13 research outputs found
What are the most salient visuoperceptual reading symptoms to identify visual stress in adults? Using exploratory factor analysis to develop the Ulster visual stress questionnaire
No full textVisual Stress (VS) is a reading disorder characterised by visuoperceptual distortion symptoms experienced when reading. VS diagnosis is on an ad-hoc basis, with symptomology and diagnostic criteria poorly understood. This study investigated reading symptoms in adults to develop a clinically useful questionnaire for VS diagnosis. A comprehensive 17-item questionnaire was developed probing reading symptoms derived from the existing literature. 1248 undergraduate students (aged 18–50 years) completed the questionnaire and pattern glare test. 294 participants (23.6 %) exhibited pattern glare (scores > 3 on a mid-spatial frequency pattern glare test) which was used as an indirect measure of cortical hyperexcitation. After exclusion of diagnosed migraineurs, data from 247 participants were analysed. Parallel analysis determined the number of distinct factors and exploratory factor analysis assigned symptoms to these factors. To ensure symptoms mapped to a single factor, retained items needed to satisfy three conditions: (i) load onto their primary factor if >0.40, (ii) cross-load onto alternative factors by <0.30 and (iii) exhibit a difference in item primary factor and subsequent factor loadings of >0.20. Five factors were identified and mapped well to aetiological theories proposed to explain visual stress: 1) Magnocellular Pathway Deficits 2) Cortical Hyperexcitability 3) Eye Movement/Tracking Issues 4) Aversion to High Temporal Frequency ‘Flicker’ and 5) Concurrent Pathologies associated with Visual Stress. Post-hoc item analysis reduced questionnaire content to ten items. Exploratory factor analysis enabled systematic creation of a robust 10-item questionnaire to aid visual stress diagnosis. The questionnaire will be applied in a clinical context and among different ages for validation purposes
Toward consistency between trends in bottom-up CO2 emissions and top-down atmospheric measurements in the Los Angeles megacity
No full textabstract: Large urban emissions of greenhouse gases result in large atmospheric enhancements relative to background that are easily measured. Using CO[subscript 2] mole fractions and Δ[superscript 14]C and δ[superscript 13]C values of CO[subscript 2] in the Los Angeles megacity observed in inland Pasadena (2006–2013) and coastal Palos Verdes peninsula (autumn 2009–2013), we have determined time series for CO[subscript 2] contributions from fossil fuel combustion (C[subscript ff]) for both sites and broken those down into contributions from petroleum and/or gasoline and natural gas burning for Pasadena. We find a 10 % reduction in Pasadena C[subscript ff] during the Great Recession of 2008–2010, which is consistent with the bottom-up inventory determined by the California Air Resources Board. The isotopic variations and total atmospheric CO[subscript 2] from our observations are used to infer seasonality of natural gas and petroleum combustion. The trend of CO[subscript 2] contributions to the atmosphere from natural gas combustion is out of phase with the seasonal cycle of total natural gas combustion seasonal patterns in bottom-up inventories but is consistent with the seasonality of natural gas usage by the area's electricity generating power plants. For petroleum, the inferred seasonality of CO[subscript 2] contributions from burning petroleum is delayed by several months relative to usage indicated by statewide gasoline taxes. Using the high-resolution Hestia-LA data product to compare C[subscript ff] from parts of the basin sampled by winds at different times of year, we find that variations in observed fossil fuel CO[subscript 2] reflect seasonal variations in wind direction. The seasonality of the local CO[subscript 2] excess from fossil fuel combustion along the coast, on Palos Verdes peninsula, is higher in autumn and winter than spring and summer, almost completely out of phase with that from Pasadena, also because of the annual variations of winds in the region. Variations in fossil fuel CO[subscript 2] signals are consistent with sampling the bottom-up Hestia-LA fossil CO[subscript 2] emissions product for sub-city source regions in the LA megacity domain when wind directions are considered.This article and any associated published material is distributed under the Creative Commons Attribution 3.0 License. View the article as published at: https://www.atmos-chem-phys.net/16/3843/2016
Prison or palace? Haven or hell? : an architectural and social study of the development of public lunatic asylums in Scotland, 1781-1930
No full textIn 1897 John Sibbald, Commissioner in Lunacy for Scotland, stated that ‘the
construction of an asylum is a more interesting subject of study for the general reader
than might be supposed.’ This thesis traces the development of the public asylum in
Scotland from 1781 to 1930.
