1. |
- Franceschini, N., et al.
(author)
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GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes
- 2018
-
In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1
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Journal article (peer-reviewed)abstract
- Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4. LD score regression reveals significant genetic correlations between cIMT and plaque traits, and both cIMT and plaque with CHD, any stroke subtype and ischemic stroke. Our study provides insights into genes and tissue-specific regulatory mechanisms linking atherosclerosis both to its functional genomic origins and its clinical consequences in humans. © 2018, The Author(s).
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2. |
- Andreoni, I., et al.
(author)
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Follow Up of GW170817 and Its Electromagnetic Counterpart by Australian-Led Observing Programmes
- 2017
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In: Publications Astronomical Society of Australia. - : Cambridge University Press (CUP). - 1323-3580 .- 1448-6083. ; 34
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Research review (peer-reviewed)abstract
- The discovery of the first electromagnetic counterpart to a gravitational wave signal has generated follow-up observations by over 50 facilities world-wide, ushering in the new era of multi-messenger astronomy. In this paper, we present follow-up observations of the gravitational wave event GW170817 and its electromagnetic counterpart SSS17a/DLT17ck (IAU label AT2017gfo) by 14 Australian telescopes and partner observatories as part of Australian-based and Australian-led research programs. We report early- to late-time multi-wavelength observations, including optical imaging and spectroscopy, mid-infrared imaging, radio imaging, and searches for fast radio bursts. Our optical spectra reveal that the transient source emission cooled from approximately 6 400 K to 2 100 K over a 7-d period and produced no significant optical emission lines. The spectral profiles, cooling rate, and photometric light curves are consistent with the expected outburst and subsequent processes of a binary neutron star merger. Star formation in the host galaxy probably ceased at least a Gyr ago, although there is evidence for a galaxy merger. Binary pulsars with short (100 Myr) decay times are therefore unlikely progenitors, but pulsars like PSR B1534+12 with its 2.7 Gyr coalescence time could produce such a merger. The displacement (similar to 2.2 kpc) of the binary star system from the centre of the main galaxy is not unusual for stars in the host galaxy or stars originating in the merging galaxy, and therefore any constraints on the kick velocity imparted to the progenitor are poor.
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3. |
- Shimwell, T. W., et al.
(author)
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The LOFAR Two-metre Sky Survey: V. Second data release
- 2022
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 659
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Journal article (peer-reviewed)abstract
- In this data release from the ongoing LOw-Frequency ARray (LOFAR) Two-metre Sky Survey we present 120a 168 MHz images covering 27% of the northern sky. Our coverage is split into two regions centred at approximately 12h45m +44 30a and 1h00m +28 00a and spanning 4178 and 1457 square degrees respectively. The images were derived from 3451 h (7.6 PB) of LOFAR High Band Antenna data which were corrected for the direction-independent instrumental properties as well as direction-dependent ionospheric distortions during extensive, but fully automated, data processing. A catalogue of 4 396 228 radio sources is derived from our total intensity (Stokes I) maps, where the majority of these have never been detected at radio wavelengths before. At 6a resolution, our full bandwidth Stokes I continuum maps with a central frequency of 144 MHz have: a median rms sensitivity of 83 μJy beama 1; a flux density scale accuracy of approximately 10%; an astrometric accuracy of 0.2a; and we estimate the point-source completeness to be 90% at a peak brightness of 0.8 mJy beama 1. By creating three 16 MHz bandwidth images across the band we are able to measure the in-band spectral index of many sources, albeit with an error on the derived spectral index of > a ±a 0.2 which is a consequence of our flux-density scale accuracy and small fractional bandwidth. Our circular polarisation (Stokes V) 20a resolution 120a168 MHz continuum images have a median rms sensitivity of 95 μJy beama 1, and we estimate a Stokes I to Stokes V leakage of 0.056%. Our linear polarisation (Stokes Q and Stokes U) image cubes consist of 480a A a 97.6 kHz wide planes and have a median rms sensitivity per plane of 10.8 mJy beama 1 at 4a and 2.2 mJy beama 1 at 20a; we estimate the Stokes I to Stokes Q/U leakage to be approximately 0.2%. Here we characterise and publicly release our Stokes I, Q, U and V images in addition to the calibrated uv-data to facilitate the thorough scientific exploitation of this unique dataset.
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4. |
- Hudson, Lawrence N, et al.
(author)
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The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project
- 2017
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In: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 7:1, s. 145-188
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Journal article (peer-reviewed)abstract
- The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.
