balanced scorecard in a mental health trust case study.

PubMed

Schmidt, Stefan; Bateman, Ian; Breinlinger-O'Reilly, Jochen; Smith, Peter

2006-01-01

Achieving excellence is a current preoccupation in U.K. public health organisations. This article aims to use a case study to explain how a mental health trust delivers excellent performance using a balanced scorecard (BSC) management approach. Reports a project to implement a BSC approach in the South West Yorkshire Mental Health NHS Trust to achieve its "excellence" objectives. The authors were participants in the project. The design of the pilot project was informed theoretically by the work of Kaplan and Norton and practically by in-house discussions on a strategy to achieve excellence. Explains the process of building a BSC strategy step-by-step. Discusses how the vision and strategies of a mental health trust can be translated into tangible measures, which are the basis for actions that are driven strategically. There are many possibilities for a BSC management approach and this case study is specific to mental health trusts in the UK, although it is believed that the case has a universally applicable modus operandi. This article will help healthcare managers to evaluate the benefits of a BSC management approach. This article explains how actions can be structured in connection with a BSC management approach.

The impact of staff case manager-case management supervisor relationship on job satisfaction and retention of RN case managers.

PubMed

Hogan, Tierney D

2005-01-01

A positive relationship between staff RN case managers and their case management supervisor significantly impacts job satisfaction and retention in case managers. Literature review supports the premise that staff need to trust their supervisor and that there is a connection between this trust and job satisfaction. Staff case managers need to have a voice at work and feel empowered, and a supervisor's leadership style can influence job satisfaction and retention in their staff.

Mining the human phenome using allelic scores that index biological intermediates.

PubMed

Evans, David M; Brion, Marie Jo A; Paternoster, Lavinia; Kemp, John P; McMahon, George; Munafò, Marcus; Whitfield, John B; Medland, Sarah E; Montgomery, Grant W; Timpson, Nicholas J; St Pourcain, Beate; Lawlor, Debbie A; Martin, Nicholas G; Dehghan, Abbas; Hirschhorn, Joel; Smith, George Davey

2013-10-01

It is common practice in genome-wide association studies (GWAS) to focus on the relationship between disease risk and genetic variants one marker at a time. When relevant genes are identified it is often possible to implicate biological intermediates and pathways likely to be involved in disease aetiology. However, single genetic variants typically explain small amounts of disease risk. Our idea is to construct allelic scores that explain greater proportions of the variance in biological intermediates, and subsequently use these scores to data mine GWAS. To investigate the approach's properties, we indexed three biological intermediates where the results of large GWAS meta-analyses were available: body mass index, C-reactive protein and low density lipoprotein levels. We generated allelic scores in the Avon Longitudinal Study of Parents and Children, and in publicly available data from the first Wellcome Trust Case Control Consortium. We compared the explanatory ability of allelic scores in terms of their capacity to proxy for the intermediate of interest, and the extent to which they associated with disease. We found that allelic scores derived from known variants and allelic scores derived from hundreds of thousands of genetic markers explained significant portions of the variance in biological intermediates of interest, and many of these scores showed expected correlations with disease. Genome-wide allelic scores however tended to lack specificity suggesting that they should be used with caution and perhaps only to proxy biological intermediates for which there are no known individual variants. Power calculations confirm the feasibility of extending our strategy to the analysis of tens of thousands of molecular phenotypes in large genome-wide meta-analyses. We conclude that our method represents a simple way in which potentially tens of thousands of molecular phenotypes could be screened for causal relationships with disease without having to expensively measure these variables in individual disease collections.

Spread of artemisinin-resistant Plasmodium falciparum in Myanmar: a cross-sectional survey of the K13 molecular marker.

PubMed

Tun, Kyaw M; Imwong, Mallika; Lwin, Khin M; Win, Aye A; Hlaing, Tin M; Hlaing, Thaung; Lin, Khin; Kyaw, Myat P; Plewes, Katherine; Faiz, M Abul; Dhorda, Mehul; Cheah, Phaik Yeong; Pukrittayakamee, Sasithon; Ashley, Elizabeth A; Anderson, Tim J C; Nair, Shalini; McDew-White, Marina; Flegg, Jennifer A; Grist, Eric P M; Guerin, Philippe; Maude, Richard J; Smithuis, Frank; Dondorp, Arjen M; Day, Nicholas P J; Nosten, François; White, Nicholas J; Woodrow, Charles J

2015-04-01

Emergence of artemisinin resistance in southeast Asia poses a serious threat to the global control of Plasmodium falciparum malaria. Discovery of the K13 marker has transformed approaches to the monitoring of artemisinin resistance, allowing introduction of molecular surveillance in remote areas through analysis of DNA. We aimed to assess the spread of artemisinin-resistant P falciparum in Myanmar by determining the relative prevalence of P falciparum parasites carrying K13-propeller mutations. We did this cross-sectional survey at malaria treatment centres at 55 sites in ten administrative regions in Myanmar, and in relevant border regions in Thailand and Bangladesh, between January, 2013, and September, 2014. K13 sequences from P falciparum infections were obtained mainly by passive case detection. We entered data into two geostatistical models to produce predictive maps of the estimated prevalence of mutations of the K13 propeller region across Myanmar. Overall, 371 (39%) of 940 samples carried a K13-propeller mutation. We recorded 26 different mutations, including nine mutations not described previously in southeast Asia. In seven (70%) of the ten administrative regions of Myanmar, the combined K13-mutation prevalence was more than 20%. Geospatial mapping showed that the overall prevalence of K13 mutations exceeded 10% in much of the east and north of the country. In Homalin, Sagaing Region, 25 km from the Indian border, 21 (47%) of 45 parasite samples carried K13-propeller mutations. Artemisinin resistance extends across much of Myanmar. We recorded P falciparum parasites carrying K13-propeller mutations at high prevalence next to the northwestern border with India. Appropriate therapeutic regimens should be tested urgently and implemented comprehensively if spread of artemisinin resistance to other regions is to be avoided. Wellcome Trust-Mahidol University-Oxford Tropical Medicine Research Programme and the Bill & Melinda Gates Foundation. Copyright © 2015 Tun et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd. All rights reserved.

A Variant in the BACH2 Gene Is Associated With Susceptibility to Autoimmune Addison's Disease in Humans.

PubMed

Pazderska, Agnieszka; Oftedal, Bergithe E; Napier, Catherine M; Ainsworth, Holly F; Husebye, Eystein S; Cordell, Heather J; Pearce, Simon H S; Mitchell, Anna L

2016-11-01

Autoimmune Addison's disease (AAD) is a rare but highly heritable condition. The BACH2 protein plays a crucial role in T lymphocyte maturation, and allelic variation in its gene has been associated with a number of autoimmune conditions. We aimed to determine whether alleles of the rs3757247 single nucleotide polymorphism (SNP) in the BACH2 gene are associated with AAD. This case-control association study was performed in two phases using Taqman chemistry. In the first phase, the rs3757247 SNP was genotyped in 358 UK AAD subjects and 166 local control subjects. Genotype data were also available from 5154 healthy UK controls from the Wellcome Trust (WTCCC2) for comparison. In the second phase, the SNP was genotyped in a validation cohort comprising 317 Norwegian AAD subjects and 365 controls. The frequency of the minor T allele was significantly higher in subjects with AAD from the United Kingdom compared to both the local and WTCCC2 control cohorts (58% vs 45 and 48%, respectively) (local controls, P = 1.1 × 10 -4 ; odds ratio [OR], 1.68; 95% confidence interval [CI], 1.29-2.18; WTCCC2 controls, P = 1.4 × 10 -6 ; OR, 1.44; 95% CI, 1.23-1.69). This finding was replicated in the Norwegian validation cohort (P = .0015; OR, 1.41; 95% CI, 1.14-1.75). Subgroup analysis showed that this association is present in subjects with both isolated AAD (OR, 1.53; 95% CI, 1.22-1.92) and autoimmune polyglandular syndrome type 2 (OR, 1.37; 95% CI, 1.12-1.69) in the UK cohort, and with autoimmune polyglandular syndrome type 2 in the Norwegian cohort (OR, 1.58; 95% CI, 1.22-2.06). We have demonstrated, for the first time, that allelic variability at the BACH2 locus is associated with susceptibility to AAD. Given its association with multiple autoimmune conditions, BACH2 can be considered a "universal" autoimmune susceptibility locus.

Integrated Enrichment Analysis of Variants and Pathways in Genome-Wide Association Studies Indicates Central Role for IL-2 Signaling Genes in Type 1 Diabetes, and Cytokine Signaling Genes in Crohn's Disease

PubMed Central

Carbonetto, Peter; Stephens, Matthew

2013-01-01

Pathway analyses of genome-wide association studies aggregate information over sets of related genes, such as genes in common pathways, to identify gene sets that are enriched for variants associated with disease. We develop a model-based approach to pathway analysis, and apply this approach to data from the Wellcome Trust Case Control Consortium (WTCCC) studies. Our method offers several benefits over existing approaches. First, our method not only interrogates pathways for enrichment of disease associations, but also estimates the level of enrichment, which yields a coherent way to promote variants in enriched pathways, enhancing discovery of genes underlying disease. Second, our approach allows for multiple enriched pathways, a feature that leads to novel findings in two diseases where the major histocompatibility complex (MHC) is a major determinant of disease susceptibility. Third, by modeling disease as the combined effect of multiple markers, our method automatically accounts for linkage disequilibrium among variants. Interrogation of pathways from eight pathway databases yields strong support for enriched pathways, indicating links between Crohn's disease (CD) and cytokine-driven networks that modulate immune responses; between rheumatoid arthritis (RA) and “Measles” pathway genes involved in immune responses triggered by measles infection; and between type 1 diabetes (T1D) and IL2-mediated signaling genes. Prioritizing variants in these enriched pathways yields many additional putative disease associations compared to analyses without enrichment. For CD and RA, 7 of 8 additional non-MHC associations are corroborated by other studies, providing validation for our approach. For T1D, prioritization of IL-2 signaling genes yields strong evidence for 7 additional non-MHC candidate disease loci, as well as suggestive evidence for several more. Of the 7 strongest associations, 4 are validated by other studies, and 3 (near IL-2 signaling genes RAF1, MAPK14, and FYN) constitute novel putative T1D loci for further study. PMID:24098138

A hidden two-locus disease association pattern in genome-wide association studies

PubMed Central

2011-01-01

Background Recent association analyses in genome-wide association studies (GWAS) mainly focus on single-locus association tests (marginal tests) and two-locus interaction detections. These analysis methods have provided strong evidence of associations between genetics variances and complex diseases. However, there exists a type of association pattern, which often occurs within local regions in the genome and is unlikely to be detected by either marginal tests or interaction tests. This association pattern involves a group of correlated single-nucleotide polymorphisms (SNPs). The correlation among SNPs can lead to weak marginal effects and the interaction does not play a role in this association pattern. This phenomenon is due to the existence of unfaithfulness: the marginal effects of correlated SNPs do not express their significant joint effects faithfully due to the correlation cancelation. Results In this paper, we develop a computational method to detect this association pattern masked by unfaithfulness. We have applied our method to analyze seven data sets from the Wellcome Trust Case Control Consortium (WTCCC). The analysis for each data set takes about one week to finish the examination of all pairs of SNPs. Based on the empirical result of these real data, we show that this type of association masked by unfaithfulness widely exists in GWAS. Conclusions These newly identified associations enrich the discoveries of GWAS, which may provide new insights both in the analysis of tagSNPs and in the experiment design of GWAS. Since these associations may be easily missed by existing analysis tools, we can only connect some of them to publicly available findings from other association studies. As independent data set is limited at this moment, we also have difficulties to replicate these findings. More biological implications need further investigation. Availability The software is freely available at http://bioinformatics.ust.hk/hidden_pattern_finder.zip. PMID:21569557

UK investments in global infectious disease research 1997-2010: a case study.

PubMed

Head, Michael G; Fitchett, Joseph R; Cooke, Mary K; Wurie, Fatima B; Hayward, Andrew C; Atun, Rifat

2013-01-01

Infectious diseases account for 15 million deaths per year worldwide, and disproportionately affect young people, elderly people, and the poorest sections of society. We aimed to describe the investments awarded to UK institutions for infectious disease research. We systematically searched databases and websites for information on research studies from funding institutions and created a comprehensive database of infectious disease research projects for the period 1997-2010. We categorised studies and funding by disease, cross-cutting theme, and by a research and development value chain describing the type of science. Regression analyses were reported with Spearman's rank correlation coefficient to establish the relation between research investment, mortality, and disease burden as measured by disability-adjusted life years (DALYs). We identified 6170 funded studies, with a total research investment of UK£2·6 billion. Studies with a clear global health component represented 35·6% of all funding (£927 million). By disease, HIV received £461 million (17·7%), malaria £346 million (13·3%), tuberculosis £149 million (5·7%), influenza £80 million (3·1%), and hepatitis C £60 million (2·3%). We compared funding with disease burden (DALYs and mortality) to show low levels of investment relative to burden for gastrointestinal infections (£254 million, 9·7%), some neglected tropical diseases (£184 million, 7·1%), and antimicrobial resistance (£96 million, 3·7%). Virology was the highest funded category (£1 billion, 38·4%). Leading funding sources were the Wellcome Trust (£688 million, 26·4%) and the Medical Research Council (£673 million, 25·8%). Research funding has to be aligned with prevailing and projected global infectious disease burden. Funding agencies and industry need to openly document their research investments to redress any inequities in resource allocation. None. Copyright © 2013 Elsevier Ltd. All rights reserved.

Providing a conceptual framework for HIV prevention cascades and assessing feasibility of empirical measurement with data from east Zimbabwe: a case study.

PubMed

Garnett, Geoffrey P; Hallett, Timothy B; Takaruza, Albert; Hargreaves, James; Rhead, Rebecca; Warren, Mitchel; Nyamukapa, Constance; Gregson, Simon

2016-07-01

The HIV treatment cascade illustrates the steps required for successful treatment and is a powerful advocacy and monitoring tool. Similar cascades for people susceptible to infection could improve HIV prevention programming. We aim to show the feasibility of using cascade models to monitor prevention programmes. Conceptual prevention cascades are described taking intervention-centric and client-centric perspectives to look at supply, demand, and efficacy of interventions. Data from two rounds of a population-based study in east Zimbabwe are used to derive the values of steps for cascades for voluntary medical male circumcision (VMMC) and for partner reduction or condom use driven by HIV testing and counselling (HTC). In 2009 to 2011 the availability of circumcision services was negligible, but by 2012 to 2013 about a third of the population had access. However, where it was available only 12% of eligible men sought to be circumcised leading to an increase in circumcision prevalence from 3·1% to 6·9%. Of uninfected men, 85·3% did not perceive themselves to be at risk of acquiring HIV. The proportions of men and women tested for HIV increased from 27·5% to 56·6% and from 61·1% to 79·6%, respectively, with 30·4% of men tested self-reporting reduced sexual partner numbers and 12·8% reporting increased condom use. Prevention cascades can be populated to inform HIV prevention programmes. In eastern Zimbabwe programmes need to provide greater access to circumcision services and the design and implementation of associated demand creation activities. Whereas, HTC services need to consider how to increase reductions in partner numbers or increased condom use or should not be considered as contributing to prevention services for the HIV-negative adults. Wellcome Trust and Bill & Melinda Gates Foundation. Copyright © 2016 Garnett et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd.. All rights reserved.

Phase 1 Trials of rVSV Ebola Vaccine in Africa and Europe.

PubMed

Agnandji, Selidji T; Huttner, Angela; Zinser, Madeleine E; Njuguna, Patricia; Dahlke, Christine; Fernandes, José F; Yerly, Sabine; Dayer, Julie-Anne; Kraehling, Verena; Kasonta, Rahel; Adegnika, Akim A; Altfeld, Marcus; Auderset, Floriane; Bache, Emmanuel B; Biedenkopf, Nadine; Borregaard, Saskia; Brosnahan, Jessica S; Burrow, Rebekah; Combescure, Christophe; Desmeules, Jules; Eickmann, Markus; Fehling, Sarah K; Finckh, Axel; Goncalves, Ana Rita; Grobusch, Martin P; Hooper, Jay; Jambrecina, Alen; Kabwende, Anita L; Kaya, Gürkan; Kimani, Domtila; Lell, Bertrand; Lemaître, Barbara; Lohse, Ansgar W; Massinga-Loembe, Marguerite; Matthey, Alain; Mordmüller, Benjamin; Nolting, Anne; Ogwang, Caroline; Ramharter, Michael; Schmidt-Chanasit, Jonas; Schmiedel, Stefan; Silvera, Peter; Stahl, Felix R; Staines, Henry M; Strecker, Thomas; Stubbe, Hans C; Tsofa, Benjamin; Zaki, Sherif; Fast, Patricia; Moorthy, Vasee; Kaiser, Laurent; Krishna, Sanjeev; Becker, Stephan; Kieny, Marie-Paule; Bejon, Philip; Kremsner, Peter G; Addo, Marylyn M; Siegrist, Claire-Anne

2016-04-28

The replication-competent recombinant vesicular stomatitis virus (rVSV)-based vaccine expressing a Zaire ebolavirus (ZEBOV) glycoprotein was selected for rapid safety and immunogenicity testing before its use in West Africa. We performed three open-label, dose-escalation phase 1 trials and one randomized, double-blind, controlled phase 1 trial to assess the safety, side-effect profile, and immunogenicity of rVSV-ZEBOV at various doses in 158 healthy adults in Europe and Africa. All participants were injected with doses of vaccine ranging from 300,000 to 50 million plaque-forming units (PFU) or placebo. No serious vaccine-related adverse events were reported. Mild-to-moderate early-onset reactogenicity was frequent but transient (median, 1 day). Fever was observed in up to 30% of vaccinees. Vaccine viremia was detected within 3 days in 123 of the 130 participants (95%) receiving 3 million PFU or more; rVSV was not detected in saliva or urine. In the second week after injection, arthritis affecting one to four joints developed in 11 of 51 participants (22%) in Geneva, with pain lasting a median of 8 days (interquartile range, 4 to 87); 2 self-limited cases occurred in 60 participants (3%) in Hamburg, Germany, and Kilifi, Kenya. The virus was identified in one synovial-fluid aspirate and in skin vesicles of 2 other vaccinees, showing peripheral viral replication in the second week after immunization. ZEBOV-glycoprotein-specific antibody responses were detected in all the participants, with similar glycoprotein-binding antibody titers but significantly higher neutralizing antibody titers at higher doses. Glycoprotein-binding antibody titers were sustained through 180 days in all participants. In these studies, rVSV-ZEBOV was reactogenic but immunogenic after a single dose and warrants further evaluation for safety and efficacy. (Funded by the Wellcome Trust and others; ClinicalTrials.gov numbers, NCT02283099, NCT02287480, and NCT02296983; Pan African Clinical Trials Registry number, PACTR201411000919191.).

Process and impact of mergers of NHS trusts: multicentre case study and management cost analysis

PubMed Central

Fulop, Naomi; Protopsaltis, Gerasimos; Hutchings, Andrew; King, Annette; Allen, Pauline; Normand, Charles; Walters, Rhiannon

2002-01-01

Objective To study the processes involved in and impact of mergers between NHS trusts, including the effect on management costs. Design Cross sectional study involving in depth interviews and documentary analysis; case study to compare savings in management costs between case trusts and control trusts. Setting Nine trusts (cross sectional study) and four trusts (case study) in London. Participants 96 interviews with trust board members, other senior managers, clinicians, service managers, and representatives of health authorities, regional office, community health councils, local authorities, other trusts in the area, and primary care groups and trusts. Main outcome measures Stated and unstated drivers, and impact of merger on delivery and development of services, management structures, and staff recruitment, retention, and morale. Effects of difference in trust size before and after the merger. Savings in management costs two years after merger. Results Some important drivers for merger are not publicly stated. Mergers had a negative effect on delivery of services because of a loss of managerial focus on services. Planned developments in services were delayed by at least 18 months. Trusts' larger sizes after mergers had unintended negative consequences, as well as predicted advantages. The tendency for one trust's management team to dominate over the other resulted in tension. No improvement in recruitment or retention of clinical and managerial staff was reported. Perceived differences in organisational culture were an important barrier to bringing together two or more organisations. Two years after merger, merged trusts had not achieved the objective of saving £500 000 a year in management costs. Conclusions Important unintended consequences need to be accounted for when mergers are planned. Mergers can cause considerable disruptions to services, and require greater management support than previously acknowledged. Other organisations undergoing restructuring, such as primary care groups developing into primary care trusts and health authorities merging into strategic health authorities, should take these findings into account. What is already known on this topicResearch suggests that effectiveness increases as the amount of activity by specialised units in certain clinical specialities increasesLittle empirical research has looked at the impact of mergers; most studies focus on financial variablesMergers result in short term disruption caused by difficulties in integrating services and personnelWhat this study addsImportant drivers for NHS mergers that are not stated publicly have implications for the process and impact of mergersMergers have positive effects, as well as unintended negative consequences that disrupt services and set back developments in servicesPerceived differences in organisational culture impede bringing organisations togetherMergers do not achieve target savings in management costs in first two years after merger PMID:12153920

26 CFR 1.1015-3 - Gift or transfer in trust before January 1, 1921.

Code of Federal Regulations, 2014 CFR

2014-04-01

... the time of the gift or at the time of the transfer in trust. (b) The principles stated in paragraph... 26 Internal Revenue 11 2014-04-01 2014-04-01 false Gift or transfer in trust before January 1... Gift or transfer in trust before January 1, 1921. (a) In the case of property acquired by gift or...

26 CFR 1.50B-3 - Estates and trusts.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 26 Internal Revenue 1 2010-04-01 2010-04-01 true Estates and trusts. 1.50B-3 Section 1.50B-3... Computing Credit for Expenses of Work Incentive Programs § 1.50B-3 Estates and trusts. (a) General rule—(1) In general. In the case of an estate or trust, WIN expenses (as defined in paragraph (a) of § 1.50B-1...

On the relation between trust and fairness in environmental risk management.

PubMed

Earle, Timothy C; Siegrist, Michael

2008-10-01

In this study, we empirically examine the relations between trust, fairness, and cooperation within two environmental risk management contexts, one in which the focal issue is of high personal moral importance and the other in which the focal issue is of low moral importance. Using an experimental design embedded in two parallel survey questionnaires, one mailed to residents of Washington State, the other to German-speaking residents of Switzerland, we either manipulated or constructed three factors, issue importance (high/low), procedural fairness (fair/unfair), and policy outcome (risk averse/risk accepting). This design enabled us to compare the predictions of the standard account of procedural fairness, that trust and cooperation are determined by judgments of fairness, with the predictions of an alternative account, that trust and cooperation will be determined by judgments of procedural fairness only when the issue involved is not morally important. Results for the American case showed that under conditions of high issue importance, policy outcome affected judged fairness, trust, and cooperation. Under conditions of low issue importance, policy outcome had no effect on judged fairness or trust but did have a moderate impact on cooperation. Analyses also showed that when issue importance was high, procedural fairness had no effects. When issue importance was low, procedural fairness had moderate effects on judged fairness and trust. Results for the Swiss case replicated the main findings for the American case. Together, these results support the alternative model of the relation between trust and fairness, suggesting that the efficacy of fair procedures is strictly limited.

Funding infectious disease research: a systematic analysis of UK research investments by funders 1997-2010.

PubMed

Fitchett, Joseph R; Head, Michael G; Cooke, Mary K; Wurie, Fatima B; Atun, Rifat

2014-01-01

Research investments are essential to address the burden of disease, however allocation of limited resources is poorly documented. We systematically reviewed the investments awarded by funding organisations to UK institutions and their global partners for infectious disease research. Public and philanthropic investments for the period 1997 to 2010 were included. We categorised studies by infectious disease, cross-cutting theme, and by research and development value chain, reflecting the type of science. We identified 6165 funded studies, with a total research investment of UK £2.6 billion. Public organisations provided £1.4 billion (54.0%) of investments compared with £1.1 billion (42.4%) by philanthropic organisations. Global health studies represented an investment of £928 million (35.7%). The Wellcome Trust was the leading investor with £688 million (26.5%), closely followed by the UK Medical Research Council (MRC) with £673 million (25.9%). Funding over time was volatile, ranging from ∼£40 million to ∼£160 million per year for philanthropic organisations and ∼£30 million to ∼£230 million for public funders. Infectious disease research funding requires global coordination and strategic long-term vision. Our analysis demonstrates the diversity and inconsistent patterns in investment, with volatility in annual funding amounts and limited investment for product development and clinical trials.

Kisspeptin modulates sexual and emotional brain processing in humans.

PubMed

Comninos, Alexander N; Wall, Matthew B; Demetriou, Lysia; Shah, Amar J; Clarke, Sophie A; Narayanaswamy, Shakunthala; Nesbitt, Alexander; Izzi-Engbeaya, Chioma; Prague, Julia K; Abbara, Ali; Ratnasabapathy, Risheka; Salem, Victoria; Nijher, Gurjinder M; Jayasena, Channa N; Tanner, Mark; Bassett, Paul; Mehta, Amrish; Rabiner, Eugenii A; Hönigsperger, Christoph; Silva, Meire Ribeiro; Brandtzaeg, Ole Kristian; Lundanes, Elsa; Wilson, Steven Ray; Brown, Rachel C; Thomas, Sarah A; Bloom, Stephen R; Dhillo, Waljit S

2017-02-01

Sex, emotion, and reproduction are fundamental and tightly entwined aspects of human behavior. At a population level in humans, both the desire for sexual stimulation and the desire to bond with a partner are important precursors to reproduction. However, the relationships between these processes are incompletely understood. The limbic brain system has key roles in sexual and emotional behaviors, and is a likely candidate system for the integration of behavior with the hormonal reproductive axis. We investigated the effects of kisspeptin, a recently identified key reproductive hormone, on limbic brain activity and behavior. Using a combination of functional neuroimaging and hormonal and psychometric analyses, we compared the effects of kisspeptin versus vehicle administration in 29 healthy heterosexual young men. We demonstrated that kisspeptin administration enhanced limbic brain activity specifically in response to sexual and couple-bonding stimuli. Furthermore, kisspeptin's enhancement of limbic brain structures correlated with psychometric measures of reward, drive, mood, and sexual aversion, providing functional significance. In addition, kisspeptin administration attenuated negative mood. Collectively, our data provide evidence of an undescribed role for kisspeptin in integrating sexual and emotional brain processing with reproduction in humans. These results have important implications for our understanding of reproductive biology and are highly relevant to the current pharmacological development of kisspeptin as a potential therapeutic agent for patients with common disorders of reproductive function. National Institute for Health Research (NIHR), Wellcome Trust (Ref 080268), and the Medical Research Council (MRC).

Funding Infectious Disease Research: A Systematic Analysis of UK Research Investments by Funders 1997–2010

PubMed Central

Fitchett, Joseph R.; Head, Michael G.; Cooke, Mary K.; Wurie, Fatima B.; Atun, Rifat

2014-01-01

Background Research investments are essential to address the burden of disease, however allocation of limited resources is poorly documented. We systematically reviewed the investments awarded by funding organisations to UK institutions and their global partners for infectious disease research. Methodology/Principal Findings Public and philanthropic investments for the period 1997 to 2010 were included. We categorised studies by infectious disease, cross-cutting theme, and by research and development value chain, reflecting the type of science. We identified 6165 funded studies, with a total research investment of UK £2.6 billion. Public organisations provided £1.4 billion (54.0%) of investments compared with £1.1 billion (42.4%) by philanthropic organisations. Global health studies represented an investment of £928 million (35.7%). The Wellcome Trust was the leading investor with £688 million (26.5%), closely followed by the UK Medical Research Council (MRC) with £673 million (25.9%). Funding over time was volatile, ranging from ∼£40 million to ∼£160 million per year for philanthropic organisations and ∼£30 million to ∼£230 million for public funders. Conclusions/Significance Infectious disease research funding requires global coordination and strategic long-term vision. Our analysis demonstrates the diversity and inconsistent patterns in investment, with volatility in annual funding amounts and limited investment for product development and clinical trials. PMID:25162631

Bioinformatics Education—Perspectives and Challenges out of Africa

PubMed Central

Adebiyi, Ezekiel F.; Alzohairy, Ahmed M.; Everett, Dean; Ghedira, Kais; Ghouila, Amel; Kumuthini, Judit; Mulder, Nicola J.; Panji, Sumir; Patterton, Hugh-G.

2015-01-01

The discipline of bioinformatics has developed rapidly since the complete sequencing of the first genomes in the 1990s. The development of many high-throughput techniques during the last decades has ensured that bioinformatics has grown into a discipline that overlaps with, and is required for, the modern practice of virtually every field in the life sciences. This has placed a scientific premium on the availability of skilled bioinformaticians, a qualification that is extremely scarce on the African continent. The reasons for this are numerous, although the absence of a skilled bioinformatician at academic institutions to initiate a training process and build sustained capacity seems to be a common African shortcoming. This dearth of bioinformatics expertise has had a knock-on effect on the establishment of many modern high-throughput projects at African institutes, including the comprehensive and systematic analysis of genomes from African populations, which are among the most genetically diverse anywhere on the planet. Recent funding initiatives from the National Institutes of Health and the Wellcome Trust are aimed at ameliorating this shortcoming. In this paper, we discuss the problems that have limited the establishment of the bioinformatics field in Africa, as well as propose specific actions that will help with the education and training of bioinformaticians on the continent. This is an absolute requirement in anticipation of a boom in high-throughput approaches to human health issues unique to data from African populations. PMID:24990350

Histopathology reveals correlative and unique phenotypes in a high-throughput mouse phenotyping screen

PubMed Central

Adissu, Hibret A.; Estabel, Jeanne; Sunter, David; Tuck, Elizabeth; Hooks, Yvette; Carragher, Damian M.; Clarke, Kay; Karp, Natasha A.; Project, Sanger Mouse Genetics; Newbigging, Susan; Jones, Nora; Morikawa, Lily; White, Jacqueline K.; McKerlie, Colin

2014-01-01

The Mouse Genetics Project (MGP) at the Wellcome Trust Sanger Institute aims to generate and phenotype over 800 genetically modified mouse lines over the next 5 years to gain a better understanding of mammalian gene function and provide an invaluable resource to the scientific community for follow-up studies. Phenotyping includes the generation of a standardized biobank of paraffin-embedded tissues for each mouse line, but histopathology is not routinely performed. In collaboration with the Pathology Core of the Centre for Modeling Human Disease (CMHD) we report the utility of histopathology in a high-throughput primary phenotyping screen. Histopathology was assessed in an unbiased selection of 50 mouse lines with (n=30) or without (n=20) clinical phenotypes detected by the standard MGP primary phenotyping screen. Our findings revealed that histopathology added correlating morphological data in 19 of 30 lines (63.3%) in which the primary screen detected a phenotype. In addition, seven of the 50 lines (14%) presented significant histopathology findings that were not associated with or predicted by the standard primary screen. Three of these seven lines had no clinical phenotype detected by the standard primary screen. Incidental and strain-associated background lesions were present in all mutant lines with good concordance to wild-type controls. These findings demonstrate the complementary and unique contribution of histopathology to high-throughput primary phenotyping of mutant mice. PMID:24652767

The activity of the Research Investments in Global Health study and ways forward within the global funding and policy landscape.

PubMed

Head, Michael G; Brown, Rebecca J

2016-01-01

The Research Investments in Global Health (ResIn, www.researchinvestments.org) study analyses funding trends in health research, with a predominant focus on infectious diseases. Since October 2015, the project is funded by the Bill & Melinda Gates Foundation and is now based at the University of Southampton in the UK. In 2016, Public Policy@Southampton provided ResIn with a small grant to explore developing links with policy, funding and research stakeholders with an interest in global health. Three meetings were organised in London (Wellcome Trust, 25 May 2016), Brussels (UK Research Office, 2 June 2016), and Geneva (WHO R&D Observatory, 8 June 2016). In total, 45 stakeholders attended and provided comment and critique on the study methodology and potential expansion into other disciplines. A theme that emerged across all three meetings concerned the use of a standardised categorisation system. A key benefit of the ResIn study is the ability to present granular detail in precise areas. Further work packages that could enhance the use of the collected R&D data included integration with geospatial, policy and scientometric methodologies. There was broad enthusiasm that outputs from these proposed projects would provide clear benefits in informing health policy and R&D strategy. Outputs from the ongoing study covering infection-related R&D investments in the G20 nations will be available in 2017.

26 CFR 1.856-3 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-04-01

... TAXES Real Estate Investment Trusts § 1.856-3 Definitions. For purposes of the regulations under part II... trustees of the real estate investment trust. In the case of securities of other qualified real estate investment trusts, fair value shall not exceed market value or asset value, whichever is higher. (b) Real...

New Superintendents: Trust, Networking, and Social Capital

ERIC Educational Resources Information Center

Ripley, Joan; Mitchell, Roxanne M.; Richman, John A.

2013-01-01

This instrumental case study explored how five newly appointed superintendents identified key stakeholders and built trust and social capital with stakeholders in their districts. Stakeholder, trust, and social capital theory were the lenses that guided this study. We utilized a pragmatic research design and thematic data analysis to interpret our…

A qualitative study of the role of workplace and interpersonal trust in shaping service quality and responsiveness in Zambian primary health centres.

PubMed

Topp, Stephanie M; Chipukuma, Julien M

2016-03-01

Human decisions, actions and relationships that invoke trust are at the core of functional and productive health systems. Although widely studied in high-income settings, comparatively few studies have explored the influence of trust on health system performance in low- and middle-income countries. This study examines how workplace and inter-personal trust impact service quality and responsiveness in primary health services in Zambia. This multi-case study included four health centres selected for urban, peri-urban and rural characteristics. Case data included provider interviews (60); patient interviews (180); direct observation of facility operations (two weeks/centre) and key informant interviews (14) that were recorded and transcribed verbatim. Case-based thematic analysis incorporated inductive and deductive coding. Findings demonstrated that providers had weak workplace trust influenced by a combination of poor working conditions, perceptions of low pay and experiences of inequitable or inefficient health centre management. Weak trust in health centre managers' organizational capacity and fairness contributed to resentment amongst many providers and promoted a culture of blame-shifting and one-upmanship that undermined teamwork and enabled disrespectful treatment of patients. Although patients expressed a high degree of trust in health workers' clinical capacity, repeated experiences of disrespectful or unresponsive care undermined patients' trust in health workers' service values and professionalism. Lack of patient-provider trust prompted some patients to circumvent clinic systems in an attempt to secure better or more timely care. Lack of resourcing and poor leadership were key factors leading to providers' weak workplace trust and contributed to often-poor quality services, driving a perverse cycle of negative patient-provider relations across the four sites. Findings highlight the importance of investing in both structural factors and organizational management to strengthen providers' trust in their employer(s) and colleagues, as an entry-point for developing both the capacity and a work culture oriented towards respectful and patient-centred care. © The Author 2015. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine.

Case-Based Behavior Adaptation Using an Inverse Trust Metric

DTIC Science & Technology

2014-06-01

Jian, Bisantz, and Drury 2000; Muir 1987), about how trust- worthy the robot was behaving. However, this might not be practical in situations that are...5). Carlson, M. S.; Desai, M.; Drury , J. L.; Kwak, H.; and Yanco, H. A. 2014. Identifying factors that influence trust in automated cars and medical...and Drury , C. G. 2000. Foundations for an empirically determined scale of trust in automated systems. International Journal of Cogni- tive Ergonomics

Social capital, trust in health information, and acceptance of Measles-Rubella vaccination campaign in Tamil Nadu: A case-control study.

PubMed

Palanisamy, B; Gopichandran, V; Kosalram, K

2018-06-18

Parents' decision about vaccination of children is influenced by social relationships and sources of information. The aim of this study was to assess the influence of social capital and trust in health information on the status of Measles-Rubella (MR) vaccination campaign in Tamil Nadu. This was a case-control study carried out in Kancheepuram district in Tamil Nadu where the MR vaccination campaign offered by Government of Tamil Nadu had poor acceptance. Cases were parents of children who had refused the MR vaccine and controls were parents having children in the same age group who had accepted the vaccine. Data on social capital and trust in health information were collected by using social capital scale developed by the researchers and trust in the source of information was measured by using simple questions on the level of trust in the information source. Nonadministration of MR vaccine was high among young parents and parents of younger children. Vaccine acceptance was higher when it was offered at school (P < 0.000) and also among parents who trusted school teachers (P < 0.003) and other school children (P < 0.014) as source of information. MR vaccine acceptance was less among parents who trusted social media and WhatsApp information. Greater levels of health-related physical social capital led to greater vaccine hesitancy. Multivariate analysis revealed that greater the age of the child, better parental attitudes toward vaccination, poorer health-related physical social capital, and greater trust in health information provided by school teachers led to overall greater acceptance of the MR vaccine. Strong homogeneous bonding social capital had a negative influence on MR vaccine acceptance. Schools and school teachers played a vital role in influencing parental decision to vaccinate.

Organizational Structure, Collegial Trust, and College Faculty Teaching Efficacy: A Case Study

ERIC Educational Resources Information Center

Okpogba, Desmond

2011-01-01

The purpose of this mixed-method study was to explore the relationship between faculty self-efficacy, organizational structure, and collegial trust. The concepts of teacher self-efficacy, organizational structure, and collegial trust were used to investigate any possible empirical relationships existing between these variables in a private,…

26 CFR 1.663(b)-2 - Election.

Code of Federal Regulations, 2010 CFR

2010-04-01

..., 1968. In the case of a trust for which an election was made under prior law, the fiduciary shall make... TAXES Estates and Trusts Which May Accumulate Income Or Which Distribute Corpus § 1.663(b)-2 Election. (a) Manner and time of election; irrevocability—(1) When return is required to be filed. If a trust...

43 CFR 2532.2 - Trust patent.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 43 Public Lands: Interior 2 2014-10-01 2014-10-01 false Trust patent. 2532.2 Section 2532.2 Public... OF THE INTERIOR LAND RESOURCE MANAGEMENT (2000) INDIAN ALLOTMENTS Allotments § 2532.2 Trust patent... patent will be suspended for a period of 2 years from date of settlement; but in those cases where that...

43 CFR 2532.2 - Trust patent.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 43 Public Lands: Interior 2 2012-10-01 2012-10-01 false Trust patent. 2532.2 Section 2532.2 Public... OF THE INTERIOR LAND RESOURCE MANAGEMENT (2000) INDIAN ALLOTMENTS Allotments § 2532.2 Trust patent... patent will be suspended for a period of 2 years from date of settlement; but in those cases where that...

43 CFR 2532.2 - Trust patent.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 43 Public Lands: Interior 2 2013-10-01 2013-10-01 false Trust patent. 2532.2 Section 2532.2 Public... OF THE INTERIOR LAND RESOURCE MANAGEMENT (2000) INDIAN ALLOTMENTS Allotments § 2532.2 Trust patent... patent will be suspended for a period of 2 years from date of settlement; but in those cases where that...

43 CFR 2532.2 - Trust patent.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 43 Public Lands: Interior 2 2011-10-01 2011-10-01 false Trust patent. 2532.2 Section 2532.2 Public... OF THE INTERIOR LAND RESOURCE MANAGEMENT (2000) INDIAN ALLOTMENTS Allotments § 2532.2 Trust patent... patent will be suspended for a period of 2 years from date of settlement; but in those cases where that...

26 CFR 25.2702-5 - Personal residence trusts.

Code of Federal Regulations, 2012 CFR

2012-04-01

... that the reformation has been commenced or will be commenced within the 90-day period. In the case of a... judicial reformation (or nonjudicial reformation if effective under state law), to comply with the requirements. In the case of a trust created after December 31, 1996, the reformation must be commenced within...

26 CFR 25.2702-5 - Personal residence trusts.

Code of Federal Regulations, 2011 CFR

2011-04-01

... that the reformation has been commenced or will be commenced within the 90-day period. In the case of a... judicial reformation (or nonjudicial reformation if effective under state law), to comply with the requirements. In the case of a trust created after December 31, 1996, the reformation must be commenced within...

26 CFR 25.2702-5 - Personal residence trusts.

Code of Federal Regulations, 2013 CFR

2013-04-01

... that the reformation has been commenced or will be commenced within the 90-day period. In the case of a... judicial reformation (or nonjudicial reformation if effective under state law), to comply with the requirements. In the case of a trust created after December 31, 1996, the reformation must be commenced within...

26 CFR 25.2702-5 - Personal residence trusts.

Code of Federal Regulations, 2014 CFR

2014-04-01

... that the reformation has been commenced or will be commenced within the 90-day period. In the case of a... judicial reformation (or nonjudicial reformation if effective under state law), to comply with the requirements. In the case of a trust created after December 31, 1996, the reformation must be commenced within...

Prevalence of endocrine and genetic abnormalities in boys evaluated systematically for a disorder of sex development.

PubMed

Nixon, R; Cerqueira, V; Kyriakou, A; Lucas-Herald, A; McNeilly, J; McMillan, M; Purvis, A I; Tobias, E S; McGowan, R; Ahmed, S F

2017-10-01

What is the likelihood of identifying genetic or endocrine abnormalities in a group of boys with 46, XY who present to a specialist clinic with a suspected disorder of sex development (DSD)? An endocrine abnormality of the gonadal axis may be present in a quarter of cases and copy number variants (CNVs) or single gene variants may be present in about half of the cases. Evaluation of 46, XY DSD requires a combination of endocrine and genetic tests but the prevalence of these abnormalities in a sufficiently large group of boys presenting to one specialist multidisciplinary service is unclear. This study was a retrospective review of investigations performed on 122 boys. All boys who attended the Glasgow DSD clinic, between 2010 and 2015 were included in the study. The median external masculinization score (EMS) of this group was 9 (range 1-11). Details of phenotype, endocrine and genetic investigations were obtained from case records. An endocrine abnormality of gonadal function was present in 28 (23%) with a median EMS of 8.3 (1-10.5) whilst the median EMS of boys with normal endocrine investigations was 9 (1.5-11) (P = 0.03). Endocrine abnormalities included a disorder of gonadal development in 19 (16%), LH deficiency in 5 (4%) and a disorder of androgen synthesis in 4 (3%) boys. Of 43 cases who had array-comparative genomic hybridization (array-CGH), CNVs were reported in 13 (30%) with a median EMS of 8.5 (1.5-11). Candidate gene analysis using a limited seven-gene panel in 64 boys identified variants in 9 (14%) with a median EMS of 8 (1-9). Of the 21 boys with a genetic abnormality, 11 (52%) had normal endocrine investigations. A selection bias for performing array-CGH in cases with multiple congenital malformations may have led to a high yield of CNVs. It is also possible that the yield of single gene variants may have been higher than reported if the investigators had used a more extended gene panel. The lack of a clear association between the extent of under-masculinization and presence of endocrine and genetic abnormalities suggests a role for parallel endocrine and genetic investigations in cases of suspected XY DSD. RN was supported by the James Paterson Bursary and the Glasgow Children's Hospital Charity Summer Scholarship. SFA, RM and EST are supported by a Scottish Executive Health Department grant 74250/1 for the Scottish Genomes Partnership. EST is also supported by MRC/EPSRC Molecular Pathology Node and Wellcome Trust ISSF funding. There are no conflicts of interest. None. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology.

Prevention of sexually transmitted infections in urban communities (Peru PREVEN): a multicomponent community-randomised controlled trial.

PubMed

García, Patricia J; Holmes, King K; Cárcamo, César P; Garnett, Geoff P; Hughes, James P; Campos, Pablo E; Whittington, William L H

2012-03-24

Previous community-randomised trials of interventions to control sexually transmitted infections (STIs) have involved rural settings, were rarely multicomponent, and had varying results. We aimed to assess the effect of a multicomponent intervention on curable STIs in urban young adults and female sex workers (FSWs). In this community-randomised trial, baseline STI screening was done between August, and November, 2002, in random household samples of young adults (aged 18-29 years) and in FSWs in Peruvian cities with more than 50,000 inhabitants. Geographically separate cities were selected, matched into pairs, and randomly allocated to intervention or control groups with an S-PLUS program. Follow-up surveys of random samples were done after 2 years and 3 years. The intervention comprised four modalities: strengthened STI syndromic management by pharmacy workers and clinicians; mobile-team outreach to FSWs for STI screening and pathogen-specific treatment; periodic presumptive treatment of FSWs for trichomoniasis; and condom promotion for FSWs and the general population. Individuals in control cities received standard care. The composite primary endpoint was infection of young adults with Chlamydia trachomatis, Trichomonas vaginalis, or Neisseria gonorrhoeae, or syphilis seroreactivity. Laboratory workers and the data analyst were masked, but fieldworkers, the Peruvian study team, and participants in the outcome surveys were not. All analyses were done by intention to treat. This trial is registered, ISRCTN43722548. We did baseline surveys of 15,261 young adults in 24 Peruvian cities. Of those, 20 geographically separate cities were matched into pairs, in each of which one city was assigned to intervention and the other to standard of care. In the 2006 follow-up survey, data for the composite primary outcome were available for 12,930 young adults. We report a non-significant reduction in prevalence of STIs in young adults, adjusted for baseline prevalence, in intervention cities compared with control cities (relative risk 0·84, 95% CI 0·69-1·02; p=0·096). In subgroup analyses, significant reductions were noted in intervention cities in young adult women and FSWs. Syndromic management of STIs, mobile-team outreach to FSWs, presumptive treatment for trichomoniasis in FSWs, and condom promotion might reduce the composite prevalence of any of the four curable STIs investigated in this trial. Wellcome Trust and Burroughs Wellcome Fund, National Institutes of Health, Center for AIDS Research, CIPRA, and USAID-Peru. Copyright © 2012 Elsevier Ltd. All rights reserved.

The interleukin-6 receptor as a target for prevention of coronary heart disease: a mendelian randomisation analysis

PubMed Central

2012-01-01

Summary Background A high circulating concentration of interleukin 6 is associated with increased risk of coronary heart disease. Blockade of the interleukin-6 receptor (IL6R) with a monoclonal antibody (tocilizumab) licensed for treatment of rheumatoid arthritis reduces systemic and articular inflammation. However, whether IL6R blockade also reduces risk of coronary heart disease is unknown. Methods Applying the mendelian randomisation principle, we used single nucleotide polymorphisms (SNPs) in the gene IL6R to evaluate the likely efficacy and safety of IL6R inhibition for primary prevention of coronary heart disease. We compared genetic findings with the effects of tocilizumab reported in randomised trials in patients with rheumatoid arthritis. Findings In 40 studies including up to 133 449 individuals, an IL6R SNP (rs7529229) marking a non-synonymous IL6R variant (rs8192284; p.Asp358Ala) was associated with increased circulating log interleukin-6 concentration (increase per allele 9·45%, 95% CI 8·34–10·57) as well as reduced C-reactive protein (decrease per allele 8·35%, 95% CI 7·31–9·38) and fibrinogen concentrations (decrease per allele 0·85%, 95% CI 0·60–1·10). This pattern of effects was consistent with IL6R blockade from infusions of tocilizumab (4–8 mg/kg every 4 weeks) in patients with rheumatoid arthritis studied in randomised trials. In 25 458 coronary heart disease cases and 100 740 controls, the IL6R rs7529229 SNP was associated with a decreased odds of coronary heart disease events (per allele odds ratio 0·95, 95% CI 0·93–0·97, p=1·53×10−5). Interpretation On the basis of genetic evidence in human beings, IL6R signalling seems to have a causal role in development of coronary heart disease. IL6R blockade could provide a novel therapeutic approach to prevention of coronary heart disease that warrants testing in suitably powered randomised trials. Genetic studies in populations could be used more widely to help to validate and prioritise novel drug targets or to repurpose existing agents and targets for new therapeutic uses. Funding UK Medical Research Council; British Heart Foundation; Rosetrees Trust; US National Heart, Lung, and Blood Institute; Du Pont Pharma; Chest, Heart and Stroke Scotland; Wellcome Trust; Coronary Thrombosis Trust; Northwick Park Institute for Medical Research; UCLH/UCL Comprehensive Medical Research Centre; US National Institute on Aging; Academy of Finland; Netherlands Organisation for Health Research and Development; SANCO; Dutch Ministry of Public Health, Welfare and Sports; World Cancer Research Fund; Agentschap NL; European Commission; Swedish Heart-Lung Foundation; Swedish Research Council; Strategic Cardiovascular Programme of the Karolinska Institutet; Stockholm County Council; US National Institute of Neurological Disorders and Stroke; MedStar Health Research Institute; GlaxoSmithKline; Dutch Kidney Foundation; US National Institutes of Health; Netherlands Interuniversity Cardiology Institute of the Netherlands; Diabetes UK; European Union Seventh Framework Programme; National Institute for Healthy Ageing; Cancer Research UK; MacArthur Foundation. PMID:22421340

Trust and trust relations from the providers' perspective: the case of the healthcare system in India.

PubMed

Kane, Sumit; Calnan, Michael; Radkar, Anjali

2015-01-01

Commentators suggest that there is an erosion of trust in the relations between different actors in the health system in India. This paper presents the results of an exploratory study of the situation of providers in an urban setting in western India, the nature of their relations in terms of trust and what influences these relations. The data on relationships of trust were collected through interviews and focus group discussions with key informants, including public and private providers, regulators, managers and societal actors, such as patients/citizens, politicians and the media.

26 CFR 25.2702-2 - Definitions and valuation rules.

Code of Federal Regulations, 2010 CFR

2010-04-01

...-year term, the trust is to terminate and the trust corpus is to be paid to A's child. However, if A... term interest because a series of short-term rentals the aggregate duration of which equals the... individual both before and after the transfer in trust. In the case of the creation of a term interest, any...

26 CFR 1.665(f)-1A - Undistributed capital gain.

Code of Federal Regulations, 2010 CFR

2010-04-01

... TAX (CONTINUED) INCOME TAXES Treatment of Excess Distributions of Trusts Applicable to Taxable Years.... (ii) The amount of taxes imposed on the trust for such year attributable to such gains, as defined in § 1.665(d)-1A, and (iii) In the case of a trust that does not use the alternative method for computing...