By placing the institution in its wider social context it provides more than a historical
account, exploring how the buildings functioned as well as giving an architectural
analysis based on date, plan and style. Here the architecture represents more, and
provides a physical expression of successive stages of public philanthropy and legislative
changes during what was arguably one of the most rapidly evolving stages of history. At
a time when few medical treatments were available, public asylum buildings created truly
therapeutic environments, which allowed the mentally ill to live in relative peace and
security. The thesis explores how public asylums in Scotland introduced the segregation
or ‘classification’ of patients into separate needs-based groups under a system known as
Moral Treatment. It focuses particularly on the evolving plan forms of these institutions
from the earliest radial, prison-like structures to their development into self-sustaining
village-style colonies and shows how the plan reflects new attitudes to treatment.
While many have disappeared, the surviving Victorian and Edwardian mega-structures lie
as haunting reminders of a largely forgotten era in Scottish psychiatry. Only a few of the
original buildings are still in use today as specialist units, out-patient centres, and
administrative offices for Scotland’s Health Boards. Others have been redeveloped as
universities or luxury housing schemes, making use of the good-quality buildings and
landscaping. Whatever their current use, public asylums stand today as an outward sign
of the awakening of the Scottish people to the plight of the mentally ill in the nineteenth
and early twentieth centuries
Los Angeles megacity: a high-resolution land–atmosphere modelling system for urban CO2 emissions
No full textabstract: Megacities are major sources of anthropogenic fossil fuel CO[subscript 2] (FFCO[subscript 2]) emissions. The spatial extents of these large urban systems cover areas of 10 000 km[superscript 2] or more with complex topography and changing landscapes. We present a high-resolution land–atmosphere modelling system for urban CO[subscript 2] emissions over the Los Angeles (LA) megacity area. The Weather Research and Forecasting (WRF)-Chem model was coupled to a very high-resolution FFCO[subscript 2] emission product, Hestia-LA, to simulate atmospheric CO[subscript 2] concentrations across the LA megacity at spatial resolutions as fine as ∼ 1 km. We evaluated multiple WRF configurations, selecting one that minimized errors in wind speed, wind direction, and boundary layer height as evaluated by its performance against meteorological data collected during the CalNex-LA campaign (May–June 2010). Our results show no significant difference between moderate-resolution (4 km) and high-resolution (1.3 km) simulations when evaluated against surface meteorological data, but the high-resolution configurations better resolved planetary boundary layer heights and vertical gradients in the horizontal mean winds. We coupled our WRF configuration with the Vulcan 2.2 (10 km resolution) and Hestia-LA (1.3 km resolution) fossil fuel CO[subscript 2] emission products to evaluate the impact of the spatial resolution of the CO[subscript 2] emission products and the meteorological transport model on the representation of spatiotemporal variability in simulated atmospheric CO[subscript 2] concentrations. We find that high spatial resolution in the fossil fuel CO[subscript 2] emissions is more important than in the atmospheric model to capture CO[subscript 2] concentration variability across the LA megacity. Finally, we present a novel approach that employs simultaneous correlations of the simulated atmospheric CO[subscript 2] fields to qualitatively evaluate the greenhouse gas measurement network over the LA megacity. Spatial correlations in the atmospheric CO[subscript 2] fields reflect the coverage of individual measurement sites when a statistically significant number of sites observe emissions from a specific source or location. We conclude that elevated atmospheric CO[subscript 2] concentrations over the LA megacity are composed of multiple fine-scale plumes rather than a single homogenous urban dome. Furthermore, we conclude that FFCO[subscript 2] emissions monitoring in the LA megacity requires FFCO[subscript 2] emissions modelling with ∼ 1 km resolution because coarser-resolution emissions modelling tends to overestimate the observational constraints on the emissions estimates.This article and any associated published material is distributed under the Creative Commons Attribution 3.0 License. View the article as published at: http://www.atmos-chem-phys.net/16/9019/2016
Human genetic variants and age are the strongest predictors of humoral immune responses to common pathogens and vaccines
No full text<p>Online Supplementary Dataset of the manuscript "Human genetic variants and age are the strongest predictors of humoral immune responses to common pathogens and vaccines"</p>Full author list in main text
Charismata and compassion : Dhinakaran, Charismatic healing and Pastoral Pentecostalism in South India : a practical theological assessment
No full textThis dissertation is a theological assessment of the Jesus Calls divine healing movement as it developed in South India. It analyses the thought of the founder D. G. S.