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5. |
- Jones, Gregory T., et al.
(author)
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Meta-Analysis of Genome-Wide Association Studies for Abdominal Aortic Aneurysm Identifies Four New Disease-Specific Risk Loci
- 2017
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In: Circulation Research. - 0009-7330 .- 1524-4571. ; 120:2, s. 341-
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Journal article (peer-reviewed)abstract
- Rationale: Abdominal aortic aneurysm (AAA) is a complex disease with both genetic and environmental risk factors. Together, 6 previously identified risk loci only explain a small proportion of the heritability of AAA. Objective: To identify additional AAA risk loci using data from all available genome-wide association studies. Methods and Results: Through a meta-analysis of 6 genome-wide association study data sets and a validation study totaling 10 204 cases and 107 766 controls, we identified 4 new AAA risk loci: 1q32.3 (SMYD2), 13q12.11 (LINC00540), 20q13.12 (near PCIF1/MMP9/ZNF335), and 21q22.2 (ERG). In various database searches, we observed no new associations between the lead AAA single nucleotide polymorphisms and coronary artery disease, blood pressure, lipids, or diabetes mellitus. Network analyses identified ERG, IL6R, and LDLR as modifiers of MMP9, with a direct interaction between ERG and MMP9. Conclusions: The 4 new risk loci for AAA seem to be specific for AAA compared with other cardiovascular diseases and related traits suggesting that traditional cardiovascular risk factor management may only have limited value in preventing the progression of aneurysmal disease.
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7. |
- Broderick, J. W., et al.
(author)
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LOFAR 144-MHz follow-up observations of GW170817
- 2020
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In: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 494:4, s. 5110-5117
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Journal article (peer-reviewed)abstract
- We present low-radio-frequency follow-up observations of AT 2017gfo, the electromagnetic counterpart of GW170817, which was the first binary neutron star merger to be detected by Advanced LIGO-Virgo. These data, with a central frequency of 144 MHz, were obtained with LOFAR, the Low-Frequency Array. The maximum elevation of the target is just 13 degrees.7 when observed with LOFAR, making our observations particularly challenging to calibrate and significantly limiting the achievable sensitivity. On time-scales of 130-138 and 371-374 d after the merger event, we obtain 3s upper limits for the afterglow component of 6.6 and 19.5mJy beam(-1), respectively. Using our best upper limit and previously published, contemporaneous higher frequency radio data, we place a limit on any potential steepening of the radio spectrum between 610 and 144 MHz: the two-point spectral index alpha(610)(144) greater than or similar to -2.5. We also show that LOFAR can detect the afterglows of future binary neutron star merger events occurring at more favourable elevations.
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- Lempiainen, H, et al.
(author)
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Network analysis of coronary artery disease risk genes elucidates disease mechanisms and druggable targets
- 2018
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In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:1, s. 3434-
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Journal article (peer-reviewed)abstract
- Genome-wide association studies (GWAS) have identified over two hundred chromosomal loci that modulate risk of coronary artery disease (CAD). The genes affected by variants at these loci are largely unknown and an untapped resource to improve our understanding of CAD pathophysiology and identify potential therapeutic targets. Here, we prioritized 68 genes as the most likely causal genes at genome-wide significant loci identified by GWAS of CAD and examined their regulatory roles in 286 metabolic and vascular tissue gene-protein sub-networks (“modules”). The modules and genes within were scored for CAD druggability potential. The scoring enriched for targets of cardiometabolic drugs currently in clinical use and in-depth analysis of the top-scoring modules validated established and revealed novel target tissues, biological processes, and druggable targets. This study provides an unprecedented resource of tissue-defined gene–protein interactions directly affected by genetic variance in CAD risk loci.
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12. |
- Miller, CL, et al.
(author)
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Integrative functional genomics identifies regulatory mechanisms at coronary artery disease loci
- 2016
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7, s. 12092-
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Journal article (peer-reviewed)abstract
- Coronary artery disease (CAD) is the leading cause of mortality and morbidity, driven by both genetic and environmental risk factors. Meta-analyses of genome-wide association studies have identified >150 loci associated with CAD and myocardial infarction susceptibility in humans. A majority of these variants reside in non-coding regions and are co-inherited with hundreds of candidate regulatory variants, presenting a challenge to elucidate their functions. Herein, we use integrative genomic, epigenomic and transcriptomic profiling of perturbed human coronary artery smooth muscle cells and tissues to begin to identify causal regulatory variation and mechanisms responsible for CAD associations. Using these genome-wide maps, we prioritize 64 candidate variants and perform allele-specific binding and expression analyses at seven top candidate loci: 9p21.3, SMAD3, PDGFD, IL6R, BMP1, CCDC97/TGFB1 and LMOD1. We validate our findings in expression quantitative trait loci cohorts, which together reveal new links between CAD associations and regulatory function in the appropriate disease context.