Chair Perceptions of Trust between Mentor and Mentee in Online Doctoral Dissertation Mentoring

ERIC Educational Resources Information Center

Rademaker, Linnea L.; Duffy, Jennifer O'Connor; Wetzler, Elizabeth; Zaikina-Montgomery, Helen

2016-01-01

We explored online dissertation chairs' perceptions of trust in the mentor-mentee relationship, as trust was identified as a crucial factor in the success of doctoral students. Through the implementation of a multiple-case study, and a qualitative, online questionnaire, and through qualitative data analysis, we discovered 16 chairs' perceptions of…

Communicating Trust between Parents and Their Children: A Case Study of Adolescents' Alcohol Use in Denmark

ERIC Educational Resources Information Center

Demant, Jakob; Ravn, Signe

2013-01-01

This article discusses how Danish parents and their children communicate trust. Based on Niklas Luhmann's sociological theory, the article explores new aspects of communication about alcohol-related rules. The analysis shows how the parents emphasize the importance of communicating trust, while the adolescents, on the other hand, observe the…

External Accountability of Collaborative Arrangements; A Case Study of a Multi Academy Trust in England

ERIC Educational Resources Information Center

Ehren, Melanie C. M.; Godfrey, David

2017-01-01

This paper explores the impact of external accountability on four mechanisms of network-internal quality control and the properties of (mandated) inter-organizational networks. An explorative case study approach examines the external accountability of a newly established educational network (MAT) and how schools and the Trust are held accountable…

B2B collaboration method through trust values for e-supply chain integrator: a case study of Malaysian construction industry

NASA Astrophysics Data System (ADS)

Ab. Aziz, Norshakirah; Ahmad, Rohiza; Dhanapal Durai, Dominic

2011-12-01

Limited trust, cooperation and communication have been identified as some of the issues that hinder collaboration among business partners. These one also true in the acceptance of e-supply chain integrator among organizations that involve in the same industry. On top of that, the huge number of components in supply chain industry also makes it impossible to include entire supply chain components in the integrator. Hence, this study intends to propose a method for identifying "trusted" collaborators for inclusion into an e-supply chain integrator. For the purpose of constructing and validating the method, the Malaysian construction industry is chosen as the case study due to its size and importance to the economy. This paper puts forward the background of the research, some relevant literatures which lead to trust values elements formulation, data collection from Malaysian Construction Supply Chain and a glimpse of the proposed method for trusted partner selection. Future work is also presented to highlight the next step of this research.

Partnering Research Involving Mentoring and Education (PRIME) in Prostate Cancer

DTIC Science & Technology

2007-02-01

Nurses Symposium on Cancer in African Americans, Atlanta. 7. Price, M.M. (1994, October 28-30). “Living with Genital Herpes : Counseling the...Patient”, Paper presented and Seminar Moderator for the Burroughs Wellcome Pharmaceutical Corporation Nursing Conference on Genital Herpes , Research

When paranoia makes sense.

PubMed

Kramer, Roderick M

2002-07-01

On September 11, 2001, in the space of a few horrific minutes, Americans realized the fragility of trust. The country's evident vulnerability to deadly terrorism rocked our faith in the systems we rely on for security. Our trust was shaken again only a few months later with the stunning collapse of Enron, forcing us to question many of the methods and assumptions underpinning the way we work. These two crises are obviously very different, yet both serve as reminders of the perils of trusting too much. The abiding belief that trust is a strength now seems dangerously naive. This new doubtfulness runs contrary to most management literature, which has traditionally touted trust as an organizational asset. It's an easy case to make. When there are high levels of trust, employees can fully commit themselves to the organization because they can be confident that their efforts will be recognized and rewarded. Trust also means that leaders don't have to worry so much about putting the right spin on things. They can act and speak forthrightly and focus on essentials. In short, trust is an organizational superglue. Nevertheless, two decades of research on trust and cooperation in organizations have convinced social psychologist Roderick Kramer that--despite its costs--distrust can be beneficial in the workplace. Kramer has observed that a moderate form of suspicion, which he calls prudent paranoia, can in many cases prove highly beneficial to the distrustful individual or organization. In this article, he describes situations in which prudent paranoia makes sense and shows how, when properly deployed, it can serve as a powerful morale booster--even a competitive weapon--for organizations.

An empirical test of competing theories of hazard-related trust: the case of GM food.

PubMed

Allum, Nick

2007-08-01

Few scholars doubt the importance of trust in explaining variation in public perception of technological risk. Relatively little, however, is known about the particular types of judgments that people use in granting or withholding trust. This article presents findings from an empirical study that explores several dimensions of trust relevant for citizens' judgments of scientists involved in the development of GM food. The relationship between particular dimensions of trust and perceptions of GM food risk is also explored, using structural equation modeling. Results suggest that trust judgments based on the perception of shared values are most important in relation to GM food risk, but that judgments about scientists' technical competence are also important.

26 CFR 25.2702-1 - Special valuation rules in the case of transfers of interests in trust.

Code of Federal Regulations, 2011 CFR

2011-04-01

... the retained interest is not a qualified interest (as defined in § 25.2702-3), the retained interest... remainder interest in the trust qualifies for a deduction under section 2522. (4) Pooled income fund. A transfer of property to a pooled income fund (as defined in section 642(c)(5)). (5) Charitable lead trust...

26 CFR 1.172-2 - Net operating loss in case of a corporation.

Code of Federal Regulations, 2011 CFR

2011-04-01

... real estate investment trusts. For taxable years ending after October 4, 1976, the net operating loss of a qualified real estate investment trust (as defined in § 1.172-10(b)) is computed by taking into... allowed in computing the net operating loss of a qualified real estate investment trust. [T.D. 8107, 51 FR...

26 CFR 1.172-2 - Net operating loss in case of a corporation.

Code of Federal Regulations, 2010 CFR

2010-04-01

... real estate investment trusts. For taxable years ending after October 4, 1976, the net operating loss of a qualified real estate investment trust (as defined in § 1.172-10(b)) is computed by taking into... allowed in computing the net operating loss of a qualified real estate investment trust. [T.D. 8107, 51 FR...

26 CFR 1.172-2 - Net operating loss in case of a corporation.

Code of Federal Regulations, 2014 CFR

2014-04-01

... real estate investment trusts. For taxable years ending after October 4, 1976, the net operating loss of a qualified real estate investment trust (as defined in § 1.172-10(b)) is computed by taking into... allowed in computing the net operating loss of a qualified real estate investment trust. [T.D. 8107, 51 FR...

Honoring the Trust: Quality and Cost Containment in Higher Education.

ERIC Educational Resources Information Center

Massy, William F.

This book asserts that improvements in quality and cost containment are required not only for the well-being of individual institutions of higher education, but also to honor the trust placed in academe by society. The book outlines a practical program for improvement. The chapters of part 1, "The Case for Change," are: (1) "The Erosion of Trust";…

Trust Formation When Youth and Adults Partner to Lead School Reform: A Case Study of Supportive Structures and Challenges

ERIC Educational Resources Information Center

Biddle, Catharine

2017-01-01

Schools that build and support high levels of trust between stakeholder groups have been shown to support greater collaboration amongst those groups, including parents, teachers, administrators, and students (Tschannen-Moran, 2001). When stakeholders in schools feel the sense of psychological safety that accompanies trust, they are more willing or…

Trust in health care encounters and systems: a case study of British pensioners living in Spain

PubMed Central

Legido-Quigley, Helena; McKee, Martin; Green, Judith

2014-01-01

Research on trust in health care faces two enduring challenges. Firstly, there are conceptual ambiguities in distinguishing trust from related concepts, such as confidence or dependence. Second, the tacit understandings which underpin the ‘faith’ element of trust are difficult to explicate. A case study of British pensioners who have moved to Spain provides an opportunity to explore trust in a setting where they often have a choice of where to access health care (UK or Spain), and are therefore not in a state of dependence, and in which the ‘differences’ of a new field generates reflection on their tacit expectations of providers and systems. In accounting for decisions to use (or not to use) Spanish health care, British pensioners cited experiential knowledge of symbolic indicators of trustworthy institutions (they were hygienic, modern, efficient), which contributed to background confidence in the system, and interpersonal qualities of practitioners (respect for older people, embodied empathy and reciprocity) which evoked familiar relations, within which faith is implicit. In contrast, with limited recent access to the British system, their background confidence had been compromised by reports of poor performance, with few opportunities to rebuild the interrelational bases of trust. PMID:25470324

Contributing Factors to Driver's Over-trust in a Driving Support System for Workload Reduction

NASA Astrophysics Data System (ADS)

Itoh, Makoto

Avoiding over-trust in machines is a vital issue in order to establish intelligent driver support systems. It is necessary to distinguish systems for workload reduction from systems for accident prevention/mitigation. This study focuses on over-trust in an Adaptive Cruise Control (ACC) system as a typical driving support system for workload reduction. By conducting an experiment, we obtained a case in which a driver trusted the ACC system too much. Concretely speaking, the driver just watched the ACC system crashing into a stopped car even though the ACC system was designed to ignore such stopped cars. This paper investigates possible contributing factors to the driver' s over-trust in the ACC system. The results suggest that emerging trust in the dimension of performance may cause over-trust in the dimension of method or purpose.

Collaboration Around Research and Education (CARE) in Prostate Cancer

DTIC Science & Technology

2010-02-01

the Oncology Nurses Symposium on Cancer in African Americans, Atlanta, GA. 7. Price, M.M. (1994, October 28-30). “Living with Genital Herpes ...Counseling the Patient”. Paper presented and Seminar Moderator for the Burroughs Wellcome Pharmaceutical Corporation Nursing Conference on Genital Herpes

Collaboration around Research and Education (Care) in Prostate Cancer

DTIC Science & Technology

2008-02-01

M.M. (1994, October 28-30). “Living with Genital Herpes : Counseling the Patient”, Paper presented and Seminar Moderator for the Burroughs Wellcome...Pharmaceutical Corporation Nursing Conference on Genital Herpes , Research Triangle Park, NC. 8. Price, M.M. (1995, April, Miami; 1995, March

The history of ergot of rye (Claviceps purpurea) II: 1900-1940.

PubMed

Lee, M R

2009-12-01

Ergot, in 1900, was a 'chemical mess'. Henry Wellcome, the pharmaceutical manufacturer, invited Henry Hallett Dale, a physiologist, to join his research department and solve this problem. Dale, in turn, recruited an outstanding group of scientists, including George Barger, Arthur Ewins and Harold Dudley, who would make distinguished contributions not only to the chemistry of ergot but also to the identification of acetylcholine, histamine and tyramine and to studies on their physiological effects. Initially Barger and Dale isolated the compound ergotoxine, but this proved to be a false lead; it was later shown to be a mixture of three different ergot alkaloids. The major success of the Wellcome group was the discovery and isolation of ergometrine, which would prove to be life-saving in postpartum haemorrhage. In 1917 Arthur Stoll and his colleagues started work on ergot at Sandoz Pharmaceuticals in Basel. A series of important results emerged over the next 30 years, including the isolation of ergotamine in 1918, an effective treatment for migraine with aura.

Trust and Its Role in the Medical Encounter.

PubMed

Holland, Stephen; Stocks, David

2017-09-01

This paper addresses two research questions. The first is theoretical: What is trust? In the first half of this paper we present a distinctive tripartite analysis. We describe three attitudes, here called reliance, specific trust and general trust, each of which is characterised and illustrated. We argue that these attitudes are related, but not reducible, to one another. We suggest that the current impasse in the analysis of trust is in part due to the fact that some writers allude to these distinctions, but unclearly so, whilst others elide them altogether. The second research question focuses on doctor-patient interaction. Trust is often said to be central in medical encounters but this strikes us as too vague. The success of doctor-patient relations in part depends on adopting the most appropriate of the three attitudes we delineate. We argue that reliance is the appropriate attitude for most medical encounters. When circumstances do require trust, the distinction between specific trust and general trust is crucial. We describe medical encounters requiring specific trust. General trust is less often required in medicine; but it is appropriate in some cases and, when called for, it is called for strongly.

Influence of Cultural, Organizational, and Automation Capability on Human Automation Trust: A Case Study of Auto-GCAS Experimental Test Pilots

NASA Technical Reports Server (NTRS)

Koltai, Kolina; Ho, Nhut; Masequesmay, Gina; Niedober, David; Skoog, Mark; Cacanindin, Artemio; Johnson, Walter; Lyons, Joseph

2014-01-01

This paper discusses a case study that examined the influence of cultural, organizational and automation capability upon human trust in, and reliance on, automation. In particular, this paper focuses on the design and application of an extended case study methodology, and on the foundational lessons revealed by it. Experimental test pilots involved in the research and development of the US Air Force's newly developed Automatic Ground Collision Avoidance System served as the context for this examination. An eclectic, multi-pronged approach was designed to conduct this case study, and proved effective in addressing the challenges associated with the case's politically sensitive and military environment. Key results indicate that the system design was in alignment with pilot culture and organizational mission, indicating the potential for appropriate trust development in operational pilots. These include the low-vulnerability/ high risk nature of the pilot profession, automation transparency and suspicion, system reputation, and the setup of and communications among organizations involved in the system development.

An Extended Case Study Methoology for Investigating Influence of Cultural, Organizational, and Automation Factors on Human-Automation Trust

NASA Technical Reports Server (NTRS)

Koltai, Kolina Sun; Ho, Nhut; Masequesmay, Gina; Niedober, David; Skoog, Mark; Johnson, Walter; Cacanindin, Artemio

2014-01-01

This paper discusses a case study that examined the influence of cultural, organizational and automation capability upon human trust in, and reliance on, automation. In particular, this paper focuses on the design and application of an extended case study methodology, and on the foundational lessons revealed by it. Experimental test pilots involved in the research and development of the US Air Forces newly developed Automatic Ground Collision Avoidance System served as the context for this examination. An eclectic, multi-pronged approach was designed to conduct this case study, and proved effective in addressing the challenges associated with the cases politically sensitive and military environment. Key results indicate that the system design was in alignment with pilot culture and organizational mission, indicating the potential for appropriate trust development in operational pilots. These include the low-vulnerabilityhigh risk nature of the pilot profession, automation transparency and suspicion, system reputation, and the setup of and communications among organizations involved in the system development.

Comparative community burden and severity of seasonal and pandemic influenza: results of the Flu Watch cohort study.

PubMed

Hayward, Andrew C; Fragaszy, Ellen B; Bermingham, Alison; Wang, Lili; Copas, Andrew; Edmunds, W John; Ferguson, Neil; Goonetilleke, Nilu; Harvey, Gabrielle; Kovar, Jana; Lim, Megan S C; McMichael, Andrew; Millett, Elizabeth R C; Nguyen-Van-Tam, Jonathan S; Nazareth, Irwin; Pebody, Richard; Tabassum, Faiza; Watson, John M; Wurie, Fatima B; Johnson, Anne M; Zambon, Maria

2014-06-01

Assessment of the effect of influenza on populations, including risk of infection, illness if infected, illness severity, and consultation rates, is essential to inform future control and prevention. We aimed to compare the community burden and severity of seasonal and pandemic influenza across different age groups and study years and gain insight into the extent to which traditional surveillance underestimates this burden. Using preseason and postseason serology, weekly illness reporting, and RT-PCR identification of influenza from nasal swabs, we tracked the course of seasonal and pandemic influenza over five successive cohorts (England 2006-11; 5448 person-seasons' follow-up). We compared burden and severity of seasonal and pandemic strains. We weighted analyses to the age and regional structure of England to give nationally representative estimates. We compared symptom profiles over the first week of illness for different strains of PCR-confirmed influenza and non-influenza viruses using ordinal logistic regression with symptom severity grade as the outcome variable. Based on four-fold titre rises in strain-specific serology, on average influenza infected 18% (95% CI 16-22) of unvaccinated people each winter. Of those infected there were 69 respiratory illnesses per 100 person-influenza-seasons compared with 44 per 100 in those not infected with influenza. The age-adjusted attributable rate of illness if infected was 23 illnesses per 100 person-seasons (13-34), suggesting most influenza infections are asymptomatic. 25% (18-35) of all people with serologically confirmed infections had PCR-confirmed disease. 17% (10-26) of people with PCR-confirmed influenza had medically attended illness. These figures did not differ significantly when comparing pandemic with seasonal influenza. Of PCR-confirmed cases, people infected with the 2009 pandemic strain had markedly less severe symptoms than those infected with seasonal H3N2. Seasonal influenza and the 2009 pandemic strain were characterised by similar high rates of mainly asymptomatic infection with most symptomatic cases self-managing without medical consultation. In the community the 2009 pandemic strain caused milder symptoms than seasonal H3N2. Medical Research Council and the Wellcome Trust. Copyright © 2014 Hayward et al. Open Access article distributed under the terms of CC BY. Published by .. All rights reserved.

Genetic utility of broadly defined bipolar schizoaffective disorder as a diagnostic concept

PubMed Central

Hamshere, M. L.; Green, E. K.; Jones, I. R.; Jones, L.; Moskvina, V.; Kirov, G.; Grozeva, D.; Nikolov, I.; Vukcevic, D.; Caesar, S.; Gordon-Smith, K.; Fraser, C.; Russell, E.; Breen, G.; St Clair, D.; Collier, D. A.; Young, A. H.; Ferrier, I. N.; Farmer, A.; McGuffin, P.; Holmans, P. A.; Owen, M. J.; O’Donovan, M. C.; Craddock, N.

2009-01-01

Background Psychiatric phenotypes are currently defined according to sets of descriptive criteria. Although many of these phenotypes are heritable, it would be useful to know whether any of the various diagnostic categories in current use identify cases that are particularly helpful for biological–genetic research. Aims To use genome-wide genetic association data to explore the relative genetic utility of seven different descriptive operational diagnostic categories relevant to bipolar illness within a large UK case–control bipolar disorder sample. Method We analysed our previously published Wellcome Trust Case Control Consortium (WTCCC) bipolar disorder genome-wide association data-set, comprising 1868 individuals with bipolar disorder and 2938 controls genotyped for 276 122 single nucleotide polymorphisms (SNPs) that met stringent criteria for genotype quality. For each SNP we performed a test of association (bipolar disorder group v. control group) and used the number of associated independent SNPs statistically significant at P<0.00001 as a metric for the overall genetic signal in the sample. We next compared this metric with that obtained using each of seven diagnostic subsets of the group with bipolar disorder: Research Diagnostic Criteria (RDC): bipolar I disorder; manic disorder; bipolar II disorder; schizoaffective disorder, bipolar type; DSM–IV: bipolar I disorder; bipolar II disorder; schizoaffective disorder, bipolar type. Results The RDC schizoaffective disorder, bipolar type (v. controls) stood out from the other diagnostic subsets as having a significant excess of independent association signals (P<0.003) compared with that expected in samples of the same size selected randomly from the total bipolar disorder group data-set. The strongest association in this subset of participants with bipolar disorder was at rs4818065 (P = 2.42×10–7). Biological systems implicated included gamma amniobutyric acid (GABA)A receptors. Genes having at least one associated polymorphism at P<10–4 included B3GALTS, A2BP1, GABRB1, AUTS2, BSN, PTPRG, GIRK2 and CDH12. Conclusions Our findings show that individuals with broadly defined bipolar schizoaffective features have either a particularly strong genetic contribution or that, as a group, are genetically more homogeneous than the other phenotypes tested. The results point to the importance of using diagnostic approaches that recognise this group of individuals. Our approach can be applied to similar data-sets for other psychiatric and non-psychiatric phenotypes. PMID:19567891

Genetic risk factors for ischaemic stroke and its subtypes (the METASTROKE Collaboration): a meta-analysis of genome-wide association studies

PubMed Central

Traylor, Matthew; Farrall, Martin; Holliday, Elizabeth G; Sudlow, Cathie; Hopewell, Jemma C; Cheng, Yu-Ching; Fornage, Myriam; Ikram, M Arfan; Malik, Rainer; Bevan, Steve; Thorsteinsdottir, Unnur; Nalls, Mike A; Longstreth, WT; Wiggins, Kerri L; Yadav, Sunaina; Parati, Eugenio A; DeStefano, Anita L; Worrall, Bradford B; Kittner, Steven J; Khan, Muhammad Saleem; Reiner, Alex P; Helgadottir, Anna; Achterberg, Sefanja; Fernandez-Cadenas, Israel; Abboud, Sherine; Schmidt, Reinhold; Walters, Matthew; Chen, Wei-Min; Ringelstein, E Bernd; O'Donnell, Martin; Ho, Weang Kee; Pera, Joanna; Lemmens, Robin; Norrving, Bo; Higgins, Peter; Benn, Marianne; Sale, Michele; Kuhlenbäumer, Gregor; Doney, Alexander S F; Vicente, Astrid M; Delavaran, Hossein; Algra, Ale; Davies, Gail; Oliveira, Sofia A; Palmer, Colin N A; Deary, Ian; Schmidt, Helena; Pandolfo, Massimo; Montaner, Joan; Carty, Cara; de Bakker, Paul I W; Kostulas, Konstantinos; Ferro, Jose M; van Zuydam, Natalie R; Valdimarsson, Einar; Nordestgaard, Børge G; Lindgren, Arne; Thijs, Vincent; Slowik, Agnieszka; Saleheen, Danish; Paré, Guillaume; Berger, Klaus; Thorleifsson, Gudmar; Hofman, Albert; Mosley, Thomas H; Mitchell, Braxton D; Furie, Karen; Clarke, Robert; Levi, Christopher; Seshadri, Sudha; Gschwendtner, Andreas; Boncoraglio, Giorgio B; Sharma, Pankaj; Bis, Joshua C; Gretarsdottir, Solveig; Psaty, Bruce M; Rothwell, Peter M; Rosand, Jonathan; Meschia, James F; Stefansson, Kari; Dichgans, Martin; Markus, Hugh S

2012-01-01

Summary Background Various genome-wide association studies (GWAS) have been done in ischaemic stroke, identifying a few loci associated with the disease, but sample sizes have been 3500 cases or less. We established the METASTROKE collaboration with the aim of validating associations from previous GWAS and identifying novel genetic associations through meta-analysis of GWAS datasets for ischaemic stroke and its subtypes. Methods We meta-analysed data from 15 ischaemic stroke cohorts with a total of 12 389 individuals with ischaemic stroke and 62 004 controls, all of European ancestry. For the associations reaching genome-wide significance in METASTROKE, we did a further analysis, conditioning on the lead single nucleotide polymorphism in every associated region. Replication of novel suggestive signals was done in 13 347 cases and 29 083 controls. Findings We verified previous associations for cardioembolic stroke near PITX2 (p=2·8×10−16) and ZFHX3 (p=2·28×10−8), and for large-vessel stroke at a 9p21 locus (p=3·32×10−5) and HDAC9 (p=2·03×10−12). Additionally, we verified that all associations were subtype specific. Conditional analysis in the three regions for which the associations reached genome-wide significance (PITX2, ZFHX3, and HDAC9) indicated that all the signal in each region could be attributed to one risk haplotype. We also identified 12 potentially novel loci at p<5×10−6. However, we were unable to replicate any of these novel associations in the replication cohort. Interpretation Our results show that, although genetic variants can be detected in patients with ischaemic stroke when compared with controls, all associations we were able to confirm are specific to a stroke subtype. This finding has two implications. First, to maximise success of genetic studies in ischaemic stroke, detailed stroke subtyping is required. Second, different genetic pathophysiological mechanisms seem to be associated with different stroke subtypes. Funding Wellcome Trust, UK Medical Research Council (MRC), Australian National and Medical Health Research Council, National Institutes of Health (NIH) including National Heart, Lung and Blood Institute (NHLBI), the National Institute on Aging (NIA), the National Human Genome Research Institute (NHGRI), and the National Institute of Neurological Disorders and Stroke (NINDS). PMID:23041239

Macrophage migration inhibitory factor gene polymorphisms in inflammatory bowel disease: an association study in New Zealand Caucasians and meta-analysis.

PubMed

Falvey, James D; Bentley, Robert W; Merriman, Tony R; Hampton, Mark B; Barclay, Murray L; Gearry, Richard B; Roberts, Rebecca L

2013-10-21

To investigate the association of macrophage migration inhibitory factor (MIF) promoter polymorphisms with inflammatory bowel disease (IBD) risk. One thousand and six New Zealand Caucasian cases and 540 Caucasian controls were genotyped for the MIF SNP -173G > C (rs755622) and the repeat polymorphism CATT₅₋₈ (rs5844572) using a pre-designed TaqMan SNP assay and capillary electrophoresis, respectively. Data were analysed for single site and haplotype association with IBD risk and phenotype. Meta-analysis was employed, to assess cumulative evidence of association of MIF -173G > C with IBD. All published genotype data for MIF -173G > C in IBD were identified using PubMed and subsequently searching the references of all PubMed-identified studies. Imputed genotypes for MIF -173G > C were generated from the Wellcome Trust Case Control Consortium (and National Institute of Diabetes and Digestive and Kidney Diseases). Separate meta-analyses were performed on Caucasian Crohn's disease (CD) (3863 patients, 6031 controls), Caucasian ulcerative colitis (UC) (1260 patients, 1987 controls), and East Asian UC (416 patients and 789 controls) datasets using the Mantel-Haenszel method. The New Zealand dataset had 93% power, and the meta-analyses had 100% power to detect an effect size of OR = 1.40 at α = 0.05, respectively. In our New Zealand dataset, single-site analysis found no evidence of association of MIF polymorphisms with overall risk of CD, UC, and IBD or disease phenotype (all P values > 0.05). Haplotype analysis found the CATT₅/-173C haplotype occurred at a higher frequency in New Zealand controls compared to IBD patients (0.6 vs 0.01; P = 0.03, OR = 0.22; 95%CI: 0.05-0.99), but this association did not survive bonferroni correction. Meta-analysis of our New Zealand MIF -173G > C data with data from seven additional Caucasian datasets using a random effects model found no association of MIF polymorphisms with CD, UC, or overall IBD. Similarly, meta-analysis of all published MIF -173G > C data from East Asian datasets (416 UC patients, 789 controls) found no association of this promoter polymorphism with UC. We found no evidence of association of MIF promoter polymorphisms with IBD.

Fast and accurate imputation of summary statistics enhances evidence of functional enrichment.

PubMed

Pasaniuc, Bogdan; Zaitlen, Noah; Shi, Huwenbo; Bhatia, Gaurav; Gusev, Alexander; Pickrell, Joseph; Hirschhorn, Joel; Strachan, David P; Patterson, Nick; Price, Alkes L

2014-10-15

Imputation using external reference panels (e.g. 1000 Genomes) is a widely used approach for increasing power in genome-wide association studies and meta-analysis. Existing hidden Markov models (HMM)-based imputation approaches require individual-level genotypes. Here, we develop a new method for Gaussian imputation from summary association statistics, a type of data that is becoming widely available. In simulations using 1000 Genomes (1000G) data, this method recovers 84% (54%) of the effective sample size for common (>5%) and low-frequency (1-5%) variants [increasing to 87% (60%) when summary linkage disequilibrium information is available from target samples] versus the gold standard of 89% (67%) for HMM-based imputation, which cannot be applied to summary statistics. Our approach accounts for the limited sample size of the reference panel, a crucial step to eliminate false-positive associations, and it is computationally very fast. As an empirical demonstration, we apply our method to seven case-control phenotypes from the Wellcome Trust Case Control Consortium (WTCCC) data and a study of height in the British 1958 birth cohort (1958BC). Gaussian imputation from summary statistics recovers 95% (105%) of the effective sample size (as quantified by the ratio of [Formula: see text] association statistics) compared with HMM-based imputation from individual-level genotypes at the 227 (176) published single nucleotide polymorphisms (SNPs) in the WTCCC (1958BC height) data. In addition, for publicly available summary statistics from large meta-analyses of four lipid traits, we publicly release imputed summary statistics at 1000G SNPs, which could not have been obtained using previously published methods, and demonstrate their accuracy by masking subsets of the data. We show that 1000G imputation using our approach increases the magnitude and statistical evidence of enrichment at genic versus non-genic loci for these traits, as compared with an analysis without 1000G imputation. Thus, imputation of summary statistics will be a valuable tool in future functional enrichment analyses. Publicly available software package available at http://bogdan.bioinformatics.ucla.edu/software/. bpasaniuc@mednet.ucla.edu or aprice@hsph.harvard.edu Supplementary materials are available at Bioinformatics online. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Kisspeptin modulates sexual and emotional brain processing in humans

PubMed Central

Comninos, Alexander N.; Wall, Matthew B.; Demetriou, Lysia; Shah, Amar J.; Clarke, Sophie A.; Narayanaswamy, Shakunthala; Nesbitt, Alexander; Izzi-Engbeaya, Chioma; Prague, Julia K.; Abbara, Ali; Ratnasabapathy, Risheka; Salem, Victoria; Nijher, Gurjinder M.; Jayasena, Channa N.; Tanner, Mark; Bassett, Paul; Mehta, Amrish; Rabiner, Eugenii A.; Hönigsperger, Christoph; Silva, Meire Ribeiro; Brandtzaeg, Ole Kristian; Wilson, Steven Ray; Brown, Rachel C.; Thomas, Sarah A.; Bloom, Stephen R.; Dhillo, Waljit S.

2017-01-01

BACKGROUND. Sex, emotion, and reproduction are fundamental and tightly entwined aspects of human behavior. At a population level in humans, both the desire for sexual stimulation and the desire to bond with a partner are important precursors to reproduction. However, the relationships between these processes are incompletely understood. The limbic brain system has key roles in sexual and emotional behaviors, and is a likely candidate system for the integration of behavior with the hormonal reproductive axis. We investigated the effects of kisspeptin, a recently identified key reproductive hormone, on limbic brain activity and behavior. METHODS. Using a combination of functional neuroimaging and hormonal and psychometric analyses, we compared the effects of kisspeptin versus vehicle administration in 29 healthy heterosexual young men. RESULTS. We demonstrated that kisspeptin administration enhanced limbic brain activity specifically in response to sexual and couple-bonding stimuli. Furthermore, kisspeptin’s enhancement of limbic brain structures correlated with psychometric measures of reward, drive, mood, and sexual aversion, providing functional significance. In addition, kisspeptin administration attenuated negative mood. CONCLUSIONS. Collectively, our data provide evidence of an undescribed role for kisspeptin in integrating sexual and emotional brain processing with reproduction in humans. These results have important implications for our understanding of reproductive biology and are highly relevant to the current pharmacological development of kisspeptin as a potential therapeutic agent for patients with common disorders of reproductive function. FUNDING. National Institute for Health Research (NIHR), Wellcome Trust (Ref 080268), and the Medical Research Council (MRC). PMID:28112678

Hexose-6-phosphate dehydrogenase: a new risk gene for multiple sclerosis

PubMed Central

Alcina, Antonio; Ramagopalan, Sreeram V; Fernández, Óscar; Catalá-Rabasa, Antonio; Fedetz, María; Ndagire, Dorothy; Leyva, Laura; Arnal, Carmen; Delgado, Concepción; Lucas, Miguel; Izquierdo, Guillermo; Ebers, George C; Matesanz, Fuencisla

2010-01-01

A recent genome-wide association study (GWAS) performed by the The Wellcome Trust Case–Control Consortium based on 12 374 nonsynonymous single-nucleotide polymorphisms (SNPs) provided evidence for several genes involved in multiple sclerosis (MS) susceptibility. In this study, we aimed at verifying the association of 19 SNPs with MS, with P-values ≤0.005, in an independent cohort of 732 patients and 974 controls, all Caucasian from the South of Spain. We observed an association of the rs17368528 polymorphism with MS (P=0.04, odds ratio (OR)=0.801, 95% confidence interval (CI)=0.648–0.990). The association of this polymorphism with MS was further validated in an independent set of 1318 patients from the Canadian Collaborative Project (P=0.04, OR=0.838, 95% CI=0.716–0.964). This marker is located on chromosome 1p36.22, which is 1 Mb away from the MS-associated kinesin motor protein KIF1B, although linkage disequilibrium was not observed between these two markers. The rs17368528 SNP results in an amino-acid substitution (proline to leucine) in the fifth exon of the hexose-6-phosphate dehydrogenase (H6PD) gene, in which some variants have been reported to attenuate or abolish H6PD activity, in individuals with cortisone reductase deficiency. This study corroborates the association of one locus determined by GWAS and points to H6PD as a new candidate gene for MS. PMID:19935835

Galvanising the NHS to Adopt Innovation

PubMed Central

Parris, Stuart; Cochrane, Gavin; Marjanovic, Sonja; Ling, Tom; Chataway, Joanna

2016-01-01

Abstract The Department of Health and the Wellcome Trust, in co-operation with NHS England, asked RAND Europe to conduct a limited consultation with key stakeholders about the practicality of measures and incentives proposed as part of the NHS Accelerated Access Review (AAR), which aims to assess the pathways for the development, assessment, and adoption of innovative medicines and medical technology. Through a focused engagement exercise with key healthcare stakeholders this project explored the implications of selected interim AAR propositions and feasibility of implementation for key actors, in primary and secondary care as well as commissioners and academia. Specifically, the project investigated the feasibility of implementation of three specific propositions including: a new earmarked fund to encourage AHSNs and other key innovation actors to re-design systems to embrace innovation; mobilising the influence of clinical system leaders to champion change; and encouraging secondary care organisations to take on “innovation champion” roles linked to financial incentives and a new emphasis on accountable care organisations. Data was collected on the feasibility of the three AAR propositions from a workshop with AHSN CEOs and Commercial Directors and interviews with senior NHS staff in three AHSN regions (South West, University College London Partners, and North East, North Cumbria). The study concludes with reflections on the feasibility of each recommendation and identifies factors expected to facilitate or challenge their implementation, as well as considering the wider cross cutting issues that may influence the adoption and diffusion of innovation in the NHS. PMID:28083436

Current dichotomy between traditional molecular biological and omic research in cancer biology and pharmacology.

PubMed

Reinhold, William C

2015-12-10

There is currently a split within the cancer research community between traditional molecular biological hypothesis-driven and the more recent "omic" forms or research. While the molecular biological approach employs the tried and true single alteration-single response formulations of experimentation, the omic employs broad-based assay or sample collection approaches that generate large volumes of data. How to integrate the benefits of these two approaches in an efficient and productive fashion remains an outstanding issue. Ideally, one would merge the understandability, exactness, simplicity, and testability of the molecular biological approach, with the larger amounts of data, simultaneous consideration of multiple alterations, consideration of genes both of known interest along with the novel, cross-sample comparisons among cell lines and patient samples, and consideration of directed questions while simultaneously gaining exposure to the novel provided by the omic approach. While at the current time integration of the two disciplines remains problematic, attempts to do so are ongoing, and will be necessary for the understanding of the large cell line screens including the Developmental Therapeutics Program's NCI-60, the Broad Institute's Cancer Cell Line Encyclopedia, and the Wellcome Trust Sanger Institute's Cancer Genome Project, as well as the the Cancer Genome Atlas clinical samples project. Going forward there is significant benefit to be had from the integration of the molecular biological and the omic forms or research, with the desired goal being improved translational understanding and application.

The relaxation exercise and social support trial-resst: study protocol for a randomized community based trial

PubMed Central

2011-01-01

Background Studies suggests a possible link between vaginal discharge and common mental distress, as well as highlight the implications of the subjective burden of disease and its link with mental health. Methods/Design This is a community-based intervention trial that aims to evaluate the impact of a psycho-social intervention on medically unexplained vaginal discharge (MUVD) in a group of married, low-income Lebanese women, aged 18-49, and suffering from low to moderate levels of anxiety and/or depression. The intervention consisted of 12 sessions of structured social support, problem solving techniques, group discussions and trainer-supervised relaxation exercises (twice per week over six weeks). Women were recruited from Hey el Selloum, a southern disadvantaged suburb of Beirut, Lebanon, during an open recruitment campaign. The primary outcome was self-reported MUVD, upon ruling out reproductive tract infections (RTIs), through lab analysis. Anxiety and/or depression symptoms were the secondary outcomes for this trial. These were assessed using an Arabic validated version of the Hopkins Symptoms Checklist-25 (HSCL-25). Assessments were done at baseline and six months using face-to face interviews, pelvic examinations and laboratory tests. Women were randomized into either intervention or control group. Intent to treat analysis will be used. Discussion The results will indicate whether the proposed psychosocial intervention was effective in reducing MUVD (possibly mediated by common mental distress). Trial Registration The trial is registered at the Wellcome Trust Registry, ISRCTN assigned: ISRCTN: ISRCTN98441241 PMID:21864414

Dual-5α-Reductase Inhibition Promotes Hepatic Lipid Accumulation in Man.

PubMed

Hazlehurst, Jonathan M; Oprescu, Andrei I; Nikolaou, Nikolaos; Di Guida, Riccardo; Grinbergs, Annabel E K; Davies, Nigel P; Flintham, Robert B; Armstrong, Matthew J; Taylor, Angela E; Hughes, Beverly A; Yu, Jinglei; Hodson, Leanne; Dunn, Warwick B; Tomlinson, Jeremy W

2016-01-01

5α-Reductase 1 and 2 (SRD5A1, SRD5A2) inactivate cortisol to 5α-dihydrocortisol in addition to their role in the generation of DHT. Dutasteride (dual SRD5A1 and SRD5A2 inhibitor) and finasteride (selective SRD5A2 inhibitor) are commonly prescribed, but their potential metabolic effects have only recently been identified. Our objective was to provide a detailed assessment of the metabolic effects of SRD5A inhibition and in particular the impact on hepatic lipid metabolism. We conducted a randomized study in 12 healthy male volunteers with detailed metabolic phenotyping performed before and after a 3-week treatment with finasteride (5 mg od) or dutasteride (0.5 mg od). Hepatic magnetic resonance spectroscopy (MRS) and two-step hyperinsulinemic euglycemic clamps incorporating stable isotopes with concomitant adipose tissue microdialysis were used to evaluate carbohydrate and lipid flux. Analysis of the serum metabolome was performed using ultra-HPLC-mass spectrometry. The study was performed in the Wellcome Trust Clinical Research Facility, Queen Elizabeth Hospital, Birmingham, United Kingdom. Incorporation of hepatic lipid was measured with MRS. Dutasteride, not finasteride, increased hepatic insulin resistance. Intrahepatic lipid increased on MRS after dutasteride treatment and was associated with increased rates of de novo lipogenesis. Adipose tissue lipid mobilization was decreased by dutasteride. Analysis of the serum metabolome demonstrated that in the fasted state, dutasteride had a significant effect on lipid metabolism. Dual-SRD5A inhibition with dutasteride is associated with increased intrahepatic lipid accumulation.

fMRat: an extension of SPM for a fully automatic analysis of rodent brain functional magnetic resonance series.

PubMed

Chavarrías, Cristina; García-Vázquez, Verónica; Alemán-Gómez, Yasser; Montesinos, Paula; Pascau, Javier; Desco, Manuel

2016-05-01

The purpose of this study was to develop a multi-platform automatic software tool for full processing of fMRI rodent studies. Existing tools require the usage of several different plug-ins, a significant user interaction and/or programming skills. Based on a user-friendly interface, the tool provides statistical parametric brain maps (t and Z) and percentage of signal change for user-provided regions of interest. The tool is coded in MATLAB (MathWorks(®)) and implemented as a plug-in for SPM (Statistical Parametric Mapping, the Wellcome Trust Centre for Neuroimaging). The automatic pipeline loads default parameters that are appropriate for preclinical studies and processes multiple subjects in batch mode (from images in either Nifti or raw Bruker format). In advanced mode, all processing steps can be selected or deselected and executed independently. Processing parameters and workflow were optimized for rat studies and assessed using 460 male-rat fMRI series on which we tested five smoothing kernel sizes and three different hemodynamic models. A smoothing kernel of FWHM = 1.2 mm (four times the voxel size) yielded the highest t values at the somatosensorial primary cortex, and a boxcar response function provided the lowest residual variance after fitting. fMRat offers the features of a thorough SPM-based analysis combined with the functionality of several SPM extensions in a single automatic pipeline with a user-friendly interface. The code and sample images can be downloaded from https://github.com/HGGM-LIM/fmrat .

The psychological well-being and prenatal bonding of gestational surrogates.

PubMed

Lamba, N; Jadva, V; Kadam, K; Golombok, S

2018-02-23

How does the psychological well-being and prenatal bonding of Indian surrogates differ from a comparison group of mothers? Surrogates had higher levels of depression during pregnancy and post-birth, displayed lower emotional connection with the unborn baby, and greater care towards the healthy growth of the foetus, than the comparison group of mothers. Studies in the West have found that surrogates do not suffer long-term psychological harm. One study has shown that surrogates bond less with the foetus than expectant mothers. This study uses a prospective, longitudinal and cross-sectional design. Surrogates and a matched group of expectant mothers were seen twice, during 4-9 months of pregnancy and 4-6 months after the birth. Semi-structured interviews and standardized questionnaires were administered to 50 surrogates and 69 expectant mothers during pregnancy and 45 surrogates and 49 expectant mothers post-birth. All gestational surrogates were hosting pregnancies for international intended parents. Surrogates had higher levels of depression compared to the comparison group of mothers, during pregnancy and post-birth (P < 0.02). Low social support during pregnancy, hiding surrogacy and criticism from others were found to be predictive of higher depression in surrogates post-birth (P < 0.05). Regarding prenatal bonding, surrogates interacted less with and thought less about the foetus but adopted better eating habits and were more likely to avoid unhealthy practices during pregnancy, than expectant mothers (P < 0.05). No associations were found between greater prenatal bonding and greater psychological distress during pregnancy or after relinquishment. All surrogates were recruited from one clinic in Mumbai, and thus the representativeness of this sample is not known. Also, the possibility of socially desirable responding from surrogates cannot be ruled out. As this is the first study of the psychological well-being of surrogates in low-income countries, the findings have important policy implications. Providing support and counselling to surrogates, especially during pregnancy, may alleviate some of the psychological problems faced by surrogates. This study was supported by the Wellcome Trust [097857/Z/11/Z] and Nehru Trust, Cambridge. K.K. is the Medical Director of Corion Fertility Clinic. All other authors have no conflict of interest to declare.

Global yellow fever vaccination coverage from 1970 to 2016: an adjusted retrospective analysis.

PubMed

Shearer, Freya M; Moyes, Catherine L; Pigott, David M; Brady, Oliver J; Marinho, Fatima; Deshpande, Aniruddha; Longbottom, Joshua; Browne, Annie J; Kraemer, Moritz U G; O'Reilly, Kathleen M; Hombach, Joachim; Yactayo, Sergio; de Araújo, Valdelaine E M; da Nóbrega, Aglaêr A; Mosser, Jonathan F; Stanaway, Jeffrey D; Lim, Stephen S; Hay, Simon I; Golding, Nick; Reiner, Robert C

2017-11-01

Substantial outbreaks of yellow fever in Angola and Brazil in the past 2 years, combined with global shortages in vaccine stockpiles, highlight a pressing need to assess present control strategies. The aims of this study were to estimate global yellow fever vaccination coverage from 1970 through to 2016 at high spatial resolution and to calculate the number of individuals still requiring vaccination to reach population coverage thresholds for outbreak prevention. For this adjusted retrospective analysis, we compiled data from a range of sources (eg, WHO reports and health-service-provider registeries) reporting on yellow fever vaccination activities between May 1, 1939, and Oct 29, 2016. To account for uncertainty in how vaccine campaigns were targeted, we calculated three population coverage values to encompass alternative scenarios. We combined these data with demographic information and tracked vaccination coverage through time to estimate the proportion of the population who had ever received a yellow fever vaccine for each second level administrative division across countries at risk of yellow fever virus transmission from 1970 to 2016. Overall, substantial increases in vaccine coverage have occurred since 1970, but notable gaps still exist in contemporary coverage within yellow fever risk zones. We estimate that between 393·7 million and 472·9 million people still require vaccination in areas at risk of yellow fever virus transmission to achieve the 80% population coverage threshold recommended by WHO; this represents between 43% and 52% of the population within yellow fever risk zones, compared with between 66% and 76% of the population who would have required vaccination in 1970. Our results highlight important gaps in yellow fever vaccination coverage, can contribute to improved quantification of outbreak risk, and help to guide planning of future vaccination efforts and emergency stockpiling. The Rhodes Trust, Bill & Melinda Gates Foundation, the Wellcome Trust, the National Library of Medicine of the National Institutes of Health, the European Union's Horizon 2020 research and innovation programme. Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

Spread of yellow fever virus outbreak in Angola and the Democratic Republic of the Congo 2015-16: a modelling study.

PubMed

Kraemer, Moritz U G; Faria, Nuno R; Reiner, Robert C; Golding, Nick; Nikolay, Birgit; Stasse, Stephanie; Johansson, Michael A; Salje, Henrik; Faye, Ousmane; Wint, G R William; Niedrig, Matthias; Shearer, Freya M; Hill, Sarah C; Thompson, Robin N; Bisanzio, Donal; Taveira, Nuno; Nax, Heinrich H; Pradelski, Bary S R; Nsoesie, Elaine O; Murphy, Nicholas R; Bogoch, Isaac I; Khan, Kamran; Brownstein, John S; Tatem, Andrew J; de Oliveira, Tulio; Smith, David L; Sall, Amadou A; Pybus, Oliver G; Hay, Simon I; Cauchemez, Simon

2017-03-01

Since late 2015, an epidemic of yellow fever has caused more than 7334 suspected cases in Angola and the Democratic Republic of the Congo, including 393 deaths. We sought to understand the spatial spread of this outbreak to optimise the use of the limited available vaccine stock. We jointly analysed datasets describing the epidemic of yellow fever, vector suitability, human demography, and mobility in central Africa to understand and predict the spread of yellow fever virus. We used a standard logistic model to infer the district-specific yellow fever virus infection risk during the course of the epidemic in the region. The early spread of yellow fever virus was characterised by fast exponential growth (doubling time of 5-7 days) and fast spatial expansion (49 districts reported cases after only 3 months) from Luanda, the capital of Angola. Early invasion was positively correlated with high population density (Pearson's r 0·52, 95% CI 0·34-0·66). The further away locations were from Luanda, the later the date of invasion (Pearson's r 0·60, 95% CI 0·52-0·66). In a Cox model, we noted that districts with higher population densities also had higher risks of sustained transmission (the hazard ratio for cases ceasing was 0·74, 95% CI 0·13-0·92 per log-unit increase in the population size of a district). A model that captured human mobility and vector suitability successfully discriminated districts with high risk of invasion from others with a lower risk (area under the curve 0·94, 95% CI 0·92-0·97). If at the start of the epidemic, sufficient vaccines had been available to target 50 out of 313 districts in the area, our model would have correctly identified 27 (84%) of the 32 districts that were eventually affected. Our findings show the contributions of ecological and demographic factors to the ongoing spread of the yellow fever outbreak and provide estimates of the areas that could be prioritised for vaccination, although other constraints such as vaccine supply and delivery need to be accounted for before such insights can be translated into policy. Wellcome Trust. Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY license. Published by Elsevier Ltd.. All rights reserved.

Common genetic variants associated with disease from genome-wide association studies are mutually exclusive in prostate cancer and rheumatoid arthritis.

PubMed

Orozco, Gisela; Goh, Chee L; Al Olama, Ali Amin; Benlloch-Garcia, Sara; Govindasami, Koveela; Guy, Michelle; Muir, Kenneth R; Giles, Graham G; Severi, Gianluca; Neal, David E; Hamdy, Freddie C; Donovan, Jenny L; Kote-Jarai, Zsofia; Easton, Douglas F; Eyre, Steve; Eeles, Rosalind A

2013-06-01

WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: The link between inflammation and cancer has long been reported and inflammation is thought to play a role in the pathogenesis of many cancers, including prostate cancer (PrCa). Over the last 5 years, genome-wide association studies (GWAS) have reported numerous susceptibility loci that predispose individuals to many different traits. The present study aims to ascertain if there are common genetic risk profiles that might predispose individuals to both PrCa and the autoimmune inflammatory condition, rheumatoid arthritis. These results could have potential public heath impact in terms of screening and chemoprevention. To investigate if potential common pathways exist for the pathogenesis of autoimmune disease and prostate cancer (PrCa). To ascertain if the single nucleotide polymorphisms (SNPs) reported by genome-wide association studies (GWAS) as being associated with susceptibility to PrCa are also associated with susceptibility to the autoimmune disease rheumatoid arthritis (RA). The original Wellcome Trust Case Control Consortium (WTCCC) UK RA GWAS study was expanded to include a total of 3221 cases and 5272 controls. In all, 37 germline autosomal SNPs at genome-wide significance associated with PrCa risk were identified from a UK/Australian PrCa GWAS. Allele frequencies were compared for these 37 SNPs between RA cases and controls using a chi-squared trend test and corrected for multiple testing (Bonferroni). In all, 33 SNPs were able to be analysed in the RA dataset. Proxies could not be located for the SNPs in 3q26, 5p15 and for two SNPs in 17q12. After applying a Bonferroni correction for the number of SNPs tested, the SNP mapping to CCHCR1 (rs130067) retained statistically significant evidence for association (P = 6 × 10(-4) ; odds ratio [OR] = 1.15, 95% CI: 1.06-1.24); this has also been associated with psoriasis. However, further analyses showed that the association of this allele was due to confounding by RA-associated HLA-DRB1 alleles. There is currently no evidence that SNPs associated with PrCa at genome-wide significance are associated with the development of RA. Studies like this are important in determining if common genetic risk profiles might predispose individuals to many diseases, which could have implications for public health in terms of screening and chemoprevention. © 2012 BJU International.

Trust via disasters: the case of Chile's 2010 earthquake.

PubMed

Dussaillant, Francisca; Guzmán, Eugenio

2014-10-01

Chile has a long-standing history of natural disasters and, in particular, earthquakes. The latest big earthquake hit Chile on 27 February 2010 with a magnitude of 8.8 on the Richter scale. As an event that had a profound impact on significant portions of the population, the earthquake could theoretically have served to build trust by promoting new trust networks through the enhancement of distant family ties and the interaction between affected neighbours. This study offers an empirical analysis of this theory in the Chilean case. It finds that if initial social capital is very low (thus allowing for post-disaster looting and violence), then the impact of the trust-increasing effect is smaller. It also shows that the effect of the disaster was not transitory, but that it persisted and actually increased over time. © 2014 The Author(s). Disasters © Overseas Development Institute, 2014.

The Erosion of Public Trust: Normalization of Deviance In The Air Force

DTIC Science & Technology

2016-02-13

to forge, and building a reputation of professionalism and trustworthiness requires significant effort and investment. And, public trust grows ...clearly a special trust between society and the military profession . Normalization of Deviance Now that military professionalism and the special...their armed forces will operate in a competent, professional , and ethical manner. In the case of the United States Air Force, there has been an

26 CFR 25.2702-1 - Special valuation rules in the case of transfers of interests in trust.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 26 Internal Revenue 14 2010-04-01 2010-04-01 false Special valuation rules in the case of transfers of interests in trust. 25.2702-1 Section 25.2702-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) ESTATE AND GIFT TAXES GIFT TAX; GIFTS MADE AFTER DECEMBER 31, 1954 Special Valuation Rules § 25.2702-1 Special...