Dhinakaran, India's pre-eminent healing evangelist and explores its potential and adequacy as a pastoral theology. It draws out Dhinakaran's healing theology and model for ministry that has significantly contributed to Indian mission and attained international recognition. Until now, this movement has received no critical analysis.
The author, a native of South India, as an observer-participant, takes up this task.
The emergence and impact of the modem Pentecostal movement and the `full gospel' with healing as its flagship is discussed. The study highlights lesser-known precursors
and theological roots that give Indian Pentecostalism its distinct identity from the 1906 Azusa Street Revival, USA. It reveals how Charismatic Christianity flourishes due to
its bhakti spirituality, guru leadership, apostolic charismata and practical compassion. The thesis maintains that the dialectic of Pentecostal power and pastoral care is an effective mission strategy and proceeds to demonstrate this in Dhinakaran's ministry.
The research method progressed from a description of Dhinakaran's healing praxis via theological analysis to a critical assessment. It shows some major influences and the
appeal of his prayer movement and argues that the key to its success lies in its highly pragmatic, culturally adaptive and syncretic nature. Three doctrinal concepts that are embodied in Dhinakaran's model are presented: compassion, the wounded healer and healing evangelism, which correlate within a theological apparatus to make
interpretative sense of his praxis resulting in what is termed `Pastoral Pentecostalism'.
The hybridity in Dhinakaran's `miracle healing' is explored within two wider contextual interfaces: the traditional Hindu culture with the shamanic manthiravadi and an imported but adapted version of American faith healing. Here, an easternwestern synthesis is shown to contribute at once to a viable indigenous ministry and to global trends in Charismatic Christianity, allowing each to inform and shape the other. Dhinakaran's distinct prosperity message is located within the Guru movement and assessed against the American health-wealth gospel for pastoral integrity. The thesis advocates a Pastoral Pentecostalism that holds charismata and compassion in creative tension and re-presents Dhinakaran as a significant charismatic healing evangelist
Development and evaluation of occupational therapy - Mahidol Clinic System (OT-MCS) for post-stroke rehabiliation in Thailand
No full textIn 2011 it was estimated that in Thailand there were 498,800 stroke survivors of both sexes but most were over the age of 65. They were served by only 625 occupational therapists (OTs). Occupational therapy (OT) plays a key role in the rehabilitation service for stroke patients, in particular, by enabling stroke survivors to reengage with activities of daily living and to resume work or family tasks. OT needs to be culturally appropriate and relevant to the therapists, stroke patients and their families. The Occupational Therapy Mahidol Clinic System (OT-MCS) has been designed to be culturally relevant and is based on collaborative teamwork which can better address the needs of the stroke patients.
OT-MCS was introduced in 6 regional OT clinics. This study compared perceptions of stroke clients who took part in the new approach 8 weeks before and during the rehabilitation. One hundred and twenty stroke participants were divided into 2 functional groups (slow and fast stream rehabilitation). Stroke participants (N=120) and OTs (N=60) explored the arrangement of activity items into domains for creating a new activity card sort (ACS). Sixty stroke participants
(slow stream rehabilitation) and 60 OTs were surveyed to investigate the attitudes of “satisfaction” and “importance” via 40 therapeutic activities. Sixty stroke participants (fast stream rehabilitation) evaluated the levels of their activity engagement in diverse cultural-therapeutic
activities. Lastly, 23 stroke participants (slow and fast stream rehabilitation) were interviewed in order to ascertain their lived experiences after the use of OT-MCS and the data were analysed using thematic analysis.