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- Askling, J., et al.
(author)
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How comparable are rates of malignancies in patients with rheumatoid arthritis across the world? A comparison of cancer rates, and means to optimise their comparability, in five RA registries
- 2016
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In: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 75:10, s. 1789-1796
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Journal article (peer-reviewed)abstract
- Background The overall incidence of cancer in patients with rheumatoid arthritis (RA) is modestly elevated. The extent to which cancer rates in RA vary across clinical cohorts and patient subsets, as defined by disease activity or treatment is less known but critical for understanding the safety of existing and new antirheumatic therapies. We investigated comparability of, and means to harmonise, malignancy rates in five RA registries from four continents. Methods Participating RA registries were Consortium of Rheumatology Researchers of North America (CORRONA) (USA), Swedish Rheumatology Quality of Care Register (SRR) (Sweden), Norfolk Arthritis Register (NOAR) (UK), CORRONA International (several countries) and Institute of Rheumatology, Rheumatoid Arthritis (IORRA) (Japan). Within each registry, we analysed a main cohort of all patients with RA from January 2000 to last available data, and sensitivity analyses of sub-cohorts defined by disease activity, treatment change, prior comorbidities and restricted by calendar time or follow-up, respectively. Malignancy rates with 95% CIs were estimated, and standardised for age and sex, based on the distributions from a typical RA clinical trial programme population (fostamatinib). Results There was a high consistency in rates for overall malignancy excluding non-melanoma skin cancer (NMSC), for malignant lymphomas, but not for all skin cancers, across registries, in particular following age/sex standardisation. Standardised rates of overall malignancy excluding NMSC varied from 0.56 to 0.87 per 100 person-years. Within each registry, rates were generally consistent across sensitivity analyses, which differed little from the main analysis. Conclusion In real-world RA populations, rates of both overall malignancy and of lymphomas are consistent.
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18. |
- Franceschini, N, et al.
(author)
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GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes
- 2018
-
In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1, s. 5141-
-
Journal article (peer-reviewed)abstract
- Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4. LD score regression reveals significant genetic correlations between cIMT and plaque traits, and both cIMT and plaque with CHD, any stroke subtype and ischemic stroke. Our study provides insights into genes and tissue-specific regulatory mechanisms linking atherosclerosis both to its functional genomic origins and its clinical consequences in humans.
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- Gaupp-Berghausen, M, et al.
(author)
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Evaluation of different recruitment methods: Longitudinal, web-based, pan-european physical activity through sustainable transport approaches (PASTA) project
- 2019
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In: Journal of Medical Internet Research. - : JMIR Publications Inc.. - 1438-8871. ; 21:5, s. e11492-
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Journal article (peer-reviewed)abstract
- Background: Sufficient sample size and minimal sample bias are core requirements for empirical data analyses. Combining opportunistic recruitment with a Web-based survey and data-collection platform yields new benefits over traditional recruitment approaches. Objective: This paper aims to report the success of different recruitment methods and obtain data on participants' characteristics, participation behavior, recruitment rates, and representativeness of the sample. Methods: A longitudinal, Web-based survey was implemented as part of the European PASTA (Physical Activity through Sustainable Transport Approaches) project, between November 2014 and December 2016. During this period, participants were recruited from 7 European cities on a rolling basis. A standardized guide on recruitment strategy was developed for all cities, to reach a sufficient number of adult participants. To make use of the strengths and minimize weakness, a combination of different opportunistic recruitment methods was applied. In addition, the random sampling approach was applied in the city of Örebro. To reduce the attrition rate and improve real-time monitoring, the Web-based platform featured a participant's and a researchers' user interface and dashboard. Results: Overall, 10,691 participants were recruited; most people found out about the survey through their workplace or employer (2300/10691, 21.51%), outreach promotion (2219/10691, 20.76%), and social media (1859/10691, 17.39%). The average number of questionnaires filled in per participant varied significantly between the cities (P<.001), with the highest number in Zurich (11.0, SE 0.33) and the lowest in Örebro (4.8, SE 0.17). Collaboration with local organizations, the use of Facebook and mailing lists, and direct street recruitment were the most effective approaches in reaching a high share of participants.