HCMI Organization | Office of Cancer Genomics

Cancer.gov

Consortium The Human Cancer Models Initiative (HCMI) was created and funded by the US National Cancer Institute, Cancer Research UK, the foundation Hubrecht Organoid Technology, and the Wellcome Sanger Institute. Together, these organizations develop policy and make programmatic decisions to contribute to the function of the HCMI. National Cancer Institute

Effects of Cognitive Load on Trusting Behavior – An Experiment Using the Trust Game

PubMed Central

2015-01-01

Last decades have witnessed a progressing decline of social trust, which has been predominantly linked to worsening economic conditions and increasing social inequality. In the present research we propose a different type of explanation for the observed decline – cognitive load related to technological development and the accelerating pace of modern life. In an experimental study participants played the trust game while performing one of two different secondary tasks – listening to a disturbing noise or memorizing a sequence of characters – or with no additional task in the control condition. Results show that in both cognitive load conditions participants expressed significantly less trust in the trust game than in case of no cognitive load. Additionally, when cognitive resources were limited, participants’ behavior was more impulsive than when their resources were fully available. PMID:26010489

Food and trust in Australia: building a picture.

PubMed

Coveney, John

2008-03-01

To explore consumer trust in food, especially people's experiences that support or diminish trust in the food supply; consumer practices to strengthen trust in food; and views on how trust in the food supply could be increased. Adelaide, South Australia. In-depth qualitative research interviews and focus groups. Women and men who are primary food providers in families (n = 24). Media coverage of food scares and scandals and personal experience of food-borne illness challenged respondents' trust in the food system. Poor retail food handling practices and questionable marketing ploys by food manufacturers also decreased trust. Buying 'Made-in-Australia' produce and following food safety procedures at home were important practices to strengthen food trust. Knowledge of procedures for local food inspection and for national food regulation to keep food safe was scanty. Having a strong regulatory environment governing food safety and quality was considered by respondents to be of prime importance for trust building. The dimensions of trust found in this study are consistent with key theoretical aspects of trust. The need for trust in highly complex environments, in this case the food supply, was evident. Trust was found to be integral to food choice, and negative media reports, the sources of which themselves enjoy various levels of dependability, were found to easily damage trust relationships. The lack of visibility of authoritative monitoring and surveillance, misleading food advertising, and poor retail food handling practices were identified as areas that decreased consumer trust. Respondents also questioned the probity of food labelling, especially health claims and other mechanisms designed to guide food choice. The research highlights the role trust plays in food choice. It also emphasises the importance of a visible authoritative presence in the food system to strengthen trust and provide reassurance to consumers.

Trust Building in Virtual Communities

NASA Astrophysics Data System (ADS)

Mezgár, István

By using different types of communication networks various groups of people can come together according to their private or business interest forming a Virtual Community. In these communities cooperation and collaboration plays an important role. As trust is the base of all human interactions this fact is even more valid in case of virtual communities. According to different experiments the level of trust in virtual communities is highly influenced by the way/mode of communication and by the duration of contact. The paper discusses the ways of trust building focusing on communication technologies and security aspects in virtual communities.

Trust and Society: Suggestions for Further Development of Niklas Luhmann's Theory of Trust.

PubMed

Morgner, Christian

2018-05-01

This paper addresses an apparent gap in the work of Niklas Luhmann. While the issue of trust continues to receive widespread attention in the social sciences, Luhmann's interest in this topic declined following the development of his systems theory. It is argued that this decline does not reflect any diminished relevance of trust for systems theory, but rather that the architectural remodeling of theory cannot easily be applied to the issue of trust. Here, the issue of trust is reconceptualized as a connection medium. This entails a reconstruction of Luhmann's early theory of trust, especially with regard to function and social positioning. In this context, trust can in turn be linked to the concept of medium in Luhmann's late work. As a connection medium, trust mediates between the different levels of sociality-interaction, organization, and society. These theoretical considerations are employed to develop a more applied framework for empirical research, with a brief case study from southern Italy. From this perspective, the idea of trust as society's glue is seen to be overly simplistic. The common ethical understanding that more trust leads to a better society is also questioned on the grounds that social cooperation can also lead to social sclerosis. Finally, risk and trust are shown to accommodate the formation of different cultures of trust. The paper shows how Luhmann's updated version of trust can inspire current research and enhance our understanding of how trust operates in contemporary society. © 2018 Canadian Sociological Association/La Société canadienne de sociologie.

5 CFR 2634.413 - Public access.

Code of Federal Regulations, 2014 CFR

2014-01-01

... of each asset; (3) The report of the dissolution of the trust and a list of the assets of the trust at the time of the dissolution, categorized as to the value of each asset; (4) In the case of a blind...

5 CFR 2634.413 - Public access.

Code of Federal Regulations, 2013 CFR

2013-01-01

... of each asset; (3) The report of the dissolution of the trust and a list of the assets of the trust at the time of the dissolution, categorized as to the value of each asset; (4) In the case of a blind...

Understanding factors that influence stakeholder trust of natural resource science and institutions.

PubMed

Gray, Steven; Shwom, Rachael; Jordan, Rebecca

2012-03-01

Building trust between resource users and natural resource institutions is essential when creating conservation policies that rely on stakeholders to be effective. Trust can enable the public and agencies to engage in cooperative behaviors toward shared goals and address shared problems. Despite the increasing attention that trust has received recently in the environmental management literature, the influence that individual cognitive and behavioral factors may play in influencing levels of trust in resource management institutions, and their associated scientific assessments, remains unclear. This paper uses the case of fisheries management in the northeast to explore the relationships between an individual's knowledge of the resource, perceptions of resource health, and participatory experience on levels of trust. Using survey data collected from 244 avid recreational anglers in the Northeast U.S., we test these relationships using structural equation modeling. Results indicate that participation in fisheries management is associated with increased trust across all aspects of fisheries management. In addition, higher ratings of resource health by anglers are associated with higher levels of trust of state and regional institutions, but not federal institutions or scientific methods.

Understanding Factors That Influence Stakeholder Trust of Natural Resource Science and Institutions

NASA Astrophysics Data System (ADS)

Gray, Steven; Shwom, Rachael; Jordan, Rebecca

2012-03-01

Building trust between resource users and natural resource institutions is essential when creating conservation policies that rely on stakeholders to be effective. Trust can enable the public and agencies to engage in cooperative behaviors toward shared goals and address shared problems. Despite the increasing attention that trust has received recently in the environmental management literature, the influence that individual cognitive and behavioral factors may play in influencing levels of trust in resource management institutions, and their associated scientific assessments, remains unclear. This paper uses the case of fisheries management in the northeast to explore the relationships between an individual's knowledge of the resource, perceptions of resource health, and participatory experience on levels of trust. Using survey data collected from 244 avid recreational anglers in the Northeast U.S., we test these relationships using structural equation modeling. Results indicate that participation in fisheries management is associated with increased trust across all aspects of fisheries management. In addition, higher ratings of resource health by anglers are associated with higher levels of trust of state and regional institutions, but not federal institutions or scientific methods.

The Energy Puzzle Between the United States and China

DTIC Science & Technology

2013-03-01

information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. 1. REPORT DATE (DD-MM...development, energy growth and developments in energy technology. It concludes with the best case scenario of the two countries building a trust that...development, energy growth and developments in energy technology. It concludes with the best case scenario of the two countries building a trust that will

Communication Behaviors and Trust in Collaborative Online Teams

ERIC Educational Resources Information Center

Bulu, Saniye Tugba; Yildirim, Zahide

2008-01-01

This study investigates preservice teachers' trust levels and collaborative communication behaviors namely leadership, feedback, social interaction, enthusiasm, task and technical uncertainties, and task-oriented interactions in online learning environment. A case study design involving qualitative and quantitative data collection and analysis was…

12 CFR 585.40 - What convictions or agreements to enter into pre-trial diversions or similar programs are covered...

Code of Federal Regulations, 2010 CFR

2010-01-01

..., breach of trust, or money laundering. Convictions do not cover arrests, pending cases not brought to... for a criminal offense involving dishonesty, breach of trust or money laundering. A pretrial diversion...

Prevalence of endocrine and genetic abnormalities in boys evaluated systematically for a disorder of sex development

PubMed Central

Nixon, R.; Cerqueira, V.; Kyriakou, A.; Lucas-Herald, A.; McNeilly, J.; McMillan, M.; Purvis, A.I.; Tobias, E.S.; McGowan, R.

2017-01-01

Abstract STUDY QUESTION What is the likelihood of identifying genetic or endocrine abnormalities in a group of boys with 46, XY who present to a specialist clinic with a suspected disorder of sex development (DSD)? SUMMARY ANSWER An endocrine abnormality of the gonadal axis may be present in a quarter of cases and copy number variants (CNVs) or single gene variants may be present in about half of the cases. WHAT IS KNOWN ALREADY Evaluation of 46, XY DSD requires a combination of endocrine and genetic tests but the prevalence of these abnormalities in a sufficiently large group of boys presenting to one specialist multidisciplinary service is unclear. STUDY, DESIGN, SIZE, DURATION This study was a retrospective review of investigations performed on 122 boys. PARTICIPANTS/MATERIALS, SETTING, METHODS All boys who attended the Glasgow DSD clinic, between 2010 and 2015 were included in the study. The median external masculinization score (EMS) of this group was 9 (range 1–11). Details of phenotype, endocrine and genetic investigations were obtained from case records. MAIN RESULTS AND THE ROLE OF CHANCE An endocrine abnormality of gonadal function was present in 28 (23%) with a median EMS of 8.3 (1–10.5) whilst the median EMS of boys with normal endocrine investigations was 9 (1.5–11) (P = 0.03). Endocrine abnormalities included a disorder of gonadal development in 19 (16%), LH deficiency in 5 (4%) and a disorder of androgen synthesis in 4 (3%) boys. Of 43 cases who had array-comparative genomic hybridization (array-CGH), CNVs were reported in 13 (30%) with a median EMS of 8.5 (1.5–11). Candidate gene analysis using a limited seven-gene panel in 64 boys identified variants in 9 (14%) with a median EMS of 8 (1–9). Of the 21 boys with a genetic abnormality, 11 (52%) had normal endocrine investigations. LIMITATIONS, REASONS FOR CAUTION A selection bias for performing array-CGH in cases with multiple congenital malformations may have led to a high yield of CNVs. It is also possible that the yield of single gene variants may have been higher than reported if the investigators had used a more extended gene panel. WIDER IMPLICATIONS OF THE FINDINGS The lack of a clear association between the extent of under-masculinization and presence of endocrine and genetic abnormalities suggests a role for parallel endocrine and genetic investigations in cases of suspected XY DSD. STUDY FUNDING/COMPETING INTEREST(S) RN was supported by the James Paterson Bursary and the Glasgow Children's Hospital Charity Summer Scholarship. SFA, RM and EST are supported by a Scottish Executive Health Department grant 74250/1 for the Scottish Genomes Partnership. EST is also supported by MRC/EPSRC Molecular Pathology Node and Wellcome Trust ISSF funding. There are no conflicts of interest. TRIAL REGISTRATION NUMBER None. PMID:28938747

Fine-mapping and transethnic genotyping establish IL2/IL21 genetic association with lupus and localize this genetic effect to IL21.

PubMed

Hughes, Travis; Kim-Howard, Xana; Kelly, Jennifer A; Kaufman, Kenneth M; Langefeld, Carl D; Ziegler, Julie; Sanchez, Elena; Kimberly, Robert P; Edberg, Jeffrey C; Ramsey-Goldman, Rosalind; Petri, Michelle; Reveille, John D; Martín, Javier; Brown, Elizabeth E; Vilá, Luis M; Alarcón, Graciela S; James, Judith A; Gilkeson, Gary S; Moser, Kathy L; Gaffney, Patrick M; Merrill, Joan T; Vyse, Timothy J; Alarcón-Riquelme, Marta E; Nath, Swapan K; Harley, John B; Sawalha, Amr H

2011-06-01

Genetic association of the IL2/IL21 region at chromosome 4q27 has previously been reported in lupus and a number of autoimmune and inflammatory diseases. This study was undertaken to determine whether this genetic effect could be localized, using a very large cohort of lupus patients and controls. We genotyped 45 tag single-nucleotide polymorphisms (SNPs) across the IL2/IL21 locus in 2 large independent lupus sample sets. We studied a set of subjects of European descent consisting of 4,248 lupus patients and 3,818 healthy controls, and an African American set of 1,569 patients and 1,893 healthy controls. Imputation in 3,004 additional controls from the Wellcome Trust Case Control Consortium was also performed. Genetic association between the genotyped markers was determined, and pairwise conditional analysis was performed to localize the independent genetic effect in the IL2/IL21 locus in lupus. We established and confirmed the genetic association between IL2/IL21 and lupus. Using conditional analysis and transethnic mapping, we localized the genetic effect in this locus to 2 SNPs in high linkage disequilibrium: rs907715 located within IL21 (odds ratio 1.16 [95% confidence interval 1.10-1.22], P=2.17×10(-8)) and rs6835457 located in the 3'-untranslated flanking region of IL21 (odds ratio 1.11 [95% confidence interval 1.05-1.17], P=9.35×10(-5)). Our findings establish the genetic association between lupus and IL2/IL21 with a genome-wide level of significance. Further, our findings indicate that this genetic association within the IL2/IL21 linkage disequilibrium block is localized to IL21. If other autoimmune IL2/IL21 genetic associations are similarly localized, then the IL21 risk alleles would be predicted to operate by a fundamental mechanism that influences the course of a number of autoimmune disease processes. Copyright © 2011 by the American College of Rheumatology.

A Variant in the BACH2 Gene Is Associated With Susceptibility to Autoimmune Addison's Disease in Humans

PubMed Central

Oftedal, Bergithe E.; Napier, Catherine M.; Ainsworth, Holly F.; Husebye, Eystein S.; Cordell, Heather J.; Pearce, Simon H. S.; Mitchell, Anna L.

2016-01-01

Context: Autoimmune Addison's disease (AAD) is a rare but highly heritable condition. The BACH2 protein plays a crucial role in T lymphocyte maturation, and allelic variation in its gene has been associated with a number of autoimmune conditions. Objective: We aimed to determine whether alleles of the rs3757247 single nucleotide polymorphism (SNP) in the BACH2 gene are associated with AAD. Design, Setting, and Patients: This case-control association study was performed in two phases using Taqman chemistry. In the first phase, the rs3757247 SNP was genotyped in 358 UK AAD subjects and 166 local control subjects. Genotype data were also available from 5154 healthy UK controls from the Wellcome Trust (WTCCC2) for comparison. In the second phase, the SNP was genotyped in a validation cohort comprising 317 Norwegian AAD subjects and 365 controls. Results: The frequency of the minor T allele was significantly higher in subjects with AAD from the United Kingdom compared to both the local and WTCCC2 control cohorts (58% vs 45 and 48%, respectively) (local controls, P = 1.1 × 10−4; odds ratio [OR], 1.68; 95% confidence interval [CI], 1.29–2.18; WTCCC2 controls, P = 1.4 × 10−6; OR, 1.44; 95% CI, 1.23–1.69). This finding was replicated in the Norwegian validation cohort (P = .0015; OR, 1.41; 95% CI, 1.14–1.75). Subgroup analysis showed that this association is present in subjects with both isolated AAD (OR, 1.53; 95% CI, 1.22–1.92) and autoimmune polyglandular syndrome type 2 (OR, 1.37; 95% CI, 1.12–1.69) in the UK cohort, and with autoimmune polyglandular syndrome type 2 in the Norwegian cohort (OR, 1.58; 95% CI, 1.22–2.06). Conclusion: We have demonstrated, for the first time, that allelic variability at the BACH2 locus is associated with susceptibility to AAD. Given its association with multiple autoimmune conditions, BACH2 can be considered a “universal” autoimmune susceptibility locus. PMID:27680876

Asymptomatic infection and unrecognised Ebola virus disease in Ebola-affected households in Sierra Leone: a cross-sectional study using a new non-invasive assay for antibodies to Ebola virus.

PubMed

Glynn, Judith R; Bower, Hilary; Johnson, Sembia; Houlihan, Catherine F; Montesano, Carla; Scott, Janet T; Semple, Malcolm G; Bangura, Mohammed S; Kamara, Alie Joshua; Kamara, Osman; Mansaray, Saidu H; Sesay, Daniel; Turay, Cecilia; Dicks, Steven; Wadoum, Raoul E Guetiya; Colizzi, Vittorio; Checchi, Francesco; Samuel, Dhan; Tedder, Richard S

2017-06-01

The frequency of asymptomatic infection with Ebola virus is unclear: previous estimates vary and there is no standard test. Asymptomatic infection with Ebola virus could contribute to population immunity, reducing spread. If people with asymptomatic infection are infectious it could explain re-emergences of Ebola virus disease (EVD) without known contact. We validated a new oral fluid anti-glycoprotein IgG capture assay among survivors from Kerry Town Ebola Treatment Centre and controls from communities unaffected by EVD in Sierra Leone. We then assessed the seroprevalence of antibodies to Ebola virus in a cross-sectional study of household contacts of the survivors. All household members were interviewed. Two reactive tests were required for a positive result, with a third test to resolve any discrepancies. The assay had a specificity of 100% (95% CI 98·9-100; 339 of 339 controls tested negative) and sensitivity of 95·9% (89·8-98·9; 93 of 97 PCR-confirmed survivors tested positive). Of household contacts not diagnosed with EVD, 47·6% (229 of 481) had high level exposure (direct contact with a corpse, body fluids, or a case with diarrhoea, vomiting, or bleeding). Among the contacts, 12·0% (95% CI 6·1-20·4; 11 of 92) with symptoms at the time other household members had EVD, and 2·6% (1·2-4·7; 10 of 388) with no symptoms tested positive. Among asymptomatic contacts, seropositivity was weakly correlated with exposure level. This new highly specific and sensitive assay showed asymptomatic infection with Ebola virus was uncommon despite high exposure. The low prevalence suggests asymptomatic infection contributes little to herd immunity in Ebola, and even if infectious, would account for few transmissions. Wellcome Trust ERAES Programme, Save the Children. Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY license. Published by Elsevier Ltd.. All rights reserved.

Antenatal blood pressure for prediction of pre-eclampsia, preterm birth, and small for gestational age babies: development and validation in two general population cohorts

PubMed Central

Silverwood, Richard J; de Stavola, Bianca L; Inskip, Hazel; Cooper, Cyrus; Godfrey, Keith M; Crozier, Sarah; Fraser, Abigail; Nelson, Scott M; Lawlor, Debbie A; Tilling, Kate

2015-01-01

Study question Can routine antenatal blood pressure measurements between 20 and 36 weeks’ gestation contribute to the prediction of pre-eclampsia and its associated adverse outcomes? Methods This study used repeated antenatal measurements of blood pressure from 12 996 women in the Avon Longitudinal Study of Parents and Children (ALSPAC) to develop prediction models and validated these in 3005 women from the Southampton Women’s Survey (SWS). A model based on maternal early pregnancy characteristics only (BMI, height, age, parity, smoking, existing and previous gestational hypertension and diabetes, and ethnicity) plus initial mean arterial pressure was compared with a model additionally including current mean arterial pressure, a model including the deviation of current mean arterial pressure from a stratified normogram, and a model including both at different gestational ages from 20-36 weeks. Study answer and limitations The addition of blood pressure measurements from 28 weeks onwards improved prediction models compared with use of early pregnancy risk factors alone, but they contributed little to the prediction of preterm birth or small for gestational age. Though multiple imputation of missing data was used to increase the sample size and minimise selection bias, the validation sample might have been slightly underpowered as the number of cases of pre-eclampsia was just below the recommended 100. Several risk factors were self reported, potentially introducing measurement error, but this reflects how information would be obtained in clinical practice. What this study adds The addition of routinely collected blood pressure measurements from 28 weeks onwards improves predictive models for pre-eclampsia based on blood pressure in early pregnancy and other characteristics, facilitating a reduction in scheduled antenatal care. Funding, competing interests, data sharing UK Wellcome Trust, US National Institutes of Health, and UK Medical Research Council. Other funding sources for authors are detailed in the full online paper. With the exceptions of CM-W, HMI, and KMG there were no competing interests. PMID:26578347

Ethical and legal implications of whole genome and whole exome sequencing in African populations.

PubMed

Wright, Galen E B; Koornhof, Pieter G J; Adeyemo, Adebowale A; Tiffin, Nicki

2013-05-28

Rapid advances in high throughput genomic technologies and next generation sequencing are making medical genomic research more readily accessible and affordable, including the sequencing of patient and control whole genomes and exomes in order to elucidate genetic factors underlying disease. Over the next five years, the Human Heredity and Health in Africa (H3Africa) Initiative, funded by the Wellcome Trust (United Kingdom) and the National Institutes of Health (United States of America), will contribute greatly towards sequencing of numerous African samples for biomedical research. Funding agencies and journals often require submission of genomic data from research participants to databases that allow open or controlled data access for all investigators. Access to such genotype-phenotype and pedigree data, however, needs careful control in order to prevent identification of individuals or families. This is particularly the case in Africa, where many researchers and their patients are inexperienced in the ethical issues accompanying whole genome and exome research; and where an historical unidirectional flow of samples and data out of Africa has created a sense of exploitation and distrust. In the current study, we analysed the implications of the anticipated surge of next generation sequencing data in Africa and the subsequent data sharing concepts on the protection of privacy of research subjects. We performed a retrospective analysis of the informed consent process for the continent and the rest-of-the-world and examined relevant legislation, both current and proposed. We investigated the following issues: (i) informed consent, including guidelines for performing culturally-sensitive next generation sequencing research in Africa and availability of suitable informed consent documents; (ii) data security and subject privacy whilst practicing data sharing; (iii) conveying the implications of such concepts to research participants in resource limited settings. We conclude that, in order to meet the unique requirements of performing next generation sequencing-related research in African populations, novel approaches to the informed consent process are required. This will help to avoid infringement of privacy of individual subjects as well as to ensure that informed consent adheres to acceptable data protection levels with regard to use and transfer of such information.

Ethical and legal implications of whole genome and whole exome sequencing in African populations

PubMed Central

2013-01-01

Background Rapid advances in high throughput genomic technologies and next generation sequencing are making medical genomic research more readily accessible and affordable, including the sequencing of patient and control whole genomes and exomes in order to elucidate genetic factors underlying disease. Over the next five years, the Human Heredity and Health in Africa (H3Africa) Initiative, funded by the Wellcome Trust (United Kingdom) and the National Institutes of Health (United States of America), will contribute greatly towards sequencing of numerous African samples for biomedical research. Discussion Funding agencies and journals often require submission of genomic data from research participants to databases that allow open or controlled data access for all investigators. Access to such genotype-phenotype and pedigree data, however, needs careful control in order to prevent identification of individuals or families. This is particularly the case in Africa, where many researchers and their patients are inexperienced in the ethical issues accompanying whole genome and exome research; and where an historical unidirectional flow of samples and data out of Africa has created a sense of exploitation and distrust. In the current study, we analysed the implications of the anticipated surge of next generation sequencing data in Africa and the subsequent data sharing concepts on the protection of privacy of research subjects. We performed a retrospective analysis of the informed consent process for the continent and the rest-of-the-world and examined relevant legislation, both current and proposed. We investigated the following issues: (i) informed consent, including guidelines for performing culturally-sensitive next generation sequencing research in Africa and availability of suitable informed consent documents; (ii) data security and subject privacy whilst practicing data sharing; (iii) conveying the implications of such concepts to research participants in resource limited settings. Summary We conclude that, in order to meet the unique requirements of performing next generation sequencing-related research in African populations, novel approaches to the informed consent process are required. This will help to avoid infringement of privacy of individual subjects as well as to ensure that informed consent adheres to acceptable data protection levels with regard to use and transfer of such information. PMID:23714101

Fast and accurate imputation of summary statistics enhances evidence of functional enrichment

PubMed Central

Pasaniuc, Bogdan; Zaitlen, Noah; Shi, Huwenbo; Bhatia, Gaurav; Gusev, Alexander; Pickrell, Joseph; Hirschhorn, Joel; Strachan, David P.; Patterson, Nick; Price, Alkes L.

2014-01-01

Motivation: Imputation using external reference panels (e.g. 1000 Genomes) is a widely used approach for increasing power in genome-wide association studies and meta-analysis. Existing hidden Markov models (HMM)-based imputation approaches require individual-level genotypes. Here, we develop a new method for Gaussian imputation from summary association statistics, a type of data that is becoming widely available. Results: In simulations using 1000 Genomes (1000G) data, this method recovers 84% (54%) of the effective sample size for common (>5%) and low-frequency (1–5%) variants [increasing to 87% (60%) when summary linkage disequilibrium information is available from target samples] versus the gold standard of 89% (67%) for HMM-based imputation, which cannot be applied to summary statistics. Our approach accounts for the limited sample size of the reference panel, a crucial step to eliminate false-positive associations, and it is computationally very fast. As an empirical demonstration, we apply our method to seven case–control phenotypes from the Wellcome Trust Case Control Consortium (WTCCC) data and a study of height in the British 1958 birth cohort (1958BC). Gaussian imputation from summary statistics recovers 95% (105%) of the effective sample size (as quantified by the ratio of χ2 association statistics) compared with HMM-based imputation from individual-level genotypes at the 227 (176) published single nucleotide polymorphisms (SNPs) in the WTCCC (1958BC height) data. In addition, for publicly available summary statistics from large meta-analyses of four lipid traits, we publicly release imputed summary statistics at 1000G SNPs, which could not have been obtained using previously published methods, and demonstrate their accuracy by masking subsets of the data. We show that 1000G imputation using our approach increases the magnitude and statistical evidence of enrichment at genic versus non-genic loci for these traits, as compared with an analysis without 1000G imputation. Thus, imputation of summary statistics will be a valuable tool in future functional enrichment analyses. Availability and implementation: Publicly available software package available at http://bogdan.bioinformatics.ucla.edu/software/. Contact: bpasaniuc@mednet.ucla.edu or aprice@hsph.harvard.edu Supplementary information: Supplementary materials are available at Bioinformatics online. PMID:24990607

The influence of power dynamics and trust on multidisciplinary collaboration: a qualitative case study of type 2 diabetes mellitus

PubMed Central

2012-01-01

Background Ongoing care for chronic conditions such as diabetes is best provided by a range of health professionals working together. There are challenges in achieving this where collaboration crosses organisational and sector boundaries. The aim of this article is to explore the influence of power dynamics and trust on collaboration between health professionals involved in the management of diabetes and their impact on patient experiences. Methods A qualitative case study conducted in a rural city in Australia. Forty five health service providers from nineteen organisations (including fee-for-service practices and block funded public sector services) and eight patients from two services were purposively recruited. Data was collected through semi-structured interviews that were audio-taped and transcribed. A thematic analysis approach was used using a two-level coding scheme and cross-case comparisons. Results Three themes emerged in relation to power dynamics between health professionals: their use of power to protect their autonomy, power dynamics between private and public sector providers, and reducing their dependency on other health professionals to maintain their power. Despite the intention of government policies to support more shared decision-making, there is little evidence that this is happening. The major trust themes related to role perceptions, demonstrated competence, and the importance of good communication for the development of trust over time. The interaction between trust and role perceptions went beyond understanding each other's roles and professional identity. The level of trust related to the acceptance of each other's roles. The delivery of primary and community-based health services that crosses organisational boundaries adds a layer of complexity to interprofessional relationships. The roles of and role boundaries between and within professional groups and services are changing. The uncertainty and vulnerability associated with these changes has affected the level of trust and mistrust. Conclusions Collaboration across organisational boundaries remains challenging. Power dynamics and trust affect the strategic choices made by each health professional about whether to collaborate, with whom, and to what level. These decisions directly influenced patient experiences. Unlike the difficulties in shifting the balance of power in interprofessional relationships, trust and respect can be fostered through a mix of interventions aimed at building personal relationships and establishing agreed rules that govern collaborative care and that are perceived as fair. PMID:22413897

The influence of power dynamics and trust on multidisciplinary collaboration: a qualitative case study of type 2 diabetes mellitus.

PubMed

McDonald, Julie; Jayasuriya, Rohan; Harris, Mark Fort

2012-03-13

Ongoing care for chronic conditions such as diabetes is best provided by a range of health professionals working together. There are challenges in achieving this where collaboration crosses organisational and sector boundaries. The aim of this article is to explore the influence of power dynamics and trust on collaboration between health professionals involved in the management of diabetes and their impact on patient experiences. A qualitative case study conducted in a rural city in Australia. Forty five health service providers from nineteen organisations (including fee-for-service practices and block funded public sector services) and eight patients from two services were purposively recruited. Data was collected through semi-structured interviews that were audio-taped and transcribed. A thematic analysis approach was used using a two-level coding scheme and cross-case comparisons. Three themes emerged in relation to power dynamics between health professionals: their use of power to protect their autonomy, power dynamics between private and public sector providers, and reducing their dependency on other health professionals to maintain their power. Despite the intention of government policies to support more shared decision-making, there is little evidence that this is happening. The major trust themes related to role perceptions, demonstrated competence, and the importance of good communication for the development of trust over time. The interaction between trust and role perceptions went beyond understanding each other's roles and professional identity. The level of trust related to the acceptance of each other's roles. The delivery of primary and community-based health services that crosses organisational boundaries adds a layer of complexity to interprofessional relationships. The roles of and role boundaries between and within professional groups and services are changing. The uncertainty and vulnerability associated with these changes has affected the level of trust and mistrust. Collaboration across organisational boundaries remains challenging. Power dynamics and trust affect the strategic choices made by each health professional about whether to collaborate, with whom, and to what level. These decisions directly influenced patient experiences. Unlike the difficulties in shifting the balance of power in interprofessional relationships, trust and respect can be fostered through a mix of interventions aimed at building personal relationships and establishing agreed rules that govern collaborative care and that are perceived as fair.

Is physician-patient concordance associated with greater trust for women of low socioeconomic status?

PubMed

Scheid, Teresa L; Smith, Galen H

2017-07-01

The authors examined the association between physician-patient concordance and patient trust for low socio-economic status women who were enrolled in Medicaid case management. The data were collected from October 2006 through March 2007 from a stratified random sample of 2,815 adult beneficiaries enrolled in North Carolina Medicaid's primary care case management delivery system. We limited our analyses to women enrolled in primary care, hence controlling for gender and social class as well as access to care. We were also able to control for the availability of minority providers. The findings revealed that the enrollee's race, education, and experiences seeking help with their health providers were significantly related to patient's trust of their physicians. Neither race concordance nor gender concordance improved trust. This may be because relatively few minority providers were included in the sample. These results extend research on physician-patient concordance by examining the relationship of both racial and gender concordance with patient trust while controlling for access and social class. Research on physician-patient concordance needs to account for multiple measures of social status, as well as differences in culture and communication styles between physicians and their patients.

[Is the person of trust a reliable witness in case of organ removal from a deceased person for donation purposes?].

PubMed

Gignon, M; Manaouil, C; Jardé, O

2008-10-01

All adults (people over the age of 18) can assign a person of trust and this person can be a parent, a partner or the treating doctor. Following the introduction of the 4(th) March 2002 law, this third party is now within the doctor-patient relationship. The aim of this study is to find out who is appointed as a person of trust by patients notably concerning the level of education or medical knowledge of these people. We have equally put the person of trust to the test within the realms that they would be questioned regarding organ donation from the deceased. The included subjects were adults admitted to hospital for surgical procedures or medical biopsies that were not deemed life threatening. The data collection was done by doctors from the legal medicine department at the university hospital of Amiens over a period of 18 months. With the permission of the patient and his or her person of trust, a one-to-one discussion was held. Statistical analysis took place focusing on all the variables together and is shown by comparing the patient group versus the person of trust group. The significance threshold returned was 0.05. A total of 125 patients-persons of trust couples were interviewed. The patients and their person of trust were not different in terms of age, social status, occupational groups and education. However, a person of trust is more often a woman (64%) against 50% of patients. A person of trust more often lives as a couple than the patients. Concerning organ donation, over half of the people questioned were for donation but only a third of patients had already discussed the subject with their person of trust. The persons of trust bring in 40% of cases a response that is not concordant in the position of the patient. The creation of a person of trust due to the law of 4(th) March 2002 brings about the opportunity for the patient to take on an approach, with the doctors, of having somebody that can advise them. Yet in this study, there is no significant evidence of a difference between the level of education of patients and that of their person of trust, or a difference in the distribution of the socio-professional categories, or specific choices for the GP. The person of trust can be used to wait on behalf of the patient whilst he or she is not able to do so. Even if the patient feels that the person of trust has come first over other close friends or relatives, the persons of trust assume this role with difficulty. Since its creation, the person of trust was presented as a response to social demand; however, it seems that patients are not sufficiently informed when it comes to the possibilities that are on offer to them.

Trust in health care encounters and systems: a case study of British pensioners living in Spain.

PubMed

Legido-Quigley, Helena; McKee, Martin; Green, Judith

2014-11-01

Research on trust in health care faces two enduring challenges. Firstly, there are conceptual ambiguities in distinguishing trust from related concepts, such as confidence or dependence. Second, the tacit understandings which underpin the 'faith' element of trust are difficult to explicate. A case study of British pensioners who have moved to Spain provides an opportunity to explore trust in a setting where they often have a choice of where to access health care (UK or Spain), and are therefore not in a state of dependence, and in which the 'differences' of a new field generates reflection on their tacit expectations of providers and systems. In accounting for decisions to use (or not to use) Spanish health care, British pensioners cited experiential knowledge of symbolic indicators of trustworthy institutions (they were hygienic, modern, efficient), which contributed to background confidence in the system, and interpersonal qualities of practitioners (respect for older people, embodied empathy and reciprocity) which evoked familiar relations, within which faith is implicit. In contrast, with limited recent access to the British system, their background confidence had been compromised by reports of poor performance, with few opportunities to rebuild the interrelational bases of trust. © 2014 The Authors. Sociology of Health & Illness published by John Wiley & Sons Ltd on behalf of Foundation for Sociology of Health and Illness (SHIL).

Marketing of patent medicines in the nineteenth century via a corkscrew medicine spoon.

PubMed

Fincham, Jack E

2010-01-01

The C. T. Williamson spoon with manufactured products from a pharmaceutical company engraved on the bowl of the spoon is one of the earliest examples of a manufacturer marketing products via a drug delivery device. The Burroughs, Wellcome and Company, a British corporation using initially an American patented, and later a British patented, Williamson corkscrew spoon marketed British manufactured medicinal products in the U.S. and England to physicians and pharmacists in the late nineteenth and early twentieth century. Other corkscrew spoons were manufactured in this era without product specific notations contained on the spoons. 40 These corkscrew spoons, such as the Williamson and Noe patented apparatuses, helped patients in more easily consuming liquid medications. They also were items potentially favored by physicians and pharmacists for patient's pro- vided liquid medications. Finally, they allowed patients to open corked containers, consume liquid dosage amounts, and hopefully more appropriately comply with necessary regimens in the late nineteenth and early twentieth century. Not surprisingly, Burroughs, Wellcome and Company used the Williamson spoon to successfully market company products to physicians, pharmacists, and patients on several continents.

Does trust of patients in their physician predict loyalty to the health care insurer? The Israeli case study.

PubMed

Gabay, Gillie

2016-01-01

This pioneer study tests the relationship between patients' trust in their physicians and patients' loyalty to their health care insurers. This is a cross-sectional study using a representative sample of patients from all health care insurers with identical health care plans. Regression analyses and Baron and Kenny's model were used to test the study model. Patient trust in the physician did not predict loyalty to the insurer. Loyalty to the physician did not mediate the relationship between trust in the physician and loyalty to the insurer. Satisfaction with the physician was the only predictor of loyalty to the insurer.

How did rapid scale-up of HIV services impact on workplace and interpersonal trust in Zambian primary health centres: a case-based health systems analysis

PubMed Central

Topp, Stephanie M; Chipukuma, Julien M

2016-01-01

Background In sub-Saharan Africa, large amounts of funding continue to be directed towards HIV-specific care and treatment, often with claims of ‘health system strengthening’ effect. Such claims rarely account for the impact on human relationships and decisions that are core to functional health systems. This research examined how establishment of externally funded HIV services influenced trusting relationships in Zambian health centres. Methods An in-depth, multicase study included four health centres selected for urban, peri-urban and rural characteristics. Case data included healthcare worker (HCW) interviews (60); patient interviews (180); direct observation of facility operations (2 weeks/centre) and key informant interviews (14) which were recorded and transcribed verbatim. Thematic analysis adopted inductive and deductive coding guided by a framework incorporating concepts of workplace trust, patient–provider trust, intrinsic and extrinsic motivation. Results HIV service scale-up impacted trust in positive and negative ways. Investment in HIV-specific infrastructure, supplies and quality assurance mechanisms strengthened workplace trust, HCW motivation and patient–provider trust in HIV departments in the short-term. In the health centres more broadly and over time, however, non-governmental organisation-led investment and support of HIV departments reinforced HCW's perceptions of the government as uninterested or unable to provide a quality work environment. Exacerbating existing perceptions of systemic workplace inequity and nepotism, uneven distribution of personal and professional opportunities related to HIV service establishment contributed to interdepartmental antagonism and reinforced workplace practices designed to protect individual HCW's interests. Conclusions Findings illustrate long-term negative effects of the vertical HIV resourcing and support structures which failed to address and sometimes exacerbated HCW (dis)trust with their own government and supervisors. The short-term and long-term effects of weakened workplace trust on HCWs' motivation and performance signal the importance of understanding how such relationships play a role in generating virtuous or perverse cycles of actor interactions, with implications for service outcomes. PMID:28588985

Trust in the safety of tourist destinations: hard to gain, easy to lose? New insights on the asymmetry principle.

PubMed

Eitzinger, Claudia; Wiedemann, Peter M

2008-08-01

According to the asymmetry principle of trust, negative events decrease trust to a much higher extent than positive events increase trust. The study at hand intended to verify whether this notion of asymmetry holds true with respect to trust in the safety of tourist destinations. Thus, in contrast to previous research that analyzed trust asymmetry in the context of involuntary technological risks, the present study evaluates the validity of the asymmetry principle of trust in the context of voluntary tourism risks. The hypothesis that negative or risky information on destination safety (absence of proper safety measures and conditions) has a higher impact on distrust than, conversely, positive or nonrisk information on destination safety (provision of proper safety measures and conditions) has on trust was tested in an online survey (N= 640). In contrast to the asymmetry pattern found by Slovic (1993), results of the current work suggest symmetry rather than asymmetry of trust. The presence of proper safety measures and conditions (positive or nonrisk information) was found to have at least the same-and in some cases an even higher-impact on trust than the absence of such measures and conditions (negative or risky information) had on distrust. Findings provide empirical evidence for the thesis that the prevalence of trust asymmetry is dependent on the risk source and demonstrate that trust is symmetric rather than asymmetric in the context of voluntary tourism risks. Furthermore, results imply an influence of positive versus negative expectations as well as of prior trusting relationships on the occurrence of the asymmetry principle.

A case management agency and bank create a service innovation.

PubMed

Katz, K S; Stowe, A W

1992-01-01

Connecticut Community Care, Inc. (CCCI), a statewide, nonprofit case management agency, in collaboration with Connecticut National Bank (CNB), developed a unique model of delivering case management services to bank trust clients. No reports of such a collaborative model have been found in the published literature in the United States. The article presents a historical overview of this innovative initiative; the identification of the target population; the delivery of the assessment, coordination, and monitoring services; and the marketing techniques. Utilization statistics, a synopsis of the model outcomes as viewed by the trust officers, and suggestions for replication are also presented.

Development and validation of an abbreviated version of the Trust in Oncologist Scale-the Trust in Oncologist Scale-short form (TiOS-SF).

PubMed

Hillen, Marij A; Postma, Rosa-May; Verdam, Mathilde G E; Smets, Ellen M A

2017-03-01

The original 18-item, four-dimensional Trust in Oncologist Scale assesses cancer patients' trust in their oncologist. The current aim was to develop and validate a short form version of the scale to enable more efficient assessment of cancer patients' trust. Existing validation data of the full-length Trust in Oncologist Scale were used to create a short form of the Trust in Oncologist Scale. The resulting short form was validated in a new sample of cancer patients (n = 92). Socio-demographics, medical characteristics, trust in the oncologist, satisfaction with communication, trust in healthcare, willingness to recommend the oncologist to others and to contact the oncologist in case of questions were assessed. Internal consistency, reliability, convergent and structural validity were tested. The five-item Trust in Oncologist Scale Short Form was created by selecting the statistically best performing item from each dimension of the original scale, to ensure content validity. Mean trust in the oncologist was high in the validation sample (response rate 86%, M = 4.30, SD = 0.98). Exploratory factor analyses supported one-dimensionality of the short form. Internal consistency was high, and temporal stability was moderate. Initial convergent validity was suggested by moderate correlations between trust scores with associated constructs. The Trust in Oncologist Scale Short Form appears to efficiently, reliably and validly measures cancer patients' trust in their oncologist. It may be used in research and as a quality indicator in clinical practice. More thorough validation of the scale is recommended to confirm this initial evidence of its validity.

The Effect of Social Trust on Citizens’ Health Risk Perception in the Context of a Petrochemical Industrial Complex

PubMed Central

López-Navarro, Miguel Ángel; Llorens-Monzonís, Jaume; Tortosa-Edo, Vicente

2013-01-01

Perceived risk of environmental threats often translates into psychological stress with a wide range of effects on health and well-being. Petrochemical industrial complexes constitute one of the sites that can cause considerable pollution and health problems. The uncertainty around emissions results in a perception of risk for citizens residing in neighboring areas, which translates into anxiety and physiological stress. In this context, social trust is a key factor in managing the perceived risk. In the case of industrial risks, it is essential to distinguish between trust in the companies that make up the industry, and trust in public institutions. In the context of a petrochemical industrial complex located in the port of Castellón (Spain), this paper primarily discusses how trust—both in the companies located in the petrochemical complex and in the public institutions—affects citizens’ health risk perception. The research findings confirm that while the trust in companies negatively affects citizens’ health risk perception, trust in public institutions does not exert a direct and significant effect. Analysis also revealed that trust in public institutions and health risk perception are essentially linked indirectly (through trust in companies). PMID:23337129

The Devon NUT Campaign against Trust Schools

ERIC Educational Resources Information Center

Clinch, Dave

2008-01-01

When the Devon County Council announced that six secondary schools in the South Devon area were to become "Pathfinder Schools" for trust status, the Devon National Union of Teachers set about organising a campaign to defend the county's comprehensive schools. This campaign has proved successful in the case of Tavistock College, causing…

26 CFR 1.854-2 - Notice to shareholders.

Code of Federal Regulations, 2011 CFR

2011-04-01

...) INCOME TAXES (CONTINUED) Regulated Investment Companies and Real Estate Investment Trusts § 1.854-2... custodian of certain unit investment trusts. In any case where a notice is mailed pursuant to paragraph (a) of this section by a regulated investment company with respect to a taxable year of the regulated...

26 CFR 1.854-2 - Notice to shareholders.

Code of Federal Regulations, 2010 CFR

2010-04-01

...) INCOME TAXES Regulated Investment Companies and Real Estate Investment Trusts § 1.854-2 Notice to... unit investment trusts. In any case where a notice is mailed pursuant to paragraph (a) of this section by a regulated investment company with respect to a taxable year of the regulated investment company...

26 CFR 1.854-2 - Notice to shareholders.

Code of Federal Regulations, 2013 CFR

2013-04-01

...) INCOME TAXES (CONTINUED) Regulated Investment Companies and Real Estate Investment Trusts § 1.854-2... custodian of certain unit investment trusts. In any case where a notice is mailed pursuant to paragraph (a) of this section by a regulated investment company with respect to a taxable year of the regulated...

26 CFR 1.854-2 - Notice to shareholders.

Code of Federal Regulations, 2012 CFR

2012-04-01

...) INCOME TAXES (CONTINUED) Regulated Investment Companies and Real Estate Investment Trusts § 1.854-2... custodian of certain unit investment trusts. In any case where a notice is mailed pursuant to paragraph (a) of this section by a regulated investment company with respect to a taxable year of the regulated...

26 CFR 1.854-2 - Notice to shareholders.

Code of Federal Regulations, 2014 CFR

2014-04-01

...) INCOME TAXES (CONTINUED) Regulated Investment Companies and Real Estate Investment Trusts § 1.854-2... custodian of certain unit investment trusts. In any case where a notice is mailed pursuant to paragraph (a) of this section by a regulated investment company with respect to a taxable year of the regulated...

A Sacred Trust: The Safety of Our Children.

ERIC Educational Resources Information Center

Momentum, 2002

2002-01-01

Provides the text of the National Catholic Educational Association Statement on Child Abuse. This document, titled A Sacred Trust: The Safety of Our Children, was generated in response to the growing number of both confirmed and alleged cases of pedophilia and sexual abuse within the Catholic Church. (RC)

Shared Ageing Research Models (ShARM): a new facility to support ageing research.

PubMed

Duran, Adele L; Potter, Paul; Wells, Sara; Kirkwood, Tom; von Zglinicki, Thomas; McArdle, Anne; Scudamore, Cheryl; Meng, Qing-Jun; de Haan, Gerald; Corcoran, Anne; Bellantuono, Ilaria

2013-12-01

In order to manage the rise in life expectancy and the concomitant increased occurrence of age-related diseases, research into ageing has become a strategic priority. Mouse models are commonly utilised as they share high homology with humans and show many similar signs and diseases of ageing. However, the time and cost needed to rear aged cohorts can limit research opportunities. Sharing of resources can provide an ethically and economically superior framework to overcome some of these issues but requires dedicated infrastructure. Shared Ageing Research Models (ShARM) ( www.ShARMUK.org ) is a new, not-for-profit organisation funded by Wellcome Trust, open to all investigators. It collects, stores and distributes flash frozen tissues from aged murine models through its biorepository and provides a database of live ageing mouse colonies available in the UK and abroad. It also has an online environment (MICEspace) for collation and analysis of data from communal models and discussion boards on subjects such as the welfare of ageing animals and common endpoints for intervention studies. Since launching in July 2012, thanks to the generosity of researchers in UK and Europe, ShARM has collected more than 2,500 tissues and has in excess of 2,000 mice registered in live ageing colonies. By providing the appropriate support, ShARM has been able to bring together the knowledge and experience of investigators in the UK and Europe to maximise research outputs with little additional cost and minimising animal use in order to facilitate progress in ageing research.

Efficient analysis of mouse genome sequences reveal many nonsense variants

PubMed Central

Steeland, Sophie; Timmermans, Steven; Van Ryckeghem, Sara; Hulpiau, Paco; Saeys, Yvan; Van Montagu, Marc; Vandenbroucke, Roosmarijn E.; Libert, Claude

2016-01-01

Genetic polymorphisms in coding genes play an important role when using mouse inbred strains as research models. They have been shown to influence research results, explain phenotypical differences between inbred strains, and increase the amount of interesting gene variants present in the many available inbred lines. SPRET/Ei is an inbred strain derived from Mus spretus that has ∼1% sequence difference with the C57BL/6J reference genome. We obtained a listing of all SNPs and insertions/deletions (indels) present in SPRET/Ei from the Mouse Genomes Project (Wellcome Trust Sanger Institute) and processed these data to obtain an overview of all transcripts having nonsynonymous coding sequence variants. We identified 8,883 unique variants affecting 10,096 different transcripts from 6,328 protein-coding genes, which is about 28% of all coding genes. Because only a subset of these variants results in drastic changes in proteins, we focused on variations that are nonsense mutations that ultimately resulted in a gain of a stop codon. These genes were identified by in silico changing the C57BL/6J coding sequences to the SPRET/Ei sequences, converting them to amino acid (AA) sequences, and comparing the AA sequences. All variants and transcripts affected were also stored in a database, which can be browsed using a SPRET/Ei M. spretus variants web tool (www.spretus.org), including a manual. We validated the tool by demonstrating the loss of function of three proteins predicted to be severely truncated, namely Fas, IRAK2, and IFNγR1. PMID:27147605

Early History of the Concept of Chemical Transmission of the Nerve Impulse.

ERIC Educational Resources Information Center

Davenport, Horace W.

1991-01-01

Describes the research efforts of scientists involved in discovering chemical transmission of the nerve impulse. The work includes that of J.N. Langley, George Oliver, Edward A. Schafer, Reid Hunt, Henry Dale, Henry Wellcome, Otto Loewi, and others. The discovery and the importance of both acetylcholine and adrenaline are also discussed. (84…

Impact of star performance ratings in English acute hospital trusts.

PubMed

Mannion, Russell; Davies, Huw; Marshall, Martin

2005-01-01

To explore some of the impacts of star performance ratings in acute hospital trusts in England. A multiple case study design was used which incorporated purposeful sampling of 'low' and 'high' performing trusts using the star rating system. In each case study site, data collection comprised semi-structured interviews and documentary analysis. Between eight and 12 senior managers and senior clinicians were interviewed in each organisation. There was a general view that the star ratings as presently constituted did not represent a rounded or balanced scorecard of their own organisation's performance and a widespread belief that the information used to calculate the ratings was often incomplete and inaccurate. The star ratings were viewed by some managers as useful, in that they gave added weight to their trust's modernisation agenda. In addition to driving beneficial change, the ratings were also sometimes reported to have inadvertently induced a range of unintended and dysfunctional consequences, including tunnel vision and a distortion of clinical priorities, bullying and intimidation, erosion of public trust and reduced staff morale, and ghettoisation. Set in the context of an international body of research, this study highlights some important gaps in knowledge and failings in current policy and practice. In particular, the many dysfunctional consequences of publishing star ratings indicate a need for a re-examination of performance management policies.

A perspective on emerging law, consumer trust and social responsibility in China's food sector: the "bleaching" case study.

PubMed

Roberts, Michael T

2011-01-01

Trust underpins the Chinese social system, and yet it is lacking from a Chinese food system that is riddled with safety disasters and disgruntled consumers. Government and industry play a major role in rehabilitating consumer trust in China. To this end, food safety and quality laws have been constructed to foster this process; however, safety scandals continue even in the face of stricter regulations and increased enforcement. A potential toll to abate food-safety problems and to build trust is the implementation of Corporate Social Responsibility ("CSR"). Mandates by the government promote CSR in enterprise activity, including Article 3 of the 2009 China Food Safety Law. Officials have also recently touted the need for "moral education" of operators in the food industry. Regardless of government activity or whether CSR is employed by food enterprises, it is imperative that the food industry recognizes how critical it is to establish trust with Chinese consumers, who increasingly expect safe, quality food. The case study with pistachios highlights this evolving consumer expectation and the principles of social responsibility in the framework of the relationship between government and industry and consumers, while demonstrating the benefits of doing the right thing for food companies doing business in China.