The integrated analysis demonstrated strong satisfaction and engagement with OT-MCS. The use of the activity catalogue met with positive attitudes from the stroke participants and in particular the collaborative approach of OTs and participants gave meaning to the activities and a sense of
self management. In addition in the fast stream rehabilitation participants reported satisfaction
with the transferability of the activities to the home and external environment and their relevance to supporting family life.
The OT-MCS for Thai stroke rehabilitation is a comprehensive OT service, which improves the perception of benefit in stroke clients enabling them to perform meaningful and purposeful activities based on their local and regional lifestyles. This culturally appropriate approach helps stroke clients to re-develop their life-skills. Through the use of meaningful and relevant activities which meet their specific needs, stroke clients can lead more satisfying and fulfilling lives
Six More Ultra-faint Milky Way Companions Discovered in the DECam Local Volume Exploration Survey
No full textFull list of the authors: Cerny, W.; Martínez-Vázquez, C. E.; Drlica-Wagner, A.; Pace, A. B.; Mutlu-Pakdil, B.; Li, T. S.; Riley, A. H.; Crnojević, D.; Bom, C. R.; Carballo-Bello, J. A.; Carlin, J. L.; Chiti, A.; Choi, Y.; Collins, M. L. M.; Darragh-Ford, E.; Ferguson, P. S.; Geha, M.; Martínez-Delgado, D.; Massana, P.; Mau, S.; Medina, G. E.; Muñoz, R. R.; Nadler, E. O.; Noël, N. E. D.; Olsen, K. A. G.; Pieres, A.; Sakowska, J. D.; Simon, J. D.; Stringfellow, G. S.; Tollerud, E. J.; Vivas, A. K.; Walker, A. R.; Wechsler, R. H.; Delve CollaborationWe report the discovery of six ultra-faint Milky Way satellites identified through matched-filter searches conducted using Dark Energy Camera (DECam) data processed as part of the second data release of the DECam Local Volume Exploration (DELVE) survey. Leveraging deep Gemini/GMOS-N imaging (for four candidates) as well as follow-up DECam imaging (for two candidates), we characterize the morphologies and stellar populations of these systems. We find that these candidates all share faint absolute magnitudes (M ≥ −3.2 mag) and old, metal-poor stellar populations (τ > 10 Gyr, [Fe/H] 15 pc), while the other three are compact (r < 10 pc). From these properties, we infer that the former three systems (Boötes V, Leo Minor I, and Virgo II) are consistent with ultra-faint dwarf galaxy classifications, whereas the latter three (DELVE 3, DELVE 4, and DELVE 5) are likely ultra-faint star clusters. Using data from the Gaia satellite, we confidently measure the proper motion of Boötes V, Leo Minor I, and DELVE 4, and tentatively detect a proper-motion signal from DELVE 3 and DELVE 5; no signal is detected for Virgo II. We use these measurements to explore possible associations between the newly discovered systems and the Sagittarius dwarf spheroidal, the Magellanic Clouds, and the Vast Polar Structure, finding several plausible associations. Our results offer a preview of the numerous ultra-faint stellar systems that will soon be discovered by the Vera C. Rubin Observatory and highlight the challenges of classifying the faintest stellar systems. © 2023. The Author(s). Published by the American Astronomical Society.We thank the anonymous referee for providing specific and constructive feedback that has improved this work. It is a pleasure to