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- Michaud, K., et al.
(author)
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Can rheumatoid arthritis (RA) registries provide contextual safety data for modern RA clinical trials? The case for mortality and cardiovascular disease
- 2016
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In: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 75:10, s. 1797-1805
-
Journal article (peer-reviewed)abstract
- Background We implemented a novel method for providing contextual adverse event rates for a randomised controlled trial (RCT) programme through coordinated analyses of five RA registries, focusing here on cardiovascular disease (CVD) and mortality. Methods Each participating registry (Consortium of Rheumatology Researchers of North America (CORRONA) (USA), Swedish Rheumatology Quality of Care Register (SRR) (Sweden), Norfolk Arthritis Register (NOAR) (UK), CORRONA International (East Europe, Latin America, India) and Institute of Rheumatology, Rheumatoid Arthritis (IORRA) (Japan)) defined a main cohort from January 2000 onwards. To address comparability and potential bias, we harmonised event definitions and defined several subcohorts for sensitivity analyses based on disease activity, treatment, calendar time, duration of follow-up and RCT exclusions. Rates were standardised for age, sex and, in one sensitivity analysis, also HAQ. Results The combined registry cohorts included 57251 patients with RA (234089 person-years)24.5% men, mean (SD) baseline age 58.2 (13.8) and RA duration 8.2 (11.7) years. Standardised registry mortality rates (per 100 person-years) varied from 0.42 (CORRONA) to 0.80 (NOAR), with 0.60 for RCT patients. Myocardial infarction and major adverse cardiovascular events (MACE) rates ranged from 0.09 and 0.31 (IORRA) to 0.39 and 0.77 (SRR), with RCT rates intermediate (0.18 and 0.42), respectively. Additional subcohort analyses showed small and mostly consistent changes across registries, retaining reasonable consistency in rates across the Western registries. Additional standardisation for HAQ returned higher mortality and MACE registry rates. Conclusions This coordinated approach to contextualising RA RCT safety data demonstrated reasonable differences and consistency in rates for mortality and CVD across registries, and comparable RCT rates, and may serve as a model method to supplement clinical trial analyses for drug development programmes.
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- Roblick, U J, et al.
(author)
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Sequential proteome alterations during genesis and progression of colon cancer.
- 2004
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In: Cellular and Molecular Life Sciences (CMLS). - : Springer Science and Business Media LLC. - 1420-682X .- 1420-9071. ; 61:10
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Journal article (peer-reviewed)abstract
- Changes in the proteome of colon mucosal cells accompany the transition from normal mucosa via adenoma and invasive cancer to metastatic disease. Samples from 15 patients with sporadic sigmoid cancers were analyzed. Proteins were separated by two-dimensional gel electrophoresis. Relative differences in expression levels between normal tissue, adenoma, carcinoma and metastasis were evaluated in both intra- and inter-patient comparisons. Up- and down-regulated proteins (> twofold) during development to cancer or metastasis were excised and submitted to peptide mass fingerprinting and MS/MS sequence analysis, facilitated by the use of a compact disc workstation. In total, 112 protein spots were found to be differentially regulated, of which 72 were determined as to protein identity, 46 being up-regulated toward the progression of cancer, and 26 down-regulated. Several of the identifications correlate with proteins of the cell cycle, cytoskeleton or metabolic pathways. The pattern changes now identified have the potential for design of marker panels for assistance in diagnostics and therapeutic strategies in colorectal cancer.
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- Thunes, KH, et al.
(author)
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The arthropod community of Scots pine (Pinus sylvestris L.) canopies in Norway
- 2004
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In: Entomologica Fennica. - 0785-8760. ; 15:2, s. 65-90
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Research review (peer-reviewed)abstract
- We summarise the findings of arthropods collected by fogging the canopy of 24 pine trees in two sites in Eastern and Western Norway. From the samples, taken in 1998 and in 1999, almost 30,000 specimens were determined to 512 species, with Diptera being most species rich (210 species), followed by Coleoptera (76 species) and Araneae (49 species). Of the 96 new species records, nine were new to science (5 Diptera and 4 Oribatida), two were new to the European, three to the Scandinavian and 82 to the Norwegian faunas. The paper demonstrates the need for detailed faunistical inventories of European forests.
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35. |
- Verstappen, S. M. M., et al.