GeoTrust Hub: A Platform For Sharing And Reproducing Geoscience Applications

NASA Astrophysics Data System (ADS)

Malik, T.; Tarboton, D. G.; Goodall, J. L.; Choi, E.; Bhatt, A.; Peckham, S. D.; Foster, I.; Ton That, D. H.; Essawy, B.; Yuan, Z.; Dash, P. K.; Fils, G.; Gan, T.; Fadugba, O. I.; Saxena, A.; Valentic, T. A.

2017-12-01

Recent requirements of scholarly communication emphasize the reproducibility of scientific claims. Text-based research papers are considered poor mediums to establish reproducibility. Papers must be accompanied by "research objects", aggregation of digital artifacts that together with the paper provide an authoritative record of a piece of research. We will present GeoTrust Hub (http://geotrusthub.org), a platform for creating, sharing, and reproducing reusable research objects. GeoTrust Hub provides tools for scientists to create `geounits'--reusable research objects. Geounits are self-contained, annotated, and versioned containers that describe and package computational experiments in an efficient and light-weight manner. Geounits can be shared on public repositories such as HydroShare and FigShare, and also using their respective APIs reproduced on provisioned clouds. The latter feature enables science applications to have a lifetime beyond sharing, wherein they can be independently verified and trust be established as they are repeatedly reused. Through research use cases from several geoscience laboratories across the United States, we will demonstrate how tools provided from GeoTrust Hub along with Hydroshare as its public repository for geounits is advancing the state of reproducible research in the geosciences. For each use case, we will address different computational reproducibility requirements. Our first use case will be an example of setup reproducibility which enables a scientist to set up and reproduce an output from a model with complex configuration and development environments. Our second use case will be an example of algorithm/data reproducibility, where in a shared data science model/dataset can be substituted with an alternate one to verify model output results, and finally an example of interactive reproducibility, in which an experiment is dependent on specific versions of data to produce the result. Toward this we will use software and data used in preparing data for the MODFLOW model in Hydrology, JupyterHub used in Hydroshare, PyLith used in Computational Infrastructure for Geodynamics, and GeoSpace Collaborative Observations and Assimilative Modeling used in space science. The GeoTrust Hub is funded through the National Science Foundation EarthCube program.

Teamwork and Electronic Health Record Implementation: A Case Study of Preserving Effective Communication and Mutual Trust in a Changing Environment.

PubMed

Gross, Anne H; Leib, Ryan K; Tonachel, Anne; Tonachel, Richard; Bowers, Danielle M; Burnard, Rachel A; Rhinehart, Catherine A; Valentim, Rahila; Bunnell, Craig A

2016-11-01

This article describes how trust among team members and in the technology supporting them was eroded during implementation of an electronic health record (EHR) in an adult outpatient oncology practice at a comprehensive cancer center. Delays in care of a 38-year-old woman with high-risk breast cancer occurred because of ineffective team communication and are illustrated in a case study. The case explores how the patient's trust and mutual trust between team members were disrupted because of inaccurate assumptions about the functionality of the EHR's communication tool, resultant miscommunications between team members and the patient, and the eventual recognition that care was not being effectively coordinated, as it had been previously. Despite a well-established, team-based culture and significant preparation for the EHR implementation, the challenges that occurred point to underlying human and system failures from which other organizations going through a similar process may learn. Through an analysis and evaluation of events that transpired before and during the EHR rollout, suggested interventions for preventing this experience are offered, which include: a thorough crosswalk between old and new communication mechanisms before implementation; understanding and mitigation of gaps in the communication tool's functionality; more robust training for staff, clinicians, and patients; greater consideration given to the pace of change expected of individuals; and development of models of collaboration between EHR users and vendors in developing products that support high-quality, team-based care in the oncology setting. These interventions are transferable to any organizational or system change that threatens mutual trust and effective communication.

School Principals in Southern Thailand: Exploring Trust with Community Leaders during Conflict

ERIC Educational Resources Information Center

Brooks, Melanie C.

2015-01-01

This article reports findings from a case study of school principals in Southern Thailand who work in areas targeted by Muslim separatist groups. Data were gathered and analyzed using a conceptual framework that conceived of trust as five interrelated constructs: benevolence, honesty, openness, reliability, and competence. This study builds on…

Productive School Governance: Success Case Studies from New Zealand

ERIC Educational Resources Information Center

Piggot-Irvine, Eileen

2008-01-01

The rhetoric abounds concerning the types of effective, high trust, interactions that should exist for a school governing body. In practise, however, such interactions are often difficult to define, establish, maintain, and sustain. The study reported on in this paper attempted to identify interactions linked to perceptions of high trust via a…

The Influence of Power on Trading Partner Trust in Electronic Commerce.

ERIC Educational Resources Information Center

Ratnasingam, Pauline

2000-01-01

Discussion of power in electronic commerce focuses on the impact of power in the adoption of electronic data interchange. Presents a case study of Ford Motor Company in Australia that shows negative (coercive) power resulted in uncertainty, whereas positive (persuasive) power resulted in open communications, thus building trading partner trust.…

77 FR 74231 - Hatteras Variable Trust, et al.; Notice of Application

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-13

... 6e-3(T)(b)(15) thereunder in cases where a life insurance company separate account supporting variable life insurance contracts (``VLI Accounts'') holds shares of an existing portfolio of the Trust (an... investors also hold shares of the Funds: (i) Any life insurance company separate account supporting variable...

17 CFR 240.10b5-2 - Duties of trust or confidence in misappropriation insider trading cases.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 17 Commodity and Securities Exchanges 3 2011-04-01 2011-04-01 false Duties of trust or confidence... Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) GENERAL RULES AND REGULATIONS, SECURITIES EXCHANGE ACT OF 1934 Rules and Regulations Under the Securities Exchange Act of 1934 Manipulative and Deceptive...

17 CFR 240.10b5-2 - Duties of trust or confidence in misappropriation insider trading cases.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Duties of trust or confidence... Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) GENERAL RULES AND REGULATIONS, SECURITIES EXCHANGE ACT OF 1934 Rules and Regulations Under the Securities Exchange Act of 1934 Manipulative and Deceptive...

17 CFR 240.10b5-2 - Duties of trust or confidence in misappropriation insider trading cases.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 17 Commodity and Securities Exchanges 3 2013-04-01 2013-04-01 false Duties of trust or confidence... Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) GENERAL RULES AND REGULATIONS, SECURITIES EXCHANGE ACT OF 1934 Rules and Regulations Under the Securities Exchange Act of 1934 Manipulative and Deceptive...

17 CFR 240.10b5-2 - Duties of trust or confidence in misappropriation insider trading cases.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 17 Commodity and Securities Exchanges 4 2014-04-01 2014-04-01 false Duties of trust or confidence... Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) GENERAL RULES AND REGULATIONS, SECURITIES EXCHANGE ACT OF 1934 Rules and Regulations Under the Securities Exchange Act of 1934 Manipulative and Deceptive...

17 CFR 240.10b5-2 - Duties of trust or confidence in misappropriation insider trading cases.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 17 Commodity and Securities Exchanges 3 2012-04-01 2012-04-01 false Duties of trust or confidence... Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) GENERAL RULES AND REGULATIONS, SECURITIES EXCHANGE ACT OF 1934 Rules and Regulations Under the Securities Exchange Act of 1934 Manipulative and Deceptive...

Keeping "Community" in a Community Land Trust

ERIC Educational Resources Information Center

Gray, Karen A.; Galande, Mugdha

2011-01-01

This instrumental case study examined the role of grassroots community organizing in a community land trust (CLT) in a southern U.S. city. Twenty-nine homeowners, renters, board members, community members, and current and former CLT employees were interviewed. In addition, two focus groups of 11 and six participants composed of CLT residents and…

Strategies for Relationship and Trust Building by Successful Superintendents: A Case Study

ERIC Educational Resources Information Center

Huang, Leann L.

2012-01-01

The purpose of this study was to identify strategies and behaviors that successful superintendents used to build strong relationships and trust with their boards within their entry period. The three research questions were developed to guide this study: 1. What strategies and behaviors were successful superintendents using to build strong…

Medical bribery and the ethics of trust: the Romanian case.

PubMed

Manea, Teodora

2015-02-01

Medical bribery seems to be a global problem from Eastern Europe and the Balkans to China, a diffuse phenomenon, starting with morally acceptable gratitude and ending with institutional bribery. I focus my attention on Romania and analyze similar cases in Eastern European and postcommunist countries. Medical bribery can be regarded as a particular form of human transaction, a kind of primitive contract that occurs when people do not trust institutions or other forms of social contract that are meant to guarantee their rights and protect their interests. Concluding with strategies to fight medical bribery, I will underline better public policies for financing health and social care, and an ethic of trust that may help to restore trustworthiness of institutions and to rebuild interpersonal trust. This should be complemented by an educational program dedicated to understanding the negative consequences and mechanisms of corruption and the importance of ethical behavior. © The Author 2014. Published by Oxford University Press, on behalf of the Journal of Medicine and Philosophy Inc. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Understanding Is Key: An Analysis of Factors Pertaining to Trust in a Real-World Automation System.

PubMed

Balfe, Nora; Sharples, Sarah; Wilson, John R

2018-06-01

This paper aims to explore the role of factors pertaining to trust in real-world automation systems through the application of observational methods in a case study from the railway sector. Trust in automation is widely acknowledged as an important mediator of automation use, but the majority of the research on automation trust is based on laboratory work. In contrast, this work explored trust in a real-world setting. Experienced rail operators in four signaling centers were observed for 90 min, and their activities were coded into five mutually exclusive categories. Their observed activities were analyzed in relation to their reported trust levels, collected via a questionnaire. The results showed clear differences in activity, even when circumstances on the workstations were very similar, and significant differences in some trust dimensions were found between groups exhibiting different levels of intervention and time not involved with signaling. Although the empirical, lab-based studies in the literature have consistently found that reliability and competence of the automation are the most important aspects of trust development, understanding of the automation emerged as the strongest dimension in this study. The implications are that development and maintenance of trust in real-world, safety-critical automation systems may be distinct from artificial laboratory automation. The findings have important implications for emerging automation concepts in diverse industries including highly automated vehicles and Internet of things.

Is Consent Based on Trust Morally Inferior to Consent Based on Information?

PubMed

Kongsholm, Nana Cecilie Halmsted; Kappel, Klemens

2017-07-01

Informed consent is considered by many to be a moral imperative in medical research. However, it is increasingly acknowledged that in many actual instances of consent to participation in medical research, participants do not employ the provided information in their decision to consent, but rather consent based on the trust they hold in the researcher or research enterprise. In this article we explore whether trust-based consent is morally inferior to information-based consent. We analyse the moral values essential to valid consent - autonomy, voluntariness, non-manipulation, and non-exploitation - and assess whether these values are less protected and promoted by consent based on trust than they are by consent based on information. We find that this is not the case, and thus conclude that trust-based consent if not morally inferior to information-based consent. © 2017 John Wiley & Sons Ltd.

Capturing Trust in Social Web Applications

NASA Astrophysics Data System (ADS)

O'Donovan, John

The Social Web constitutes a shift in information flow from the traditional Web. Previously, content was provided by the owners of a website, for consumption by the end-user. Nowadays, these websites are being replaced by Social Web applications which are frameworks for the publication of user-provided content. Traditionally, Web content could be `trusted' to some extent based on the site it originated from. Algorithms such as Google's PageRank were (and still are) used to compute the importance of a website, based on analysis of underlying link topology. In the Social Web, analysis of link topology merely tells us about the importance of the information framework which hosts the content. Consumers of information still need to know about the importance/reliability of the content they are reading, and therefore about the reliability of the producers of that content. Research into trust and reputation of the producers of information in the Social Web is still very much in its infancy. Every day, people are forced to make trusting decisions about strangers on the Web based on a very limited amount of information. For example, purchasing a product from an eBay seller with a `reputation' of 99%, downloading a file from a peer-to-peer application such as Bit-Torrent, or allowing Amazon.com tell you what products you will like. Even something as simple as reading comments on a Web-blog requires the consumer to make a trusting decision about the quality of that information. In all of these example cases, and indeed throughout the Social Web, there is a pressing demand for increased information upon which we can make trusting decisions. This chapter examines the diversity of sources from which trust information can be harnessed within Social Web applications and discusses a high level classification of those sources. Three different techniques for harnessing and using trust from a range of sources are presented. These techniques are deployed in two sample Social Web applications—a recommender system and an online auction. In all cases, it is shown that harnessing an increased amount of information upon which to make trust decisions greatly enhances the user experience with the Social Web application.

The dynamics of socio-connective trust within support networks accessed by informal caregivers.

PubMed

Ray, Robin A; Street, Annette F

2011-03-01

This article introduces the concept of socio-connective trust, the synapse between the social structures and processes that underpin relationships in supportive care networks. Data from an ethnographic case study of 18 informal caregivers providing in-home care for people with life-limiting illness were analysed drawing on theoretical concepts from the work of Giddens and writings on social capital, as well as the construction of trust in the caregiving literature. While conceptions of trust were found to contribute to understanding supportive care relationships, they did not account for the dynamic nature of the availability and use of support networks. Instead, informal caregivers undertook ongoing reflexive negotiation of relationship boundaries in response to their own conception of the current situation and their perception of trust in their relationships with the various members of the support network. The concept of socio-connective trust describes the movement and flow of the flexible bonds that influence relationships among care networks and determine the type and range of support accessed by informal caregivers. Understanding the complexities of socio-connective trust in caregiving relationships will assist health and social care workers to mobilize relevant resources to support informal caregivers.

Effect of a serogroup A meningococcal conjugate vaccine (PsA-TT) on serogroup A meningococcal meningitis and carriage in Chad: a community study [corrected].

PubMed

Daugla, D M; Gami, J P; Gamougam, K; Naibei, N; Mbainadji, L; Narbé, M; Toralta, J; Kodbesse, B; Ngadoua, C; Coldiron, M E; Fermon, F; Page, A-L; Djingarey, M H; Hugonnet, S; Harrison, O B; Rebbetts, L S; Tekletsion, Y; Watkins, E R; Hill, D; Caugant, D A; Chandramohan, D; Hassan-King, M; Manigart, O; Nascimento, M; Woukeu, A; Trotter, C; Stuart, J M; Maiden, McJ; Greenwood, B M

2014-01-04

A serogroup A meningococcal polysaccharide-tetanus toxoid conjugate vaccine (PsA-TT, MenAfriVac) was licensed in India in 2009, and pre-qualified by WHO in 2010, on the basis of its safety and immunogenicity. This vaccine is now being deployed across the African meningitis belt. We studied the effect of PsA-TT on meningococcal meningitis and carriage in Chad during a serogroup A meningococcal meningitis epidemic. We obtained data for the incidence of meningitis before and after vaccination from national records between January, 2009, and June, 2012. In 2012, surveillance was enhanced in regions where vaccination with PsA-TT had been undertaken in 2011, and in one district where a reactive vaccination campaign in response to an outbreak of meningitis was undertaken. Meningococcal carriage was studied in an age-stratified sample of residents aged 1-29 years of a rural area roughly 13-15 and 2-4 months before and 4-6 months after vaccination. Meningococci obtained from cerebrospinal fluid or oropharyngeal swabs were characterised by conventional microbiological and molecular methods. Roughly 1·8 million individuals aged 1-29 years received one dose of PsA-TT during a vaccination campaign in three regions of Chad in and around the capital N'Djamena during 10 days in December, 2011. The incidence of meningitis during the 2012 meningitis season in these three regions was 2·48 per 100,000 (57 cases in the 2·3 million population), whereas in regions without mass vaccination, incidence was 43·8 per 100,000 (3809 cases per 8·7 million population), a 94% difference in crude incidence (p<0·0001), and an incidence rate ratio of 0·096 (95% CI 0·046-0·198). Despite enhanced surveillance, no case of serogroup A meningococcal meningitis was reported in the three vaccinated regions. 32 serogroup A carriers were identified in 4278 age-stratified individuals (0·75%) living in a rural area near the capital 2-4 months before vaccination, whereas only one serogroup A meningococcus was isolated in 5001 people living in the same community 4-6 months after vaccination (adjusted odds ratio 0·019, 95% CI 0·002-0·138; p<0·0001). PSA-TT was highly effective at prevention of serogroup A invasive meningococcal disease and carriage in Chad. How long this protection will persist needs to be established. The Bill & Melinda Gates Foundation, the Wellcome Trust, and Médecins Sans Frontères. Copyright © 2014 Daugla et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd. All rights reserved.

Study of African Trypanosomiasis.

DTIC Science & Technology

1979-09-30

received foot and mouth vaccine (Wellcome-Kenya). In general, the experimental animals were kept out- side and supplemental food was provided during... vaccinant dans le plasma de souris experimentalement infectees par Trypanosoma gaibiense et par Trypanosoma concolense. Bullitin de la Society...Medicine and Hyciene, 35: 165-176. Jchnson, P., Neal, R.A. and Gall, D., 1963. Protective effect of killed trypanosome vaccines with incorporated

Synergy between medicinal chemistry and biological research.

PubMed

Moncada, Salvador; Coaker, Hannah

2014-09-01

Salvador Moncada studied medicine at the University of El Salvador (El Salvador) before coming to the UK in 1971 to work on a PhD with Professor John Vane at the Institute of Basic Medical Sciences, Royal College of Surgeons (UK). After a short period of research at the University of Honduras (Honduras), he joined the Wellcome Research Laboratories (UK) where he became Head of the Department of Prostaglandin Research and later, Director of Research. He returned to academic life in 1996 as founder and director of the Wolfson Institute for Biomedical Research at University College London (UK). Moncada played a role in the discovery of the mechanism of action of aspirin-like drugs and later led the teams which discover prostacyclin and identified nitric oxide as a biological mediator. In his role as a Director of Research of the Wellcome Laboratories, he oversaw the discovery and development of medicines for epilepsy, migraine, malaria and cancer. Currently, he is working on the regulation of cell proliferation as Director of the Institute of Cancer Sciences at the University of Manchester (UK). Moncada has won numerous awards from the international scientific community and in 2010, he received a knighthood from Her Majesty Queen Elizabeth II for his services to science.

Meticillin-resistant Staphylococcus aureus with a novel mecA homologue in human and bovine populations in the UK and Denmark: a descriptive study

PubMed Central

García-Álvarez, Laura; Holden, Matthew TG; Lindsay, Heather; Webb, Cerian R; Brown, Derek FJ; Curran, Martin D; Walpole, Enid; Brooks, Karen; Pickard, Derek J; Teale, Christopher; Parkhill, Julian; Bentley, Stephen D; Edwards, Giles F; Girvan, E Kirsty; Kearns, Angela M; Pichon, Bruno; Hill, Robert LR; Larsen, Anders Rhod; Skov, Robert L; Peacock, Sharon J; Maskell, Duncan J; Holmes, Mark A

2011-01-01

Summary Background Animals can act as a reservoir and source for the emergence of novel meticillin-resistant Staphylococcus aureus (MRSA) clones in human beings. Here, we report the discovery of a strain of S aureus (LGA251) isolated from bulk milk that was phenotypically resistant to meticillin but tested negative for the mecA gene and a preliminary investigation of the extent to which such strains are present in bovine and human populations. Methods Isolates of bovine MRSA were obtained from the Veterinary Laboratories Agency in the UK, and isolates of human MRSA were obtained from diagnostic or reference laboratories (two in the UK and one in Denmark). From these collections, we searched for mecA PCR-negative bovine and human S aureus isolates showing phenotypic meticillin resistance. We used whole-genome sequencing to establish the genetic basis for the observed antibiotic resistance. Findings A divergent mecA homologue (mecALGA251) was discovered in the LGA251 genome located in a novel staphylococcal cassette chromosome mec element, designated type-XI SCCmec. The mecALGA251 was 70% identical to S aureus mecA homologues and was initially detected in 15 S aureus isolates from dairy cattle in England. These isolates were from three different multilocus sequence type lineages (CC130, CC705, and ST425); spa type t843 (associated with CC130) was identified in 60% of bovine isolates. When human mecA-negative MRSA isolates were tested, the mecALGA251 homologue was identified in 12 of 16 isolates from Scotland, 15 of 26 from England, and 24 of 32 from Denmark. As in cows, t843 was the most common spa type detected in human beings. Interpretation Although routine culture and antimicrobial susceptibility testing will identify S aureus isolates with this novel mecA homologue as meticillin resistant, present confirmatory methods will not identify them as MRSA. New diagnostic guidelines for the detection of MRSA should consider the inclusion of tests for mecALGA251. Funding Department for Environment, Food and Rural Affairs, Higher Education Funding Council for England, Isaac Newton Trust (University of Cambridge), and the Wellcome Trust. PMID:21641281

Quality of life and trust among young people with narcolepsy and their families, after the Pandemrix® vaccination: protocol for a case-control study.

PubMed

Blomberg, Karin; Carlsson, Agneta Anderzén; Hagberg, Lars; Jonsson, Östen; Leissner, Lena; Eriksson, Mats H

2017-08-23

The extensive vaccination programme against swine flu resulted in an increased incidence of narcolepsy among children and adolescents. There is a need to explore if these young persons' experiences have affected their trust in healthcare, their willingness to participate in future prevention programmes, and their contacts with the healthcare system. The overall aim is to identify factors important for the life-situation of children and adolescents with narcolepsy and their families, and factors that correlate with trust in healthcare. Data will be collected via questionnaires from all available children with narcolepsy following the vaccination and their families, as well as a control group of children with diabetes and their families. Longitudinal descriptive interviews will also be conducted with a selection of 20-25 children and their families. Techniques from media research will be used for Internet-based data collection and analysis of information relating to narcolepsy from social media. This project will use the situation of young persons with narcolepsy after the swine flu vaccination as a case to build a model that can be used in situations where trust in healthcare is essential. This model will be based on findings from the included studies on how trust is influenced by support, quality of life, burden of disease, impact on family, and use of social media. The model developed in this project will be beneficial in future situations where trust in healthcare is essential, such as new pandemic outbreaks but also for "everyday" adherence to health advice.

26 CFR 1.665(b)-2 - Exclusions from accumulation distributions in the case of trusts (other than a foreign trust...

Code of Federal Regulations, 2012 CFR

2012-04-01

... under 21. If a distribution can be made from income accumulated either before or after a beneficiary.... (iii) The following examples illustrate the application of the foregoing rules of this subparagraph (in... distribution based upon an unforeseen or unforeseeable combination of circumstances requiring immediate help to...

26 CFR 1.665(b)-2 - Exclusions from accumulation distributions in the case of trusts (other than a foreign trust...

Code of Federal Regulations, 2010 CFR

2010-04-01

... under 21. If a distribution can be made from income accumulated either before or after a beneficiary.... (iii) The following examples illustrate the application of the foregoing rules of this subparagraph (in... distribution based upon an unforeseen or unforeseeable combination of circumstances requiring immediate help to...

26 CFR 1.665(b)-2 - Exclusions from accumulation distributions in the case of trusts (other than a foreign trust...

Code of Federal Regulations, 2013 CFR

2013-04-01

... under 21. If a distribution can be made from income accumulated either before or after a beneficiary.... (iii) The following examples illustrate the application of the foregoing rules of this subparagraph (in... distribution based upon an unforeseen or unforeseeable combination of circumstances requiring immediate help to...

26 CFR 1.665(b)-2 - Exclusions from accumulation distributions in the case of trusts (other than a foreign trust...

Code of Federal Regulations, 2014 CFR

2014-04-01

... under 21. If a distribution can be made from income accumulated either before or after a beneficiary.... (iii) The following examples illustrate the application of the foregoing rules of this subparagraph (in... distribution based upon an unforeseen or unforeseeable combination of circumstances requiring immediate help to...

26 CFR 1.665(b)-2 - Exclusions from accumulation distributions in the case of trusts (other than a foreign trust...

Code of Federal Regulations, 2011 CFR

2011-04-01

... under 21. If a distribution can be made from income accumulated either before or after a beneficiary.... (iii) The following examples illustrate the application of the foregoing rules of this subparagraph (in... distribution based upon an unforeseen or unforeseeable combination of circumstances requiring immediate help to...

Learning and Growing: Trust, Leadership, and Response to Crisis

ERIC Educational Resources Information Center

Sutherland, Ian E.

2017-01-01

Purpose: The purpose of this paper is to explore the nature of trust in a school community related to the leadership response to crisis. Design/Methodology/Approach: This study was a multiple-source qualitative study of a single case of a PreK-12 international school called The Learning School. Findings: The findings revealed the nature of how…

Trusted Operations on Sensor Data †

PubMed Central

Joosen, Wouter; Michiels, Sam; Hughes, Danny

2018-01-01

The widespread use of mobile devices has allowed the development of participatory sensing systems that capture various types of data using the existing or external sensors attached to mobile devices. Gathering data from such anonymous sources requires a mechanism to establish the integrity of sensor readings. In many cases, sensor data need to be preprocessed on the device itself before being uploaded to the target server while ensuring the chain of trust from capture to the delivery of the data. This can be achieved by a framework that provides a means to implement arbitrary operations to be performed on trusted sensor data, while guaranteeing the security and integrity of the data. This paper presents the design and implementation of a framework that allows the capture of trusted sensor data from both external and internal sensors on a mobile phone along with the development of trusted operations on sensor data while providing a mechanism for performing predefined operations on the data such that the chain of trust is maintained. The evaluation shows that the proposed system ensures the security and integrity of sensor data with minimal performance overhead. PMID:29702601

Further evaluation of the characteristics of Treponema pallidum-specific IgM antibody in syphilis serofast reaction patients.

PubMed

Lin, Li-Rong; Zheng, Wei-Hong; Tong, Man-Li; Fu, Zuo-Gen; Liu, Gui-Li; Fu, Jian-Guo; Zhang, Dai-Wei; Yang, Tian-Ci; Liu, Li-Li

2011-11-01

Syphilis serofast reaction (SSR) is common in clinical work. From June 2005 to May 2009, 1208 syphilis patients were chosen for research by the Xiamen Center of Clinical Laboratory in China. Serologic tests were performed with toluidine red unheated serum test (TRUST) and Treponema pallidum particle agglutination (TPPA). Then, T. pallidum-specific IgM antibody (TP-IgM) was detected with fluorescent treponemal antibody absorption (FTA-Abs) and TPPA. In this study, patients were divided into the following experimental groups according to the results of TRUST and TPPA: (1) the SSR group consisted of 411 cases with (+) TRUST and (+) TPPA, and without clinical manifestations after 1 year of recommended syphilis treatment; (2) the serum cure group, which was further subdivided into group A consisting of 251cases with (-) TRUST and (+) TPPA; (3) group B consisting of 546 cases with (-) TRUST and (-) TPPA; and (4) the blood donor control group which consisted of 100 cases. We demonstrated that a total of 136 cases (33.09%) of 411 SSR patients were TP-IgM positive by TPPA, and this percentage was markedly higher than that in serum cure group A (9.16%). FTA-Abs analyses revealed similar results. All samples in serum cure group B and the control group were TP-IgM negative, which is identical to our previous report. The present study also indicated that the TP-IgM positive rate was not significantly different among patients with different ages, genders, and clinical phases after 1 year of recommended therapy. From the total of 1208 syphilis patients, 289 were randomly selected for TP-DNA detection by fluorescence quantitative polymerase chain reaction, and the positive rate of TP-DNA was 32.53%, which was slightly higher than that of FTA-Abs TP-IgM, and no statistically significant difference by chi-square tests, indicating the TP-DNA result is preferably consistent with FTA-Abs and supporting our deduction that TP-IgM could be used as a serologic marker for the relapse and infection of syphilis. Copyright © 2011 Elsevier Inc. All rights reserved.

Co-operation and conflict under hard and soft contracting regimes: case studies from England and Wales.

PubMed

Hughes, David; Allen, Pauline; Doheny, Shane; Petsoulas, Christina; Vincent-Jones, Peter

2013-01-01

This paper examines NHS secondary care contracting in England and Wales in a period which saw increasing policy divergence between the two systems. At face value, England was making greater use of market levers and utilising harder-edged service contracts incorporating financial penalties and incentives, while Wales was retreating from the 1990 s internal market and emphasising cooperation and flexibility in the contracting process. But there were also cross-border spill-overs involving common contracting technologies and management cultures that meant that differences in on-the-ground contracting practices might be smaller than headline policy differences suggested. The nature of real-world contracting behaviour was investigated by undertaking two qualitative case studies in England and two in Wales, each based on a local purchaser/provider network. The case studies involved ethnographic observations and interviews with staff in primary care trusts (PCTs) or local health boards (LHBs), NHS or Foundation trusts, and the overseeing Strategic Health Authority or NHS Wales regional office, as well as scrutiny of relevant documents. Wider policy differences between the two NHS systems were reflected in differing contracting frameworks, involving regional commissioning in Wales and commissioning by either a PCT, or co-operating pair of PCTs in our English case studies, and also in different oversight arrangements by higher tiers of the service. However, long-term relationships and trust between purchasers and providers had an important role in both systems when the financial viability of organisations was at risk. In England, the study found examples where both PCTs and trusts relaxed contractual requirements to assist partners faced with deficits. In Wales, news of plans to end the purchaser/provider split meant a return to less precisely-specified block contracts and a renewed concern to build cooperation between LHB and trust staff. The interdependency of local purchasers and providers fostered long-term relationships and co-operation that shaped contracting behaviour, just as much as the design of contracts and the presence or absence of contractual penalties and incentives. Although conflict and tensions between contracting partners sometimes surfaced in both the English and Welsh case studies, cooperative behaviour became crucial in times of trouble.

Trust During the Early Stages of the 2009 H1N1 Pandemic

PubMed Central

FREIMUTH, VICKI S.; MUSA, DON; HILYARD, KAREN; QUINN, SANDRA CROUSE; KIM, KEVIN

2013-01-01

Distrust of the government often stands in the way of cooperation with public health recommendations in a crisis. The purpose of this paper is to describe the public’s trust in government recommendations during the early stages of the H1N1 pandemic and identify factors that might account for these trust levels. We surveyed 1543 respondents about their experiences and attitudes related to H1N1 influenza between June 3, 2009 and July 6, 2009, during the first wave of the pandemic using the Knowledge Networks (KN) online panel. This panel is representative of the US population, and uses a combination of random-digit dial and address-based probability sampling frames covering 99% of the US household population to recruit participants. To ensure participation of low-income individuals and those without Internet access, KN provides hardware and access to the Internet if needed. Measures included standard demographics, a trust scale, trust ratings for individual spokespersons, involvement with H1N1, experience with H1N1, and past discrimination in health care. We found that trust of government was low (2.3 out of 4) and varied across demographic groups. Blacks and Hispanics reported higher trust in government than did Whites. Of the spokespersons included, personal health professionals received the highest trust ratings and religious leaders the lowest. Attitudinal and experience variables predicted trust better than demographic characteristics. Closely following the news about the flu virus, having some self-reported knowledge about H1N1, self-reporting of local cases and previously experiencing discrimination were the significant attitudinal and experience predictors of trust. Using a second longitudinal survey, trust in the early stages of the pandemic did predict vaccine acceptance later but only for white, non-Hispanic individuals. PMID:24117390

Trust-based environmental regulation.

PubMed

Lange, Bettina; Gouldson, Andy

2010-10-15

Within this paper, we examine the contribution that trust-based relationships can make to achieving better-and particularly more effective, efficient and equitable-environmental regulation. While levels of trust in regulators, regulatory processes and outcomes are often discussed, the influence of trust on different actors and on different measures of regulatory performance is poorly understood. Within this paper, we define trust-based environmental regulation as a specific regulatory style that involves openness and cooperation in interaction between regulated, regulators and third-party stakeholders in order to achieve environmental protection objectives. We then discuss the pros and cons of trust relationships between regulators, regulated businesses and citizens for achieving behavioural change towards greater environmental protection. To illustrate the significance of these issues, we then examine three forms of contractual regulatory style where trust relationships are critically important: responsive regulation, self-regulation and environmental agreements. Based on this analysis, we highlight the importance of trust-based relationships, and we argue that one of the greatest contributions of trust-based environmental regulation is to challenge how we think about regulation. Trust is often understood as enabling existing regulatory relationships or in the case of self-regulation as a complement to regulation. However, we argue that the real potential of trust is to open up new ways for participants in regulatory regimes to engage in collective action, to go beyond a perception of regulation as driven by the competing interests of individual actors, and thus, to open up new channels of influence for behavioural change towards greater environmental protection. Our analysis therefore has great relevance for future research and for on-going debates on the future of regulation. Copyright © 2010. Published by Elsevier B.V.

Performance of serological tests for syphilis in sexually transmitted diseases clinics in Guangxi Autonomous Region, China: implications for syphilis surveillance and control.

PubMed

Yin, Yue-Ping; Wei, Wan-Hui; Wang, Hong-Chun; Zhu, Bang-Yong; Yu, Yan-Hua; Chen, Xiang-Sheng; Peeling, Rosanna W; Cohen, Myron S

2009-03-01

China is experiencing a growing syphilis epidemic. Individuals are currently screened and cases are confirmed using traditional serological testing methods. A total of 11 558 serum specimens from patients at 14 sexually transmitted diseases (STD) clinics at provincial, prefecture and county levels in Guangxi Autonomous Region were tested at local clinics using the toluidine red unheated serum test (TRUST) and the SD Bioline Syphilis 3.0 Treponema Pallidum (SD-TP) test and then transported to the National STD Reference Laboratory for TRUST and confirmatory Treponema pallidum particle assay (TPPA) testing. In local clinics, 13.2% of specimens were TRUST positive and 12.8% were TRUST and SD-TP positive. At the Reference Laboratory, 15.4% of specimens were TRUST positive and 11.8% were TRUST and TPPA positive. Local clinics showed a significantly higher prevalence of active syphilis compared with results from the Reference Laboratory (12.8 v. 11.8%, chi(2) = 4.59, P = 0.03). The local TRUST tests had consistent results with Reference Laboratory tests qualitatively among 96.2% of the specimens and quantitatively among 95.5% of the specimens. The algorithm of TRUST screening and then SD-TP confirmation among positive TRUST specimens at local STD clinics had 96.6% sensitivity and 99.3% specificity in diagnosing active syphilis compared with the 'gold standard' based on TRUST and TPPA positivity at the Reference Laboratory (positive predictive value 95.1% and negative predictive value 99.5%). The TRUST screening and SD-TP confirmation in combination can be used at local STD clinics for the efficient diagnosis of serologically active syphilis. However, continuing capacity building and quality assurance remain critical in ensuring the quality of syphilis diagnosis at local clinics.

Trust makers, breakers and brokers: building trust in the Australian food system

PubMed Central

2013-01-01

Background The importance of consumer trust in the food supply has previously been identified, and dimensions of consumer trust in food—who they trust and the type of trust that they exhibit—has been explored. However, there is a lack of research about the mechanisms through which consumer trust in the food supply is developed, maintained, broken and repaired. This study seeks to address this gap by exploring if, and how, consumer trust in the food supply is considered by the media, food industry and governments when responding to food scares. The aim of the research is to develop models of trust building that can be implemented following food scares. Methods Semi-structured interviews will be undertaken with media, public relations officials and policy makers in Australia, New Zealand and the United Kingdom. Participants will be recruited through purposive sampling and will be asked to discuss a hypothetical case study outlining a food incident, and any experiences of specific food scares. Models of trust development, maintenance and repair will be developed from interview data. Comment on these models will be sought from experts in food-related organizations through a Delphi study, where participants will be asked to consider the usefulness of the models. Participants’ comments will be used to revise the models until consensus is reached on the suitability and usability of the models. Discussion This study will contribute to the literature about systems-based trust, and explore trust as a social and regulatory process. The protocol and results will be of interest and use to the food industry, food regulators, consumer advocate groups, media seeking to report food-related issues and policy makers concerned with public health and consumer health and well-being. This research represents an important contribution to the translation of the theoretical conceptualizations of trust into practical use in the context of food. PMID:23496819

Exploring pathways for building trust in vaccination and strengthening health system resilience.

PubMed

Ozawa, Sachiko; Paina, Ligia; Qiu, Mary

2016-11-15

Trust is critical to generate and maintain demand for vaccines in low and middle income countries. However, there is little documentation on how health system insufficiencies affect trust in vaccination and the process of re-building trust once it has been compromised. We reflect on how disruptions to immunizations systems can affect trust in vaccination and can compromise vaccine utilization. We then explore key pathways for overcoming system vulnerabilities in order to restore trust, to strengthen the resilience of health systems and communities, and to promote vaccine utilization. Utilizing secondary data and a review of the literature, we developed a causal loop diagram (CLD) to map the determinants of building trust in immunizations. Using the CLD, we devised three scenarios to illustrate common vulnerabilities that compromise trust and pathways to strengthen trust and utilization of vaccines, specifically looking at weak health systems, harmful communication channels, and role of social capital. Spill-over effects, interactions and other dynamics in the CLD were then examined to assess leverage points to counter these vulnerabilities. Trust in vaccination arises from the interactions among experiences with the health system, the various forms of communication and social capital - both external and internal to communities. When experiencing system-wide shocks such as the case in Ebola-affected countries, distrust is reinforced by feedback between the health and immunization systems where distrust often lingers even after systems are restored and spills over beyond vaccination in the broader health system. Vaccine myths or anti-vaccine movements reinforce distrust. Social capital - the collective value of social networks of community members - plays a central role in increasing levels of trust. Trust is important, yet underexplored, in the context of vaccine utilization. Using a CLD to illustrate various scenarios helped to explore how common health and vaccine vulnerabilities can reinforce and spill over distrust through vicious, reinforcing feedback. Restoring trust requires a careful balance between eliminating vulnerabilities and strengthening social capital and interactions among communication channels.

Trust makers, breakers and brokers: building trust in the Australian food system.

PubMed

Wilson, Annabelle; Coveney, John; Henderson, Julie; Meyer, Samantha; Calnan, Michael; Caraher, Martin; Webb, Trevor; Elliott, Anthony; Ward, Paul

2013-03-15

The importance of consumer trust in the food supply has previously been identified, and dimensions of consumer trust in food-who they trust and the type of trust that they exhibit-has been explored. However, there is a lack of research about the mechanisms through which consumer trust in the food supply is developed, maintained, broken and repaired. This study seeks to address this gap by exploring if, and how, consumer trust in the food supply is considered by the media, food industry and governments when responding to food scares. The aim of the research is to develop models of trust building that can be implemented following food scares. Semi-structured interviews will be undertaken with media, public relations officials and policy makers in Australia, New Zealand and the United Kingdom. Participants will be recruited through purposive sampling and will be asked to discuss a hypothetical case study outlining a food incident, and any experiences of specific food scares. Models of trust development, maintenance and repair will be developed from interview data. Comment on these models will be sought from experts in food-related organizations through a Delphi study, where participants will be asked to consider the usefulness of the models. Participants' comments will be used to revise the models until consensus is reached on the suitability and usability of the models. This study will contribute to the literature about systems-based trust, and explore trust as a social and regulatory process. The protocol and results will be of interest and use to the food industry, food regulators, consumer advocate groups, media seeking to report food-related issues and policy makers concerned with public health and consumer health and well-being. This research represents an important contribution to the translation of the theoretical conceptualizations of trust into practical use in the context of food.

Trust and terrorism: citizen responses to anti-terrorism performance history.

PubMed

Johnson, Branden B

2010-09-01

The "intuitive detection theorists" model of trust posits greater trust for correctly distinguishing danger from safety and an activist response under uncertainty about danger. An American sample evaluated U.S. Department of Homeland Security (DHS) performance after two possible terrorism events in which DHS has the same activist or nonactivist response bias. Outcomes were two successes (bombing prevented or lack of threat accurately foretold), two failures (bombing or DHS action against high school prank leads to student deaths), or a mix. Hindsight empathy (a belief one would have made the same decision) differed across treatments but trust less so; contrary to a similar one-event experiment in Germany, an active but incorrect response did not raise trust relative to passive incorrect action. Political conservatives were much more trusting and empathetic than liberals, and all ideological groups (including moderates) exhibited little internal variation reflecting experimental conditions. Consistently accurate outcomes rated significantly higher in empathy than either inconsistent results or consistent inaccuracy (the lowest rated); trust exhibited no significant differences. Results in this study show actual (experimentally manipulated) performance being trumped by the interpretive screen of political ideology, but this seemed less the case in the earlier German study, despite its finding of a strong moderating effect of right-wing authoritarianism. Trust scholars need to attend more to effects of performance history (i.e., a sequence of events) and their limiting factors. More systematic testing of effects of ideology and performance history would enhance future research on trust. © 2010 Society for Risk Analysis.

Understanding Is Key: An Analysis of Factors Pertaining to Trust in a Real-World Automation System

PubMed Central

Balfe, Nora; Sharples, Sarah; Wilson, John R.

2018-01-01

Objective: This paper aims to explore the role of factors pertaining to trust in real-world automation systems through the application of observational methods in a case study from the railway sector. Background: Trust in automation is widely acknowledged as an important mediator of automation use, but the majority of the research on automation trust is based on laboratory work. In contrast, this work explored trust in a real-world setting. Method: Experienced rail operators in four signaling centers were observed for 90 min, and their activities were coded into five mutually exclusive categories. Their observed activities were analyzed in relation to their reported trust levels, collected via a questionnaire. Results: The results showed clear differences in activity, even when circumstances on the workstations were very similar, and significant differences in some trust dimensions were found between groups exhibiting different levels of intervention and time not involved with signaling. Conclusion: Although the empirical, lab-based studies in the literature have consistently found that reliability and competence of the automation are the most important aspects of trust development, understanding of the automation emerged as the strongest dimension in this study. The implications are that development and maintenance of trust in real-world, safety-critical automation systems may be distinct from artificial laboratory automation. Application: The findings have important implications for emerging automation concepts in diverse industries including highly automated vehicles and Internet of things. PMID:29613815

The company you keep: spreading effects of financial fraud on investor trust.

PubMed

Bernet, Patrick Michael; Getzen, Thomas E

2007-01-01

Investor trust is valuable to health care organizations. Without it, they may face higher capital costs. This study explores recent cases of fraud and the appearance of impropriety by health care organizations, focusing on the manners in which trust was violated, the systems that allowed those violations, and the effects on financial markets. Increases in the incidence and scale of such transgressions may be harbingers of worse times ahead. This article examines how recent events have affected the cost of capital, and what health care organizations can do to avoid being judged by the company they keep.

Improving Access to, Use of, and Outcomes from Public Health Programs: The Importance of Building and Maintaining Trust with Patients/Clients.

PubMed

Ward, Paul Russell

2017-01-01

The central argument in this paper is that "public trust" is critical for developing and maintaining the health and wellbeing of individuals, communities, and societies. I argue that public health practitioners and policy makers need to take "public trust" seriously if they intend to improve both the public's health and the engagement between members of the public and public health systems. Public health practitioners implement a range of services and interventions aimed at improving health but implicit a requirement for individuals to trust the practitioners and the services/interventions, before they engage with them. I then go on to provide an overview of the theory of trust within sociology and show why it is important to understand this theory in order to promote trust in public health services. I then draw on literature in three classic areas of public health-hospitals, cancer screening, and childhood immunization-to show why trust is vital in terms of understanding and potentially improving uptake of services. The case studies in this paper reveal that public health practitioners need to understand the centrality of building and maintaining trusting relationships with patients/clients because people who distrust public health services are less likely to use them, less likely to follow advice or recommendations, and more likely to have poorer health outcomes.

25 CFR 140.5 - Bureau of Indian Affairs employees not to contract or trade with Indians except in certain cases.

Code of Federal Regulations, 2010 CFR

2010-04-01

... trust by the United States for Indians, or on land subject to a restriction against alienation imposed... property, not held in trust by the United States or subject to a restriction against alienation imposed by... restriction against alienation imposed by the United States is otherwise authorized by law. (2) Trading by...

Multiscale Airflow Model and Aerosol Deposition in Healthy and Emphysematous Rat Lungs

NASA Astrophysics Data System (ADS)

Oakes, Jessica; Marsden, Alison; Grandmont, Celine; Darquenne, Chantal; Vignon-Clementel, Irene

2012-11-01

The fate of aerosol particles in healthy and emphysematic lungs is needed to determine the toxic or therapeutic effects of inhalable particles. In this study we used a multiscale numerical model that couples a 0D resistance and capacitance model to 3D airways generated from MR images. Airflow simulations were performed using an in-house 3D finite element solver (SimVascular, simtk.org). Seven simulations were performed; 1 healthy, 1 uniform emphysema and 5 different cases of heterogeneous emphysema. In the heterogeneous emphysema cases the disease was confined to a single lobe. As a post processing step, 1 micron diameter particles were tracked in the flow field using Lagrangian particle tracking. The simulation results showed that the inhaled flow distribution was equal for the healthy and uniform emphysema cases. However, in the heterogeneous emphysema cases the delivery of inhaled air was larger in the diseased lobe. Additionally, there was an increase in delivery of aerosol particles to the diseased lobe. This suggests that as the therapeutic particles would reach the diseased areas of the lung, while toxic particles would increasingly harm the lung. The 3D-0D model described here is the first of its kind to be used to study healthy and emphysematic lungs. NSF Graduate Fellowship (Oakes), Burroughs Wellcome Fund (Marsden, Oakes) 1R21HL087805-02 from NHLBI at NIH, INRIA Team Grant.

Overview | Office of Cancer Genomics

Cancer.gov

The Human Cancer Model Initiative (HCMI) is an international consortium that is generating novel human tumor-derived culture models with associated genomic and clinical data. The HCMI consortium includes the US-National Cancer Institute, part of the National Institutes of Health, Cancer Research UK, foundation Hubrecht Organoid Technology, and Wellcome Sanger Institute. The goal of HCMI is to create up to one thousand cancer models from patient tumors.

Partnering Research Involving Mentoring and Education (PRIME) in Prostate Cancer

DTIC Science & Technology

2008-08-01

Genital Herpes , Research Triangle Park, NC. 8. Price, M.M. (1995, April, Miami; 1995, March, Washington, DC; & 1995, February, Philadelphia...Workshop during the Oncology Nurses Symposium on Cancer in African Americans, Atlanta. 7. Price, M.M. (1994, October 28-30). “Living with Genital ... Herpes : Counseling the Patient”, Paper presented and Seminar Moderator for the Burroughs Wellcome Pharmaceutical Corporation Nursing Conference on

Natural hazard events and social capital: the social impact of natural disasters.

PubMed

Albrecht, Frederike

2018-04-01

This study investigates if and to what extent natural disasters affect social capital. Twelve different events in Europe are examined in a quantitative analysis, using data derived from the European Social Survey and the EM-DAT International Disaster Database. The study uses social trust as an indicator of social capital and offers evidence that a change in social trust is a possible occurrence during or after a disaster, but that it is not an inevitable consequence of it. The results reveal that social trust decreases after a disaster with a death toll of at least nine. Changes in social capital, therefore, are found to be more probable as the severity of the event increases. National, rather than regional, disasters lead more frequently to significant shifts in social trust. This evaluation of 12 separate cases pinpoints several disasters that have had an effect on social trust, but it does not identify any general patterns, underlining the significance of contextual dependency. © 2018 The Author(s). Disasters © Overseas Development Institute, 2018.

Hospital CEOs Need Health IT Knowledge and Trust in CIOs: Insights from a Qualitative Study.

PubMed

Thye, Johannes; Hübner, Ursula; Weiß, Jan-Patrick; Teuteberg, Frank; Hüsers, Jens; Liebe, Jan-David; Babitsch, Birgit

2018-01-01

IT is getting an increasing importance in hospitals. In this context, major IT decisions are often made by CEOs who are not necessarily IT experts. Therefore, this study aimed at a) exploring different types of IT decision makers at CEO level, b) identifying hypotheses if trust exists between these different types of CEOs and their CIOs and c) building hypotheses on potential consequences regarding risk taking and innovation. To this end, 14 qualitative interviews with German hospital CEOs were conducted to explore the research questions. The study revealed three major types: IT savvy CEOs, IT enthusiastic CEOs and IT indifferent CEOs. Depending on these types, their relationship with the CIO varied in terms of trust and common language. In case of IT indifferent CEOs, a potential vicious circle of lack of IT knowledge, missing trust, low willingness to take risks and low innovation power could be identified. In order to break of this circle, CEOs seem to need more IT knowledge and/or greater trust in their CIO.

“The One Who Chases You Away Does Not Tell You Go”: Silent Refusals and Complex Power Relations in Research Consent Processes in Coastal Kenya

PubMed Central

Kamuya, Dorcas M.; Theobald, Sally J.; Marsh, Vicki; Parker, Michael; Geissler, Wenzel P.; Molyneux, Sassy C.

2015-01-01

Consent processes have attracted significant research attention over the last decade, including in the global south. Although relevant studies suggest consent is a complex negotiated process involving multiple actors, most guidelines assume consent is a one-off encounter with a clear ‘yes’ or ‘no’ decision. In this paper we explore the concept of ‘silent refusals’, a situation where it is not clear whether potential participants want to join studies or those in studies want to withdraw from research, as they were not actively saying no. We draw on participant observation, in-depth interviews and group discussions conducted with a range of stakeholders in two large community based studies conducted by the KEMRI Wellcome Trust programme in coastal Kenya. We identified three broad inter-related rationales for silent refusals: 1) a strategy to avoid conflicts and safeguard relations within households, - for young women in particular—to appear to conform to the wishes of elders; 2) an approach to maintain friendly, appreciative and reciprocal relationships with fieldworkers, and the broader research programme; and 3) an effort to retain study benefits, either for individuals, whole households or wider communities. That refusals and underlying rationales were silent posed multiple dilemmas for fieldworkers, who are increasingly recognised to play a key interface role between researchers and communities in many settings. Silent refusals reflect and reinforce complex power relations embedded in decisions about research participation, with important implications for consent processes and broader research ethics practice. Fieldworkers need support to reflect upon and respond to the ethically charged environment they work in. PMID:25978465

Do gifts increase consent to home-based HIV testing? A difference-in-differences study in rural KwaZulu-Natal, South Africa

PubMed Central

McGovern, Mark E; Herbst, Kobus; Tanser, Frank; Mutevedzi, Tinofa; Canning, David; Gareta, Dickman; Pillay, Deenan; Bärnighausen, Till

2016-01-01

Abstract Background: Despite the importance of HIV testing for controlling the HIV epidemic, testing rates remain low. Efforts to scale up testing coverage and frequency in hard-to-reach and at-risk populations commonly focus on home-based HIV testing. This study evaluates the effect of a gift (a US$5 food voucher for families) on consent rates for home-based HIV testing. Methods: We use data on 18 478 individuals (6 418 men and 12 060 women) who were successfully contacted to participate in the 2009 and 2010 population-based HIV surveillance carried out by the Wellcome Trust's Africa Health Research Institute in rural KwaZulu-Natal, South Africa. Of 18 478 potential participants contacted in both years, 35% (6 518) consented to test in 2009, and 41% (7 533) consented to test in 2010. Our quasi-experimental difference-in-differences approach controls for unobserved confounding in estimating the causal effect of the intervention on HIV-testing consent rates. Results: Allocation of the gift to a family in 2010 increased the probability of family members consenting to test in the same year by 25 percentage points [95% confidence interval (CI) 21–30 percentage points; P < 0.001]. The intervention effect persisted, slightly attenuated, in the year following the intervention (2011). Conclusions: In HIV hyperendemic settings, a gift can be highly effective at increasing consent rates for home-based HIV testing. Given the importance of HIV testing for treatment uptake and individual health, as well as for HIV treatment-as-prevention strategies and for monitoring the population impact of the HIV response, gifts should be considered as a supportive intervention for HIV-testing initiatives where consent rates have been low. PMID:27940483

The extant World War 1 dysentery bacillus NCTC1: a genomic analysis.