thank Simon Smith, Alan McConnachie, and the UNIONS collaboration for pleasant and productive discussions during which we coordinated the submission of our independent manuscripts reporting the discovery of Booetes V. We thank the staff of Gemini Observatory North and Cerro Tololo Inter-American Observatory for their support in the execution of our observations, and we are grateful to the directors of each observatory for granting our requests for Director's Discretionary time to study some of the candidates presented here. This project is partially supported by the NASA Fermi Guest Investigator Program Cycle 9 No. 91201. This work is partially supported by Fermilab LDRD project L2019-011. W.C. gratefully acknowledges support from a Gruber Science Fellowship at Yale University. A.B.P. acknowledges support from NSF grant AST-1813881. A.H.R. acknowledges support from an NSF Graduate Research Fellowship through grant DGE-1746932 and a Research Fellowship from the Royal Commission for the Exhibition of 1851. R.R.M. gratefully acknowledges support by the ANID BASAL project FB210003 and ANID Fondecyt project 1221695.This work was enabled in part by observations made from the Gemini North telescope, located within the Maunakea Science Reserve and adjacent to the summit of Maunakea. We are grateful for the privilege of observing the universe from a place that is unique in both its astronomical quality and its cultural significance. This work is based in part on observations obtained at the international Gemini Observatory, a program of NSFs NOIRLab (processed using DRAGONS (Data Reduction for Astronomy from Gemini Observatory North and South), which is managed by the Association of Universities for Research in Astronomy (AURA) under a cooperative agreement with the National Science Foundation on behalf of the Gemini Observatory partnership: the National Science Foundation (United States), National Research Council (Canada), Agencia Nacional de Investigacion y Desarrollo (Chile), Ministerio de Ciencia, Tecnologia e Innovacion (Argentina), Ministerio da Ciencia, Tecnologia, Inovacoes e Comunicacoes (Brazil), and Korea Astronomy and Space Science Institute (Republic of Korea). C.E.M-V thanks Kathleen Labrie and Chris Simpson for useful advice regarding the GMOS DRAGONS data reduction. This project used data obtained with the Dark Energy Camera (DECam), which was constructed by the Dark Energy Survey (DES) collaboration. Funding for the DES Projects has been provided by the DOE and NSF (USA), MISE (Spain), STFC (UK), HEFCE (UK), NCSA (UIUC), KICP (U. Chicago), CCAPP (Ohio State), MIFPA (Texas A & M University), CNPQ, FAPERJ, FINEP (Brazil), MINECO (Spain), DFG (Germany), and the collaborating institutions in the Dark Energy Survey, which are Argonne Lab, UC Santa Cruz, University of Cambridge, CIEMAT-Madrid, University of Chicago, University College London, DES-Brazil Consortium, University of Edinburgh, ETH Zuerich, Fermilab, University of Illinois, ICE (IEEC-CSIC), IFAE Barcelona, Lawrence Berkeley Lab, LMU Muenchen, and the associated Excellence Cluster Universe, University of Michigan, NSF's National Optical-Infrared Astronomy Research Laboratory, University of Nottingham, Ohio State University, OzDES Membership Consortium University of Pennsylvania, University of Portsmouth, SLAC National Lab, Stanford University, University of Sussex, and Texas A & M University.