(author)
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Methodological Challenges When Comparing Demographic and Clinical Characteristics of International Observational Registries
- 2015
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In: Arthritis Care & Research. - : Wiley. - 2151-464X .- 2151-4658. ; 67:12, s. 1637-1645
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Journal article (peer-reviewed)abstract
- Objective. Comparisons of data from different registries can be helpful in understanding variations in many aspects of rheumatoid arthritis (RA). The study aim was to assess and improve the comparability of demographic, clinical, and comorbidity data from 5 international RA registries. Methods. Using predefined definitions, 2 subsets of patients (main cohort and subcohort) from 5 international observational registries (Consortium of Rheumatology Researchers of North America Registry [CORRONA], the Swedish Rheumatology Quality of Care Register [SRR], the Norfolk Arthritis Register [NOAR], the Institute of Rheumatology Rheumatoid Arthritis cohort [IORRA], and CORRONA International) were evaluated and compared. Patients ages >18 years with RA, and present in or recruited to the registry from January 1, 2000, were included in the main cohort. Patients from the main cohort with positive rheumatoid factor and/or erosive RA who had received >= 1 synthetic disease-modifying antirheumatic drug (DMARD), and switched to or added another DMARD, were included in the subcohort at time of treatment switch. Results. Age and sex distributions were fairly similar across the registries. The percentage of patients with a high Disease Activity Score in 28 joints score varied between main cohorts (17.5% IORRA, 18.9% CORRONA, 24.7% NOAR, 27.7% CORRONA International, and 36.8% SRR), with IORRA, CORRONA, and CORRONA International including more prevalent cases of RA; the differences were smaller for the subcohort. Prevalence of comorbidities varied across registries (e.g., coronary artery disease ranged from 1.5% in IORRA to 7.9% in SRR), partly due to the way comorbidity data were captured and general cultural differences; the pattern was similar for the subcohorts. Conclusion. Despite different inclusion criteria for the individual RA registries, it is possible to improve the comparability and interpretability of differences across RA registries by applying well-defined cohort definitions.
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36. |
- Yamanaka, H., et al.
(author)
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Infection rates in patients from five rheumatoid arthritis (RA) registries: Contextualising an RA clinical trial programme
- 2017
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In: RMD Open. - : BMJ. - 2056-5933. ; 3:2
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Journal article (peer-reviewed)abstract
- Objective Patients with rheumatoid arthritis (RA) have an increased risk of serious infections. Comparing infection rates across RA populations is complicated by differences in background infection risk, population composition and study methodology. We measured infection rates from five RA registries globally, with the aim to contextualise infection rates from an RA clinical trials population. Methods We used data from Consortium of Rheumatology Research of North America (CORRONA) (USA), Swedish Rheumatology Quality of Care Register (Sweden), Norfolk Arthritis Register (UK), CORRONA International (multiple countries) and Institute of Rheumatology Rheumatoid Arthritis (Japan) and an RA clinical trial programme (fostamatinib). Within each registry, we analysed a main cohort of all patients with RA from January 2000 to last available data. Infection definitions were harmonised across registries. Sensitivity analyses to address potential confounding explored subcohorts defined by disease activity, treatment change and/or prior comorbidities and restriction by calendar time or follow-up. Rates of infections were estimated and standardised to the trial population for age/sex and, in one sensitivity analysis also, for Health Assessment Questionnaire (HAQ) score. Results Overall, age/sex-standardised rates of hospitalised infection were quite consistent across registries (range 1.14-1.62 per 100 patient-years). Higher and more consistent rates across registries and with the trial programme overall were seen when adding standardisation for HAQ score (registry range 1.86-2.18, trials rate 2.92) or restricting to a treatment initiation subcohort followed for 18 months (registry range 0.99-2.84, trials rate 2.74). Conclusion This prospective, coordinated analysis of RA registries provided incidence rate estimates for infection events to contextualise infection rates from an RA clinical trial programme and demonstrated relative comparability of hospitalised infection rates across registries. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved.
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- Bhat, N. D. R., et al.