PubMed

Baker, Kate S; Mather, Alison E; McGregor, Hannah; Coupland, Paul; Langridge, Gemma C; Day, Martin; Deheer-Graham, Ana; Parkhill, Julian; Russell, Julie E; Thomson, Nicholas R

2014-11-08

Shigellosis (previously bacillary dysentery) was the primary diarrhoeal disease of World War 1, but outbreaks still occur in military operations, and shigellosis causes hundreds of thousands of deaths per year in developing nations. We aimed to generate a high-quality reference genome of the historical Shigella flexneri isolate NCTC1 and to examine the isolate for resistance to antimicrobials. In this genomic analysis, we sequenced the oldest extant Shigella flexneri serotype 2a isolate using single-molecule real-time (SMRT) sequencing technology. Isolated from a soldier with dysentery from the British forces fighting on the Western Front in World War 1, this bacterium, NCTC1, was the first isolate accessioned into the National Collection of Type Cultures. We created a reference sequence for NCTC1, investigated the isolate for antimicrobial resistance, and undertook comparative genetics with S flexneri reference strains isolated during the 100 years since World War 1. We discovered that NCTC1 belonged to a 2a lineage of S flexneri, with which it shares common characteristics and a large core genome. NCTC1 was resistant to penicillin and erythromycin, and contained a complement of chromosomal antimicrobial resistance genes similar to that of more recent isolates. Genomic islands gained in the S flexneri 2a lineage over time were predominately associated with additional antimicrobial resistances, virulence, and serotype conversion. This S flexneri 2a lineage is a well adapted pathogen that has continued to respond to selective pressures. We have created a valuable historical benchmark for shigellae in the form of a high-quality reference sequence for a publicly available isolate. The Wellcome Trust. Copyright © 2014 Baker et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd. All rights reserved.

Sandscape - engaging people in Met Office science through sand sculpture

NASA Astrophysics Data System (ADS)

Liggins, Felicity; Dowell, Ellen; Wardley, Jamie; Jamieson, Claire

2017-04-01

In 2015, the Met Office's award-winning outreach programme, designed to inspire the next generation of scientists and engineers, delivered one of its most ambitious and creative activities to date. It explored how scientists and artists can come together to create an engaging experience for young people and families. This activity was called Sandscape. Sandscape is an interactive sand sculpture workshop exploring how weather and climate affect our health. Budding sand sculptors are shown how to fashion elaborate structures from sand and water - creating a landscape with bridges, skyscrapers, forests and factories. As they work, participants are encouraged by the scientists delivering the activity to reflect on what makes a healthy city, considering how the natural and built environments influence air quality and circulation and how this impacts our health. Topics discussed include urban heat islands, air pollution and dispersion modelling, pollen forecasting and predicting the wind-borne spread of animal diseases. Each hour long workshop culminates in a dramatic demonstration that uses dry ice to represent clean air circulating from mountains, along rivers and into cities. Here we present an overview of Sandscape, identify the strengths and challenges of such a collaborative, innovative and playful approach to public engagement and share the results of our evaluation. Sandscape was originally supported by the Met Office and the Wellcome Trust, and produced by Einstein's Garden in collaboration with the Met Office, scientists from the University of Exeter and sand sculptors from Sand in Your Eye. It was first presented in Einstein's Garden at Green Man festival 2015, an independent music and arts festival held annually in Wales, and has since been invited to run at the 2015 Bournemouth Arts By the Sea Festival and Teignmouth's TRAIL Sculpture Festival in the summer of 2016.

Does the world need a global project on artificial photosynthesis?

PubMed Central

Faunce, Thomas

2015-01-01

This paper introduces a theme issue of Interface Focus derived from papers presented at the Royal Society supported meeting ‘Do we need a global project on artificial photosynthesis?’ held at Chicheley Hall in July 2014. At that meeting, leaders of national solar fuels and chemicals projects and research presented ‘state of the art’ on artificial photosynthesis (AP) in the context of the policy challenges for globalizing a practical technology to address climate change and energy and food security concerns. The discussions included contributions from many experts with legal and policy skills and uniquely focused on producing principles for prioritizing and specializing work while enhancing the funding and attendant public policy profile. To this end, representatives of major public, philanthropic and private potential stakeholders in such a project (such as the Wellcome Trust, the Moore Foundation, Shell, the Leighty Foundation, the EPSRC and Deutsche Alternative Asset Management) were invited to provide feedback at various points in the meeting. For this Interface Focus issue, speakers at the Chicheley Hall meeting were required to present a snapshot of their cutting edge research related to AP and then draw upon the Chicheley Hall discussions to innovatively analyse how their research could best be advanced by a global AP project. Such multidisciplinary policy analysis was not a skill many of these researchers were experienced or trained in. Nonetheless their efforts here represent one of the first published collections to attempt such a significant task. This introduction contains a brief summary of those papers, focusing particularly on their policy aspects. It then summarizes the core discussions that took place at the Chicheley Hall meeting and sets out some of the central ethical principles that were considered during those discussions.

Reliability and validity of the combined heart rate and movement sensor Actiheart.

PubMed

Brage, S; Brage, N; Franks, P W; Ekelund, U; Wareham, N J

2005-04-01

Accurate quantification of physical activity energy expenditure is a key part of the effort to understand disorders of energy metabolism. The Actiheart, a combined heart rate (HR) and movement sensor, is designed to assess physical activity in populations. To examine aspects of Actiheart reliability and validity in mechanical settings and during walking and running. In eight Actiheart units, technical reliability (coefficients of variation, CV) and validity for movement were assessed with sinusoid accelerations (0.1-20 m/s(2)) and for HR by simulated R-wave impulses (25-250 bpm). Agreement between Actiheart and ECG was determined during rest and treadmill locomotion (3.2-12.1 km/h). Walking and running intensity (in J/min/kg) was assessed with indirect calorimetry in 11 men and nine women (26-50 y, 20-29 kg/m(2)) and modelled from movement, HR, and movement + HR by multiple linear regression, adjusting for sex. Median intrainstrument CV was 0.5 and 0.03% for movement and HR, respectively. Corresponding interinstrument CV values were 5.7 and 0.03% with some evidence of heteroscedasticity for movement. The linear relationship between movement and acceleration was strong (R(2) = 0.99, P < 0.001). Simulated R-waves were detected within 1 bpm from 30 to 250 bpm. The 95% limits of agreement between Actiheart and ECG were -4.2 to 4.3 bpm. Correlations with intensity were generally high (R(2) > 0.84, P < 0.001) but significantly highest when combining HR and movement (SEE < 1 MET). The Actiheart is technically reliable and valid. Walking and running intensity may be estimated accurately but further studies are needed to assess validity in other activities and during free-living. The study received financial support from the Wellcome Trust and SB was supported by a scholarship from Unilever, UK.

Open Access Publishing in the Field of Medical Informatics.

PubMed

Kuballa, Stefanie

2017-05-01

The open access paradigm has become an important approach in today's information and communication society. Funders and governments in different countries stipulate open access publications of funded research results. Medical informatics as part of the science, technology and medicine disciplines benefits from many research funds, such as National Institutes of Health in the US, Wellcome Trust in UK, German Research Foundation in Germany and many more. In this study an overview of the current open access programs and conditions of major journals in the field of medical informatics is presented. It was investigated whether there are suitable options and how they are shaped. Therefore all journals in Thomson Reuters Web of Science that were listed in the subject category "Medical Informatics" in 2014 were examined. An Internet research was conducted by investigating the journals' websites. It was reviewed whether journals offer an open access option with a subsequent check of conditions as for example the type of open access, the fees and the licensing. As a result all journals in the field of medical informatics that had an impact factor in 2014 offer an open access option. A predominantly consistent pricing range was determined with an average fee of 2.248 € and a median fee of 2.207 €. The height of a journals' open access fee did not correlate with the height of its Impact Factor. Hence, medical informatics journals have recognized the trend of open access publishing, though the vast majority of them are working with the hybrid method. Hybrid open access may however lead to problems in questions of double dipping and the often stipulated gold open access.

The genetic association between personality and major depression or bipolar disorder. A polygenic score analysis using genome-wide association data

PubMed Central

Middeldorp, C M; de Moor, M H M; McGrath, L M; Gordon, S D; Blackwood, D H; Costa, P T; Terracciano, A; Krueger, R F; de Geus, E J C; Nyholt, D R; Tanaka, T; Esko, T; Madden, P A F; Derringer, J; Amin, N; Willemsen, G; Hottenga, J-J; Distel, M A; Uda, M; Sanna, S; Spinhoven, P; Hartman, C A; Ripke, S; Sullivan, P F; Realo, A; Allik, J; Heath, A C; Pergadia, M L; Agrawal, A; Lin, P; Grucza, R A; Widen, E; Cousminer, D L; Eriksson, J G; Palotie, A; Barnett, J H; Lee, P H; Luciano, M; Tenesa, A; Davies, G; Lopez, L M; Hansell, N K; Medland, S E; Ferrucci, L; Schlessinger, D; Montgomery, G W; Wright, M J; Aulchenko, Y S; Janssens, A C J W; Oostra, B A; Metspalu, A; Abecasis, G R; Deary, I J; Räikkönen, K; Bierut, L J; Martin, N G; Wray, N R; van Duijn, C M; Smoller, J W; Penninx, B W J H; Boomsma, D I

2011-01-01

The relationship between major depressive disorder (MDD) and bipolar disorder (BD) remains controversial. Previous research has reported differences and similarities in risk factors for MDD and BD, such as predisposing personality traits. For example, high neuroticism is related to both disorders, whereas openness to experience is specific for BD. This study examined the genetic association between personality and MDD and BD by applying polygenic scores for neuroticism, extraversion, openness to experience, agreeableness and conscientiousness to both disorders. Polygenic scores reflect the weighted sum of multiple single-nucleotide polymorphism alleles associated with the trait for an individual and were based on a meta-analysis of genome-wide association studies for personality traits including 13 835 subjects. Polygenic scores were tested for MDD in the combined Genetic Association Information Network (GAIN-MDD) and MDD2000+ samples (N=8921) and for BD in the combined Systematic Treatment Enhancement Program for Bipolar Disorder and Wellcome Trust Case–Control Consortium samples (N=6329) using logistic regression analyses. At the phenotypic level, personality dimensions were associated with MDD and BD. Polygenic neuroticism scores were significantly positively associated with MDD, whereas polygenic extraversion scores were significantly positively associated with BD. The explained variance of MDD and BD, ∼0.1%, was highly comparable to the variance explained by the polygenic personality scores in the corresponding personality traits themselves (between 0.1 and 0.4%). This indicates that the proportions of variance explained in mood disorders are at the upper limit of what could have been expected. This study suggests shared genetic risk factors for neuroticism and MDD on the one hand and for extraversion and BD on the other. PMID:22833196

Protective Effect of Natural Rotavirus Infection in an Indian Birth Cohort

PubMed Central

Gladstone, Beryl P.; Ramani, Sasirekha; Mukhopadhya, Indrani; Muliyil, Jayaprakash; Sarkar, Rajiv; Rehman, Andrea M.; Jaffar, Shabbar; Gomara, Miren Iturriza; Gray, James J.; Brown, David W.G.; Desselberger, Ulrich; Crawford, Sue E.; John, Jacob; Babji, Sudhir; Estes, Mary K.; Kang, Gagandeep

2013-01-01

BACKGROUND More than 500,000 deaths are attributed to rotavirus gastroenteritis annually worldwide, with the highest mortality in India. Two successive, naturally occurring rotavirus infections have been shown to confer complete protection against moderate or severe gastroenteritis during subsequent infections in a birth cohort in Mexico. We studied the protective effect of rotavirus infection on subsequent infection and disease in a birth cohort in India (where the efficacy of oral vaccines in general has been lower than expected). METHODS We recruited children at birth in urban slums in Vellore; they were followed for 3 years after birth, with home visits twice weekly. Stool samples were collected every 2 weeks, as well as on alternate days during diarrheal episodes, and were tested by means of enzyme-linked immunosorbent assay and polymerase-chain-reaction assay. Serum samples were obtained every 6 months and evaluated for seroconversion, defined as an increase in the IgG antibody level by a factor of 4 or in the IgA antibody level by a factor of 3. RESULTS Of 452 recruited children, 373 completed 3 years of follow-up. Rotavirus infection generally occurred early in life, with 56% of children infected by 6 months of age. Levels of reinfection were high, with only approximately 30% of all infections identified being primary. Protection against moderate or severe disease increased with the order of infection but was only 79% after three infections. With G1P[8], the most common viral strain, there was no evidence of homotypic protection. CONCLUSIONS Early infection and frequent reinfection in a locale with high viral diversity resulted in lower protection than has been reported elsewhere, providing a possible explanation why rotavirus vaccines have had lower-than-expected efficacy in Asia and Africa. (Funded by the Wellcome Trust.) PMID:21793745

Origins of the current outbreak of multidrug-resistant malaria in southeast Asia: a retrospective genetic study.

PubMed

Amato, Roberto; Pearson, Richard D; Almagro-Garcia, Jacob; Amaratunga, Chanaki; Lim, Pharath; Suon, Seila; Sreng, Sokunthea; Drury, Eleanor; Stalker, Jim; Miotto, Olivo; Fairhurst, Rick M; Kwiatkowski, Dominic P

2018-03-01

Antimalarial resistance is rapidly spreading across parts of southeast Asia where dihydroartemisinin-piperaquine is used as first-line treatment for Plasmodium falciparum malaria. The first published reports about resistance to antimalarial drugs came from western Cambodia in 2013. Here, we analyse genetic changes in the P falciparum population of western Cambodia in the 6 years before those reports. We analysed genome sequence data on 1492 P falciparum samples from 11 locations across southeast Asia, including 464 samples collected in western Cambodia between 2007 and 2013. Different epidemiological origins of resistance were identified by haplotypic analysis of the kelch13 artemisinin resistance locus and the plasmepsin 2-3 piperaquine resistance locus. We identified more than 30 independent origins of artemisinin resistance, of which the KEL1 lineage accounted for 140 (91%) of 154 parasites resistant to dihydroartemisinin-piperaquine. In 2008, KEL1 combined with PLA1, the major lineage associated with piperaquine resistance. By 2013, the KEL1/PLA1 co-lineage had reached a frequency of 63% (24/38) in western Cambodia and had spread to northern Cambodia. The KEL1/PLA1 co-lineage emerged in the same year that dihydroartemisinin-piperaquine became the first-line antimalarial drug in western Cambodia and spread rapidly thereafter, displacing other artemisinin-resistant parasite lineages. These findings have important implications for management of the global health risk associated with the current outbreak of multidrug-resistant malaria in southeast Asia. Wellcome Trust, Bill & Melinda Gates Foundation, Medical Research Council, UK Department for International Development, and the Intramural Research Program of the National Institute of Allergy and Infectious Diseases. Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

Utilizing a 'systems' approach to improve the management of waste from healthcare facilities: best practice case studies from England and Wales.

PubMed

Tudor, Terry L; Woolridge, Anne C; Bates, Margaret P; Phillips, Paul S; Butler, Sharon; Jones, Keith

2008-06-01

Changes in environmental legislation and standards governing healthcare waste, such as the Hazardous Waste Regulations are expected to have a significant impact on healthcare waste quantities and costs in England and Wales. This paper presents findings from two award winning case study organizations, the Cardiff and Vale NHS Trust and the Cornwall NHS Trust on 'systems' they have employed for minimizing waste. The results suggest the need for the development and implementation of a holistic range of systems in order to develop best practice, including waste minimization strategies, key performance indicators, and staff training and awareness. The implications for the sharing of best practice from the two case studies are also discussed.

Trust and the regulation of pharmaceuticals: South Asia in a globalised world.

PubMed

Brhlikova, Petra; Harper, Ian; Jeffery, Roger; Rawal, Nabin; Subedi, Madhusudhan; Santhosh, Mr

2011-04-29

Building appropriate levels of trust in pharmaceuticals is a painstaking and challenging task, involving participants from different spheres of life, including producers, distributors, retailers, prescribers, patients and the mass media. Increasingly, however, trust is not just a national matter, but involves cross-border flows of knowledge, threats and promises. Data for this paper comes from the project 'Tracing Pharmaceuticals in South Asia', which used ethnographic fieldwork and qualitative interviews to compared the trajectories of three pharmaceuticals (Rifampicin, Oxytocin and Fluoxetine) from producer to patient in three sites (north India, West Bengal and Nepal) between 2005-08. We argue that issues of trust are crucial in reducing the likelihood of appropriate use of medicines. Unlike earlier discussions of trust, we suggest that trust contexts beyond the patient-practitioner relationship are important. We illustrate these arguments through three case studies: (i) a conflict over ethics in Nepal, involving a suggested revised ethical code for retailers, medical representatives, producers and prescribers; (ii) disputes over counterfeit, fake, substandard and spurious medicines, and quality standards in Indian generic companies, looking particularly at the role played by the US FDA; and (iii) the implications of lack of trust in the DOTS programmes in India and Nepal for the relationships among patients, government and the private sector. We conclude that the building of trust is a necessary but always vulnerable and contingent process. While it might be desirable to outline steps that can be taken to build trust, the range of conflicting interests in the pharmaceutical field make feasible solutions hard to implement.

Trust and the regulation of pharmaceuticals: South Asia in a globalised world

PubMed Central

2011-01-01

Background Building appropriate levels of trust in pharmaceuticals is a painstaking and challenging task, involving participants from different spheres of life, including producers, distributors, retailers, prescribers, patients and the mass media. Increasingly, however, trust is not just a national matter, but involves cross-border flows of knowledge, threats and promises. Methods Data for this paper comes from the project 'Tracing Pharmaceuticals in South Asia', which used ethnographic fieldwork and qualitative interviews to compared the trajectories of three pharmaceuticals (Rifampicin, Oxytocin and Fluoxetine) from producer to patient in three sites (north India, West Bengal and Nepal) between 2005-08. Results We argue that issues of trust are crucial in reducing the likelihood of appropriate use of medicines. Unlike earlier discussions of trust, we suggest that trust contexts beyond the patient-practitioner relationship are important. We illustrate these arguments through three case studies: (i) a conflict over ethics in Nepal, involving a suggested revised ethical code for retailers, medical representatives, producers and prescribers; (ii) disputes over counterfeit, fake, substandard and spurious medicines, and quality standards in Indian generic companies, looking particularly at the role played by the US FDA; and (iii) the implications of lack of trust in the DOTS programmes in India and Nepal for the relationships among patients, government and the private sector. Conclusions We conclude that the building of trust is a necessary but always vulnerable and contingent process. While it might be desirable to outline steps that can be taken to build trust, the range of conflicting interests in the pharmaceutical field make feasible solutions hard to implement. PMID:21529358

Superintendent Communication Strategies and Experiences That Promote Trust and Positive Relationships with the School Board during the Entry Period: A Case Study

ERIC Educational Resources Information Center

Jimenez, Alfonso

2012-01-01

Superintendents have vast demands placed upon them by their school boards and via the political pipeline. The purpose of the study was to identify strategies/behaviors that successful superintendents used to build strong relationships and trust with their school boards within their entry period. It is during the entry period that determines…

Universal Lessons Learned by a Gastroenterologist from a Deaf and Mute Patient: The Importance of Nonverbal Communication and Establishing Patient Rapport and Trust

ERIC Educational Resources Information Center

Cappel, Mitchell S.

2009-01-01

Deaf and mute patients may require minimal extra attention to establish trust and allay anxieties before minor medical maneuvers such as rectal examination. An "extreme" case is reported of the consequences from failure to accomplish this. A generally cooperative deaf and mute patient struggled and suffered a rectal tear and perforation during…

The timing is never right: Mexican views of condom use.

PubMed

McQuiston, C; Gordon, A

2000-06-01

Unprotected sex is a critical issue in the Hispanic community, with the incidence of new Hispanic acquired immune deficiency syndrome (AIDS) cases three times that of non-Hispanic Whites. The researchers used focus groups to examine: (a) whether newly immigrated Mexican men and women in the Southeast United States discussed human immunodeficiency virus (HIV)/sexually transmitted disease (STD) prevention with each other, and (b) how condom use was discussed. For the women, communication was safe sex, and for the men, trust was safe sex. Both communication and trust were dependent on timing in the relationship. Participants could not discuss condoms in a new or established relationship because of issues of trust. This study highlights the complexity of HIV/STD prevention and suggests that trust and timing should be considered within the cultural context of condom introduction.

Managing and Securing Critical Infrastructure - A Semantic Policy and Trust Driven Approach

DTIC Science & Technology

2011-08-01

enviromental factors, then it is very likely that the corresponding device has been compromised and controlled by an adversary. In this case, the report... Enviromental Factors in Faulty Case (b) Result of Policy Execution in Faulty Case Figure 7: Policy Execution in Faulty Case (a) Enviromental Factors

Equity and adequacy of international donor assistance for global malaria control: an analysis of populations at risk and external funding commitments.

PubMed

Snow, Robert W; Okiro, Emelda A; Gething, Peter W; Atun, Rifat; Hay, Simon I

2010-10-23

Financing for malaria control has increased as part of international commitments to achieve the Millennium Development Goals (MDGs). We aimed to identify the unmet financial needs that would be biologically and economically equitable and would increase the chances of reaching worldwide malaria-control ambitions. Populations at risk of stable Plasmodium falciparum or Plasmodium vivax transmission were calculated for 2007 and 2009 for 93 malaria-endemic countries to measure biological need. National per-person gross domestic product (GDP) was used to define economic need. An analysis of external donor assistance for malaria control was done for the period 2002-09 to compute overall and annualised per-person at-risk-funding commitments. Annualised malaria donor assistance was compared with independent predictions of funding needed to reach international targets of 80% coverage of best practices in case-management and effective disease prevention. Countries were ranked in relation to biological, economic, and unmet needs to examine equity and adequacy of support by 2010. International financing for malaria control has increased by 166% (from $0·73 billion to $1·94 billion) since 2007 and is broadly consistent with biological needs. African countries have become major recipients of external assistance; however, countries where P vivax continues to pose threats to control ambitions are not as well funded. 21 countries have reached adequate assistance to provide a comprehensive suite of interventions by 2009, including 12 countries in Africa. However, this assistance was inadequate for 50 countries representing 61% of the worldwide population at risk of malaria-including ten countries in Africa and five in Asia that coincidentally are some of the poorest countries. Approval of donor funding for malaria control does not correlate with GDP. Funding for malaria control worldwide is 60% lower than the US$4·9 billion needed for comprehensive control in 2010; this includes funding shortfalls for a wide range of countries with different numbers of people at risk and different levels of domestic income. More efficient targeting of financial resources against biological need and national income should create a more equitable investment portfolio that with increased commitments will guarantee sustained financing of control in countries most at risk and least able to support themselves. Wellcome Trust. Copyright © 2010 Elsevier Ltd. All rights reserved.

Equity and adequacy of international donor assistance for global malaria control: an analysis of populations at risk and external funding commitments

PubMed Central

Snow, Robert W; Okiro, Emelda A; Gething, Peter W; Atun, Rifat; Hay, Simon I

2010-01-01

Summary Background Financing for malaria control has increased as part of international commitments to achieve the Millennium Development Goals (MDGs). We aimed to identify the unmet financial needs that would be biologically and economically equitable and would increase the chances of reaching worldwide malaria-control ambitions. Methods Populations at risk of stable Plasmodium falciparum or Plasmodium vivax transmission were calculated for 2007 and 2009 for 93 malaria-endemic countries to measure biological need. National per-person gross domestic product (GDP) was used to define economic need. An analysis of external donor assistance for malaria control was done for the period 2002–09 to compute overall and annualised per-person at-risk-funding commitments. Annualised malaria donor assistance was compared with independent predictions of funding needed to reach international targets of 80% coverage of best practices in case-management and effective disease prevention. Countries were ranked in relation to biological, economic, and unmet needs to examine equity and adequacy of support by 2010. Findings International financing for malaria control has increased by 166% (from $0·73 billion to $1·94 billion) since 2007 and is broadly consistent with biological needs. African countries have become major recipients of external assistance; however, countries where P vivax continues to pose threats to control ambitions are not as well funded. 21 countries have reached adequate assistance to provide a comprehensive suite of interventions by 2009, including 12 countries in Africa. However, this assistance was inadequate for 50 countries representing 61% of the worldwide population at risk of malaria—including ten countries in Africa and five in Asia that coincidentally are some of the poorest countries. Approval of donor funding for malaria control does not correlate with GDP. Interpretation Funding for malaria control worldwide is 60% lower than the US$4·9 billion needed for comprehensive control in 2010; this includes funding shortfalls for a wide range of countries with different numbers of people at risk and different levels of domestic income. More efficient targeting of financial resources against biological need and national income should create a more equitable investment portfolio that with increased commitments will guarantee sustained financing of control in countries most at risk and least able to support themselves. Funding Wellcome Trust. PMID:20889199

Benefits and payments for research participants: Experiences and views from a research centre on the Kenyan coast

PubMed Central

2012-01-01

Background There is general consensus internationally that unfair distribution of the benefits of research is exploitative and should be avoided or reduced. However, what constitutes fair benefits, and the exact nature of the benefits and their mode of provision can be strongly contested. Empirical studies have the potential to contribute viewpoints and experiences to debates and guidelines, but few have been conducted. We conducted a study to support the development of guidelines on benefits and payments for studies conducted by the KEMRI-Wellcome Trust programme in Kilifi, Kenya. Methods Following an initial broad based survey of cash, health services and other items being offered during research by all programme studies (n = 38 studies), interviews were held with research managers (n = 9), and with research staff involved in 8 purposively selected case studies (n = 30 interviewees). Interviews explored how these ‘benefits’ were selected and communicated, experiences with their administration, and recommendations for future guidelines. Data fed into a consultative workshop attended by 48 research staff and health managers, which was facilitated by an external ethicist. Findings The most commonly provided benefits were medical care (for example free care, and strengthened quality of care), and lunch or snacks. Most cash given to participants was reimbursement of transport costs (for example to meet appointments or facilitate use of services when unexpectedly sick), but these payments were often described by research participants as benefits. Challenges included: tensions within households and communities resulting from lack of clarity and agreement on who is eligible for benefits; suspicion regarding motivation for their provision; and confusion caused by differences between studies in types and levels of benefits. Conclusions Research staff differed in their views on how benefits should be approached. Echoing elements of international benefit sharing and ancillary care debates, some research staff saw research as based on goodwill and partnership, and aimed to avoid costs to participants and a commercial relationship; while others sought to maximise participant benefits given the relative wealth of the institution and the multiple community needs. An emerging middle position was to strengthen collateral or indirect medical benefits to communities through collaborations with the Ministry of Health to support sustainability. PMID:22726531

Linking international clinical research with stateless populations to justice in global health

PubMed Central

2014-01-01

Background In response to calls to expand the scope of research ethics to address justice in global health, recent scholarship has sought to clarify how external research actors from high-income countries might discharge their obligation to reduce health disparities between and within countries. An ethical framework—‘research for health justice’—was derived from a theory of justice (the health capability paradigm) and specifies how international clinical research might contribute to improved health and research capacity in host communities. This paper examines whether and how external funders, sponsors, and researchers can fulfill their obligations under the framework. Methods Case study research was undertaken on the Shoklo Malaria Research Unit’s (SMRU) vivax malaria treatment trial, which was performed on the Thai-Myanmar border with Karen and Myanmar refugees and migrants. We conducted nineteen in-depth interviews with trial stakeholders, including investigators, trial participants, community advisory board members, and funder representatives; directly observed at trial sites over a five-week period; and collected trial-related documents for analysis. Results The vivax malaria treatment trial drew attention to contextual features that, when present, rendered the ‘research for health justice’ framework’s guidance partially incomplete. These insights allowed us to extend the framework to consider external research actors’ obligations to stateless populations. Data analysis then showed that framework requirements are largely fulfilled in relation to the vivax malaria treatment trial by Wellcome Trust (funder), Oxford University (sponsor), and investigators. At the same time, this study demonstrates that it may be difficult for long-term collaborations to shift the focus of their research agendas in accordance with the changing burden of illness in their host communities and to build the independent research capacity of host populations when working with refugees and migrants. Obstructive factors included the research funding environment and staff turnover due to resettlement or migration. Conclusions Our findings show that obligations for selecting research targets, research capacity strengthening, and post-trial benefits that link clinical trials to justice in global health can be upheld by external research actors from high-income countries when working with stateless populations in LMICs. However, meeting certain framework requirements for long-term collaborations may not be entirely feasible. PMID:24969638

Infusion of Autologous Lysed Plasma Into the Baboon: Assessment of Coagulation, Platelet, and Pulmonary Function

DTIC Science & Technology

1993-06-03

obtained from whole blood collected into a commercially available tube containing thrombin and epsilon aminocaproic acid (Wellcome 44 Diagnostics...first proposed by Hall & Slayter in 1959 as an extended, multidomained molecule. Electron microscopy, amino acid sequencing and proteolytic studies have...Plasminogen (Figure 7) is a single chain, 88 kilodalton glycoprotein. It contains 790 amino acids , 24 disulfide bridges and five homologous triple loop

Surveillance and Epidemiology of Drug Resistant Infections Consortium (SEDRIC): Supporting the transition from strategy to action

PubMed Central

Fukuda, Keiji; Limmathurotsakul, Direk; Okeke, Iruka N.; Shetty, Nandini; van Doorn, Rogier; Feasey, Nicholas A.; Chiara, Francesca; Zoubiane, Ghada; Jinks, Tim; Parkhill, Julian; Patel, Jean; Reid, Stuart W.J.; Holmes, Alison H.; Peacock, Sharon J.

2018-01-01

In recognition of the central importance of surveillance and epidemiology in the control of antimicrobial resistance and the need to strengthen surveillance at all levels, Wellcome has brought together a new international expert group SEDRIC (Surveillance and Epidemiology of Drug Resistant Infections Consortium). SEDRIC aims to advance and transform the ways of tracking, sharing and analysing rates of infection and drug resistance, burden of disease, information on antibiotic use, opportunities for preventative measures such as vaccines, and contamination of the environment. SEDRIC will strengthen the availability of information needed to monitor and track risks, including an evaluation of access to, and utility of data generated by pharma and research activities, and will support the translation of surveillance data into interventions, changes in policy and more effective practices. Ways of working will include the provision of independent scientific analysis, advocacy and expert advice to groups, such as the Wellcome Drug Resistant Infection Priority Programme. A priority for SEDRIC’s first Working Group is to review mechanisms to strengthen the generation, collection, collation and dissemination of high quality data, together with the need for creativity in the use of existing data and proxy measures, and linking to existing in-country networking infrastructure. SEDRIC will also promote the translation of technological innovations into public health solutions. PMID:29904730

Risk communication and trust in decision-maker action: a case study of the Giant Mine Remediation Plan.

PubMed

Jardine, Cynthia G; Banfield, Laura; Driedger, S Michelle; Furgal, Christopher M

2013-01-01

The development and implementation of a remediation plan for the residual arsenic trioxide stored at the former Giant Mine site in the Canadian Northwest Territories has raised important issues related to trust. Social and individual trust of those responsible for making decisions on risks is critically important in community judgements on risk and the acceptability of risk management decisions. Trust is known to be affected by value similarity and confidence in past performance, which serve as interacting sources of cooperation in acting toward a common goal. To explore the elements of trust associated with the development and implementation of the Giant Mine Remediation Plan. Semi-structured interviews were conducted with eight purposively selected key informants representing both various interested and affected parties and the two government proponents. Five primary issues related to trust were identified by the participants: (1) a historical legacy of mistrust between the community (particularly Aboriginal peoples) and government; (2) barriers to building trust with the federal government; (3) limited community input and control over the decision-making process; (4) the conflicted and confounded role of the government agencies being both proponent and regulator, and the resulting need for independent oversight; and (5) distrust of the government to commit to the perpetual care required for the remediation option selected. The dual-mode model of trust and confidence was shown to be a useful framework for understanding the pivotal role of trust in the development of the Giant Mine Remediation Plan. Failure to recognize issues of trust based on value dissimilarity and lack of confidence based on past performance have resulted in a lack of cooperation characterized by delayed remediation and a prolonged and expensive consultation process. Government recognition of the importance of trust to these issues will hopefully improve future communication and public engagement endeavours.

IT Governance in SMEs: Trust or Control?

NASA Astrophysics Data System (ADS)

Devos, Jan; van Landeghem, Hendrik; Deschoolmeester, Dirk

It is believed by many scholars that a small and medium-sized enterprise (SME) cannot be seen through the lens of a large firm. Theories which explain IT governance in large organizations and methodologies used by practitioners can therefore not be extrapolated to SMEs, which have a completely different economic, cultural and managerial environment. SMEs suffer from resource poverty, have less IS experience and need more external support. SMEs largely contribute to the failure of many IS projects. We define an outsourced information system failure (OISF) as a failure of IT governance in an SME environment and propose a structure for stating propositions derived from both agency theory and theory of trust. The theoretical question addressed in this paper is: how and why do OISFs occur in SMEs? We have chosen a qualitative and positivistic IS case study research strategy based on multiple cases. Eight cases of IS projects were selected. We found that trust is more important than control issues like output-based contracts and structured controls for eliminating opportunistic behaviour in SMEs. We conclude that the world of SMEs is significantly different from that of large companies. This necessitates extra care to be taken on the part of researchers and practitioners when designing artefacts for SMEs.

Co-operation and conflict under hard and soft contracting regimes: case studies from England and Wales

PubMed Central

2013-01-01

Background This paper examines NHS secondary care contracting in England and Wales in a period which saw increasing policy divergence between the two systems. At face value, England was making greater use of market levers and utilising harder-edged service contracts incorporating financial penalties and incentives, while Wales was retreating from the 1990s internal market and emphasising cooperation and flexibility in the contracting process. But there were also cross-border spill-overs involving common contracting technologies and management cultures that meant that differences in on-the-ground contracting practices might be smaller than headline policy differences suggested. Methods The nature of real-world contracting behaviour was investigated by undertaking two qualitative case studies in England and two in Wales, each based on a local purchaser/provider network. The case studies involved ethnographic observations and interviews with staff in primary care trusts (PCTs) or local health boards (LHBs), NHS or Foundation trusts, and the overseeing Strategic Health Authority or NHS Wales regional office, as well as scrutiny of relevant documents. Results Wider policy differences between the two NHS systems were reflected in differing contracting frameworks, involving regional commissioning in Wales and commissioning by either a PCT, or co-operating pair of PCTs in our English case studies, and also in different oversight arrangements by higher tiers of the service. However, long-term relationships and trust between purchasers and providers had an important role in both systems when the financial viability of organisations was at risk. In England, the study found examples where both PCTs and trusts relaxed contractual requirements to assist partners faced with deficits. In Wales, news of plans to end the purchaser/provider split meant a return to less precisely-specified block contracts and a renewed concern to build cooperation between LHB and trust staff. Conclusions The interdependency of local purchasers and providers fostered long-term relationships and co-operation that shaped contracting behaviour, just as much as the design of contracts and the presence or absence of contractual penalties and incentives. Although conflict and tensions between contracting partners sometimes surfaced in both the English and Welsh case studies, cooperative behaviour became crucial in times of trouble. PMID:23734604

The acceptability of care delegation in skill-mix: the salience of trust.

PubMed

Dyer, Thomas Anthony; Owens, Janine; Robinson, Peter Glenn

2014-08-01

The aim of this research was to explore the acceptability of care delegation in skill-mix, using the views and experiences of patients and parents of children treated by dental therapists as a case study. A purposive sample of 15 adults whose care, or that of their children, had been delegated to dental therapists in English dental practices was interviewed using narrative and ethnographic techniques (July 2011 - May 2012). Experiences were overwhelmingly positive with the need for trust in clinicians and the health system emerging as a key factor in its acceptability. Perceptions of general and dental health services ranged from them being a collectivist public service to a more consumerist marketised service, with the former seemingly associated with notions of dentistry as a trusted system working for the social good. Interpersonal trust appeared built, sustained (and undermined) by the affective behaviour, perceived competence, and continuity of care with clinicians providing care, and contributed to trust in the system. It also appeared to compensate for gaps in knowledge needed for patient decision-making. Overall, where trust existed, delegation of care was acceptable. An increasingly marketised health system, and emphasis on the patient as a consumer, may challenge trust and acceptability of delegation, and undermine the notion of patient-centred health care. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Exploring factors affecting owners' trust of contractors in construction projects: a case of China.

PubMed

Tai, Shuangliang; Sun, Chengshuang; Zhang, Shoujian

2016-01-01

It has been found that a low level of trust among members of a construction project team leads to poor performance in China. Many researchers have described the challenges, consequently advocating partnering as an attractive approach for more valuable cooperation. Because substantial investments have been poured into construction projects since the year 2000, trust research will improve the performance of construction projects and will be meaningful to the Chinese construction industry. The purpose of this paper is to investigate the attributes affecting owners' trust of contractors, to understand the potential properties of these factors, and to rank the factors in order of importance. Twenty-four attributes are identified from a literature review. Supported by qualitative reviews, a questionnaire is conducted to obtain relevant data, and 168 valid responses are obtained for data analysis. Principal component analysis (PCA) is employed to find the factor structure of the identified trust attributes. By the method of PCA, the attributes are extracted into eight factors, including interaction history, information sharing and communication, contract and institution, relation-specific investment, reputation, integrity, competence, and opportunistic behaviour. The value and originality of this paper are embodied in using PCA to understand the various attribute groupings and to illuminate trust impact factors in the Chinese context. When they understand the critical factors affecting trust better, owners and contractors can devise more appropriate strategies to improve performance.

Trust Building as a Strategy to Avoid Unintended Consequences of Education. The Case Study of International Summer Camps Designed to Promote Peace and Intercultural Dialogue among Adolescents

ERIC Educational Resources Information Center

Farini, Federico

2014-01-01

This article aims to offer both a theoretical contribution and examples of practices of trust building in peace education; the article presents an empirical analysis of videotaped interactions in the context of peace education activities in international groups of adolescents. The analysis regards two international summer camps promoted by the…

'Civil skepticism' and the social construction of knowledge: A case in dendroclimatology.

PubMed

Ramírez-I-Ollé, Meritxell

2018-03-01

Early Science and Technology Studies (STS) scholars recognized that the social construction of knowledge depends on skepticism's parasitic relationship to background expectations and trust. Subsequent generations have paid less empirical attention to skepticism in science and its relationship with trust. I seek to rehabilitate skepticism in STS - particularly, Merton's view of skepticism as a scientific norm sustained by trust among status peers - with a study of what I call 'civil skepticism'. The empirical grounding is a case in contemporary dendroclimatology and the development of a method ('Blue Intensity') for generating knowledge about climate change from trees. I present a sequence of four instances of civil skepticism involved in making Blue Intensity more resistant to critique, and hence credible (in laboratory experiments, workshops, conferences, and peer-review of articles). These skeptical interactions depended upon maintaining communal notions of civility among an increasingly extended network of mutually trusted peers through a variety of means: by making Blue Intensity complementary to existing methods used to study a diverse natural world (tree-ring patterns) and by contributing to a shared professional goal (the study of global climate change). I conclude with a sociological theory about the role of civil skepticism in constituting knowledge-claims of greater generality and relevance.

Friendship trust and psychological well-being from late adolescence to early adulthood: A structural equation modelling approach.

PubMed

Miething, Alexander; Almquist, Ylva B; Edling, Christofer; Rydgren, Jens; Rostila, Mikael

2017-05-01

This study explored the sex-specific associations between friendship trust and the psychological well-being of young Swedes from late adolescence to early adulthood. A random sample of native Swedes born in 1990 was surveyed at age 19 years and again at age 23 years regarding their own well-being and their relationships with a maximum of five self-named peers. The response rate was 31.3%, resulting in 782 cases to be analysed. We used sex-stratified structural equation models to explore the associations between trust and well-being. Psychological well-being was constructed as the latent variable in the measurement part. The structural part accounted for the autocorrelation of trust with respect to well-being over time and incorporated the cross-lagged effects between late adolescence and early adulthood. It was found that trust increased while well-being decreased for young men and remained stable for young women from 19 to 23 years of age. The young women reported lower well-being at both time points, whereas no sex difference was found for trust. Based on model fit comparisons, a simple model without forward or reward causation was accepted for young men, whereas reversed causation from well-being to trust was suggested for young women. Subsequent analysis based on these assumptions confirmed the reversed effect for young women. The findings suggest that young people do not benefit from trustful social relations to the same extent as adult populations. Young women who express impaired well-being run a greater risk of being members of networks characterized by low friendship trust over time.

Online trust, trustworthiness, or assurance?

PubMed

Cheshire, Coye

2011-01-01

Every day, individuals around the world retrieve, share, and exchange information on the Internet. We interact online to share personal information, find answers to questions, make financial transactions, play social games, and maintain professional and personal relationships. Sometimes our online interactions take place between two or more humans. In other cases, we rely on computers to manage information on our behalf. In each scenario, risk and uncertainty are essential for determining possible actions and outcomes. This essay highlights common deficiencies in our understanding of key concepts such as trust, trustworthiness, cooperation, and assurance in online environments. Empirical evidence from experimental work in computer-mediated environments underscores the promises and perils of overreliance on security and assurance structures as replacements for interpersonal trust. These conceptual distinctions are critical because the future shape of the Internet will depend on whether we build assurance structures to limit and control ambiguity or allow trust to emerge in the presence of risk and uncertainty.

The national one week prevalence audit of universal meticillin-resistant Staphylococcus aureus (MRSA) admission screening 2012.

PubMed

Fuller, Christopher; Robotham, Julie; Savage, Joanne; Hopkins, Susan; Deeny, Sarah R; Stone, Sheldon; Cookson, Barry

2013-01-01

The English Department of Health introduced universal MRSA screening of admissions to English hospitals in 2010. It commissioned a national audit to review implementation, impact on patient management, admission prevalence and extra yield of MRSA identified compared to "high-risk" specialty or "checklist-activated" screening (CLAS) of patients with MRSA risk factors. National audit May 2011. Questionnaires to infection control teams in all English NHS acute trusts, requesting number patients admitted and screened, new or previously known MRSA; MRSA point prevalence; screening and isolation policies; individual risk factors and patient management for all new MRSA patients and random sample of negatives. 144/167 (86.2%) trusts responded. Individual patient data for 760 new MRSA patients and 951 negatives. 61% of emergency admissions (median 67.3%), 81% (median 59.4%) electives and 47% (median 41.4%) day-cases were screened. MRSA admission prevalence: 1% (median 0.9%) emergencies, 0.6% (median 0.4%) electives, 0.4% (median 0%) day-cases. Approximately 50% all MRSA identified was new. Inpatient MRSA point prevalence: 3.3% (median 2.9%). 104 (77%) trusts pre-emptively isolated patients with previous MRSA, 63 (35%) pre-emptively isolated admissions to "high-risk" specialties; 7 (5%) used PCR routinely. Mean time to MRSA positive result: 2.87 days (±1.33); 37% (219/596) newly identified MRSA patients discharged before result available; 55% remainder (205/376) isolated post-result. In an average trust, CLAS would reduce screening by 50%, identifying 81% of all MRSA. "High risk" specialty screening would reduce screening by 89%, identifying 9% of MRSA. Implementation of universal screening was poor. Admission prevalence (new cases) was low. CLAS reduced screening effort for minor decreases in identification, but implementation may prove difficult. Cost effectiveness of this and other policies, awaits evaluation by transmission dynamic economic modelling, using data from this audit. Until then trusts should seek to improve implementation of current policy and use of isolation facilities.

Will forensic use of medical biobanks decrease public trust in healthcare services? Some empirical observations.

PubMed

Bexelius, Christin; Hoeyer, Klaus; Lynöe, Niels

2007-01-01

The authors tested the prevalent hypothesis that forensic use of medical biobanks has a negative impact on public trust in healthcare services. A questionnaire was sent to 1,184 inhabitant in the age group 20-80 years in Stockholm County, Sweden, in November 2005. With a response rate of 68.4%, the results showed that a majority (88.1%) of the respondents thought that it would be acceptable for the police to gain access to genetic samples stored in relation to healthcare; 5.6% said no and 6.3% were uncertain. In the case of police access to medical biobanks, a minority (6.3%) indicated that this would have a negative impact on their trust, a larger proportion (37.8%) that it would influence their trust in the healthcare services positively, and 56% stated that it would not affect their trust at all. The hypothesis tested appears to be unfounded. This should cause us to reconsider prevalent assumptions and current policies on the interface of medical and forensic genetics.

Investigating the governance of autonomous public hospitals in England: multi-site case study of NHS foundation trusts.

PubMed

Allen, Pauline; Keen, Justin; Wright, John; Dempster, Paul; Townsend, Jean; Hutchings, Andrew; Street, Andrew; Verzulli, Rossella

2012-04-01

To investigate the external and internal governance of NHS foundation trusts (FTs), which have increased autonomy, and local members and governors unlike other NHS trusts. In depth, three-year case studies of four FTs; and analysis of national quantitative data on all FT hospitals and NHS Trust hospitals to give national context. Data included 111 interviews with managers, clinicians, governors and members, and local purchasers; observation of meetings; and analysis of FTs' documents. The four case study FTs were similar to other FTs. They had used their increased autonomy to develop more business-like practices. The FT regulator, Monitor, intervened only when there were reported problems in FT performance. National targets applying to the NHS also had a large effect on FT behaviour. FTs saw themselves as part of the local health economy and tried to maintain good relationships with local organisations. Relationships between governors and the FTs' executives were still developing, and not all governors felt able to hold their FT to account. The skills and experience of staff members and governors were under-used in the new governance structures. It is easier to increase autonomy for public hospitals than to increase local accountability. Hospital managers are likely to be interested in making decisions with less central government control, whilst mechanisms for local accountability are notoriously difficult to design and operate. Further consideration of internal governance of FTs is needed. In a deteriorating financial climate, FTs should be better placed to make savings, due to their more business-like practices.

A comprehensive Reputation mechanism for ubiquitous healthcare environment exploiting cloud model.

PubMed

Athanasiou, Georgia; Lymberopoulos, Dimitrios

2016-08-01

Absence of trust foundations may outweigh benefits of ubiquitous and personalized mental healthcare supervision provided within a Ubiquitous Healthcare environment (UH). Trust is composed by patient's Personal Interaction Experience (PIE) and social entourage accumulated PIE, i.e. Reputation (R). In this paper, a cloud-based Reputation mechanism is proposed. Since PIE is the elementary trust information source, also an Updating mechanism of PIE, is introduced, in this paper. Cloud materialization of combined mechanisms provides adaptability to UH Providers' dynamic behavior, facilitates detection of milking behaviors and complex malicious attacks while meets the challenge of limited accuracy in case of data sparseness. The effectiveness of the proposed mechanisms is verified via simulation in MATLAB.

Access and use of human tissues from the developing world: ethical challenges and a way forward using a tissue trust

PubMed Central

2011-01-01

Background Scientists engaged in global health research are increasingly faced with barriers to access and use of human tissues from the developing world communities where much of their research is targeted. In part, the problem can be traced to distrust of researchers from affluent countries, given the history of 'scientific-imperialism' and 'biocolonialism' reflected in past well publicized cases of exploitation of research participants from low to middle income countries. Discussion To a considerable extent, the failure to adequately engage host communities, the opacity of informed consent, and the lack of fair benefit-sharing have played a significant role in eroding trust. These ethical considerations are central to biomedical research in low to middle income countries and failure to attend to them can inadvertently contribute to exploitation and erode trust. A 'tissue trust' may be a plausible means for enabling access to human tissues for research in a manner that is responsive to the ethical challenges considered. Summary Preventing exploitation and restoring trust while simultaneously promoting global health research calls for innovative approaches to human tissues research. A tissue trust can reduce the risk of exploitation and promote host capacity as a key benefit. PMID:21266076

Pain Assessment: Subjectivity, Objectivity, and the Use of Neurotechnology Part One: Practical and Ethical Issues

DTIC Science & Technology

2010-07-08

assessment, neurotechnology, biotechnology, neuroethics , medicine Pain Physician 2010; 13:305-315 Ethics Pain Assessment: Subjectivity, Objectivity...Studies, Arlington, VA, USA; Wellcome Centre for Neuroethics , University of Oxford, Oxford, UK; 2Institute for BioTechnology Futures, New York, NY, USA...which to guide care. a role for technology? PossIbIlItIes, Problems, and the neuroethIcs of PaIn care Can biotechnology provide the means and tools

Doctors charged with manslaughter in the course of medical practice, 1795-2005: a literature review

PubMed Central

Ferner, R E; McDowell, Sarah E

2006-01-01

Objectives: To quantify the number of doctors charged with manslaughter in the course of legitimate medical practice and to classify cases, as mistakes, slips (or lapses), and violations, using a recognized classification of human error system. Design: We searched newspaper databases, Medline, Embase, and the Wellcome library catalogue to identify relevant cases from 1795 to December 2005. Setting: Medical practice in the United Kingdom. Main outcome measure: Number of doctors charged with manslaughter in the course of medical practice. Results: We identified 85 doctors charged with manslaughter since 1795. The number of doctors charged was relatively high in the mid-19th century and the inter-war years, and has dramatically increased since 1990. Sixty of the doctors were acquitted, 22 were convicted, and three pleaded guilty. Most doctors were charged as a consequence of mistakes (37) or slips (17), and a minority because of alleged violations (16). Conclusions: The number of doctors prosecuted for manslaughter has risen steeply since 1990, but the proportion of doctors convicted remains low. Prosecution for deliberately violating rules is understandable, but accounts for only a minority of these cases. Unconscious errors—mistakes and slips (or lapses)—are an inescapable consequence of human actions and prosecution of individuals is unlikely to improve patient safety. That requires improvement to the complex systems of health care. PMID:16738374

[Health information on the Internet and trust marks as quality indicators: vaccines case study].