This work has made use of data from the European Space Agency (ESA) mission Gaia (https://www.cosmos.esa.int/gaia), processed by the Gaia Data Processing and Analysis Consortium (DPAC, https://www.cosmos.esa.int/web/gaia/dpac/consortium). Funding for the DPAC has been provided by national institutions, in particular the institutions participating in the Gaia Multilateral Agreement. Based on observations at Cerro Tololo Inter-American Observatory, NSF's National Optical-Infrared Astronomy Research Laboratory (2019A-0305; PI: Drlica-Wagner), which is operated by the Association of Universities for Research in Astronomy (AURA) under a cooperative agreement with the National Science Foundation. This manuscript has been authored by Fermi Research Alliance, LLC, under contract No. DE-AC02-07CH11359 with the US Department of Energy, Office of Science, Office of High Energy Physics. The United States Government retains and the publisher, by accepting the article for publication, acknowledges that the United States Government retains a nonexclusive, paid-up, irrevocable, worldwide license to publish or reproduce the published form of this manuscript, or allow others to do so, for United States Government purposes. The Legacy Surveys consist of three individual and complementary projects: the Dark Energy Camera Legacy Survey (DECaLS; Proposal ID 2014B-0404; PIs: David Schlegel and Arjun Dey), the Beijing-Arizona Sky Survey (BASS; NOAO Prop. ID 2015A-0801; PIs: Zhou Xu and Xiaohui Fan), and the Mayall z-band Legacy Survey (MzLS; Prop. ID 2016A-0453; PI: Arjun Dey). DECaLS, BASS, and MzLS together include data obtained, respectively, at the Blanco telescope, Cerro Tololo Inter-American Observatory, NSFs NOIRLab; the Bok telescope, Steward Observatory, University of Arizona; and the Mayall telescope, Kitt Peak National Observatory, NOIRLab. Pipeline processing and analyses of the data were supported by NOIRLab and the Lawrence Berkeley National Laboratory (LBNL). The Legacy Surveys project is honored to be permitted to conduct astronomical research on Iolkam Duag (Kitt Peak), a mountain with particular significance to the Tohono Oodham Nation. NOIRLab is operated by the Association of Universities for Research in Astronomy (AURA) under a cooperative agreement with the National Science Foundation. LBNL is managed by the Regents of the University of California under contract to the U.S. Department of Energy. This project used data obtained with the Dark Energy Camera (DECam), which was constructed by the Dark Energy Survey (DES) collaboration. Funding for the DES Projects has been provided by the U.S. Department of Energy, the U.S.
National Science Foundation, the Ministry of Science and Education of Spain, the Science and Technology Facilities Council of the United Kingdom, the Higher Education Funding Council for England, the National Center for Supercomputing Applications at the University of Illinois at Urbana-Champaign, the Kavli Institute of Cosmological Physics at the University of Chicago, Center for Cosmology and Astro-Particle Physics at the Ohio State University, the Mitchell Institute for Fundamental Physics and Astronomy at Texas A & M University, Financiadora de Estudos e Projetos, Fundacao Carlos Chagas Filho de Amparo, Financiadora de Estudos e Projetos, Fundacao Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro, Conselho Nacional de Desenvolvimento Cientifico e Tecnologico and the Ministerio da Ciencia, Tecnologia e Inovacao, the Deutsche Forschungsgemeinschaft and the Collaborating Institutions in the Dark Energy Survey. The Collaborating Institutions are Argonne National Laboratory, the University of California at Santa Cruz, the University of Cambridge, Centro de Investigaciones Energeticas, Medioambientales y Tecnologicas-Madrid, the University of Chicago, University College London, the DES-Brazil Consortium, the University of Edinburgh, the Eidgenossische Technische Hochschule (ETH) Zurich, Fermi National Accelerator Laboratory, the University of Illinois at Urbana-Champaign, the Institut de Ciencies de lEspai (IEEC/CSIC), the Institut de Fisica dAltes Energies, Lawrence Berkeley National Laboratory, the Ludwig Maximilians Universitat Munchen and the associated Excellence Cluster Universe, the University of Michigan, NSFs NOIRLab, the University of Nottingham, the Ohio State University, the University of Pennsylvania, the University of Portsmouth, SLAC National Accelerator Laboratory, Stanford University, the University of Sussex, and Texas A & M University. BASS is a key project of the Telescope Access Program (TAP), which has been funded by the National Astronomical Observatories of China, the Chinese Academy of Sciences (the Strategic Priority Research Program The Emergence of Cosmological Structures grant No. XDB09000000), and the Special Fund for Astronomy from the Ministry of Finance. BASS is also supported by the External Cooperation Program of Chinese Academy of Sciences (grant No. 114A11KYSB20160057), and Chinese National Natural Science Foundation (grant Nos. 12120101003 and 11433005).The Legacy Survey team makes use of data products from the Near-Earth Object Wide-field Infrared Survey Explorer (NEOWISE), which is a project of the Jet Propulsion Laboratory/California Institute of Technology. NEOWISE is funded by the National Aeronautics and Space Administration. The Legacy Surveys imaging of the DESI footprint is supported by the Director, Office of Science, Office of High Energy Physics of the U.S. Department of Energy under contract No. DE-AC02-05CH1123, by the National Energy Research Scientific Computing Center, a DOE Office of Science User Facility under the same contract; and by the U.S. National Science Foundation, Division of Astronomical Sciences under contract No. AST-0950945 to NOAO. Facilities: Blanco (DECam), Gemini:Gillett (GMOS-N), Gaia, Astro Data Lab, Astro Data Archive. Software: astropy (Astropy Collaboration et al. 2013; Price-Whelan et al. 2018), emcee (Foreman-Mackey et al. 2013), fitsio, 42 42 https://github.com/esheldon/fitsio HEALPix (Gorski et al. 2005), 43 43 http://healpix.sourceforge.net healpy (Zonca et al. 2019), 44 44 https://github.