(author)
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Observations of Low-frequency Radio Emission from Millisecond Pulsars and Multipath Propagation in the Interstellar Medium
- 2018
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In: Astrophysical Journal, Supplement Series. - : American Astronomical Society. - 1538-4365 .- 0067-0049. ; 238:1
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Journal article (peer-reviewed)abstract
- Studying the gravitational-wave sky with pulsar timing arrays (PTAs) is a key science goal for the Square Kilometre Array (SKA) and its pathfinder telescopes. With current PTAs reaching sub-microsecond timing precision, making accurate measurements of interstellar propagation effects and mitigating them effectively has become increasingly important to realize PTA goals. As these effects are much stronger at longer wavelengths, low-frequency observations are most appealing for characterizing the interstellar medium (ISM) along the sight lines toward PTA pulsars. The Murchison Widefield Array (MWA) and the Engineering Development Array (EDA), which utilizes MWA technologies, present promising opportunities for undertaking such studies, particularly for PTA pulsars located in the southern sky. Such pulsars are also the prime targets for PTA efforts planned with the South African MeerKAT, and eventually with the SKA. In this paper we report on observations of two bright southern millisecond pulsars, PSR J0437-4715 and PSR J2145-0750, made with these facilities; MWA observations sampled multiple frequencies across the 80-250 MHz frequency range, while the EDA provided direct-sampled baseband data to yield a large instantaneous usable bandwidth of similar to 200 MHz. Using these exploratory observations, we investigate various aspects relating to pulsar emission and ISM properties, such as spectral evolution of the mean pulse shape, scintillation as a function of frequency, chromaticity in interstellar dispersion, and flux density spectra at low frequencies. Systematic and regular monitoring observations will help ascertain the role of low-frequency measurements in PTA experiments, while simultaneously providing a detailed characterization of the ISM toward the pulsars, which will be useful in devising optimal observing strategies for future PTA experiments.
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- Bjermer, Leif, et al.
(author)
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Radiation-induced increase in hyaluronan and fibronectin in bronchoalveolar lavage fluid from breast cancer patients is suppressed by smoking
- 1992
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In: European Respiratory Journal. - 1399-3003. ; 5:7, s. 785-790
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Journal article (peer-reviewed)abstract
- Bronchoalveolar lavage (BAL) fluid was analysed from 21 patients with breast cancer, stage T1N0M0, who had undergone tumour resection and post-operative local irradiation (accumulated dose 56 Gy). The lavage was performed two months after radiotherapy, in the anterior part of the lingula (left side) or of the right middle lobe (right side), depending on which side had been exposed to radiation. The patients had significantly increased concentrations of fibronectin (FN) (p less than 0.001), hyaluronan (HA) (p less than 0.01) and albumin (p less than 0.05) in BAL fluid compared with the healthy controls (n = 19). However, when the patients were separated, according to smoking history, it was obvious that the inflammatory reaction occurred entirely in the nonsmoking patient group (n = 10), whilst no difference could be found between the smoking patients (n = 11) and the controls. In the nonsmoking patient group, there was a sevenfold increase in BAL concentrations of FN and a threefold increase in HA. Moreover, four patients had detectable levels of procollagen III peptide in BAL, all were nonsmokers. The smoking habits of the controls had no influence on the BAL measurements. These findings indicate that smoking interferes with the radiation-induced early inflammatory connective tissue reaction of the lung. Finally, the results justify further investigation of interaction of smoking with cancer treatment, both from the view of therapy effectiveness and reduction of adverse effects.
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47. |
- Bomfim, I L, et al.
(author)
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The immunogenetics of narcolepsy associated with A(H1N1)pdm09 vaccination (Pandemrix) supports a potent gene-environment interaction.
- 2017
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In: Genes and immunity. - : Springer Science and Business Media LLC. - 1476-5470 .- 1466-4879. ; 18, s. 75-81
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Journal article (peer-reviewed)abstract
- The influenza A(H1N1)pdm09 vaccination campaign from 2009 to 2010 was associated with a sudden increase in the incidence of narcolepsy in several countries. Narcolepsy with cataplexy is strongly associated with the human leukocyte antigen (HLA) class II DQB1*06:02 allele, and protective associations with the DQB1*06:03 allele have been reported. Several non-HLA gene loci are also associated, such as common variants of the T-cell receptor-α (TRA), the purinergic receptor P2RY11, cathepsin H (CTSH) and TNFSF4/OX40L/CD252. In this retrospective multicenter study, we investigated if these predisposing gene loci were also involved in vaccination-associated narcolepsy. We compared HLA- along with single-nucleotide polymorphism genotypes for non-HLA regions between 42 Pandemrix-vaccinated narcolepsy cases and 1990 population-based controls. The class II gene loci associations supported previous findings. Nominal association (P-value<0.05) with TRA as well as suggestive (P-value<0.1) associations with P2RY11 and CTSH were found. These associations suggest a very strong gene-environment interaction, in which the influenza A(H1N1)pdm09 strain or Pandemrix vaccine can act as potent environmental triggers.Genes and Immunity advance online publication, 23 March 2017; doi:10.1038/gene.2017.1.
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