PubMed

Mayer, Miguel Angel; Leis, Angela; Sanz, Ferran

2009-10-01

To find out the prevalence of quality trust marks present in websites and to analyse the quality of these websites displaying trust marks compared with those that do not display them, in order to put forward these trust marks as a quality indicator. Cross-sectional study. Internet. Websites on vaccines. Using "vacunas OR vaccines" as key words, the features of 40 web pages were analysed. These web pages were selected from the page results of two search engines, Google and Yahoo! Based on a total of 9 criteria, the average score of criteria fulfilled was 7 (95% CI 3.96-10.04) points for the web pages offered by Yahoo! and 7.3 (95% CI 3.86-10.74) offered by Google. Amongst web pages offered by Yahoo!, there were three with clearly inaccurate information, while there were four in the pages offered by Google. Trust marks were displayed in 20% and 30% medical web pages, respectively, and their presence reached statistical significance (P=0.033) when fulfilling the quality criteria compared with web pages where trust marks were not displayed. A wide variety of web pages was obtained by search engines and a large number of them with useless information. Although the websites analysed had a good quality, between 15% and 20% showed inaccurate information. Websites where trust marks were displayed had more quality than those that did not display one and none of them were included amongst those where inaccurate information was found.

Guillain-Barré Syndrome outbreak associated with Zika virus infection in French Polynesia: a case-control study.

PubMed

Cao-Lormeau, V M; Blake, A; Mons, S; Lastere, S; Roche, C; Vanhomwegen, J; Dub, T; Baudouin, L; Teissier, A; Larre, P; Vial, A L; Decam, C; Choumet, V; Halstead, S K; Willison, H J; Musset, L; Manuguerra, J C; Despres, P; Fournier, E; Mallet, H P; Musso, D; Fontanet, A; Neil, J; Ghawché, F

2016-04-09

Between October, 2013, and April, 2014, French Polynesia experienced the largest Zika virus outbreak ever described at that time. During the same period, an increase in Guillain-Barré syndrome was reported, suggesting a possible association between Zika virus and Guillain-Barré syndrome. We aimed to assess the role of Zika virus and dengue virus infection in developing Guillain-Barré syndrome. In this case-control study, cases were patients with Guillain-Barré syndrome diagnosed at the Centre Hospitalier de Polynésie Française (Papeete, Tahiti, French Polynesia) during the outbreak period. Controls were age-matched, sex-matched, and residence-matched patients who presented at the hospital with a non-febrile illness (control group 1; n=98) and age-matched patients with acute Zika virus disease and no neurological symptoms (control group 2; n=70). Virological investigations included RT-PCR for Zika virus, and both microsphere immunofluorescent and seroneutralisation assays for Zika virus and dengue virus. Anti-glycolipid reactivity was studied in patients with Guillain-Barré syndrome using both ELISA and combinatorial microarrays. 42 patients were diagnosed with Guillain-Barré syndrome during the study period. 41 (98%) patients with Guillain-Barré syndrome had anti-Zika virus IgM or IgG, and all (100%) had neutralising antibodies against Zika virus compared with 54 (56%) of 98 in control group 1 (p<0.0001). 39 (93%) patients with Guillain-Barré syndrome had Zika virus IgM and 37 (88%) had experienced a transient illness in a median of 6 days (IQR 4-10) before the onset of neurological symptoms, suggesting recent Zika virus infection. Patients with Guillain-Barré syndrome had electrophysiological findings compatible with acute motor axonal neuropathy (AMAN) type, and had rapid evolution of disease (median duration of the installation and plateau phases was 6 [IQR 4-9] and 4 days [3-10], respectively). 12 (29%) patients required respiratory assistance. No patients died. Anti-glycolipid antibody activity was found in 13 (31%) patients, and notably against GA1 in eight (19%) patients, by ELISA and 19 (46%) of 41 by glycoarray at admission. The typical AMAN-associated anti-ganglioside antibodies were rarely present. Past dengue virus history did not differ significantly between patients with Guillain-Barré syndrome and those in the two control groups (95%, 89%, and 83%, respectively). This is the first study providing evidence for Zika virus infection causing Guillain-Barré syndrome. Because Zika virus is spreading rapidly across the Americas, at risk countries need to prepare for adequate intensive care beds capacity to manage patients with Guillain-Barré syndrome. Labex Integrative Biology of Emerging Infectious Diseases, EU 7th framework program PREDEMICS. and Wellcome Trust. Copyright © 2016 Elsevier Ltd. All rights reserved.

HealthTrust: a social network approach for retrieving online health videos.

PubMed

Fernandez-Luque, Luis; Karlsen, Randi; Melton, Genevieve B

2012-01-31

Social media are becoming mainstream in the health domain. Despite the large volume of accurate and trustworthy health information available on social media platforms, finding good-quality health information can be difficult. Misleading health information can often be popular (eg, antivaccination videos) and therefore highly rated by general search engines. We believe that community wisdom about the quality of health information can be harnessed to help create tools for retrieving good-quality social media content. To explore approaches for extracting metrics about authoritativeness in online health communities and how these metrics positively correlate with the quality of the content. We designed a metric, called HealthTrust, that estimates the trustworthiness of social media content (eg, blog posts or videos) in a health community. The HealthTrust metric calculates reputation in an online health community based on link analysis. We used the metric to retrieve YouTube videos and channels about diabetes. In two different experiments, health consumers provided 427 ratings of 17 videos and professionals gave 162 ratings of 23 videos. In addition, two professionals reviewed 30 diabetes channels. HealthTrust may be used for retrieving online videos on diabetes, since it performed better than YouTube Search in most cases. Overall, of 20 potential channels, HealthTrust's filtering allowed only 3 bad channels (15%) versus 8 (40%) on the YouTube list. Misleading and graphic videos (eg, featuring amputations) were more commonly found by YouTube Search than by searches based on HealthTrust. However, some videos from trusted sources had low HealthTrust scores, mostly from general health content providers, and therefore not highly connected in the diabetes community. When comparing video ratings from our reviewers, we found that HealthTrust achieved a positive and statistically significant correlation with professionals (Pearson r₁₀ = .65, P = .02) and a trend toward significance with health consumers (r₇ = .65, P = .06) with videos on hemoglobinA(1c), but it did not perform as well with diabetic foot videos. The trust-based metric HealthTrust showed promising results when used to retrieve diabetes content from YouTube. Our research indicates that social network analysis may be used to identify trustworthy social media in health communities.

Tranexamic acid for treatment of women with post-partum haemorrhage in Nigeria and Pakistan: a cost-effectiveness analysis of data from the WOMAN trial.

PubMed

Li, Bernadette; Miners, Alec; Shakur, Haleema; Roberts, Ian

2018-02-01

Sub-Saharan Africa and southern Asia account for almost 85% of global maternal deaths from post-partum haemorrhage. Early administration of tranexamic acid, within 3 h of giving birth, was shown to reduce the risk of death due to bleeding in women with post-partum haemorrhage in the World Maternal Antifibrinolytic (WOMAN) trial. We aimed to assess the cost-effectiveness of early administration of tranexamic acid for treatment of post-partum haemorrhage. For this economic evaluation we developed a decision model to assess the cost-effectiveness of the addition of tranexamic acid to usual care for treatment of women with post-partum haemorrhage in Nigeria and Pakistan. We used data from the WOMAN trial to inform model parameters, supplemented by estimates from the literature. We estimated costs (calculated in 2016 US$), life-years, and quality-adjusted life-years (QALYs) with and without tranexamic acid, calculated incremental cost-effectiveness ratios (ICERs), and compared these to threshold values in each country. Costs were assessed from the health-care provider perspective and discounted at 3% per year in the base case analysis. We did a series of one-way sensitivity analyses and probabilistic sensitivity analysis to assess the robustness of the results to parameter uncertainty. Early treatment of post-partum haemorrhage with tranexamic acid generated an average gain of 0·18 QALYs at an additional cost of $37·12 per patient in Nigeria and an average gain of 0·08 QALYs at an additional cost of $6·55 per patient in Pakistan. The base case ICER results were $208 per QALY in Nigeria and $83 per QALY in Pakistan. These ICERs were below the lower bound of the cost-effectiveness threshold range in both countries. The ICERs were most sensitive to uncertainty in parameter inputs for the relative risk of death due to bleeding with tranexamic acid, the discount rate, the cost of the drug, and the baseline probability of death due to bleeding. Early treatment of post-partum haemorrhage with tranexamic acid is highly cost-effective in Nigeria and Pakistan, and is likely to be cost-effective in countries in sub-Saharan Africa and southern Asia with a similar baseline risk of death due to bleeding. London School of Hygiene & Tropical Medicine, Pfizer, UK Department of Health, Wellcome Trust, and Bill & Melinda Gates Foundation. Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

The psychological well-being and prenatal bonding of gestational surrogates

PubMed Central

Lamba, N; Jadva, V; Kadam, K; Golombok, S

2018-01-01

Abstract STUDY QUESTION How does the psychological well-being and prenatal bonding of Indian surrogates differ from a comparison group of mothers? SUMMARY ANSWER Surrogates had higher levels of depression during pregnancy and post-birth, displayed lower emotional connection with the unborn baby, and greater care towards the healthy growth of the foetus, than the comparison group of mothers. WHAT IS ALREADY KNOWN Studies in the West have found that surrogates do not suffer long-term psychological harm. One study has shown that surrogates bond less with the foetus than expectant mothers. STUDY, DESIGN, SIZE, DURATION This study uses a prospective, longitudinal and cross-sectional design. Surrogates and a matched group of expectant mothers were seen twice, during 4–9 months of pregnancy and 4–6 months after the birth. PARTICIPANTS/MATERIALS, SETTING, METHODS Semi-structured interviews and standardized questionnaires were administered to 50 surrogates and 69 expectant mothers during pregnancy and 45 surrogates and 49 expectant mothers post-birth. All gestational surrogates were hosting pregnancies for international intended parents. MAIN RESULTS AND THE ROLE OF CHANCE Surrogates had higher levels of depression compared to the comparison group of mothers, during pregnancy and post-birth (P < 0.02). Low social support during pregnancy, hiding surrogacy and criticism from others were found to be predictive of higher depression in surrogates post-birth (P < 0.05). Regarding prenatal bonding, surrogates interacted less with and thought less about the foetus but adopted better eating habits and were more likely to avoid unhealthy practices during pregnancy, than expectant mothers (P < 0.05). No associations were found between greater prenatal bonding and greater psychological distress during pregnancy or after relinquishment. LIMITATIONS, REASONS FOR CAUTION All surrogates were recruited from one clinic in Mumbai, and thus the representativeness of this sample is not known. Also, the possibility of socially desirable responding from surrogates cannot be ruled out. WIDER IMPLICATIONS OF THE FINDINGS As this is the first study of the psychological well-being of surrogates in low-income countries, the findings have important policy implications. Providing support and counselling to surrogates, especially during pregnancy, may alleviate some of the psychological problems faced by surrogates. STUDY FUNDING/COMPETING INTEREST(S) This study was supported by the Wellcome Trust [097857/Z/11/Z] and Nehru Trust, Cambridge. K.K. is the Medical Director of Corion Fertility Clinic. All other authors have no conflict of interest to declare. PMID:29566176

Facilitation of Risk Communication During the Anthrax Attacks of 2001: The Organizational Backstory

PubMed Central

Chess, Caron; Clarke, Lee

2007-01-01

The anthrax attacks of 2001 created risk communication problems that cannot be fully understood without appreciating the dynamics among organizations. Case studies of communication in New Jersey, consisting of interviews with a range of participants, found that existing organizational and professional networks facilitated trust among decisionmakers. This interpersonal trust improved communication among agencies and thereby risk communication with the public. For example, “white powder scares” were a problem even in places without contamination. Professionals’ trust in each other was vital for responding productively. Conversely, organizational challenges, including conflict among agencies, hindered communication with key audiences. Although centralization and increased control are often seen as the remedy for communicative confusion, they also can quash the improvisational responses needed during crises. PMID:17666692

The design of a corporate identity for a department of medical illustration: a case study.

PubMed

Thompson, G

2001-06-01

This paper outlines the author's attempt to design and introduce a corporate identity into the Department of Medical Illustration at the South Buckinghamshire NHS Trust. It is intended to furnish the reader with an insight into the process of designing a corporate identity and to relate one department's experience. This may be useful for those who wish to develop a corporate identity of their own or contribute, as a department, towards an identity for their own Trust or other institution. A major change in government policy about the identity of NHS Trusts has meant that use of the department's new logo has had to be abandoned in favour of the new NHS corporate identity.

Water law - Public Trust Doctrine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Casey, E.S.

In a case involving California's Mono Lake, the State Supreme Court held that infringement of the values protected by the Public Trust Doctrine is a separate ground for challenging water appropriations, and that the continuing nature of the state's duty as trustee prevents the acquisition of a vested right to appropriations that injure navigation, commerce, and fisheries. The author summarizes the history and the competing claims of the Doctrine and the California Appropriative Water Rights System. The National Audubon suit now makes it possible for any member of the public to challenge any surface water diversion as injurious to themore » public trust, but it also offers the California courts an opportunity to redirect the state's water policies. 130 references.« less

A Method to Increase Drivers' Trust in Collision Warning Systems Based on Reliability Information of Sensor

NASA Astrophysics Data System (ADS)

Tsutsumi, Shigeyoshi; Wada, Takahiro; Akita, Tokihiko; Doi, Shun'ichi

Driver's workload tends to be increased during driving under complicated traffic environments like a lane change. In such cases, rear collision warning is effective for reduction of cognitive workload. On the other hand, it is pointed out that false alarm or missing alarm caused by sensor errors leads to decrease of driver' s trust in the warning system and it can result in low efficiency of the system. Suppose that reliability information of the sensor is provided in real-time. In this paper, we propose a new warning method to increase driver' s trust in the system even with low sensor reliability utilizing the sensor reliability information. The effectiveness of the warning methods is shown by driving simulator experiments.

Facilitation of risk communication during the anthrax attacks of 2001: the organizational backstory.

PubMed

Chess, Caron; Clarke, Lee

2007-09-01

The anthrax attacks of 2001 created risk communication problems that cannot be fully understood without appreciating the dynamics among organizations. Case studies of communication in New Jersey, consisting of interviews with a range of participants, found that existing organizational and professional networks facilitated trust among decisionmakers. This interpersonal trust improved communication among agencies and thereby risk communication with the public. For example, "white powder scares" were a problem even in places without contamination. Professionals' trust in each other was vital for responding productively. Conversely, organizational challenges, including conflict among agencies, hindered communication with key audiences. Although centralization and increased control are often seen as the remedy for communicative confusion, they also can quash the improvisational responses needed during crises.

Management of Barrett's high-grade dysplasia: initial results from a population-based national audit.

PubMed

Chadwick, Georgina; Groene, Oliver; Taylor, Angelina; Riley, Stuart; Hardwick, Richard H; Crosby, Tom; Greenaway, Kimberley; Cromwell, David A

2016-04-01

Previous studies reported significant variation in the management of patients with Barrett's esophagus. However, these are based on self-reported clinical practice. The aim of this study was to examine the management of high-grade dysplasia in Barrett's esophagus in England by using patient-level data and to compare practice with guidelines. From April 2012 to March 2013, National Health Service (NHS) trusts in England prospectively collected data on patients newly diagnosed with high-grade dysplasia (HGD) of the esophagus as part of the National Oesophago-Gastric Cancer Audit. Data were collected on patient characteristics, diagnosis and endoscopic findings, treatment planning, and therapy. Between April 2012 and March 2013, NHS trusts reported 465 cases of HGD. Diagnosis was confirmed by a second pathologist in 79.4% of cases (270/340), and 86.0% (374/465) had their treatment planned at a multidisciplinary team meeting. A total of 290 patients (62.4%) were managed endoscopically (frequently with endoscopic resection or radiofrequency ablation), whereas 26 patients (5.6%) had esophagectomy. The proportion of patients managed by surveillance varied by age (P < .001), ranging from 19.5% in patients aged <65 years to 63.8% in patients aged ≥85 years. More patients received active treatment if their cases were discussed at a multidisciplinary meeting (73.5% vs 44.3%; P < .001) or managed at higher-volume trusts (87.8% vs 55.4%; P < .001). There was marked variation in the management of HGD across England, with a third of patients receiving no active treatment. Patients discussed at a specialist multidisciplinary meeting or managed in high-volume trusts were more likely to receive active treatment. Copyright © 2016 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

Finding The Limit: The Strategic Potential Of The Network Based Actor

DTIC Science & Technology

2016-12-01

6  E.  CASE STUDY SELECTION AND PROCESS .......................................6  1.  Selection of Baseline Case Studies: Pierre-Charles...Pathé and the Trust ..................................................................................7  2.  Selection of Test Case Studies...academic debate, which argues that non-state, network-based actors can have a strategic planning capacity. E. CASE STUDY SELECTION AND PROCESS This

Improving Access to, Use of, and Outcomes from Public Health Programs: The Importance of Building and Maintaining Trust with Patients/Clients

PubMed Central

Ward, Paul Russell

2017-01-01

The central argument in this paper is that “public trust” is critical for developing and maintaining the health and wellbeing of individuals, communities, and societies. I argue that public health practitioners and policy makers need to take “public trust” seriously if they intend to improve both the public’s health and the engagement between members of the public and public health systems. Public health practitioners implement a range of services and interventions aimed at improving health but implicit a requirement for individuals to trust the practitioners and the services/interventions, before they engage with them. I then go on to provide an overview of the theory of trust within sociology and show why it is important to understand this theory in order to promote trust in public health services. I then draw on literature in three classic areas of public health—hospitals, cancer screening, and childhood immunization—to show why trust is vital in terms of understanding and potentially improving uptake of services. The case studies in this paper reveal that public health practitioners need to understand the centrality of building and maintaining trusting relationships with patients/clients because people who distrust public health services are less likely to use them, less likely to follow advice or recommendations, and more likely to have poorer health outcomes. PMID:28337430

The management of ultrasound equipment at Sheffield Teaching Hospitals NHS Foundation Trust

PubMed Central

Peacock, M

2013-01-01

Management of ultrasound equipment at Sheffield Teaching Hospitals NHS Foundation Trust is described. The organisation and input of various stakeholders and their involvement with ultrasound equipment management and scientific ultrasound is discussed. Two important stakeholders are the Medical Equipment Management Group and the Radiation Safety Steering Committee. The Medical Equipment Management Group has a specific sub-group, the Ultrasound sub-group, and its role is to coordinate the purchase, replacement and quality assurance of ultrasound equipment in the Trust. The Radiation Safety Steering Committee has a non-ionising radiation representative and the role of this committee is to provide corporate assurance that any health and safety issues arising from the use of radiation to either patients, members of the public or staff within the Trust are being effectively managed. The Ultrasound sub-group of the Medical Equipment Management Group has successfully brought together management of all ultrasound equipment within the Trust and is in the process of fulfilling the quality assurance and training milestones set out by the Medical Equipment Management Group. Advice from the Radiation Safety Steering Committee has helped to increase awareness of ultrasound safety and good scanning practice, especially in the case of neonatal ultrasound imaging, within the Trust. In addition, the RSSC has given advice on clinical pathways for patients undergoing ionising radiation imaging while being treated by extra-corporeal shockwave lithotripsy. PMID:27433195

Take the Money and Run: Psychopathic Behavior in the Trust Game

PubMed Central

Ibáñez, Manuel I.; Sabater-Grande, Gerardo; Barreda-Tarrazona, Iván; Mezquita, Laura; López-Ovejero, Sandra; Villa, Helena; Perakakis, Pandelis; Ortet, Generós; García-Gallego, Aurora; Georgantzís, Nikolaos

2016-01-01

We study the association among different sources of individual differences such as personality, cognitive ability and risk attitudes with trust and reciprocate behavior in an incentivized experimental binary trust game in a sample of 220 (138 females) undergraduate students. The game involves two players, player 1 (P1) and player 2 (P2). In the first stage, P1 decides whether to trust and let P2 decide, or to secure an egalitarian payoff for both players. If P1 trusts P2, the latter can choose between a symmetric payoff that is double than the secure alternative discarded by P1, and an asymmetric payoff in which P2 earns more than in any other case but makes P1 worse off. Before the main experiment, we obtained participants’ scores for Abstract Reasoning (AR), risk attitudes, basic personality characteristics, and specific traits such as psychopathy and impulsivity. During the main experiment, we measured Heart Rate (HR) and ElectroDermal Activity (EDA) variation to account for emotional arousal caused by the decision and feedback processes. Our main findings indicate that, on one hand, P1 trust behavior associates to positive emotionality and, specifically, to the extraversion’s warmth facet. In addition, the impulsivity facet of positive urgency also favors trust behavior. No relation to trusting behavior was found for either other major personality aspects or risk attitudes. The physiological results show that participants scoring high in psychopathy exhibit increased EDA and reduced evoked HR deceleration at the moment in which they are asked to decide whether or not to trust. Regarding P2, we find that AR ability and mainly low disagreeable disinhibition favor reciprocal behavior. Specifically, lack of reciprocity significantly relates with a psychopathic, highly disinhibited and impulsive personality. Thus, the present study suggests that personality characteristics would play a significant role in different behaviors underlying cooperation, with extraversion/positive emotionality being more relevant for initiating cooperation, and low disagreeable disinhibition for maintaining it. PMID:27965606

26 CFR 55.6091-2 - Exceptional cases.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 26 Internal Revenue 17 2010-04-01 2010-04-01 false Exceptional cases. 55.6091-2 Section 55.6091-2 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) MISCELLANEOUS EXCISE TAXES (CONTINUED) EXCISE TAX ON REAL ESTATE INVESTMENT TRUSTS AND REGULATED INVESTMENT COMPANIES...

26 CFR 55.6091-2 - Exceptional cases.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 26 Internal Revenue 17 2011-04-01 2011-04-01 false Exceptional cases. 55.6091-2 Section 55.6091-2 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) MISCELLANEOUS EXCISE TAXES (CONTINUED) EXCISE TAX ON REAL ESTATE INVESTMENT TRUSTS AND REGULATED INVESTMENT COMPANIES...

26 CFR 55.6091-2 - Exceptional cases.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 26 Internal Revenue 17 2013-04-01 2013-04-01 false Exceptional cases. 55.6091-2 Section 55.6091-2 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) MISCELLANEOUS EXCISE TAXES (CONTINUED) EXCISE TAX ON REAL ESTATE INVESTMENT TRUSTS AND REGULATED INVESTMENT COMPANIES...

26 CFR 55.6091-2 - Exceptional cases.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 26 Internal Revenue 17 2012-04-01 2012-04-01 false Exceptional cases. 55.6091-2 Section 55.6091-2 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) MISCELLANEOUS EXCISE TAXES (CONTINUED) EXCISE TAX ON REAL ESTATE INVESTMENT TRUSTS AND REGULATED INVESTMENT COMPANIES...

26 CFR 55.6091-2 - Exceptional cases.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 26 Internal Revenue 17 2014-04-01 2014-04-01 false Exceptional cases. 55.6091-2 Section 55.6091-2 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) MISCELLANEOUS EXCISE TAXES (CONTINUED) EXCISE TAX ON REAL ESTATE INVESTMENT TRUSTS AND REGULATED INVESTMENT COMPANIES...

[Application of case-based learning in clinical internship teaching of conservative dentistry and endodontics].

PubMed

Liu, Sheng-bo; Peng, Bin; Song, Ya-ling; Xu, Qing-an

2013-12-01

To investigate the education effect of case-based learning (CBL) pattern on clinical internship of conservative dentistry and endodontics. Forty-one undergraduates were randomly assigned into CBL group and traditional teaching group. After clinical internship in the department of conservative dentistry and endodontics for 11 weeks, each student in the 2 groups underwent comprehensive examinations including medical record writing, case analysis, academic knowledge, professional skills and the ability of winning the trust of the patients. The scores were compared between the 2 groups using SPSS 13.0 software package. There was no significant difference between the 2 groups with regard to the scores of academic knowledge and profession skills (P>0.05). However, the results of medical record writing, case analysis and the ability of winning the trust of the patients showed significant difference between the 2 groups(P<0.05). Proper application of CBL in clinical internship of conservative dentistry and endodontics contributes to improve students' ability of clinical thinking, synthetical analysis and adaptability to different patients.

Trust Betrayed.

ERIC Educational Resources Information Center

Hardy, Lawrence

2002-01-01

Describes several cases involving the sexual abuse of students by teachers and other staff members; suggests ways school districts can protect their students from abusive staff members, especially pedophiles. (PKP)

26 CFR 1.611-5 - Depreciation of improvements.

Code of Federal Regulations, 2010 CFR

2010-04-01

.... Section 611 provides in the case of mines, oil and gas wells, other natural deposits, and timber that... governing the apportioning of depreciation allowances under sections 611 and 167 in the case of property held by one person for life with remainder to another or in the case of property held in trust or by an...

Risk communication of vaccines: challenges in the post-trust environment.

PubMed

Bouder, Frederic

2015-01-01

Highly publicised vaccine scares and recent debates about the risks suggest that public trust in immunisation programmes is fragile. For instance, the recent outbreak of Measles in Wales was the direct result of almost fifteen years of distrust for the MMR vaccine in the UK. This article shows how the latest science on risk communication will help critical actors, especially policy-makers, to build trust when they communicate risks to citizens and patients. The article offers policy advice on risk communication based on the results of three vaccines case studies. Five procedural principles which were developed for the UK government - the so-called "five As" of public risk communication are used to structure the discussion. Conclusions and recommendations suggest ways to move forward and build a two-way proactive risk communication practice.

Culturally Responsive Teaching in the Context of Mathematics: A Grounded Theory Case Study

ERIC Educational Resources Information Center

Bonner, Emily P.; Adams, Thomasenia L.

2012-01-01

In this grounded theory case study, four interconnected, foundational cornerstones of culturally responsive mathematics teaching (CRMT), communication, knowledge, trust/relationships, and constant reflection/revision, were systematically unearthed to develop an initial working theory of CRMT that directly informs classroom practice. These…

Analysis of public responses to preparedness policies: the cases of H1N1 influenza vaccination and gas mask distribution

PubMed Central

2013-01-01

Background During several months in 2009–2010, the Israeli population was asked to take part in two preparedness programs: Acquisition of gas masks against a potential chemical-warfare attack, and vaccination against the A/H1N1 influenza pandemics. Compliance with the first request was moderate and did not attract much attention, whereas compliance with the second request was very low and was accompanied by significant controversy. The aims of this study are to compare the public’s attitudes towards these two preparedness campaigns, and to explore the roles of trust, reasoned assessment, and reflexive reactions in the public’s response to governmental preparedness policies. Methods The comparative analysis was based on a telephone survey of 2,018 respondents representing a cross-section of the adult Israeli population. Univariate analysis to describe associations of public response and attitude was performed by Chi-square tests. Findings A set of queries related to actual compliance, trust in credibility of authorities, personal opinions, reasons for non-compliance, and attitudes towards uncertainties was used to characterize the response to mask-acquisition and vaccination. In the case of mask-acquisition, the dominant response profile was of trusting compliance based on non-conditional belief in the need to adhere to the recommendation (35.6% of respondents). In the case of vaccination, the dominant response profile was of trusting non-compliance based on a reflective belief in the need for adherence (34.8% of respondents). Among the variables examined in the study, passivity was found to be the major reason for non-compliance with mask-acquisition, whereas reasoned assessment of risk played a major role in non-compliance with vaccination. Realization of the complexity in dealing with uncertainty related to developing epidemics and to newly-developed vaccines was identified in the public’s response to the H1N1 vaccination campaign. Conclusions The newly identified profile of “trusting-reflective-non-complier” individuals should be of concern to policy makers. The public is not accepting governmental recommendations in an unconditional manner. This is not driven by lack of trust in authorities, but rather by the perception of the responsibility of individuals in confronting forthcoming risks. Nevertheless, under certain conditions the public may respond in a non-reflective way and delegate this responsibly to authorities in an uncontested manner. This leaves the policy makers with the complex challenge of interacting with a passive non-involved public or alternatively with an opinionated, reflexive public. PMID:23537171

The Courage to Collaborate: The Case for Labor-Management Partnerships in Education

ERIC Educational Resources Information Center

Futernick, Ken

2016-01-01

In "The Courage to Collaborate," school turnaround expert Ken Futernick makes the case that collaboration between school management and teacher unions is a necessary condition for educational improvement. The author cites evidence showing that collaboration often leads to increased trust, stronger professional relationships, better…

The interweaving of pharmaceutical and medical expectations as dynamics of micro-pharmaceuticalisation: advanced-stage cancer patients' hope in medicines alongside trust in professionals.

PubMed

Brown, Patrick; de Graaf, Sabine; Hillen, Marij; Smets, Ellen; van Laarhoven, Hanneke

2015-04-01

Existing pharmaceuticalisation research denotes the salience of expectations in novel medicines and in the medical contexts through which these may be accessed. Specific processes of expectation such as hope and trust, alongside their shaping of patients' lifeworlds around pharmaceutical use, remain neglected however. Considering data from in-depth interviews and observations involving thirteen patients with advanced-stage cancer diagnoses who were or had recently been involved in clinical trials, we develop an interpretative phenomenological analysis of the influence of hope and trust upon the accessing of novel medicines through trials, illuminating the depth and texture of pharmaceuticalisation at the micro-level. Trust in clinicians and hope in trial medicines, for self and future patients, were important in the reconfiguring of patients' horizon of possibilities when accessing new medicines. Interwoven processes of trust and hope, embedded within heightened vulnerability, sustained the bracketing out of doubts regarding medicines, trials and professionals. The need to maintain hopes, and trusting relations with professionals who facilitated these hopes, generated meaning and momentum of medicines use which inhibited disengagement from trials. Findings indicate the taken-for-granted, as well as more reflexive, pursuit of solutions through medicines, which in this case-study enabled the generation of evidence through trial involvement. Analyses of micro-level dynamics within both downstream-consumption and upstream-substantiation of pharmaceutical solutions assist more nuanced accounts of interests, agency and expectations within pharmaceuticalisation. Copyright © 2014 Elsevier Ltd. All rights reserved.

From vision to reality--managing change in the provision of library and information services to nurses, midwives, health visitors and PAMs: (professions allied to medicine) a case study of the North Thames experience with the Inner London Consortium.

PubMed

Godbolt, S; Williamson, J; Wilson, A

1997-06-01

One of the North Thames' pioneering consortia, the Inner London Consortium (ILC) is a complex body which includes NHS Trusts with teaching hospital university connections, community-based Trusts and general hospital acute Trusts. Within the consortium there are 12,000 trained nurses, midwives, health visitors and other professional staff working in the professions allied to medicine (PAMs), all of whom require access to and provision of appropriate library information services. In 1994, taking into account experiences elsewhere in the Region and nationally, it became clear that library issues were complex and would become acute with the move of nursing libraries from ILC Trust sites over a very short timescale. A report on the issues commissioned by the Consortium recommended that a library project, which built on existing NHS Trust PGMDE funded library resources and moved these to a multidisciplinary base to serve the consortium membership, be implemented. The objective of providing access to library information services for nurses and PAMs was achieved. Successes that emerged from the implementation included: The registration in Trust libraries of almost 12 000 new members within the initial 6-month monitoring period. The development of service level agreements and standards for the delivery of services to these new user groups. This paper describes the processes behind these significant and complex changes.

Fully Automated Driving: Impact of Trust and Practice on Manual Control Recovery.

PubMed

Payre, William; Cestac, Julien; Delhomme, Patricia

2016-03-01

An experiment was performed in a driving simulator to investigate the impacts of practice, trust, and interaction on manual control recovery (MCR) when employing fully automated driving (FAD). To increase the use of partially or highly automated driving efficiency and to improve safety, some studies have addressed trust in driving automation and training, but few studies have focused on FAD. FAD is an autonomous system that has full control of a vehicle without any need for intervention by the driver. A total of 69 drivers with a valid license practiced with FAD. They were distributed evenly across two conditions: simple practice and elaborate practice. When examining emergency MCR, a correlation was found between trust and reaction time in the simple practice group (i.e., higher trust meant a longer reaction time), but not in the elaborate practice group. This result indicated that to mitigate the negative impact of overtrust on reaction time, more appropriate practice may be needed. Drivers should be trained in how the automated device works so as to improve MCR performance in case of an emergency. The practice format used in this study could be used for the first interaction with an FAD car when acquiring such a vehicle. © 2015, Human Factors and Ergonomics Society.

Improving patient safety incident reporting systems by focusing upon feedback - lessons from English and Welsh trusts.

PubMed

Wallace, Louise M; Spurgeon, Peter; Benn, Jonathan; Koutantji, Maria; Vincent, Charles

2009-08-01

This paper describes practical implications and learning from a multi-method study of feedback from patient safety incident reporting systems. The study was performed using the Safety Action and Information Feedback from Incident Reporting model, a model of the requirements of the feedback element of a patient safety incident reporting and learning system, derived from a scoping review of research and expert advice from world leaders in safety in high-risk industries. We present the key findings of the studies conducted in the National Health Services (NHS) trusts in England and Wales in 2006. These were a survey completed by risk managers for 351 trusts in England and Wales, three case studies including interviews with staff concerning an example of good practice feedback and an audit of 90 trusts clinical risk staff newsletters. We draw on an Expert Workshop that included 71 experts from the NHS, from regulatory bodies in health care, Royal Colleges, Health and Safety Executive and safety agencies in health care and high-risk industries (commercial aviation, rail and maritime industries). We draw recommendations of enduring relevance to the UK NHS that can be used by trust staff to improve their systems. The recommendations will be of relevance in general terms to health services worldwide.

Consumer trust in food safety--a multidisciplinary approach and empirical evidence from Taiwan.

PubMed

Chen, Mei-Fang

2008-12-01

Food scandals that happened in recent years have increased consumers' risk perceptions of foods and decreased their trust in food safety. A better understanding of the consumer trust in food safety can improve the effectiveness of public policy and allow the development of the best practice in risk communication. This study proposes a research framework from a psychometric approach to investigate the relationships between the consumer's trust in food safety and the antecedents of risk perceptions of foods based on a reflexive modernization perspective and a cultural theory perspective in the hope of benefiting the future empirical study. The empirical results from a structural equation modeling analysis of Taiwan as a case in point reveal that this research framework based on a multidisciplinary perspective can be a valuable tool for a growing understanding of consumer trust in food safety. The antecedents in the psychometric research framework comprised reflexive modernization factors and cultural theory factors have all been supported in this study except the consumer's perception of pessimism toward food. Moreover, the empirical results of repeated measures analysis of variance give more detailed information to grasp empirical implications and to provide some suggestions to the actors and institutions involved in the food supply chain in Taiwan.

Whether Visual Information Loss of Expression by Community Pharmacist Masks to Effect a Change in Feeling of Trust among Help-seeker?

PubMed

Kishimoto, Keiko; Hasaka, Akiko; Yamaura, Katsunori; Fukushima, Noriko

2016-01-01

Pharmacy is required to shift toward human service such as hearing the complaints of health. But the study about help-seeking behavior to pharmacist is not really investigated. We hypothesized that a decrease in expression visibility, due to pharmacists' typical masks, may negatively impact help-seeker' trust in pharmacist. The sample included 100 drugstore customers aged ≥18 years. Participants were stratified by gender and randomly assigned to two groups: evaluation of clear-masked and normal-masked pharmacists. After viewing a video with either male or female pharmacists wearing either clear or normal masks, participants completed a questionnaire. The primary outcome was trust in pharmacist measured by the Trust Scale and the secondary outcome was impression of the pharmacist measured by nineteen pairs of adjectives. There were no differences by gender on trust scores. Results revealed that both male and female pharmacists who wore clear masks were rated as more trustworthy than normal-masked pharmacists (p<0.001, d=0.903, and p=0.001, d=0.716, respectively). Sixteen of nineteen adjectives reported for pharmacists wearing normal masks indicated greater negative intention than those with clear masks (d=0.431-1.469). In most cases, among pharmacists wearing clear masks, results showed positive correlations between trust and each impression adjective (r=0.279-0.710). Our findings indicate that pharmacists wearing normal masks, which partially hide facial expressions, may decrease customer's trust in pharmacist. Further, normal masks were associated with negative impression. To avoid the inhibition of help-seek behavior, we recommend that pharmacists wear a clear mask and increase non-verbal communication.

Exploratory study of the impacts of Mutual Health Organizations on social dynamics in Benin.

PubMed

Ridde, Valery; Haddad, Slim; Yacoubou, Moussa; Yacoubou, Ismaelou

2010-08-01

The primary aim of Mutual Health Organizations (MHOs) is the financial protection of their members. However, given their community-based, participative and voluntary nature, it is conceivable that MHOs, as social organizations, would affect social dynamics. In an exploratory study in Benin, we studied social dynamics related to mutual aid, relationships of trust, and empowerment. Four MHOs, as contrasted cases, were selected from among the 11 in the region. Focus groups (n = 20) and individual interviews (n = 29) were conducted with members, non-members, and elected leaders of the four MHOs, and with professionals from the health facilities concerned. We carried out a qualitative thematic analysis of the content. Mutual aid practices, which pre-date MHOs, can be mobilized to promote MHO membership. Mutual aid practices are based on relationships of trust. The primary reason for joining an MHO is to improve financial accessibility to health services. Non-members see that members have a strong sense of empowerment in this regard, based on a high level of trust in MHOs and their elected leaders, even if their trust in health professionals is not as strong. Non-members share these feelings of confidence in MHOs and their leadership, although they trust health professionals somewhat less than do the members. The MHOs' low penetration rate therefore cannot be explained by lack of trust, as this study shows that, even with some distrust of the professionals, the overall level of trust in MHOs is high and MHOs and their leaders function as intermediaries with health professionals. Other explanatory factors are the lack of information available to villagers and, most especially, the problems they face in being able to pay the MHO premiums. Copyright 2010 Elsevier Ltd. All rights reserved.

Distribution and Correlates of Self-Reported Crimes of Trust.

PubMed

Menard, Scott; Morris, Robert G; Gerber, Jurg; Covey, Herbert C

2011-11-01

This study examines the distribution and correlates of a special class of property crimes, crimes of trust, using longitudinal and cross sectional self-report data from a national sample. We begin by defining crimes of trust and consider their conceptual relationship to "conventional" property crimes, which we here characterize as crimes of stealth, and to white collar crimes, which are defined in terms of the social status of the perpetrators. Crimes of trust are here defined as property crimes that typically involve deliberate contact with the victim or, where there is more than one victim, with at least one or more victims, in which there is typically more of a focus on concealing the fact that a crime has been committed than on concealing the identity of the perpetrator (as is the case in crimes of stealth), without regard to the socioeconomic status of the perpetrator (thus including but not limited to white collar crimes). The focus here is on crimes of trust committed by individuals (as opposed to corporate crime). We first examine their distribution by sociodemographic characteristics, then examine the correlation of crimes of trust with other types of illegal behavior, using data from the National Youth Survey Family Study, including (1) longitudinal self-report data from a nationally representative panel of individuals who were 11-18 years old in 1976-77 and who were followed through early middle age (ages 36-44) in 2002-2003, plus (2) cross-sectional data on these individuals plus their parents, spouses, and children age 11 and older in 2002-2003 (total age range 11-88). The results suggest that crimes of trust have a different age-crime curve from conventional crimes, and that they are not as strongly correlated with problem substance use, gender, and other socioeconomic indicators as conventional crimes.

The work of case managers as experienced by older persons (75+) with multi-morbidity - a focused ethnography.

PubMed

Hjelm, Markus; Holst, Göran; Willman, Ania; Bohman, Doris; Kristensson, Jimmie

2015-12-17

Complex health systems make it difficult for older persons (75+) with multi-morbidity to achieve continuity of care. Case management could be one way to address this difficulty. Currently, there is a need to extend the knowledge regarding case management as experienced by those utilising the services, namely older persons (75+) with multi-morbidity. The study aimed to explore older persons' (75+) with multi-morbidity experiences of case managers. The study design was qualitative and used a focused ethnographic approach. Data was collected through individual interviews with 13 older persons and by participant observations with accompanying field notes, all conducted in 2012-2013. The data revealed four themes illustrating the older persons' experiences of case managers: 1) Someone providing me with a trusting relationship; 2) Someone assisting me; 3) Someone who is on my side; and 4) Someone I do not need at present. This study illustrates the importance of establishing trusting relationships between older persons and their case managers in order to truly provide assistance. The older persons valued the case managers acting as informed but unbiased facilitators. The findings could be of help in the development of case management interventions better designed for older persons with multi-morbidity.

Career Benchmarks From the Burroughs Wellcome Fund's Early Faculty Career Development Awards.

PubMed

McGovern, Victoria; Kramarik, Jean; Wilkins, Gary

2013-11-01

Documenting the career characteristics of a highly selective group of researchers provides some insight into how a successful career begins. This knowledge is of value to early-career faculty and those who evaluate them, as well as trainees who aspire to the professoriate and those who educate them. In 2010, the authors extracted information by hand from the curricula vitae of 196 basic scientists who have been supported by the Burroughs Wellcome Fund's early faculty career development programs from 1982 to 2010. Data were collected on awardees' education, awards and honors, funding, promotion, publication, service, and training activities. The end point for data was December 2010. Analyses quantified participants' time to terminal degree, faculty appointment, and first R01; determined their publication productivity; and calculated their rates of training graduate students and postdoctoral fellows. This group moved into jobs and gained first R01s faster than average. Surprisingly, those who train the most students and fellows do not publish the most. Women and men trained different numbers of undergraduates, PhDs, and postdocs. Women awardees had fewer publications on average than men. Researchers who are highly competitive at the early faculty career stage have generally been both timely in their arrival at important benchmarks and productive in terms of their scientific output. Newly trained researchers and the people and institutions that train them share responsibility for attaining expeditious progress, developing a substantial track record, and staking out fertile intellectual ground from which to grow an independent faculty career.

Trustworthy Research Institutions: The Challenging Case of Studying the Genetics of Intelligence.

PubMed

Johnston, Josephine; Banerjee, Mohini P; Geller, Gail

2015-01-01

It is simple enough to claim that academic research institutions ought to be trustworthy. Building the culture and taking the steps necessary to earn and preserve institutional trust are, however, complex processes. The experience motivating this special report--a request for the Center for Talented Youth at Johns Hopkins University to collaborate on research regarding the genetics of intelligence--illustrates how ensuring institutional trustworthiness can be in tension with a commitment to fostering research. In this essay, we explore the historical context for biomedical research institutions like Johns Hopkins that have worked to build local community trust. In so doing, we consider how the example under focus in this special report can lead to greater consideration of how research institutions balance fostering trust with their other commitments. © 2015 The Hastings Center.

Preventing Unintended Pregnancy and HIV Transmission: Effects of the HIV Treatment Cascade on Contraceptive Use and Choice in Rural KwaZulu-Natal

PubMed Central

Raifman, Julia; Chetty, Terusha; Tanser, Frank; Mutevedzi, Tinofa; Matthews, Philippa; Herbst, Kobus; Pillay, Deenan

2014-01-01

Background: For women living with HIV, contraception using condoms is recommended because it prevents not only unintended pregnancy but also acquisition of other sexually transmitted infections and onward transmission of HIV. Dual-method dual-protection contraception (condoms with other contraceptive methods) is preferable over single-method dual-protection contraception (condoms alone) because of its higher contraceptive effectiveness. We estimate the effect of progression through the HIV treatment cascade on contraceptive use and choice among HIV-infected women in rural South Africa. Methods: We linked population-based surveillance data on contraception collected by the Wellcome Trust Africa Centre for Health and Population Studies to data from the local antiretroviral treatment (ART) program in Hlabisa subdistrict, KwaZulu-Natal. In bivariate probit regression, we estimated the effects of progressing through the cascade on contraceptive choice among HIV-infected sexually active women aged 15–49 years (N = 3169), controlling for a wide range of potential confounders. Findings: Contraception use increased across the cascade from <40% among HIV-infected women who did not know their status to >70% among women who have been on ART for 4–7 years. Holding other factors equal (1) awareness of HIV status, (2) ART initiation, and (3) being on ART for 4–7 years increased the likelihood of single-method/dual-method dual protection by the following percentage points (pp), compared with women who were unaware of their HIV status: (1) 4.6 pp (P = 0.030)/3.5 pp (P = 0.001), (2) 10.3 pp (P = 0.003)/5.2 pp (P = 0.007), and (3) 21.6 pp (P < 0.001)/11.2 pp (P < 0.001). Conclusions: Progression through the HIV treatment cascade significantly increased the likelihood of contraception in general and contraception with condoms in particular. ART programs are likely to contribute to HIV prevention through the behavioral pathway of changing contraception use and choice. PMID:25436821

Preventing unintended pregnancy and HIV transmission: effects of the HIV treatment cascade on contraceptive use and choice in rural KwaZulu-Natal.

PubMed

Raifman, Julia; Chetty, Terusha; Tanser, Frank; Mutevedzi, Tinofa; Matthews, Philippa; Herbst, Kobus; Pillay, Deenan; Bärnighausen, Till

2014-12-01

For women living with HIV, contraception using condoms is recommended because it prevents not only unintended pregnancy but also acquisition of other sexually transmitted infections and onward transmission of HIV. Dual-method dual-protection contraception (condoms with other contraceptive methods) is preferable over single-method dual-protection contraception (condoms alone) because of its higher contraceptive effectiveness. We estimate the effect of progression through the HIV treatment cascade on contraceptive use and choice among HIV-infected women in rural South Africa. We linked population-based surveillance data on contraception collected by the Wellcome Trust Africa Centre for Health and Population Studies to data from the local antiretroviral treatment (ART) program in Hlabisa subdistrict, KwaZulu-Natal. In bivariate probit regression, we estimated the effects of progressing through the cascade on contraceptive choice among HIV-infected sexually active women aged 15-49 years (N = 3169), controlling for a wide range of potential confounders. Contraception use increased across the cascade from <40% among HIV-infected women who did not know their status to >70% among women who have been on ART for 4-7 years. Holding other factors equal (1) awareness of HIV status, (2) ART initiation, and (3) being on ART for 4-7 years increased the likelihood of single-method/dual-method dual protection by the following percentage points (pp), compared with women who were unaware of their HIV status: (1) 4.6 pp (P = 0.030)/3.5 pp (P = 0.001), (2) 10.3 pp (P = 0.003)/5.2 pp (P = 0.007), and (3) 21.6 pp (P < 0.001)/11.2 pp (P < 0.001). Progression through the HIV treatment cascade significantly increased the likelihood of contraception in general and contraception with condoms in particular. ART programs are likely to contribute to HIV prevention through the behavioral pathway of changing contraception use and choice.

The contribution of poor and rural populations to national trends in reproductive, maternal, newborn, and child health coverage: analyses of cross-sectional surveys from 64 countries.

PubMed

Victora, Cesar G; Barros, Aluisio J D; França, Giovanny V A; da Silva, Inácio C M; Carvajal-Velez, Liliana; Amouzou, Agbessi

2017-04-01

Coverage levels for essential interventions aimed at reducing deaths of mothers and children are increasing steadily in most low-income and middle-income countries. We assessed how much poor and rural populations in these countries are benefiting from national-level progress. We analysed trends in a composite coverage indicator (CCI) based on eight reproductive, maternal, newborn, and child health interventions in 209 national surveys in 64 countries, from Jan 1, 1994, to Dec 31, 2014. Trends by wealth quintile and urban or rural residence were fitted with multilevel modelling. We used an approach akin to the calculation of population attributable risk to quantify the contribution of poor and rural populations to national trends. From 1994 to 2014, the CCI increased by 0·82 percent points a year across all countries; households in the two poorest quintiles had an increase of 0·99 percent points a year, which was faster than that for the three wealthiest quintiles (0·68 percent points). Gains among poor populations were faster in lower-middle-income and upper-middle-income countries than in low-income countries. Globally, national level increases in CCI were 17·5% faster than they would have been without the contribution of the two poorest quintiles. Coverage increased more rapidly annually in rural (0·93 percent points) than urban (0·52 percent points) areas. National coverage gains were accelerated by important increases among poor and rural mothers and children. Despite progress, important inequalities persist, and need to be addressed to achieve the Sustainable Development Goals. UNICEF, Wellcome Trust. Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY license. Published by Elsevier Ltd.. All rights reserved.

Stepped-wedge cluster-randomised controlled trial to assess the cardiovascular health effects of a managed aquifer recharge initiative to reduce drinking water salinity in southwest coastal Bangladesh: study design and rationale

PubMed Central

Naser, Abu Mohd; Unicomb, Leanne; Doza, Solaiman; Ahmed, Kazi Matin; Rahman, Mahbubur; Uddin, Mohammad Nasir; Quraishi, Shamshad B; Selim, Shahjada; Shamsudduha, Mohammad; Burgess, William; Chang, Howard H; Gribble, Matthew O; Clasen, Thomas F; Luby, Stephen P

2017-01-01

Introduction Saltwater intrusion and salinisation have contributed to drinking water scarcity in many coastal regions globally, leading to dependence on alternative sources for water supply. In southwest coastal Bangladesh, communities have few options but to drink brackish groundwater which has been associated with high blood pressure among the adult population, and pre-eclampsia and gestational hypertension among pregnant women. Managed aquifer recharge (MAR), the purposeful recharge of surface water or rainwater to aquifers to bring hydrological equilibrium, is a potential solution for salinity problem in southwest coastal Bangladesh by creating a freshwater lens within the brackish aquifer. Our study aims to evaluate whether consumption of MAR water improves human health, particularly by reducing blood pressure among communities in coastal Bangladesh. Methods and analysis The study employs a stepped-wedge cluster-randomised controlled community trial design in 16 communities over five monthly visits. During each visit, we will collect data on participants’ source of drinking and cooking water and measure the salinity level and electrical conductivity of household stored water. At each visit, we will also measure the blood pressure of participants ≥20 years of age and pregnant women and collect urine samples for urinary sodium and protein measurements. We will use generalised linear mixed models to determine the association of access to MAR water on blood pressure of the participants. Ethics and dissemination The study protocol has been reviewed and approved by the Institutional Review Boards of the International Centre for Diarrheal Disease Research, Bangladesh (icddr,b). Informed written consent will be taken from all the participants. This study is funded by Wellcome Trust, UK. The study findings will be disseminated to the government partners, at research conferences and in peer-reviewed journals. Trial registration number NCT02746003; Pre-results. PMID:28864689

Frontal responses during learning predict vulnerability to the psychotogenic effects of ketamine: linking cognition, brain activity, and psychosis.