com/healpy/healpy Matplotlib (Hunter 2007), numpy (van der Walt et al. 2011), scipy (Jones et al. 2001), ugali (Bechtol et al. 2015) 45 45 https://github.com/DarkEnergySurvey/ugali , gala (Price-Whelan 2017
Type I interferon in patients with systemic autoimmune rheumatic disease is associated with haematological abnormalities and specific autoantibody profiles
No full textObjectives To investigate the relationships between interferon-alpha (IFNα) and the clinical and serological phenotype of patients with systemic autoimmune rheumatic disease (SARDs) in order to determine whether a distinct subpopulation of patients can be identified. Methods We recruited patients with at least 1 SARD clinical feature, and at least 1 SARD-related autoantibody from two NHS Trusts in Greater Manchester. A 6-gene interferon-stimulated gene (ISG) score was calculated in all patients and in a subgroup, a 30-gene ISG score was produced using NanoString. A digital Single Molecule Array (Simoa) was used to measure plasma IFNα protein. In an exploratory analysis, whole blood RNA sequencing was conducted in 12 patients followed by RT-qPCR confirmation of expression of 6 nucleic acid receptors (NARs) in the whole cohort. Results Sixty three of 164 (38%) patients had a positive ISG score. The 3 measures of IFNα all correlated strongly with each other (p<0.0001). There were no differences in mucocutaneous or internal organ involvement between the ISG subgroups. The ISG-positive group had increased frequency of specific autoantibodies and haematological abnormalities which remained significant after adjusting for the SARD subtype. Expression of DDX58, MB21D1 and TLR7 was correlated with the ISG score whilst TLR3, TLR9 and MB21D1 were associated with neutrophil count. Conclusion In SARD patients, IFNα-positivity was associated with specific autoantibodies and haematological parameters but not with other clinical features. The variable NAR expression suggests that different pathways may drive IFNα production in individual patients. The identification of an IFNα-positive subgroup within a mixed SARD cohort supports a pathology-based approach to treatment
Standardized whole blood stimulation improves immunomonitoring of induced immune responses in multi-center study
No full textInternational audienceFunctional immune responses are increasingly important for clinical studies, providing in depth biomarker information to assess immunotherapy or vaccination. Incorporating functional immune assays into routine clinical practice has remained limited due to challenges in standardizing sample preparation. We recently described the use of a whole blood syringe-based system, TruCulture®, which permits point-of-care standardized immune stimulation. Here, we report on a multi-center clinical study in seven FOCIS Centers of Excellence to directly compare TruCulture to conventional PBMC methods. Whole blood and PBMCs from healthy donors were exposed to LPS, anti-CD3 anti-CD28 antibodies, or media alone. 55 protein analytes were analyzed centrally by Luminex multi-analyte profiling in a CLIA-certified laboratory. TruCulture responses showed greater reproducibility and improved the statistical power for monitoring differential immune response activation. The use of TruCulture addresses a major unmet need through a robust and flexible method for immunomonitoring that can be reproducibly applied in multi-center clinical studies