PubMed

Corlett, Philip R; Honey, Garry D; Aitken, Michael R F; Dickinson, Anthony; Shanks, David R; Absalom, Anthony R; Lee, Michael; Pomarol-Clotet, Edith; Murray, Graham K; McKenna, Peter J; Robbins, Trevor W; Bullmore, Edward T; Fletcher, Paul C

2006-06-01

Establishing a neurobiological account of delusion formation that links cognitive processes, brain activity, and symptoms is important to furthering our understanding of psychosis. To explore a theoretical model of delusion formation that implicates prediction error-dependent associative learning processes in a pharmacological functional magnetic resonance imaging study using the psychotomimetic drug ketamine. Within-subject, randomized, placebo-controlled study. Hospital-based clinical research facility, Addenbrooke's Hospital, Cambridge, England. The work was completed within the Wellcome Trust and Medical Research Council Behavioral and Clinical Neuroscience Institute, Cambridge. Fifteen healthy, right-handed volunteers (8 of whom were male) with a mean +/- SD age of 29 +/- 7 years and a mean +/- SD predicted full-scale IQ of 113 +/- 4 were recruited from within the local community by advertisement. Subjects were given low-dose ketamine (100 ng/mL of plasma) or placebo while performing a causal associative learning task during functional magnetic resonance imaging. In a separate session outside the scanner, the dose was increased (to 200 ng/mL of plasma) and subjects underwent a structured clinical interview. Brain activation, blood plasma levels of ketamine, and scores from psychiatric ratings scales (Brief Psychiatric Ratings Scale, Present State Examination, and Clinician-Administered Dissociative States Scale). Low-dose ketamine perturbs error-dependent learning activity in the right frontal cortex (P = .03). High-dose ketamine produces perceptual aberrations (P = .01) and delusion-like beliefs (P = .007). Critically, subjects showing the highest degree of frontal activation with placebo show the greatest occurrence of drug-induced perceptual aberrations (P = .03) and ideas or delusions of reference (P = .04). These findings relate aberrant prediction error-dependent associative learning to referential ideas and delusions via a perturbation of frontal cortical function. They are consistent with a model of delusion formation positing disruptions in error-dependent learning.

Do gifts increase consent to home-based HIV testing? A difference-in-differences study in rural KwaZulu-Natal, South Africa.

PubMed

McGovern, Mark E; Herbst, Kobus; Tanser, Frank; Mutevedzi, Tinofa; Canning, David; Gareta, Dickman; Pillay, Deenan; Bärnighausen, Till

2016-12-01

Despite the importance of HIV testing for controlling the HIV epidemic, testing rates remain low. Efforts to scale up testing coverage and frequency in hard-to-reach and at-risk populations commonly focus on home-based HIV testing. This study evaluates the effect of a gift (a US$5 food voucher for families) on consent rates for home-based HIV testing. We use data on 18 478 individuals (6 418 men and 12 060 women) who were successfully contacted to participate in the 2009 and 2010 population-based HIV surveillance carried out by the Wellcome Trust's Africa Health Research Institute in rural KwaZulu-Natal, South Africa. Of 18 478 potential participants contacted in both years, 35% (6 518) consented to test in 2009, and 41% (7 533) consented to test in 2010. Our quasi-experimental difference-in-differences approach controls for unobserved confounding in estimating the causal effect of the intervention on HIV-testing consent rates. Allocation of the gift to a family in 2010 increased the probability of family members consenting to test in the same year by 25 percentage points [95% confidence interval (CI) 21-30 percentage points; P  < 0.001]. The intervention effect persisted, slightly attenuated, in the year following the intervention (2011). In HIV hyperendemic settings, a gift can be highly effective at increasing consent rates for home-based HIV testing. Given the importance of HIV testing for treatment uptake and individual health, as well as for HIV treatment-as-prevention strategies and for monitoring the population impact of the HIV response, gifts should be considered as a supportive intervention for HIV-testing initiatives where consent rates have been low. © The Author 2016. Published by Oxford University Press on behalf of the International Epidemiological Association

Improving health research governance and management in the Western Pacific: a WHO expert consultation.

PubMed

Rani, Manju; Bekedam, Hendrik; Buckley, Brian S

2011-11-01

Repeated calls have been made in recent decades to increase investments in health research, especially in low- and middle-income countries (LMIC). However, the perceived low relevance and quality of health research, poor visibility of outputs, and difficulties in tracking current levels of and returns on investments have undermined efforts to advocate for additional investments in these countries. Some of these issues emanate from inadequate governance and management systems for health research at the national level, which are ineffective in tracking and steering the research portfolio and investments, ensuring quality, and facilitating access to research outputs. In spite of this, the value, necessity, and cost of performing health research management and governance functions are not well appreciated, especially in LMIC. To address this, the World Health Organization (WHO) Regional Office for the Western Pacific organized an expert consultation in August 2011, involving experts from 14 of its developed and developing member states and from leading research organizations such as the Wellcome Trust. The consultation identified essential health research governance and management functions that must be performed by appropriate organizational entities to maximize returns on health research investments. In addition, three specific areas for intervention were considered: (1) prospective research registration in publicly accessible national health research registries; (2) systematic health research data archiving and wider access; and (3) national research ethics systems. A consensus was reached on the need to invest more in essential health research and management functions, including establishing publicly accessible web-based national health research registries for prospective registration of health research, setting up systems to archive and share health research data, and improving the governance of research ethics committees. The consultation also concluded that the costs of performing these functions are legitimate and necessary research costs that must be shouldered by research funding organizations. © 2011 Blackwell Publishing Asia Pty Ltd and Chinese Cochrane Center, West China Hospital of Sichuan University.

Investments in respiratory infectious disease research 1997–2010: a systematic analysis of UK funding

PubMed Central

Head, Michael G; Fitchett, Joseph R; Cooke, Mary K; Wurie, Fatima B; Hayward, Andrew C; Lipman, Marc C; Atun, Rifat

2014-01-01

Objectives Respiratory infections are responsible for a large global burden of disease. We assessed the public and philanthropic investments awarded to UK institutions for respiratory infectious disease research to identify areas of underinvestment. We aimed to identify projects and categorise them by pathogen, disease and position along the research and development value chain. Setting The UK. Participants Institutions that host and carry out infectious disease research. Primary and secondary outcome measures The total amount spent and number of studies with a focus on several different respiratory pathogens or diseases, and to correlate these against the global burden of disease; also the total amount spent and number of studies relating to the type of science, the predominant funder in each category and the mean and median award size. Results We identified 6165 infectious disease studies with a total investment of £2·6 billion. Respiratory research received £419 million (16.1%) across 1192 (19.3%) studies. The Wellcome Trust provided greatest investment (£135.2 million; 32.3%). Tuberculosis received £155 million (37.1%), influenza £80 million (19.1%) and pneumonia £27.8 million (6.6%). Despite high burden, there was relatively little investment in vaccine-preventable diseases including diphtheria (£0.1 million, 0.03%), measles (£5.0 million, 1.2%) and drug-resistant tuberculosis. There were 802 preclinical studies (67.3%) receiving £273 million (65.2%), while implementation research received £81 million (19.3%) across 274 studies (23%). There were comparatively few phase I–IV trials or product development studies. Global health research received £68.3 million (16.3%). Relative investment was strongly correlated with 2010 disease burden. Conclusions The UK predominantly funds preclinical science. Tuberculosis is the most studied respiratory disease. The high global burden of pneumonia-related disease warrants greater investment than it has historically received. Other priority areas include antimicrobial resistance (particularly within tuberculosis), economics and proactive investments for emerging infectious threats. PMID:24670431

The science commons in health research: structure, function, and value.

PubMed

Cook-Deegan, Robert

The "science commons," knowledge that is widely accessible at low or no cost, is a uniquely important input to scientific advance and cumulative technological innovation. It is primarily, although not exclusively, funded by government and nonprofit sources. Much of it is produced at academic research centers, although some academic science is proprietary and some privately funded R&D enters the science commons. Science in general aspires to Mertonian norms of openness, universality, objectivity, and critical inquiry. The science commons diverges from proprietary science primarily in being open and being very broadly available. These features make the science commons particularly valuable for advancing knowledge, for training innovators who will ultimately work in both public and private sectors, and in providing a common stock of knowledge upon which all players-both public and private-can draw readily. Open science plays two important roles that proprietary R&D cannot: it enables practical benefits even in the absence of profitable markets for goods and services, and its lays a shared foundation for subsequent private R&D. The history of genomics in the period 1992-2004, covering two periods when genomic startup firms attracted significant private R&D investment, illustrates these features of how a science commons contributes value. Commercial interest in genomics was intense during this period. Fierce competition between private sector and public sector genomics programs was highly visible. Seemingly anomalous behavior, such as private firms funding "open science," can be explained by unusual business dynamics between established firms wanting to preserve a robust science commons to prevent startup firms from limiting established firms' freedom to operate. Deliberate policies to create and protect a large science commons were pursued by nonprofit and government funders of genomics research, such as the Wellcome Trust and National Institutes of Health. These policies were crucial to keeping genomic data and research tools widely available at low cost.

Investments in respiratory infectious disease research 1997-2010: a systematic analysis of UK funding.

PubMed

Head, Michael G; Fitchett, Joseph R; Cooke, Mary K; Wurie, Fatima B; Hayward, Andrew C; Lipman, Marc C; Atun, Rifat

2014-03-26

Respiratory infections are responsible for a large global burden of disease. We assessed the public and philanthropic investments awarded to UK institutions for respiratory infectious disease research to identify areas of underinvestment. We aimed to identify projects and categorise them by pathogen, disease and position along the research and development value chain. The UK. Institutions that host and carry out infectious disease research. The total amount spent and number of studies with a focus on several different respiratory pathogens or diseases, and to correlate these against the global burden of disease; also the total amount spent and number of studies relating to the type of science, the predominant funder in each category and the mean and median award size. We identified 6165 infectious disease studies with a total investment of £2·6 billion. Respiratory research received £419 million (16.1%) across 1192 (19.3%) studies. The Wellcome Trust provided greatest investment (£135.2 million; 32.3%). Tuberculosis received £155 million (37.1%), influenza £80 million (19.1%) and pneumonia £27.8 million (6.6%). Despite high burden, there was relatively little investment in vaccine-preventable diseases including diphtheria (£0.1 million, 0.03%), measles (£5.0 million, 1.2%) and drug-resistant tuberculosis. There were 802 preclinical studies (67.3%) receiving £273 million (65.2%), while implementation research received £81 million (19.3%) across 274 studies (23%). There were comparatively few phase I-IV trials or product development studies. Global health research received £68.3 million (16.3%). Relative investment was strongly correlated with 2010 disease burden. The UK predominantly funds preclinical science. Tuberculosis is the most studied respiratory disease. The high global burden of pneumonia-related disease warrants greater investment than it has historically received. Other priority areas include antimicrobial resistance (particularly within tuberculosis), economics and proactive investments for emerging infectious threats.

Stepped-wedge cluster-randomised controlled trial to assess the cardiovascular health effects of a managed aquifer recharge initiative to reduce drinking water salinity in southwest coastal Bangladesh: study design and rationale.

PubMed

Naser, Abu Mohd; Unicomb, Leanne; Doza, Solaiman; Ahmed, Kazi Matin; Rahman, Mahbubur; Uddin, Mohammad Nasir; Quraishi, Shamshad B; Selim, Shahjada; Shamsudduha, Mohammad; Burgess, William; Chang, Howard H; Gribble, Matthew O; Clasen, Thomas F; Luby, Stephen P

2017-09-01

Saltwater intrusion and salinisation have contributed to drinking water scarcity in many coastal regions globally, leading to dependence on alternative sources for water supply. In southwest coastal Bangladesh, communities have few options but to drink brackish groundwater which has been associated with high blood pressure among the adult population, and pre-eclampsia and gestational hypertension among pregnant women. Managed aquifer recharge (MAR), the purposeful recharge of surface water or rainwater to aquifers to bring hydrological equilibrium, is a potential solution for salinity problem in southwest coastal Bangladesh by creating a freshwater lens within the brackish aquifer. Our study aims to evaluate whether consumption of MAR water improves human health, particularly by reducing blood pressure among communities in coastal Bangladesh. The study employs a stepped-wedge cluster-randomised controlled community trial design in 16 communities over five monthly visits. During each visit, we will collect data on participants' source of drinking and cooking water and measure the salinity level and electrical conductivity of household stored water. At each visit, we will also measure the blood pressure of participants ≥20 years of age and pregnant women and collect urine samples for urinary sodium and protein measurements. We will use generalised linear mixed models to determine the association of access to MAR water on blood pressure of the participants. The study protocol has been reviewed and approved by the Institutional Review Boards of the International Centre for Diarrheal Disease Research, Bangladesh (icddr,b). Informed written consent will be taken from all the participants. This study is funded by Wellcome Trust, UK. The study findings will be disseminated to the government partners, at research conferences and in peer-reviewed journals. NCT02746003; Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Systematic analysis of funding awarded for mycology research to institutions in the UK, 1997–2010

PubMed Central

Head, Michael G; Fitchett, Joseph R; Atun, Rifat; May, Robin C

2014-01-01

Objectives Fungal infections cause significant global morbidity and mortality. We have previously described the UK investments in global infectious disease research, and here our objective is to describe the investments awarded to UK institutions for mycology research and outline potential funding gaps in the UK portfolio. Design Systematic analysis. Setting UK institutions carrying out infectious disease research. Primary and secondary outcome measures Primary outcome is the amount of funding and number of studies related to mycology research. Secondary outcomes are describing the investments made to specific fungal pathogens and diseases, and also the type of science along the R&D value chain. Methods We systematically searched databases and websites for information on research studies from public and philanthropic funding institutions awarded between 1997 and 2010, and highlighted the mycology-related projects. Results Of 6165 funded studies, we identified 171 studies related to mycology (total investment £48.4 million, 1.9% of all infection research, with mean annual funding £3.5 million). Studies related to global health represented 5.1% of this funding (£2.4 million, compared with 35.6% of all infectious diseases). Leading funders were the Biotechnology and Biological Sciences Research Council (£14.8 million, 30.5%) and Wellcome Trust (£12.0 million, 24.7%). Preclinical studies received £42.2 million (87.3%), with clinical trials, intervention studies and implementation research in total receiving £6.2 million (12.7%). By institution, University of Aberdeen received most funding (£16.9 million, 35%). Studies investigating antifungal resistance received £1.5 million (3.2%). Conclusions There is little translation of preclinical research into clinical trials or implementation research in spite of substantial disease burden globally, and there are few UK institutions that carry out significant quantities of mycology research of any type. In the context of global health and the burden of disease in low-income countries, more investment is required for mycology research. PMID:24413353

Systematic analysis of funding awarded for mycology research to institutions in the UK, 1997-2010.

PubMed

Head, Michael G; Fitchett, Joseph R; Atun, Rifat; May, Robin C

2014-01-09

Fungal infections cause significant global morbidity and mortality. We have previously described the UK investments in global infectious disease research, and here our objective is to describe the investments awarded to UK institutions for mycology research and outline potential funding gaps in the UK portfolio. Systematic analysis. UK institutions carrying out infectious disease research. Primary outcome is the amount of funding and number of studies related to mycology research. Secondary outcomes are describing the investments made to specific fungal pathogens and diseases, and also the type of science along the R&D value chain. We systematically searched databases and websites for information on research studies from public and philanthropic funding institutions awarded between 1997 and 2010, and highlighted the mycology-related projects. Of 6165 funded studies, we identified 171 studies related to mycology (total investment £48.4 million, 1.9% of all infection research, with mean annual funding £3.5 million). Studies related to global health represented 5.1% of this funding (£2.4 million, compared with 35.6% of all infectious diseases). Leading funders were the Biotechnology and Biological Sciences Research Council (£14.8 million, 30.5%) and Wellcome Trust (£12.0 million, 24.7%). Preclinical studies received £42.2 million (87.3%), with clinical trials, intervention studies and implementation research in total receiving £6.2 million (12.7%). By institution, University of Aberdeen received most funding (£16.9 million, 35%). Studies investigating antifungal resistance received £1.5 million (3.2%). There is little translation of preclinical research into clinical trials or implementation research in spite of substantial disease burden globally, and there are few UK institutions that carry out significant quantities of mycology research of any type. In the context of global health and the burden of disease in low-income countries, more investment is required for mycology research.

Prevalence of dementia in Latin America, India, and China: a population-based cross-sectional survey

PubMed Central

Rodriguez, Juan J Llibre; Ferri, Cleusa P; Acosta, Daisy; Guerra, Mariella; Huang, Yueqin; Jacob, KS; Krishnamoorthy, ES; Salas, Aquiles; Sosa, Ana Luisa; Acosta, Isaac; Dewey, Michael E; Gaona, Ciro; Jotheeswaran, AT; Li, Shuran; Rodriguez, Diana; Rodriguez, Guillermina; Kumar, P Senthil; Valhuerdi, Adolfo; Prince, Martin

2008-01-01

Summary Background Studies have suggested that the prevalence of dementia is lower in developing than in developed regions. We investigated the prevalence and severity of dementia in sites in low-income and middle-income countries according to two definitions of dementia diagnosis. Methods We undertook one-phase cross-sectional surveys of all residents aged 65 years and older (n=14 960) in 11 sites in seven low-income and middle-income countries (China, India, Cuba, Dominican Republic, Venezuela, Mexico, and Peru). Dementia diagnosis was made according to the culturally and educationally sensitive 10/66 dementia diagnostic algorithm, which had been prevalidated in 25 Latin American, Asian, and African centres; and by computerised application of the dementia criterion from the Diagnostic and Statistical Manual of Mental Disorders (DSM IV). We also compared prevalence of DSM-IV dementia in each of the study sites with that from estimates in European studies. Findings The prevalence of DSM-IV dementia varied widely, from 0·3% (95% CI 0·1–0·5) in rural India to 6·3% (5·0–7·7) in Cuba. After standardisation for age and sex, DSM-IV prevalence in urban Latin American sites was four-fifths of that in Europe (standardised morbidity ratio 80 [95% CI 70–91]), but in China the prevalence was only half (56 [32–91] in rural China), and in India and rural Latin America a quarter or less of the European prevalence (18 [5–34] in rural India). 10/66 dementia prevalence was higher than that of DSM-IV dementia, and more consistent across sites, varying between 5·6% (95% CI 4·2–7·0) in rural China and 11·7% (10·3–13·1) in the Dominican Republic. The validity of the 847 of 1345 cases of 10/66 dementia not confirmed by DSM-IV was supported by high levels of associated disability (mean WHO Disability Assessment Schedule II score 33·7 [SD 28·6]). Interpretation As compared with the 10/66 dementia algorithm, the DSM-IV dementia criterion might underestimate dementia prevalence, especially in regions with low awareness of this emerging public-health problem. Funding Wellcome Trust (UK); WHO; the US Alzheimer's Association; and Fondo Nacional De Ciencia Y Tecnologia, Consejo De Desarrollo Cientifico Y Humanistico, and Universidad Central De Venezuela (Venezuela). PMID:18657855

Blantyre Malaria Project Epilepsy Study (BMPES) of neurological outcomes in retinopathy-positive paediatric cerebral malaria survivors: a prospective cohort study.

PubMed

Birbeck, Gretchen L; Molyneux, Malcolm E; Kaplan, Peter W; Seydel, Karl B; Chimalizeni, Yamikani F; Kawaza, Kondwani; Taylor, Terrie E

2010-12-01

Cerebral malaria, a disorder characterised by coma, parasitaemia, and no other evident cause of coma, is challenging to diagnose definitively in endemic regions that have high rates of asymptomatic parasitaemia and limited neurodiagnostic facilities. A recently described malaria retinopathy improves diagnostic specificity. We aimed to establish whether retinopathy-positive cerebral malaria is a risk factor for epilepsy or other neurodisabilities. Between 2005 and 2007, we did a prospective cohort study of survivors of cerebral malaria with malaria retinopathy in Blantyre, Malawi. Children with cerebral malaria were identified at the time of their index admission and age-matched to concurrently admitted children without coma or nervous system infection. Initially matching of cases to controls was 1:1 but, in 2006, enrolment criteria for cerebral malaria survivors were revised to limit inclusion to children with cerebral malaria and retinopathy on the basis of indirect ophthalmoscopic examination; matching was then changed to 1:2 and the revised inclusion criteria were applied retrospectively for children enrolled previously. Clinical assessments at discharge and standardised nurse-led follow-up every 3 months thereafter were done to identify children with new seizure disorders or other neurodisabilities. A Kaplan-Meier survival analysis was done for incident epilepsy. 132 children with retinopathy-positive cerebral malaria and 264 age-matched, non-comatose controls were followed up for a median of 495 days (IQR 195-819). 12 of 132 cerebral malaria survivors developed epilepsy versus none of 264 controls (odds ratio [OR] undefined; p<0·0001). 28 of 121 cerebral malaria survivors developed new neurodisabilities, characterised by gross motor, sensory, or language deficits, compared with two of 253 controls (OR 37·8, 95% CI 8·8-161·8; p<0·0001). The risk factors for epilepsy in children with cerebral malaria were a higher maximum temperature (39·4°C [SD 1·2] vs 38·5°C [1·1]; p=0·01) and acute seizures (11/12 vs 76/120; OR 6·37, 95% CI 1·02-141·2), and male sex was a risk factor for new neurodisabilities (20/28 vs 38/93; OR 3·62, 1·44-9·06). Almost a third of retinopathy-positive cerebral malaria survivors developed epilepsy or other neurobehavioural sequelae. Neuroprotective clinical trials aimed at managing hyperpyrexia and optimising seizure control are warranted. US National Institutes of Health and Wellcome Trust. Copyright © 2010 Elsevier Ltd. All rights reserved.

Rapid, comprehensive, and affordable mycobacterial diagnosis with whole-genome sequencing: a prospective study

PubMed Central

Pankhurst, Louise J; del Ojo Elias, Carlos; Votintseva, Antonina A; Walker, Timothy M; Cole, Kevin; Davies, Jim; Fermont, Jilles M; Gascoyne-Binzi, Deborah M; Kohl, Thomas A; Kong, Clare; Lemaitre, Nadine; Niemann, Stefan; Paul, John; Rogers, Thomas R; Roycroft, Emma; Smith, E Grace; Supply, Philip; Tang, Patrick; Wilcox, Mark H; Wordsworth, Sarah; Wyllie, David; Xu, Li; Crook, Derrick W

2016-01-01

Summary Background Slow and cumbersome laboratory diagnostics for Mycobacterium tuberculosis complex (MTBC) risk delayed treatment and poor patient outcomes. Whole-genome sequencing (WGS) could potentially provide a rapid and comprehensive diagnostic solution. In this prospective study, we compare real-time WGS with routine MTBC diagnostic workflows. Methods We compared sequencing mycobacteria from all newly positive liquid cultures with routine laboratory diagnostic workflows across eight laboratories in Europe and North America for diagnostic accuracy, processing times, and cost between Sept 6, 2013, and April 14, 2014. We sequenced specimens once using local Illumina MiSeq platforms and processed data centrally using a semi-automated bioinformatics pipeline. We identified species or complex using gene presence or absence, predicted drug susceptibilities from resistance-conferring mutations identified from reference-mapped MTBC genomes, and calculated genetic distance to previously sequenced UK MTBC isolates to detect outbreaks. WGS data processing and analysis was done by staff masked to routine reference laboratory and clinical results. We also did a microcosting analysis to assess the financial viability of WGS-based diagnostics. Findings Compared with routine results, WGS predicted species with 93% (95% CI 90–96; 322 of 345 specimens; 356 mycobacteria specimens submitted) accuracy and drug susceptibility also with 93% (91–95; 628 of 672 specimens; 168 MTBC specimens identified) accuracy, with one sequencing attempt. WGS linked 15 (16% [95% CI 10–26]) of 91 UK patients to an outbreak. WGS diagnosed a case of multidrug-resistant tuberculosis before routine diagnosis was completed and discovered a new multidrug-resistant tuberculosis cluster. Full WGS diagnostics could be generated in a median of 9 days (IQR 6–10), a median of 21 days (IQR 14–32) faster than final reference laboratory reports were produced (median of 31 days [IQR 21–44]), at a cost of £481 per culture-positive specimen, whereas routine diagnosis costs £518, equating to a WGS-based diagnosis cost that is 7% cheaper annually than are present diagnostic workflows. Interpretation We have shown that WGS has a scalable, rapid turnaround, and is a financially feasible method for full MTBC diagnostics. Continued improvements to mycobacterial processing, bioinformatics, and analysis will improve the accuracy, speed, and scope of WGS-based diagnosis. Funding National Institute for Health Research, Department of Health, Wellcome Trust, British Colombia Centre for Disease Control Foundation for Population and Public Health, Department of Clinical Microbiology, Trinity College Dublin. PMID:26669893

Interpersonal Consulting Skills for Instructional Technology Consultants: A Multiple Case Study

ERIC Educational Resources Information Center

van Leusen, Peter; Ottenbreit-Lefwich, Anne T.; Brush, Thomas

2016-01-01

Building a trust-based relationship with faculty is one of the most important attributes of effective Instructional Technology Consultants (ITC) in order to integrate emerging technologies into higher education. Utilizing a multiple case study research design, four experienced ITCs at a large urban research university located in the Midwest showed…

Emotional and Social Competencies of a Principal School Leader

ERIC Educational Resources Information Center

Williams, Angelina M.

2017-01-01

Emotional and Social Competencies (ESCs) are considered important to school leadership because it is believed that they can help to build trusting relationships with staff and improve organizational capacity within the school. Limited case study research has been conducted on how ESCs are manifested in principal practice. This case study is…

Education and Modernization of Micronesia: A Case Study in Development and Development Planning.

ERIC Educational Resources Information Center

Pearse, Richard; Bezanson, Keith A.

The case study examined the development of an overall education plan for the Trust Territory of the Pacific Islands. The methodology of multidisciplinary education planning through the use of general comparative analysis models of political, economic, and social development is explained: Almond and Powell's framework for the analysis of political…

33 CFR 326.5 - Legal action.

Code of Federal Regulations, 2010 CFR

2010-07-01

... directly to the U.S. Attorney. Because of the unique legal system in the Trust Territories, all cases over... 33 Navigation and Navigable Waters 3 2010-07-01 2010-07-01 false Legal action. 326.5 Section 326.5... § 326.5 Legal action. (a) General. For cases the district engineer determines to be appropriate, he will...

The Campus Diversity Initiative: A Case Study

ERIC Educational Resources Information Center

Nayak, Sharada

2005-01-01

This Case Study presents the Campus Diversity Initiative (CDI), a three-phase project lead by the Educational Resources Project Centre Trust, in New Delhi, India. In a historic and cultural context different from that of India, the American Diversity Initiative was launched by the Ford Foundation in 1990 and addressed their diversity issues by…

HealthTrust: A Social Network Approach for Retrieving Online Health Videos

PubMed Central

Karlsen, Randi; Melton, Genevieve B

2012-01-01

Background Social media are becoming mainstream in the health domain. Despite the large volume of accurate and trustworthy health information available on social media platforms, finding good-quality health information can be difficult. Misleading health information can often be popular (eg, antivaccination videos) and therefore highly rated by general search engines. We believe that community wisdom about the quality of health information can be harnessed to help create tools for retrieving good-quality social media content. Objectives To explore approaches for extracting metrics about authoritativeness in online health communities and how these metrics positively correlate with the quality of the content. Methods We designed a metric, called HealthTrust, that estimates the trustworthiness of social media content (eg, blog posts or videos) in a health community. The HealthTrust metric calculates reputation in an online health community based on link analysis. We used the metric to retrieve YouTube videos and channels about diabetes. In two different experiments, health consumers provided 427 ratings of 17 videos and professionals gave 162 ratings of 23 videos. In addition, two professionals reviewed 30 diabetes channels. Results HealthTrust may be used for retrieving online videos on diabetes, since it performed better than YouTube Search in most cases. Overall, of 20 potential channels, HealthTrust’s filtering allowed only 3 bad channels (15%) versus 8 (40%) on the YouTube list. Misleading and graphic videos (eg, featuring amputations) were more commonly found by YouTube Search than by searches based on HealthTrust. However, some videos from trusted sources had low HealthTrust scores, mostly from general health content providers, and therefore not highly connected in the diabetes community. When comparing video ratings from our reviewers, we found that HealthTrust achieved a positive and statistically significant correlation with professionals (Pearson r 10 = .65, P = .02) and a trend toward significance with health consumers (r 7 = .65, P = .06) with videos on hemoglobinA1 c, but it did not perform as well with diabetic foot videos. Conclusions The trust-based metric HealthTrust showed promising results when used to retrieve diabetes content from YouTube. Our research indicates that social network analysis may be used to identify trustworthy social media in health communities. PMID:22356723

Community engagement to enhance trust between Gypsy/Travellers, and maternity, early years' and child dental health services: protocol for a multi-method exploratory study.

PubMed

McFadden, Alison; Atkin, Karl; Bell, Kerry; Innes, Nicola; Jackson, Cath; Jones, Helen; MacGillivray, Steve; Siebelt, Lindsay

2016-11-14

Gypsy/Travellers have poor health and experience discrimination alongside structural and cultural barriers when accessing health services and consequently may mistrust those services. Our study aims to investigate which approaches to community engagement are most likely to be effective at enhancing trust between Gypsy/Travellers and mainstream health services. This multi-method 30-month study, commenced in June 2015, and comprises four stages. 1. Three related reviews: a) systematic review of Gypsy/Travellers' access to health services; b) systematic review of reviews of how trust has been conceptualised within healthcare; c) realist synthesis of community engagement approaches to enhance trust and increase Gypsy/Travellers' participation in health services. The reviews will consider any economic literature; 2. Online consultation with health and social care practitioners, and civil society organisations on existing engagement activities, including perceptions of barriers and good practice; 3. Four in-depth case studies of different Gypsy/Traveller communities, focusing on maternity, early years and child dental health services. The case studies include the views of 32-48 mothers of pre-school children, 32-40 healthcare providers and 8-12 informants from third sector organisations. 4. Two stakeholder workshops exploring whether policy options are realistic, sustainable and replicable. Case study data will be analysed thematically informed by the evaluative framework derived from the realist synthesis in stage one. The main outputs will be: a) an evaluative framework of Gypsy/Travellers' engagement with health services; b) recommendations for policy and practice; c) evidence on which to base future implementation strategies including estimation of costs. Our novel multi-method study seeks to provide recommendations for policy and practice that have potential to improve uptake and delivery of health services, and to reduce lifetime health inequalities for Gypsy/Travellers. The findings may have wider resonance for other marginalised populations. Strengths and limitations of the study are discussed. Prospero registration for literature reviews: CRD42015021955 and CRD42015021950 UKCRN reference: 20036.

A secured e-tendering modeling using misuse case approach

NASA Astrophysics Data System (ADS)

Mohd, Haslina; Robie, Muhammad Afdhal Muhammad; Baharom, Fauziah; Darus, Norida Muhd; Saip, Mohamed Ali; Yasin, Azman

2016-08-01

Major risk factors relating to electronic transactions may lead to destructive impacts on trust and transparency in the process of tendering. Currently, electronic tendering (e-tendering) systems still remain uncertain in issues relating to legal and security compliance and most importantly it has an unclear security framework. Particularly, the available systems are lacking in addressing integrity, confidentiality, authentication, and non-repudiation in e-tendering requirements. Thus, one of the challenges in developing an e-tendering system is to ensure the system requirements include the function for secured and trusted environment. Therefore, this paper aims to model a secured e-tendering system using misuse case approach. The modeling process begins with identifying the e-tendering process, which is based on the Australian Standard Code of Tendering (AS 4120-1994). It is followed by identifying security threats and their countermeasure. Then, the e-tendering was modelled using misuse case approach. The model can contribute to e-tendering developers and also to other researchers or experts in the e-tendering domain.

Improving the trust in results of numerical simulations and scientific data analytics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cappello, Franck; Constantinescu, Emil; Hovland, Paul

This white paper investigates several key aspects of the trust that a user can give to the results of numerical simulations and scientific data analytics. In this document, the notion of trust is related to the integrity of numerical simulations and data analytics applications. This white paper complements the DOE ASCR report on Cybersecurity for Scientific Computing Integrity by (1) exploring the sources of trust loss; (2) reviewing the definitions of trust in several areas; (3) providing numerous cases of result alteration, some of them leading to catastrophic failures; (4) examining the current notion of trust in numerical simulation andmore » scientific data analytics; (5) providing a gap analysis; and (6) suggesting two important research directions and their respective research topics. To simplify the presentation without loss of generality, we consider that trust in results can be lost (or the results’ integrity impaired) because of any form of corruption happening during the execution of the numerical simulation or the data analytics application. In general, the sources of such corruption are threefold: errors, bugs, and attacks. Current applications are already using techniques to deal with different types of corruption. However, not all potential corruptions are covered by these techniques. We firmly believe that the current level of trust that a user has in the results is at least partially founded on ignorance of this issue or the hope that no undetected corruptions will occur during the execution. This white paper explores the notion of trust and suggests recommendations for developing a more scientifically grounded notion of trust in numerical simulation and scientific data analytics. We first formulate the problem and show that it goes beyond previous questions regarding the quality of results such as V&V, uncertainly quantification, and data assimilation. We then explore the complexity of this difficult problem, and we sketch complementary general approaches to address it. This paper does not focus on the trust that the execution will actually complete. The product of simulation or of data analytic executions is the final element of a potentially long chain of transformations, where each stage has the potential to introduce harmful corruptions. These corruptions may produce results that deviate from the user-expected accuracy without notifying the user of this deviation. There are many potential sources of corruption before and during the execution; consequently, in this white paper we do not focus on the protection of the end result after the execution.« less

FSAW for REIT selection in multi-criteria decision making

NASA Astrophysics Data System (ADS)

Adawiyah, C. W. Rabiatul; Abdullah, Lazim

2014-07-01

Real Estate Investment Trust (REIT) is profitable investments that gain Malaysian investors' attention. It can be a great way to increase our net worth. Due to the existence of many property trusts, investors face difficulties in determining the best property trusts to invest their wealth. This high risk investment makes investors cautious in choosing the platform for investing their wealth. In real world situation, the data collected are inexact and ambiguous. Investment reminds investors to beware because it carries risk no matter low or high. There are lots of things that investors need to consider before invest in any property or trust. The aim of this paper is to identify the best criteria of REIT and determine the best property trust that helps investors gain profits in their investment. Four experts in areas of investment are randomly selected to assess and provide information regarding to Malaysia's REITs. Decision makers were asked to rate the criteria for every alternatives by using the linguistic variables. The five linguistic variables were used as input data to test fuzzy simple additive weighting (FSAW) model. From the study conducted, transparency indicates the necessary criteria for each property trust. This decision making model used to be possible to test FSAW model in investment sector. The decision makers also asked to evaluate the alternatives based on the linguistic ranking variables to rank the alternatives and the result shows the best alternative in this case is Amanah Harta Tanah PNB. The ranking signifies the impact of the criterion and alternatives to investors especially REITs investors.

What's the evidence that NICE guidance has been implemented? Results from a national evaluation using time series analysis, audit of patients' notes, and interviews.

PubMed

Sheldon, Trevor A; Cullum, Nicky; Dawson, Diane; Lankshear, Annette; Lowson, Karin; Watt, Ian; West, Peter; Wright, Dianne; Wright, John

2004-10-30

To assess the extent and pattern of implementation of guidance issued by the National Institute for Clinical Excellence (NICE). Interrupted time series analysis, review of case notes, survey, and interviews. Acute and primary care trusts in England and Wales. All primary care prescribing, hospital pharmacies; a random sample of 20 acute trusts, 17 mental health trusts, and 21 primary care trusts; and senior clinicians and managers from five acute trusts. Rates of prescribing and use of procedures and medical devices relative to evidence based guidance. 6308 usable patient audit forms were returned. Implementation of NICE guidance varied by trust and by topic. Prescribing of some taxanes for cancer (P < 0.002) and orlistat for obesity (P < 0.001) significantly increased in line with guidance. Prescribing of drugs for Alzheimer's disease and prophylactic extraction of wisdom teeth showed trends consistent with, but not obviously a consequence of, the guidance. Prescribing practice often did not accord with the details of the guidance. No change was apparent in the use of hearing aids, hip prostheses, implantable cardioverter defibrillators, laparoscopic hernia repair, and laparoscopic colorectal cancer surgery after NICE guidance had been issued. Implementation of NICE guidance has been variable. Guidance seems more likely to be adopted when there is strong professional support, a stable and convincing evidence base, and no increased or unfunded costs, in organisations that have established good systems for tracking guidance implementation and where the professionals involved are not isolated. Guidance needs to be clear and reflect the clinical context.

Gaining trust as well as respect in communicating to motivated audiences about science topics

PubMed Central

Fiske, Susan T.; Dupree, Cydney

2014-01-01

Expertise is a prerequisite for communicator credibility, entailing the knowledge and ability to be accurate. Trust also is essential to communicator credibility. Audiences view trustworthiness as the motivation to be truthful. Identifying whom to trust follows systematic principles. People decide quickly another’s apparent intent: Who is friend or foe, on their side or not, or a cooperator or competitor. Those seemingly on their side are deemed warm (friendly, trustworthy). People then decide whether the other is competent to enact those intents. Perception of scientists, like other social perceptions, involves inferring both their apparent intent (warmth) and capability (competence). To illustrate, we polled adults online about typical American jobs, rated as American society views them, on warmth and competence dimensions, as well as relevant emotions. Ambivalently perceived high-competence but low-warmth, “envied” professions included lawyers, chief executive officers, engineers, accountants, scientists, and researchers. Being seen as competent but cold might not seem problematic until one recalls that communicator credibility requires not just status and expertise but also trustworthiness (warmth). Other research indicates the risk from being enviable. Turning to a case study of scientific communication, another online sample of adults described public attitudes toward climate scientists specifically. Although distrust is low, the apparent motive to gain research money is distrusted. The literature on climate science communicators agrees that the public trusts impartiality, not persuasive agendas. Overall, communicator credibility needs to address both expertise and trustworthiness. Scientists have earned audiences’ respect, but not necessarily their trust. Discussing, teaching, and sharing information can earn trust to show scientists’ trustworthy intentions. PMID:25225372

The dynamics of commissioning across organisational and clinical boundaries.

PubMed

Baxter, Kate; Weiss, Marjorie; Le Grand, Julian

2008-01-01

The purpose of the paper is to investigate the inter- and intra-organisational relationships in the commissioning of secondary care by primary care trusts in England, using a principal-agent framework. The methodology is a qualitative study of three case studies. A total of 13 commissioning-related meetings were observed. In total, 21 managers and six consultant surgeons were interviewed. There are a number of different levels at which contractual and managerial control take place. Different strengths of control at one level can affect willingness to comply with agreements at other levels. Agreements at one level do not necessarily result in appropriate or expected action at another. The system for commissioning in the National Health Service (NHS) has changed with the introduction of payment by results and practice-based commissioning. However, the dynamics of the inter- and intra-organisational relationships studied remain. Incentives within organisations are as important as those between organisations. Within a chain of principal-agent relations, it is important that a strong link in the chain does not result in the exploitation of weaknesses in other links. If government targets and frameworks are to be met through commissioning, it may be advantageous to concentrate efforts on developing incentives that align clinician with NHS trust objectives as well as NHS trust with primary care trust (PCT) and government objectives. This paper is based on original empirical work. It uses a principal-agent framework to understand the relationships between PCTs and NHS trusts and highlights the importance of internal NHS trust governance systems in the fulfilment of commissioning agreements.

Problems with traditional science publishing and finding a wider niche for post-publication peer review.

PubMed

Teixeira da Silva, Jaime A; Dobránszki, Judit

2015-01-01

Science affects multiple basic sectors of society. Therefore, the findings made in science impact what takes place at a commercial level. More specifically, errors in the literature, incorrect findings, fraudulent data, poorly written scientific reports, or studies that cannot be reproduced not only serve as a burden on tax-payers' money, but they also serve to diminish public trust in science and its findings. Therefore, there is every need to fortify the validity of data that exists in the science literature, not only to build trust among peers, and to sustain that trust, but to reestablish trust in the public and private academic sectors that are witnessing a veritable battle-ground in the world of science publishing, in some ways spurred by the rapid evolution of the open access (OA) movement. Even though many science journals, traditional and OA, claim to be peer reviewed, the truth is that different levels of peer review occur, and in some cases no, insufficient, or pseudo-peer review takes place. This ultimately leads to the erosion of quality and importance of science, allowing essentially anything to become published, provided that an outlet can be found. In some cases, predatory OA journals serve this purpose, allowing papers to be published, often without any peer review or quality control. In the light of an explosion of such cases in predatory OA publishing, and in severe inefficiencies and possible bias in the peer review of even respectable science journals, as evidenced by the increasing attention given to retractions, there is an urgent need to reform the way in which authors, editors, and publishers conduct the first line of quality control, the peer review. One way to address the problem is through post-publication peer review (PPPR), an efficient complement to traditional peer-review that allows for the continuous improvement and strengthening of the quality of science publishing. PPPR may also serve as a way to renew trust in scientific findings by correcting the literature. This article explores what is broadly being said about PPPR in the literature, so as to establish awareness and a possible first-tier prototype for the sciences for which such a system is undeveloped or weak.

Complicated Grief

MedlinePlus

... in your sadness. As painful as it is, trust that in most cases, your pain will start to lift if you allow yourself to feel it. Support. Family members, friends, social support groups and your faith community are all ...

Was the tragedy of Tovia Laufau caused by an absence of trust?

PubMed

Gray, Ben; Gillett, Grant

2014-06-01

The case of Tovia Laufau concerned a Samoan boy who died of osteosarcoma of the leg. He was diagnosed after a delay and eventually died after his parents did not present him for the treatment recommended for his condition. His parents were given a suspended sentence under s 152 of the New Zealand Crimes Act for failing to provide a child with necessary medical treatment. The case is analysed in terms of the need to enter into a conversation in which trust is the underpinning of a constructive discussion of the possibilities of treatment and the formulation of mutually acceptable regimens of care for difficult and uncertain treatments. This need is heightened when there are cultural barriers to be overcome and a significant divergence in understandings of an illness and value commitments between parents, or patients, and their caregivers.

The perceived health risks of indoor radon gas and overhead powerlines: a comparative multilevel approach.

PubMed

Poortinga, Wouter; Cox, Patrick; Pidgeon, Nick F

2008-02-01

Radon and overhead powerlines are two radiation risk cases that have raised varying levels of concern among the general public and experts. Despite both involving radiation-a typically feared and unseen health hazard-individuals' perceptions of the two risk cases may invoke rather different factors. We examined individual and geographic-contextual factors influencing public perceptions of the health risks of indoor radon gas and overhead powerlines in a comparative research design, utilizing a postal questionnaire with 1,528 members of the general public (response rate 28%) and multilevel modeling techniques. This study found that beliefs about the two risk cases mainly differed according to the level of "exposure"-defined here in terms of spatial proximity. We argue that there are two alternative explanations for this pattern of findings: that risk perception itself varies directly with proximity, or that risk is more salient to concerned people in the exposed areas. We also found that while people living in high radon areas are more concerned about the risks of indoor radon gas, they find these risks more acceptable and have more trust in authorities. These results might reflect the positive effects of successive radon campaigns in high radon areas, which may have raised awareness and concern, and at the same time may have helped to increase trust by showing that the government takes the health risks of indoor radon gas seriously, suggesting that genuine risk communication initiatives may have positive impacts on trust in risk management institutions.

Modelling trading networks and the role of trust

NASA Astrophysics Data System (ADS)

Barrio, Rafael A.; Govezensky, Tzipe; Ruiz-Gutiérrez, Élfego; Kaski, Kimmo K.

2017-04-01

We present a simple dynamical model for describing trading interactions between agents in a social network by considering only two dynamical variables, namely money and goods or services, that are assumed conserved over the whole time span of the agents' trading transactions. A key feature of the model is that agent-to-agent transactions are governed by the price in units of money per goods, which is dynamically changing, and by a trust variable, which is related to the trading history of each agent. All agents are able to sell or buy, and the decision to do either has to do with the level of trust the buyer has in the seller, the price of the goods and the amount of money and goods at the disposal of the buyer. Here we show the results of extensive numerical calculations under various initial conditions in a random network of agents and compare the results with the available related data. In most cases the agreement between the model results and real data turns out to be fairly good, which allow us to draw some general conclusions as how different trading strategies could affect the distribution of wealth in different kinds of societies. Our calculations reveal the striking effects of trust in commercial relations, namely that trust makes trading links more robust and the wealth distribution more even as well as allows for the existence of a healthy middle class.

Trust in government and support for governmental regulation: the case of electronic health records.

PubMed

Herian, Mitchel N; Shank, Nancy C; Abdel-Monem, Tarik L

2014-12-01

This paper presents results from a public engagement effort in Nebraska, USA, which measured public opinions about governmental involvement in encouraging the use of electronic health records (EHRs). We examine the role of trust in government in contributing to public support for government involvement in the development of EHR technologies. We hypothesize that trust in government will lead to support for federal and state governmental encouragement of the use of EHRs among doctors and insurance companies. Further, because individual experiences with health-care professionals will reduce perceptions of risk, we expect that support for governmental involvement will be tempered by greater personal experience with the health-care industry. Examining a small survey of individuals on the issue, we find general support for both of our hypotheses. The findings suggest that trust in government does have a positive relationship with support for government involvement in the policy domain, but that the frequency of personal experiences with health-care providers reduces the extent to which the public supports governmental involvement in the development of EHR technology. This inquiry contributes to our understanding of public attitudes towards government involvement in EHRs in the United States specifically and contributes to social science examining links between trust in government and support for governmental activity in the emerging policy domain regarding electronic health records systems. © 2012 John Wiley & Sons Ltd.

Perceptions of the authority of health information. Case study: digital interactive television and the Internet.

PubMed

Nicholas, David; Huntington, Paul; Williams, Peter; Gunter, Barrie

2003-12-01

As part of a Department of Health funded project nearly 2000 people were surveyed as to their use of two digital health information services, one on the Web and the other on digital interactive television (DiTV). The website was of a commercial company-Surgerydoor-and the DiTV service NHS based. This paper concentrates on the issue of trust in digital health information. Two of the main findings were that advertising was found to have an effect on trust, though the quality and type of advertising will impact in different ways on trustworthiness. DiTV subscribers who had either used the Living Health channel which carried NHS branded health information or had heard of the service, were more likely to say that the NHS was a symbol of trust for them compared with DiTV subscribers who had not used the service.

Patient Perspectives on the Learning Health System: The Importance of Trust and Shared Decision Making.

PubMed

Kelley, Maureen; James, Cyan; Alessi Kraft, Stephanie; Korngiebel, Diane; Wijangco, Isabelle; Rosenthal, Emily; Joffe, Steven; Cho, Mildred K; Wilfond, Benjamin; Lee, Sandra Soo-Jin

2015-01-01

We conducted focus groups to assess patient attitudes toward research on medical practices in the context of usual care. We found that patients focus on the implications of this research for their relationship with and trust in their physicians. Patients view research on medical practices as separate from usual care, demanding dissemination of information and in most cases, individual consent. Patients expect information about this research to come through their physician, whom they rely on to identify and filter associated risks. In general, patients support this research, but worry that participation in research involving randomization may undermine individualized care that acknowledges their unique medical histories. These findings suggest the need for public education on variation in practice among physicians and the need for a collaborative approach to the governance of research on medical practices that addresses core values of trust, transparency, and partnership.

Business planning: can the health service move from strategy into action?

PubMed

Bennett, A R

1994-01-01

Advances the case for the use of one particular business planning technique within a National Health Service Trust. At the present time, NHS trusts are required to write strategic direction statements. Evidence suggests that these documents provide an accurate account of past performance and present position of the trust, but do not express the future position intended to be achieved. These documents also tend to be lengthy and lack strategic focus, which means that they are not helpful to managers who want clear organizational goals and objectives to which to work. Attempts to address the difficulties associated with determining how existing skills and resources can be used as the platform for future growth strategies by using the Ansoff Matrix and SWOT Analysis planning tools, given the external changes in the marketplace. Also attempts to shed light on some of the important links between busines strategy and management development by extending planning theory into practice.

Reflections of a Vaccinologist: Lessons Learned About What We Can Do to Improve Trust in Vaccines and Vaccine Programsa.

PubMed

Halsey, Neal A

2017-03-01

Public trust can be improved by learning from past mistakes, by establishing a standing forum for review of new concerns as they arise, and by maintaining a robust vaccine safety system. Developing standard guidelines for reporting causality assessment in case reports would help educate physicians and prevent future unnecessary concerns based on false assumptions of causal relationships. © The Author 2015. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Reciprocal Relationships: Something for Everyone.

PubMed

Tumosa, Nina

2017-01-01

Reciprocal relationships based on mutual goals, respect and trust are key to maintaining working relationships and getting reliable research results. Yet relationship building is not a concept taught in academia. These skills are often learned the hard way, with singular solutions found for case-by-case scenarios. Several journeys to identify the components, barriers and rewards of reciprocal relationships are discussed.

Rural Governance, Community Empowerment and the New Institutionalism: A Case Study of the Isle of Wight

ERIC Educational Resources Information Center

Clark, David; Southern, Rebekah; Beer, Julian

2007-01-01

This article compares two different institutional models--state-sponsored rural partnerships and community-based development trusts--for engaging and empowering local communities in area-based regeneration, using the Isle of Wight as a case study. Following a critical review of the literature on community governance, we evaluate the effectiveness…

A Case Study in Market Transformation for Residential Energy Efficiency Programs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Building Technologies Office

This case study describes how the Midwest Energy Efficiency Alliance (MEEA) partnered with gas and electric utilities in Iowa to establish the Iowa residential heating, ventilation, and air conditioning System Adjustment and Verified Efficiency (HVAC SAVE) program, taking it to scale improving the performance and energy efficiency of HVAC systems, growing businesses, and gaining consumer trust.

Case study - human body relay race.

PubMed

Lewis, Heather

2017-04-01

This case presentation introduces the work of Heather Lewis, Graphic Designer from Birmingham Community Healthcare Foundation Trust, Clinical Illustration department. The graphic design team offer professional design solutions in a variety of formats such as scientific posters, banners, patient information booklets and promotional items. This particular project was requested by the Combined Community Dental Service, a Specialist Division in Birmingham.

Neuro-Linguistic Programming and Learning: Teacher Case Studies on the Impact of NLP in Education

ERIC Educational Resources Information Center

Carey, John; Churches, Richard; Hutchinson, Geraldine; Jones, Jeff; Tosey, Paul

2010-01-01

This research paper reports on evidence from 24 teacher-led action research case studies and builds on the 2008 CfBT Education Trust published paper by Richard Churches and John West-Burnham "Leading learning through relationships: the implications of Neurolinguistic programming for personalisation and the children's agenda in England".…

Bowland Maths: Problem Solving in Key Stage 3

ERIC Educational Resources Information Center

Lane, Peter; Lister, Adelaide; Onion, Alice; Wintle, Karen

2008-01-01

A project has been developed for KS3 maths, funded by the Bowland Trust (www.bowlandmaths.org.uk) with additional support from the DCSF. It consists of a teaching resource of about 20 case-study problems aimed at developing thinking, reasoning and problem-solving skills and has been distributed to all UK secondary schools. Each case study includes…

12 CFR 977.3 - Trustee powers.

Code of Federal Regulations, 2010 CFR

2010-01-01

..., as trustee of any trust affecting the business of any member or any institution or group applying for..., investors, or borrowers, or for the promotion of sound and economical home financing; and (b) In the case of...

Public trust and confidence in legal authorities: What do majority and minority group members want from the law and legal institutions?

PubMed

Tyler, T R

2001-01-01

Discussions of public trust and confidence in the police and the courts often assume that the key to public feelings is the public's evaluation of the outcomes that the public receives from these legal authorities. In the case of the courts, discontent is often assumed to be linked to issues of cost and delay-instrumental concerns about the outcomes delivered to the public by the courts. In the case of the police, the inability to effectively control crime is frequently seen as driving public evaluations. This article presents an alternative procedural justice based model that links public trust and confidence to views about the manner in which legal authorities treat the public. Drawing upon psychological research about public evaluations of institutions and authorities it is argued that the key issue that shapes public views is a process based evaluation of the fairness of the procedures that the police and courts use to exercise their authority. Analyses from several studies exploring the basis of public views support this procedural justice based model of public evaluation. In addition, the results provide suggestions about the elements of procedures that are central to public judgments about their fairness. Copyright 2001 John Wiley & Sons, Ltd.

Information spreading in Delay Tolerant Networks based on nodes' behaviors

NASA Astrophysics Data System (ADS)

Wu, Yahui; Deng, Su; Huang, Hongbin

2014-07-01

Information spreading in DTNs (Delay Tolerant Networks) adopts a store-carry-forward method, and nodes receive the message from others directly. However, it is hard to judge whether the information is safe in this communication mode. In this case, a node may observe other nodes' behaviors. At present, there is no theoretical model to describe the varying rule of the nodes' trusting level. In addition, due to the uncertainty of the connectivity in DTN, a node is hard to get the global state of the network. Therefore, a rational model about the node's trusting level should be a function of the node's own observing result. For example, if a node finds k nodes carrying a message, it may trust the information with probability p(k). This paper does not explore the real distribution of p(k), but instead presents a unifying theoretical framework to evaluate the performance of the information spreading in above case. This framework is an extension of the traditional SI (susceptible-infected) model, and is useful when p(k) conforms to any distribution. Simulations based on both synthetic and real motion traces show the accuracy of the framework. Finally, we explore the impact of the nodes' behaviors based on certain special distributions through numerical results.

Length of FMR1 repeat alleles within the normal range does not substantially affect the risk of early menopause

PubMed Central

Ruth, Katherine S.; Bennett, Claire E.; Schoemaker, Minouk J.; Weedon, Michael N.; Swerdlow, Anthony J.; Murray, Anna

2016-01-01

STUDY QUESTION Is the length of FMR1 repeat alleles within the normal range associated with the risk of early menopause? SUMMARY ANSWER The length of repeat alleles within the normal range does not substantially affect risk of early menopause. WHAT IS KNOWN ALREADY There is a strong, well-established relationship between length of premutation FMR1 alleles and age at menopause, suggesting that this relationship could continue into the normal range. Within the normal range, there is conflicting evidence; differences in ovarian reserve have been identified with FMR1 repeat allele length, but a recent population-based study did not find any association with age at menopause as a quantitative trait. STUDY DESIGN, SIZE, DURATION We analysed cross-sectional baseline survey data collected at recruitment from 2004 to 2010 from a population-based, prospective epidemiological cohort study of >110 000 women to investigate whether repeat allele length was associated with early menopause. PARTICIPANTS/MATERIALS, SETTING, METHOD We included 4333 women from the Breakthrough Generations Study (BGS), of whom 2118 were early menopause cases (menopause under 46 years) and 2215 were controls. We analysed the relationship between length of FMR1 alleles and early menopause using logistic regression with allele length as continuous and categorical variables. We also conducted analyses with the outcome age at menopause as a quantitative trait as well as appropriate sensitivity and exploratory analyses. MAIN RESULTS AND THE ROLE OF CHANCE There was no association of the shorter or longer FMR1 allele or their combined genotype with the clinically relevant end point of early menopause in our main analysis. Likewise, there were no associations with age at menopause as a quantitative trait in our secondary analysis. LIMITATIONS, REASONS FOR CAUTION Women with homozygous alleles in the normal range may have undetected FMR1 premutation alleles, although there was no evidence to suggest this. We estimate minor dilution of risk of early menopause from the likely inclusion of some women with menopause at over 45 years in the early menopause cases due to age-rounding bias in self-reports. WIDER IMPLICATIONS OF THE FINDINGS There is no robust evidence in this large study that variation within the normal range of FMR1 repeat alleles influences timing of menopause in the general population, which contradicts findings from some earlier, mainly smaller studies. The FMR1 CGG repeat polymorphism in the normal range is unlikely to contribute to genetic susceptibility to early menopause. STUDY FUNDING/COMPETING INTEREST(S) We thank Breast Cancer Now and The Institute of Cancer Research for funding the BGS. The Institute of Cancer Research acknowledges NHS funding to the NIHR Biomedical Research Centre. The study was funded by the Wellcome Trust (grant number 085943). There are no competing interests. TRIAL REGISTRATION NUMBER Not applicable. PMID:27614355

Self-harm in prisons in England and Wales: an epidemiological study of prevalence, risk factors, clustering, and subsequent suicide

PubMed Central

Hawton, Keith; Linsell, Louise; Adeniji, Tunde; Sariaslan, Amir; Fazel, Seena

2014-01-01

Summary Background Self-harm and suicide are common in prisoners, yet robust information on the full extent and characteristics of people at risk of self-harm is scant. Furthermore, understanding how frequently self-harm is followed by suicide, and in which prisoners this progression is most likely to happen, is important. We did a case-control study of all prisoners in England and Wales to ascertain the prevalence of self-harm in this population, associated risk factors, clustering effects, and risk of subsequent suicide after self-harm. Methods Records of self-harm incidents in all prisons in England and Wales were gathered routinely between January, 2004, and December, 2009. We did a case-control comparison of prisoners who self-harmed and those who did not between January, 2006, and December, 2009. We also used a Bayesian approach to look at clustering of people who self-harmed. Prisoners who self-harmed and subsequently died by suicide in prison were compared with other inmates who self-harmed. Findings 139 195 self-harm incidents were recorded in 26 510 individual prisoners between 2004 and 2009; 5–6% of male prisoners and 20–24% of female inmates self-harmed every year. Self-harm rates were more than ten times higher in female prisoners than in male inmates. Repetition of self-harm was common, particularly in women and teenage girls, in whom a subgroup of 102 prisoners accounted for 17 307 episodes. In both sexes, self-harm was associated with younger age, white ethnic origin, prison type, and a life sentence or being unsentenced; in female inmates, committing a violent offence against an individual was also a factor. Substantial evidence was noted of clustering in time and location of prisoners who self-harmed (adjusted intra-class correlation 0·15, 95% CI 0·11–0·18). 109 subsequent suicides in prison were reported in individuals who self-harmed; the risk was higher in those who self-harmed than in the general prison population, and more than half the deaths occurred within a month of self-harm. Risk factors for suicide after self-harm in male prisoners were older age and a previous self-harm incident of high or moderate lethality; in female inmates, a history of more than five self-harm incidents within a year was associated with subsequent suicide. Interpretation The burden of self-harm in prisoners is substantial, particularly in women. Self-harm in prison is associated with subsequent suicide in this setting. Prevention and treatment of self-harm in prisoners is an essential component of suicide prevention in prisons. Funding Wellcome Trust, National Institute for Health Research, National Offender Management Service, and Department of Health. PMID:24351319

Relationships among trust in messages, risk perception, and risk reduction preferences based upon avian influenza in Taiwan.

PubMed

Fang, David; Fang, Chen-Ling; Tsai, Bi-Kun; Lan, Li-Chi; Hsu, Wen-Shan

2012-08-01

Improvements in communications technology enable consumers to receive information through diverse channels. In the case of avian influenza, information repeated by the mass media socially amplifies the consumer awareness of risks. Facing indeterminate risks, consumers may feel anxious and increase their risk perception. When consumers trust the information published by the media, their uncertainty toward avian influenza may decrease. Consumers might take some actions to reduce risk. Therefore, this study focuses on relationships among trust in messages, risk perception and risk reduction preferences. This study administered 525 random samples and consumer survey questionnaires in different city of Taiwan in 2007. Through statistical analysis, the results demonstrate: (1) the higher the trust consumers have in messages about avian influenza, the lower their risk perceptions are; (2) the higher the consumers' risk perceptions are and, therefore, the higher their desired level of risk reductive, the more likely they are to accept risk reduction strategies; (3) consumer attributes such as age, education level, and marital status correlate with significant differences in risk perception and risk reduction preferences acceptance. Gender has significant differences only in risk reduction preferences and not in risk perception.

Relationships among Trust in Messages, Risk Perception, and Risk Reduction Preferences Based upon Avian Influenza in Taiwan

PubMed Central

Fang, David; Fang, Chen-Ling; Tsai, Bi-Kun; Lan, Li-Chi; Hsu, Wen-Shan

2012-01-01

Improvements in communications technology enable consumers to receive information through diverse channels. In the case of avian influenza, information repeated by the mass media socially amplifies the consumer awareness of risks. Facing indeterminate risks, consumers may feel anxious and increase their risk perception. When consumers trust the information published by the media, their uncertainty toward avian influenza may decrease. Consumers might take some actions to reduce risk. Therefore, this study focuses on relationships among trust in messages, risk perception and risk reduction preferences. This study administered 525 random samples and consumer survey questionnaires in different city of Taiwan in 2007. Through statistical analysis, the results demonstrate: (1) the higher the trust consumers have in messages about avian influenza, the lower their risk perceptions are; (2) the higher the consumers’ risk perceptions are and, therefore, the higher their desired level of risk reductive, the more likely they are to accept risk reduction strategies; (3) consumer attributes such as age, education level, and marital status correlate with significant differences in risk perception and risk reduction preferences acceptance. Gender has significant differences only in risk reduction preferences and not in risk perception. PMID:23066394

Distribution and Correlates of Self-Reported Crimes of Trust

PubMed Central

Menard, Scott; Morris, Robert G.; Gerber, Jurg; Covey, Herbert C.

2012-01-01

This study examines the distribution and correlates of a special class of property crimes, crimes of trust, using longitudinal and cross sectional self-report data from a national sample. We begin by defining crimes of trust and consider their conceptual relationship to “conventional” property crimes, which we here characterize as crimes of stealth, and to white collar crimes, which are defined in terms of the social status of the perpetrators. Crimes of trust are here defined as property crimes that typically involve deliberate contact with the victim or, where there is more than one victim, with at least one or more victims, in which there is typically more of a focus on concealing the fact that a crime has been committed than on concealing the identity of the perpetrator (as is the case in crimes of stealth), without regard to the socioeconomic status of the perpetrator (thus including but not limited to white collar crimes). The focus here is on crimes of trust committed by individuals (as opposed to corporate crime). We first examine their distribution by sociodemographic characteristics, then examine the correlation of crimes of trust with other types of illegal behavior, using data from the National Youth Survey Family Study, including (1) longitudinal self-report data from a nationally representative panel of individuals who were 11–18 years old in 1976–77 and who were followed through early middle age (ages 36–44) in 2002–2003, plus (2) cross-sectional data on these individuals plus their parents, spouses, and children age 11 and older in 2002–2003 (total age range 11–88). The results suggest that crimes of trust have a different age-crime curve from conventional crimes, and that they are not as strongly correlated with problem substance use, gender, and other socioeconomic indicators as conventional crimes. PMID:22347761

What's the evidence that NICE guidance has been implemented? Results from a national evaluation using time series analysis, audit of patients' notes, and interviews

PubMed Central

Sheldon, Trevor A; Cullum, Nicky; Dawson, Diane; Lankshear, Annette; Lowson, Karin; Watt, Ian; West, Peter; Wright, Dianne; Wright, John

2004-01-01

Objectives To assess the extent and pattern of implementation of guidance issued by the National Institute for Clinical Excellence (NICE). Design Interrupted time series analysis, review of case notes, survey, and interviews. Setting Acute and primary care trusts in England and Wales. Participants All primary care prescribing, hospital pharmacies; a random sample of 20 acute trusts, 17 mental health trusts, and 21 primary care trusts; and senior clinicians and managers from five acute trusts. Main outcome measures Rates of prescribing and use of procedures and medical devices relative to evidence based guidance. Results 6308 usable patient audit forms were returned. Implementation of NICE guidance varied by trust and by topic. Prescribing of some taxanes for cancer (P < 0.002) and orlistat for obesity (P < 0.001) significantly increased in line with guidance. Prescribing of drugs for Alzheimer's disease and prophylactic extraction of wisdom teeth showed trends consistent with, but not obviously a consequence of, the guidance. Prescribing practice often did not accord with the details of the guidance. No change was apparent in the use of hearing aids, hip prostheses, implantable cardioverter defibrillators, laparoscopic hernia repair, and laparoscopic colorectal cancer surgery after NICE guidance had been issued. Conclusions Implementation of NICE guidance has been variable. Guidance seems more likely to be adopted when there is strong professional support, a stable and convincing evidence base, and no increased or unfunded costs, in organisations that have established good systems for tracking guidance implementation and where the professionals involved are not isolated. Guidance needs to be clear and reflect the clinical context. PMID:15514342

Trusted Advisors, Decision Models and Other Keys to Communicating Science to Decision Makers

NASA Astrophysics Data System (ADS)

Webb, E.

2006-12-01

Water resource management decisions often involve multiple parties engaged in contentious negotiations that try to navigate through complex combinations of legal, social, hydrologic, financial, and engineering considerations. The standard approach for resolving these issues is some form of multi-party negotiation, a formal court decision, or a combination of the two. In all these cases, the role of the decision maker(s) is to choose and implement the best option that fits the needs and wants of the community. However, each path to a decision carries the risk of technical and/or financial infeasibility as well as the possibility of unintended consequences. To help reduce this risk, decision makers often rely on some type of predictive analysis from which they can evaluate the projected consequences of their decisions. Typically, decision makers are supported in the analysis process by trusted advisors who engage in the analysis as well as the day to day tasks associated with multi-party negotiations. In the case of water resource management, the analysis is frequently a numerical model or set of models that can simulate various management decisions across multiple systems and output results that illustrate the impact on areas of concern. Thus, in order to communicate scientific knowledge to the decision makers, the quality of the communication between the analysts, the trusted advisor, and the decision maker must be clear and direct. To illustrate this concept, a multi-attribute decision analysis matrix will be used to outline the value of computer model-based collaborative negotiation approaches to guide water resources decision making and communication with decision makers. In addition, the critical role of the trusted advisor and other secondary participants in the decision process will be discussed using examples from recent water negotiations.

Robot Lies in Health Care: When Is Deception Morally Permissible?

PubMed

Matthias, Andreas

2015-06-01

Autonomous robots are increasingly interacting with users who have limited knowledge of robotics and are likely to have an erroneous mental model of the robot's workings, capabilities, and internal structure. The robot's real capabilities may diverge from this mental model to the extent that one might accuse the robot's manufacturer of deceiving the user, especially in cases where the user naturally tends to ascribe exaggerated capabilities to the machine (e.g. conversational systems in elder-care contexts, or toy robots in child care). This poses the question, whether misleading or even actively deceiving the user of an autonomous artifact about the capabilities of the machine is morally bad and why. By analyzing trust, autonomy, and the erosion of trust in communicative acts as consequences of deceptive robot behavior, we formulate four criteria that must be fulfilled in order for robot deception to be morally permissible, and in some cases even morally indicated.

Community outreach library services in the UK: a case study of Wirral Hospital NHS Trust (WHNT).

PubMed

Dowse, Frances Maria; Sen, Barbara

2007-09-01

The study evaluates the Community Outreach Library Service at Wirral Hospital National Health Service Trust (WHNT). It considers the information seeking behaviour and information needs of primary care staff, and service effectiveness in meeting those needs. A literature review established the current context and areas of best practice. The investigative case study used postal questionnaires to 250 primary care staff and an interview with the Community Outreach Librarian. Themes emerged from the literature regarding information seeking behaviour, information needs, and meeting user needs through effective service delivery. Outreach services have value in terms of improving information skills and providing services at point of need. Time is a major constraint for both users and service providers. Investment is needed from appropriate funding sources to support the provision and marketing of outreach library services. Librarians benefit from sharing best practice. The continued evaluation of outreach library services is recommended.

The ethics and politics of patient-physician mistrust in contemporary China.

PubMed

Yan, Yunxiang

2018-03-01

Focusing on the shared sense of victimization and disadvantage-ness by both patients and doctors/medical workers in cases of medical conflicts, this paper aims to examine the current patient-doctor tensions in the larger context of moral transformation in Chinese society since the 1980s. Although the decline of public trust in certain aspects is closely associated with the impact of commodification and commercialization of medical sector during the past two decades, other factors play important role as well. In the case of patient-doctor tension, mutual disrespect and mistrust also result from the ongoing process of individualization and the remaking of moral self, in which the individual demand for respect, dignity, and trust seem to have unexpectedly and ironically contributed to the rise of tensions and conflicts between patients and doctors as well as other medical workers. © 2017 John Wiley & Sons Ltd.

Human Research Program Space Human Factors Engineering (SHFE) Standing Review Panel (SRP)

NASA Technical Reports Server (NTRS)

Wichansky, Anna; Badler, Norman; Butler, Keith; Cummings, Mary; DeLucia, Patricia; Endsley, Mica; Scholtz, Jean

2009-01-01

The Space Human Factors Engineering (SHFE) Standing Review Panel (SRP) evaluated 22 gaps and 39 tasks in the three risk areas assigned to the SHFE Project. The area where tasks were best designed to close the gaps and the fewest gaps were left out was the Risk of Reduced Safety and Efficiency dire to Inadequate Design of Vehicle, Environment, Tools or Equipment. The areas where there were more issues with gaps and tasks, including poor or inadequate fit of tasks to gaps and missing gaps, were Risk of Errors due to Poor Task Design and Risk of Error due to Inadequate Information. One risk, the Risk of Errors due to Inappropriate Levels of Trust in Automation, should be added. If astronauts trust automation too much in areas where it should not be trusted, but rather tempered with human judgment and decision making, they will incur errors. Conversely, if they do not trust automation when it should be trusted, as in cases where it can sense aspects of the environment such as radiation levels or distances in space, they will also incur errors. This will be a larger risk when astronauts are less able to rely on human mission control experts and are out of touch, far away, and on their own. The SRP also identified 11 new gaps and five new tasks. Although the SRP had an extremely large quantity of reading material prior to and during the meeting, we still did not feel we had an overview of the activities and tasks the astronauts would be performing in exploration missions. Without a detailed task analysis and taxonomy of activities the humans would be engaged in, we felt it was impossible to know whether the gaps and tasks were really sufficient to insure human safety, performance, and comfort in the exploration missions. The SRP had difficulty evaluating many of the gaps and tasks that were not as quantitative as those related to concrete physical danger such as excessive noise and vibration. Often the research tasks for cognitive risks that accompany poor task or information design addressed only part, but not all, of the gaps they were programmed to fill. In fact the tasks outlined will not close the gap but only scratch the surface in many cases. In other cases, the gap was written too broadly, and really should be restated in a more constrained way that can be addressed by a well-organized and complementary set of tasks. In many cases, the research results should be turned into guidelines for design. However, it was not clear whether the researchers or another group would construct and deliver these guidelines.

76 FR 62470 - MFS Series Trust I, et al.

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-07

...] MFS Series Trust I, et al.; Notice of Application September 30, 2011. AGENCY: Securities and Exchange... Series Trust I, MFS Series Trust II, MFS Series Trust III, MFS Series Trust IV, MFS Series Trust V, MFS Series Trust VI, MFS Series Trust VII, MFS Series Trust VIII, MFS Series Trust IX, MFS Series Trust X...

Trust Pathways, Trust Catalysts, Theory of Change and Citizen Science: A COASST Case Study

NASA Astrophysics Data System (ADS)

Burgess, H. K.; Parrish, J.; Dolliver, J.; Metes, J.; Ballard, H. L.

2017-12-01

Environmental challenges, from local water quality to the effects of global climate change, are overwhelming the mainstream science community. We need help. Citizen science offers one solution pathway - in the ideal, thousands of participants engaged in authentic science that delivers high quality information not otherwise obtainable. But in the real world, are citizen science data used? And more broadly: what are the interactions between citizen science and natural resource management in service of conserving or protecting system structure and function? The Coastal Observation and Seabird Survey Team (COASST) is a rigoros citizen science program focused on documenting patterns of beached bird and marine debris abundance on beaches along the coast of the Pacific Northwest and Alaska. Housed at the University of Washington, COASST partners directly with a wide range of local, tribal, state and federal agencies to effect positive change and a wide range of scientific, community and educational outcomes. Following from years of trial, error and adaptive management, we propose a "trust pathway" between citizen science and agencies that moves from an initial contact and multiple interaction types to eventual partnership and capacity sharing. Along the way are trust catalysts, including but not limited to: stakeholder engagement, data QA/QC, interactive data analysis, housing at an academic institution, and timely, repeated communication. In this presentation, we will discuss strategies and outcomes employed by COASST for fostering trust and successful partnerships, drawing on 20 years of program experience as well as reflections from a variety of partners and stakholdres.

Preliminary perspectives on DNA collection in anti-human trafficking efforts.

PubMed

Katsanis, Sara H; Kim, Joyce; Minear, Mollie A; Chandrasekharan, Subhashini; Wagner, Jennifer K

2014-01-01

Forensic DNA methodologies have potential applications in the investigation of human trafficking cases. DNA and relationship testing may be useful for confirmation of biological relationship claims in immigration, identification of trafficked individuals who are missing persons, and family reunification of displaced individuals after mass disasters and conflicts. As these applications rely on the collection of DNA from non-criminals and potentially vulnerable individuals, questions arise as to how to address the ethical challenges of collection, security, and privacy of collected samples and DNA profiles. We administered a survey targeted to victims' advocates to gain preliminary understanding of perspectives regarding human trafficking definitions, DNA and sex workers, and perceived trust of authorities potentially involved in DNA collection. We asked respondents to consider the use of DNA for investigating adoption fraud, sex trafficking, and post-conflict child soldier cases. We found some key differences in perspectives on defining what qualifies as "trafficking." When we varied terminology between "sex worker" and "sex trafficking victim" we detected differences in perception on which authorities can be trusted. Respondents were supportive of the hypothetical models proposed to collect DNA. Most were favorable of DNA specimens being controlled by an authority outside of law enforcement. Participants voiced concerns focused on privacy, misuse of DNA samples and data, unintentional harms, data security, and infrastructure. These preliminary data indicate that while there is perceived value in programs to use DNA for investigating cases of human trafficking, these programs may need to consider levels of trust in authorities as their logistics are developed and implemented.

Perceptions of self, significant others, and teacher-child relationships in indiscriminately friendly children.

PubMed

Vervoort, Eleonora; Bosmans, Guy; Doumen, Sarah; Minnis, Helen; Verschueren, Karine

2014-11-01

Despite increasing research on indiscriminate friendliness in children, almost no research exists on social-cognitive deficits that are supposed to underlie indiscriminately friendly behavior. In this study, we compared indiscriminately friendly children with controls regarding their perceptions of self, reliability trust in significant others, and perceptions of the teacher-child relationship. Children's perceptions were compared in two samples: a sample of 33 likely cases for disinhibited reactive attachment disorder (RAD) from special education for children with emotional and behavioral disorders (75.76% boys, Mage=8.52, 96.9% Caucasian, 33.3% and 45.5% of their mothers completed primary or secondary education, respectively) was matched on sex, age, and socio-economic status with a sample of 33 controls from general education. Children participated individually in several interviews assessing global and social self-concept, reliability trust in significant others, teacher-child relationship perceptions, and vocabulary. Parents and teachers completed a screening questionnaire for RAD and the Strengths and Difficulties Questionnaire. Likely disinhibited RAD-cases showed more indiscriminate friendliness and more problem behavior in general according to their parents and teachers than controls. Furthermore, likely RAD-cases reported a more positive global self-concept, more reliability trust in significant others, and more dependency in the teacher-child relationship than controls. The results are in line with clinical observations of indiscriminately friendly children and findings in clinical samples of maltreated or attachment disrupted children but contrast hypotheses from developmental attachment research. Further research is needed to explain the more positive perceptions of indiscriminately friendly children. Copyright © 2014 Elsevier Ltd. All rights reserved.

Collaboration management framework for OEM - suppliers relationships: a trust-based conceptual approach

NASA Astrophysics Data System (ADS)

Belkadi, Farouk; Messaadia, Mourad; Bernard, Alain; Baudry, David

2017-08-01

Due to the increased competitiveness and the diversity of requirements in today's markets, manufacturing companies need to join their competencies and resources to propose innovative solutions for each specific market, with the possibility to transpose these solutions to another market, by means of slight adaptations. Thus, manufacturing firms must constantly conduct new collaborations with known partners in most cases, but also with new partners. The critical question for managers in this latter case is how to define the best collaborative strategy according to the goals of the project and the specificity of the target market. This paper tackles the problem by proposing a conceptual framework for supporting the management of collaborative situations in the case of Original equipment manufacturers (OEMs). Based on the concept of trust level, the framework proposes a classification of different collaboration modes to be adopted in various contexts of inter-enterprise relationships, in manufacturing sector. The aim is to support the flexible navigation between different collaborative situations by taking into account all decision-making levels from the strategy to the implementation of the information technologies (IT) systems at the operational level.

[Increased revenues from secondary diagnoses : A comparison from dermatology, ophthalmology, and infectious diseases].

PubMed

Blaschke, V; Brauns, B; Khaladj, N; Schmidt, C; Emmert, S

2018-02-27

Hospital revenues generated by diagnosis-related groups (DRGs) are in part dependent on the coding of secondary diagnoses. Therefore, more and more hospitals trust specialized coders with this task, thereby relieving doctors from time-consuming administrative burdens and establishing a highly professionalized coding environment. However, it is vastly unknown if the revenues generated by the coders do indeed exceed their incurred costs. Coding data from the departments of dermatology, ophthalmology, and infectious diseases from Rostock University Hospital from 2007-2016 were analyzed for the effects of secondary diagnoses on the resulting DRG, i. e., hospital charges. Ophthalmological case were highly resistant to the addition of secondary diagnoses. In contrast, adding secondary diagnoses to cases from infectious diseases resulted in 15% higher revenues. Although dermatological and infectious cases share the same sensitivity to secondary diagnoses, higher revenues could only rarely be realized in dermatology, probably owing to a younger, less multimorbid patient population. Except for ophthalmology, trusting specialized coders with clinical coding generates additional revenues through the coding of secondary diagnoses which exceed the costs for employing these coders.

Trusted Storage: Putting Security and Data Together

NASA Astrophysics Data System (ADS)

Willett, Michael; Anderson, Dave

State and Federal breach notification legislation mandates that the affected parties be notified in case of a breach of sensitive personal data, unless the data was provably encrypted. Self-encrypting hard drives provide the superior solution for encrypting data-at-rest when compared to software-based solutions. Self-encrypting hard drives, from the laptop to the data center, have been standardized across the hard drive industry by the Trusted Computing Group. Advantages include: simplified management (including keys), no performance impact, quick data erasure and drive re-purposing, no interference with end-to-end data integrity metrics, always encrypting, no cipher-text exposure, and scalability in large data centers.

An analysis on the research ethics cases managed by the Committee on Publication Ethics (COPE) between 1997 and 2010.

PubMed

Foo, Jong Yong Abdiel; Wilson, Stephen James

2012-12-01

The growing emphasis on the importance of publishing scientific findings in the academic world has led to increasing prevalence of potentially significant publications in which scientific and ethical rigour may be questioned. This has not only hindered research progress, but also eroded public trust in all scientific advances. In view of the increasing concern and the complexity of research misconduct, the Committee on Publication Ethics (COPE) was established in 1997 to manage cases with ethical implications. In order to review the outcomes of cases investigated by COPE, a total of 408 cases that had been managed by COPE were successfully extracted and analysed with respect to 7 distinct criteria. The results obtained indicate that the number of ethical implications per case has not changed significantly (p > 0.01) since the year COPE was instigated. Interestingly, the number of ethical cases, and to some extent, research misconduct, is not diminishing. Therefore, journal editors and publishers need to work closely together with COPE to inculcate adoption of appropriate research ethics and values in younger researchers while discouraging others from lowering standards. It is hoped that with a more concerted effort from the academic community and better public awareness, there will be fewer incidences of ethically and scientifically challenged publications. The ultimate aim being to enhance the quality of published works with concomittant public trust in the results.

The cataract national data set electronic multi-centre audit of 55,567 operations: case-mix adjusted surgeon's outcomes for posterior capsule rupture.

PubMed

Sparrow, J M; Taylor, H; Qureshi, K; Smith, R; Johnston, R L

2011-08-01

To develop a methodology for case-mix adjustment of surgical outcomes for individual cataract surgeons using electronically collected multi-centre data conforming to the cataract national data set (CND). Routinely collected anonymised data were remotely extracted from electronic patient record (EPR) systems in 12 participating NHS Trusts undertaking cataract surgery. Following data checks and cleaning, analyses were carried out to risk adjust outcomes for posterior capsule rupture rates for individual surgeons, with stratification by surgical grade. A total of 406 surgeons from 12 NHS Trusts submitted data on 55,567 cataract operations between November 2001 and July 2006 (86% from January 2004). In all, 283 surgeons contributed data on >25 cases, providing 54,319 operations suitable for detailed analysis. Case-mix adjusted results of individual surgeons are presented as funnel plots for all surgeons together, and separately for three different grades of surgeon. Plots include 95 and 99.8% confidence limits around the case-mix adjusted outcomes for detection of surgical outliers. Routinely collected electronic data conforming to the CND provides sufficient detail for case-mix adjustment of cataract surgical outcomes. The validation of these risk indicators should be carried out using fresh data to confirm the validity of the risk model. Once validated this model should provide an equitable approach for peer-to-peer comparisons in the context of revalidation.

Replacing missing values using trustworthy data values from web data sources

NASA Astrophysics Data System (ADS)

Izham Jaya, M.; Sidi, Fatimah; Mat Yusof, Sharmila; Suriani Affendey, Lilly; Ishak, Iskandar; Jabar, Marzanah A.

2017-09-01

In practice, collected data usually are incomplete and contains missing value. Existing approaches in managing missing values overlook the importance of trustworthy data values in replacing missing values. In view that trusted completed data is very important in data analysis, we proposed a framework of missing value replacement using trustworthy data values from web data sources. The proposed framework adopted ontology to map data values from web data sources to the incomplete dataset. As data from web is conflicting with each other, we proposed a trust score measurement based on data accuracy and data reliability. Trust score is then used to select trustworthy data values from web data sources for missing values replacement. We successfully implemented the proposed framework using financial dataset and presented the findings in this paper. From our experiment, we manage to show that replacing missing values with trustworthy data values is important especially in a case of conflicting data to solve missing values problem.

How trust and emotions influence policy acceptance: The case of the Irish water charges.

PubMed

Rodriguez-Sanchez, Carla; Schuitema, Geertje; Claudy, Marius; Sancho-Esper, Franco

2018-02-01

The introduction of new policies can evoke strong emotional reactions by the public. Yet, social-psychological research has paid little attention to affective determinants of individual-level policy acceptance. Building on recent theoretical and empirical advances around emotions and decision-making, we evaluate how people's trust and integral emotions function as important antecedents of cognitive evaluations, and subsequent acceptance of policies. We test our hypotheses within a sample of Irish citizens (n = 505), who were subject to the introduction of water charges in 2015. In line with our hypotheses, results show that general trust in government shapes emotions regarding water charges, which in turn, directly and via expected costs and benefits, influence policy acceptance. Additionally, we find that negative emotions have a larger direct effect on policy acceptance than positive emotions. Specifically, 'anger' was the main negative emotion that influenced the acceptance of the water charge. We conclude by discussing directions for future research around emotions and policy acceptance. © 2018 The British Psychological Society.

26 CFR 1.6050J-1T - Questions and answers concerning information returns relating to foreclosures and abandonments of...

Code of Federal Regulations, 2013 CFR

2013-04-01

... apply in the case of pools, fixed investment trusts, or other similar arrangements through which... clear and convincing evidence to the contrary, the proceeds of the foreclosure, execution, or similar...

26 CFR 1.6050J-1T - Questions and answers concerning information returns relating to foreclosures and abandonments of...

Code of Federal Regulations, 2012 CFR

2012-04-01

... apply in the case of pools, fixed investment trusts, or other similar arrangements through which... clear and convincing evidence to the contrary, the proceeds of the foreclosure, execution, or similar...

26 CFR 1.6050J-1T - Questions and answers concerning information returns relating to foreclosures and abandonments of...

Code of Federal Regulations, 2011 CFR

2011-04-01

... apply in the case of pools, fixed investment trusts, or other similar arrangements through which... clear and convincing evidence to the contrary, the proceeds of the foreclosure, execution, or similar...

Reporting Deferred Gifts: CASE-NACUBO Guidelines Ensure Consistency.

ERIC Educational Resources Information Center

Ridenour, James F.; Munger, Peter L.

1983-01-01

Three methods for reporting the value of a deferred gift are described: the tax method, net realizable value, and fair market value. Three major categories of deferred gifts are identified: pooled income funds, charitable remainder trusts, and charitable gift annuities. (MLW)

Use of Anthropomorphic Brand Mascots for Student Motivation and Engagement: A Promotional Case Study with Pablo the Penguin at the University of Portsmouth Library

ERIC Educational Resources Information Center

Bennett, David E.; Thompson, Paula

2016-01-01

A case study demonstrating how an online narrative featuring the adventures of a cuddly toy penguin, Pablo Penguin (@uoppenguin on Twitter) has been introduced at the University of Portsmouth Library to build trust and engagement between university students and library services and facilities. Evidence for the benefits of anthropomorphic brand…

Encounters with Wisdom: A Case Study of Community Worker Reflection Circles in San Antonio, TX

ERIC Educational Resources Information Center

Arispe, Don D.

2013-01-01

This case study focuses upon the transformational experiences of 28 social service and pastoral workers engaged in a Reflection Circle Process (RCP) in San Antonio, TX. The RCP involves the writing of a holistic journal entry, known as a process note, coupled with an in-depth exploration of the note with the help of a group of trusted peers, known…

Glucose-6-phosphate dehydrogenase deficiency and the risk of malaria and other diseases in children in Kenya: a case-control and a cohort study

PubMed Central

Uyoga, Sophie; Ndila, Carolyne M; Macharia, Alex W; Nyutu, Gideon; Shah, Shivang; Peshu, Norbert; Clarke, Geraldine M; Kwiatkowski, Dominic P; Rockett, Kirk A; Williams, Thomas N

2015-01-01

Summary Background The global prevalence of X-linked glucose-6-phosphate dehydrogenase (G6PD) deficiency is thought to be a result of selection by malaria, but epidemiological studies have yielded confusing results. We investigated the relationships between G6PD deficiency and both malaria and non-malarial illnesses among children in Kenya. Methods We did this study in Kilifi County, Kenya, where the G6PD c.202T allele is the only significant cause of G6PD deficiency. We tested the associations between G6PD deficiency and severe and complicated Plasmodium falciparum malaria through a case-control study of 2220 case and 3940 control children. Cases were children aged younger than 14 years, who visited the high dependency ward of Kilifi County Hospital with severe malaria between March 1, 1998, and Feb 28, 2010. Controls were children aged between 3–12 months who were born within the same study area between August 2006, and September 2010. We assessed the association between G6PD deficiency and both uncomplicated malaria and other common diseases of childhood in a cohort study of 752 children aged younger than 10 years. Participants of this study were recruited from a representative sample of households within the Ngerenya and Chonyi areas of Kilifi County between Aug 1, 1998, and July 31, 2001. The primary outcome measure for the case-control study was the odds ratio for hospital admission with severe malaria (computed by logistic regression) while for the cohort study it was the incidence rate ratio for uncomplicated malaria and non-malaria illnesses (computed by Poisson regression), by G6PD deficiency category. Findings 2863 (73%) children in the control group versus 1643 (74%) in the case group had the G6PD normal genotype, 639 (16%) versus 306 (14%) were girls heterozygous for G6PD c.202T, and 438 (11%) versus 271 (12%) children were either homozygous girls or hemizygous boys. Compared with boys and girls without G6PD deficiency, we found significant protection from severe malaria (odds ratio [OR] 0·82, 95% CI 0·70–0·97; p=0·020) among G6PD c.202T heterozygous girls but no evidence for protection among G6PD c.202T hemizygous boys and homozygous girls (OR 1·18, 0·99–1·40; p=0·056). Median follow-up for the mild disease cohort study was 2·24 years (IQR 2·22–2·85). G6PD c.202T had no effect on other common diseases of childhood in heterozygous girls (incidence rate ratio 0·98, 95% CI 0·86–1·11; p=0·82) or homozygous girls or hemizygous boys (0·93, 0·82–1·04; p=0·25), with the sole exception of a marginally significant increase in the incidence of helminth infections among heterozygous girls. Interpretation Heterozygous girls might be the driving force for the positive selection of G6PD deficiency alleles. Further studies are needed to definitively establish the mechanisms by which G6PD deficiency confers an advantage against malaria in heterozygous individuals. Such studies could lead to the development of new treatments. Funding Wellcome Trust, UK Medical Research Council, European Union, and Foundation for the National Institutes of Health (as part of the Bill & Melinda Gates Grand Challenges in Global Health Initiative). PMID:26686045

Glucose-6-phosphate dehydrogenase deficiency and the risk of malaria and other diseases in children in Kenya: a case-control and a cohort study.

PubMed

Uyoga, Sophie; Ndila, Carolyne M; Macharia, Alex W; Nyutu, Gideon; Shah, Shivang; Peshu, Norbert; Clarke, Geraldine M; Kwiatkowski, Dominic P; Rockett, Kirk A; Williams, Thomas N

2015-10-01

The global prevalence of X-linked glucose-6-phosphate dehydrogenase (G6PD) deficiency is thought to be a result of selection by malaria, but epidemiological studies have yielded confusing results. We investigated the relationships between G6PD deficiency and both malaria and non-malarial illnesses among children in Kenya. We did this study in Kilifi County, Kenya, where the G6PD c.202T allele is the only significant cause of G6PD deficiency. We tested the associations between G6PD deficiency and severe and complicated Plasmodium falciparum malaria through a case-control study of 2220 case and 3940 control children. Cases were children aged younger than 14 years, who visited the high dependency ward of Kilifi County Hospital with severe malaria between March 1, 1998, and Feb 28, 2010. Controls were children aged between 3-12 months who were born within the same study area between August 2006, and September 2010. We assessed the association between G6PD deficiency and both uncomplicated malaria and other common diseases of childhood in a cohort study of 752 children aged younger than 10 years. Participants of this study were recruited from a representative sample of households within the Ngerenya and Chonyi areas of Kilifi County between Aug 1, 1998, and July 31, 2001. The primary outcome measure for the case-control study was the odds ratio for hospital admission with severe malaria (computed by logistic regression) while for the cohort study it was the incidence rate ratio for uncomplicated malaria and non-malaria illnesses (computed by Poisson regression), by G6PD deficiency category. 2863 (73%) children in the control group versus 1643 (74%) in the case group had the G6PD normal genotype, 639 (16%) versus 306 (14%) were girls heterozygous for G6PD c.202T, and 438 (11%) versus 271 (12%) children were either homozygous girls or hemizygous boys. Compared with boys and girls without G6PD deficiency, we found significant protection from severe malaria (odds ratio [OR] 0·82, 95% CI 0·70-0·97; p=0·020) among G6PD c.202T heterozygous girls but no evidence for protection among G6PD c.202T hemizygous boys and homozygous girls (OR 1·18, 0·99-1·40; p=0·056). Median follow-up for the mild disease cohort study was 2·24 years (IQR 2·22-2·85). G6PD c.202T had no effect on other common diseases of childhood in heterozygous girls (incidence rate ratio 0·98, 95% CI 0·86-1·11; p=0·82) or homozygous girls or hemizygous boys (0·93, 0·82-1·04; p=0·25), with the sole exception of a marginally significant increase in the incidence of helminth infections among heterozygous girls. Heterozygous girls might be the driving force for the positive selection of G6PD deficiency alleles. Further studies are needed to definitively establish the mechanisms by which G6PD deficiency confers an advantage against malaria in heterozygous individuals. Such studies could lead to the development of new treatments. Wellcome Trust, UK Medical Research Council, European Union, and Foundation for the National Institutes of Health (as part of the Bill & Melinda Gates Grand Challenges in Global Health Initiative). Copyright © 2015 Uyoga et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd.. All rights reserved.

Medical leadership arrangements in English healthcare organisations: findings from a national survey and case studies of NHS trusts.

PubMed

Dickinson, Helen; Ham, Chris; Snelling, Iain; Spurgeon, Peter

2013-11-01

This project sought to describe the involvement of doctors in leadership roles in the NHS and the organisational structures and management processes in use in NHS trusts. A mixed methods approach was adopted combining a questionnaire survey of English NHS trusts and in-depth case studies of nine organisations who responded to the survey. Respondents identified a number of challenges in the development of medical leadership, and there was often perceived to be an engagement gap between medical leaders and doctors in clinical roles. While some progress has been made in the development of medical leadership in the NHS in England, much remains to be done to complete the journey that started with the Griffiths Report in 1983. We conclude that a greater degree of professionalism needs to be brought to bear in the development of medical leadership. This includes developing career structures to make it easier for doctors to take on leadership roles; providing training, development and support in management and leadership at different stages of doctors' careers; and ensuring that pay and other rewards are commensurate with the responsibilities of medical leaders. The time commitment of medical leaders and the proportion of doctors in leadership roles both need to increase. The paper concludes considering the implications of these findings for other health systems. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

[The pandemic of the experts in the mass media. How to create trust in public communication by acknowledging ignorance and uncertainty].

PubMed

Stollorz, V

2013-01-01

The first influenza pandemic in the twenty-first century is an example of how public trust in expert recommendations can erode if prognostic ability of these experts is suddenly doubted in the mass media. A highly consonant pandemic alarm communicated through the mass media can later cause heightened resonance concerning the appropriateness of the same alarm. In this case a paradoxical effect can develop, in which the same media outlet first paints an overly risky picture of an unfolding pandemic only to later condemn this assessment as alarmist. Can such behavior be considered a defect of journalism? In this article I describe the circumstances under which such media dynamics and "hypes" without trust in expertise are more likely to develop: when there is nontransparent decision making; when uncertainty and nescience of expert judgments are not communicated transparently; when warnings and measures taken are not readily adapted to the evolving risk situation in reality. If these basic principles are recognized in future pandemic risk communication, long-term public trust in scientific expertise can be secured. In this way, despite a public health crisis, a long-lasting break in the credibility of sound science can be avoided.

The value of using top-down and bottom-up approaches for building trust and transparency in biobanking.

PubMed

Meslin, Eric M

2010-01-01

With the domestic and international proliferation of biobanks and their associated connections to health information databases, scholarly attention has been turning from the ethical issues arising from the construction of biobanks to the ethical issues that emerge in their operation and management. Calls for greater transparency in governance structures, coupled with stern reminders of the value of maintaining public trust, are seen as critical components in the success of these resources. Two different approaches have been adopted for addressing these types of ethical issues: the first is a 'top-down' approach which focuses on developing policy, procedures, regulations and guidelines to aid decision-makers. The second is a 'bottom-up' approach, which begins with those who are most affected by the issues and attempts to inductively develop consensus recommendations and policy. While both approaches have merit, I argue that more work needs to be done on 'bottom-up' strategies if trust and transparency are to be more than mere slogans. Using 2 case examples from Indiana, the paper summarizes data from a set of surveys we recently conducted that address issues arising from biobanks that provide some insight into issues associated with trust and transparency. Copyright 2010 S. Karger AG, Basel.

Clinical Intuition in Family Medicine: More Than First Impressions

PubMed Central

Woolley, Amanda; Kostopoulou, Olga

2013-01-01

PURPOSE The clinical literature advises physicians not to trust their intuition. Studies of clinical intuition, however, equate it to early impressions, the first thing that comes to the physician’s mind. This study aimed to investigate the validity of this perspective by examining real cases of intuition in family medicine. METHODS Eighteen family physicians were interviewed about patient cases in which they believed that they had experienced an intuition. Cases were included if (1) participants were unaware of the basis of their judgment, or (2) participants talked about the basis of their judgment but believed that it was irrational or unsubstantiated. During the interview, case descriptions were systematically probed following the Critical Decision Method. Transcripts were coded for judgments, informational cues, expectancies, goals, and actions and were reordered into chronological accounts of the decision process. The 2 authors independently categorized cases into 3 emerging decision process types. RESULTS Participants reported 31 cases, 24 of which met inclusion criteria. Three types of decision process emerged: gut feelings, recognitions, and insights (κ = 0.78). In all cases, participants thought that their intuitive judgment was in conflict with a more rational explanation or what other colleagues would do. CONCLUSIONS Automatic, nonanalytical processes in clinical judgment extend beyond first impressions. Rather than admonishing clinicians not to trust their intuition, it should be acknowledged that little is currently known about the different types of intuitive processes and what determines their success or failure. Research on the conditions for accurate clinical intuitions is needed. PMID:23319507

Clinical intuition in family medicine: more than first impressions.

PubMed

Woolley, Amanda; Kostopoulou, Olga

2013-01-01

The clinical literature advises physicians not to trust their intuition. Studies of clinical intuition, however, equate it to early impressions, the first thing that comes to the physician's mind. This study aimed to investigate the validity of this perspective by examining real cases of intuition in family medicine. Eighteen family physicians were interviewed about patient cases in which they believed that they had experienced an intuition. Cases were included if (1) participants were unaware of the basis of their judgment, or (2) participants talked about the basis of their judgment but believed that it was irrational or unsubstantiated. During the interview, case descriptions were systematically probed following the Critical Decision Method. Transcripts were coded for judgments, informational cues, expectancies, goals, and actions and were reordered into chronological accounts of the decision process. The 2 authors independently categorized cases into 3 emerging decision process types. Participants reported 31 cases, 24 of which met inclusion criteria. Three types of decision process emerged: gut feelings, recognitions, and insights (κ = 0.78). In all cases, participants thought that their intuitive judgment was in conflict with a more rational explanation or what other colleagues would do. Automatic, nonanalytical processes in clinical judgment extend beyond first impressions. Rather than admonishing clinicians not to trust their intuition, it should be acknowledged that little is currently known about the different types of intuitive processes and what determines their success or failure. Research on the conditions for accurate clinical intuitions is needed.

The impact of global health initiatives on trust in health care provision under extreme resource scarcity: presenting an agenda for debate from a case study of emergency obstetric care in Northern Tanzania

PubMed Central

2010-01-01

Background Through the nearly three decades that have passed since the Alma Ata conference on Primary Health Care, a wide range of global health initiatives and ideas have been advocated to improve the health of people living in developing countries. The issues raised in the Primary Health Care concept, the Structural Adjustment Programmes and the Health Sector Reforms have all influenced health service delivery. Increasingly however, health systems in developing countries are being described as having collapsed Do the advocated frameworks contribute to this collapse through not adequately including population trust as a determinant of the revival of health services, or are they primarily designed to satisfy the values of other actors within the health care system? This article argues there is an urgent need to challenge common thinking on health care provision under extreme resource scarcity. Methods This article sets out to discuss and analyze the described collapse of health services through a brief case study on provision of Emergency Obstetric Care in Northern Tanzania. Results The article argues that post the Alma Ata conference on Primary Health Care developments in global health initiatives have not been successful in incorporating population trust into the frameworks, instead focusing narrowly on expert-driven solutions through concepts such as prevention and interventions. The need for quantifiable results has pushed international policy makers and donors towards vertical programmes, intervention approaches, preventive services and quantity as the coverage parameter. Health systems have consequently been pushed away from generalized horizontal care, curative services and quality assurance, all important determinants of trust. Conclusions Trust can be restored, and to further this objective a new framework is proposed placing generalized services and individual curative care in the centre of the health sector policy domain. Preventive services are important, but should increasingly be handled by other sectors in a service focused health care system. To facilitate such a shift in focus we should acknowledge that limited resources are available and accept the conflict between population demand and expert opinion, with the aim of providing legitimate, accountable and trustworthy services through fair, deliberative, dynamic and incremental processes. A discussion of the acceptable level of quality, given the available resources, can then be conducted. The article presents for debate that an increased focus on quality and accountability to secure trust is an important precondition for enabling the political commitment to mobilize necessary resources to the health sector. PMID:20500857

The Development of Behavior Control Competency in Preadolescence: A Case Vignette

ERIC Educational Resources Information Center

Cooper, Atha J.; And Others

1972-01-01

The utility of a crisis intervention approach for helping preadolescents build competency in behavior control is demonstrated. The following dimensions are highlighted: immediacy of intervention, trust relationship, structural interventions, facilitating versus controlling, problem solving orientation, and mobilization of group membership…

Income inequality, distributive fairness and political trust in Latin America.

PubMed

Zmerli, Sonja; Castillo, Juan Carlos

2015-07-01

In the wake of rising levels of income inequality during the past two decades, widespread concerns emerged about the social and political consequences of the widening gap between the poor and the rich that can be observed in many established democracies. Several empirical studies substantiate the link between macro-level income inequality and political attitudes and behavior, pointing at its broad and negative implications for political equality. Accordingly, these implications are expected to be accentuated in contexts of high inequality, as is the case in Latin America. Despite these general concerns about the consequences of income inequality, few studies have accounted for the importance of individual perceptions of distributive fairness in regard to trust in political institutions. Even less is known about the extent to which distributive fairness perceptions co-vary with objective indicators of inequality. Moreover, the research in this area has traditionally focused on OECD countries, which have lower indexes of inequality than the rest of the world. This study aims at filling this gap by focusing on the relevance of distributive fairness perceptions and macro-level inequality for political trust and on how these two levels interact in Latin American countries. The analyses are based on the Latinobarometer survey 2011, which consists of 18 countries. Multilevel estimations suggest that both dimensions of inequality are negatively associated with political trust but that higher levels of macro-level inequality attenuate rather than increase the strength of the negative association between distributive fairness perceptions and political trust. Copyright © 2015 Elsevier Inc. All rights reserved.