| 1. |
- Franceschini, N., et al.
(författare)
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GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes
- 2018
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1
-
Tidskriftsartikel (refereegranskat)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. |
- Hudson, Lawrence N, et al.
(författare)
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The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project
- 2017
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Ingår i: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 7:1, s. 145-188
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Tidskriftsartikel (refereegranskat)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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| 3. |
- Andreoni, I., et al.
(författare)
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Follow Up of GW170817 and Its Electromagnetic Counterpart by Australian-Led Observing Programmes
- 2017
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Ingår i: Publications Astronomical Society of Australia. - : Cambridge University Press (CUP). - 1323-3580 .- 1448-6083. ; 34
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Forskningsöversikt (refereegranskat)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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| 4. |
- De Palma, Adriana, et al.
(författare)
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Predicting bee community responses to land-use changes : effects of geographic and taxonomic biases
- 2016
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 6, s. 1-14
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Tidskriftsartikel (refereegranskat)abstract
- Land-use change and intensification threaten bee populations worldwide, imperilling pollination services. Global models are needed to better characterise, project, and mitigate bees' responses to these human impacts. The available data are, however, geographically and taxonomically unrepresentative; most data are from North America and Western Europe, overrepresenting bumblebees and raising concerns that model results may not be generalizable to other regions and taxa. To assess whether the geographic and taxonomic biases of data could undermine effectiveness of models for conservation policy, we have collated from the published literature a global dataset of bee diversity at sites facing land-use change and intensification, and assess whether bee responses to these pressures vary across 11 regions (Western, Northern, Eastern and Southern Europe; North, Central and South America; Australia and New Zealand; South East Asia; Middle and Southern Africa) and between bumblebees and other bees. Our analyses highlight strong regionally-based responses of total abundance, species richness and Simpson's diversity to land use, caused by variation in the sensitivity of species and potentially in the nature of threats. These results suggest that global extrapolation of models based on geographically and taxonomically restricted data may underestimate the true uncertainty, increasing the risk of ecological surprises.
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| 5. |
- Broderick, J. W., et al.
(författare)
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LOFAR 144-MHz follow-up observations of GW170817
- 2020
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Ingår i: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 494:4, s. 5110-5117
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Tidskriftsartikel (refereegranskat)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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| 6. |
- Franceschini, N, et al.
(författare)
-
GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes
- 2018
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1, s. 5141-
-
Tidskriftsartikel (refereegranskat)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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| 7. |
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| 8. |
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| 9. |
- Imamura, K, et al.
(författare)
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Reduced activity in the extrastriate visual cortex of individuals with strabismic amblyopia
- 1997
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Ingår i: NEUROSCIENCE LETTERS. - : ELSEVIER SCI IRELAND LTD. - 0304-3940. ; 225:3, s. 173-176
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- In order to examine the relationship between reduced visual acuity in human strabismic amblyopia and the cortical activation pattern, we studied, by use of positron emission tomography (PET) and the (H2O)-O-15 bolus technique, changes in the regional cer
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| 10. |
- Shimwell, T. W., et al.
(författare)
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The LOFAR Two-metre Sky Survey: V. Second data release
- 2022
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 659
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Tidskriftsartikel (refereegranskat)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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| 11. |
- De Gasperin, F., et al.
(författare)
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Cassiopeia A, Cygnus A, Taurus A, and Virgo A at ultra-low radio frequencies
- 2020
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 635
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Tidskriftsartikel (refereegranskat)abstract
- The four persistent radio sources in the northern sky with the highest flux density at metre wavelengths are Cassiopeia A, Cygnus A, Taurus A, and Virgo A; collectively they are called the A-team. Their flux densities at ultra-low frequencies (< 100 MHz) can reach several thousands of janskys, and they often contaminate observations of the low-frequency sky by interfering with image processing. Furthermore, these sources are foreground objects for all-sky observations hampering the study of faint signals, such as the cosmological 21 cm line from the epoch of reionisation. Aims. We aim to produce robust models for the surface brightness emission as a function of frequency for the A-team sources at ultra-low frequencies. These models are needed for the calibration and imaging of wide-area surveys of the sky with low-frequency interferometers. This requires obtaining images at an angular resolution better than 15″ with a high dynamic range and good image fidelity. Methods. We observed the A-team with the Low Frequency Array (LOFAR) at frequencies between 30 MHz and 77 MHz using the Low Band Antenna system. We reduced the datasets and obtained an image for each A-team source. Results. The paper presents the best models to date for the sources Cassiopeia A, Cygnus A, Taurus A, and Virgo A between 30 MHz and 77 MHz. We were able to obtain the aimed resolution and dynamic range in all cases. Owing to its compactness and complexity, observations with the long baselines of the International LOFAR Telescope will be required to improve the source model for Cygnus A further.
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| 12. |
- Frago, Enric, et al.
(författare)
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Common pheromone use among host-associated populations of the browntail moth, euproctis chrysorrhoea, displaying different adult phenologies
- 2019
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Ingår i: Entomologia Generalis. - : Schweizerbart. - 0171-8177. ; 39:3-4, s. 295-306
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Tidskriftsartikel (refereegranskat)abstract
- The diversity of herbivorous insects may arise from colonization and subsequent specialization on different host plants. Such specialization requires changes in several insect traits, which may lead to host race formation if they reduce gene flow among populations that feed on different plants. Behavioural changes may play a relevant role in host race formation, for example if different races evolve distinct sexual communication signals or adult phenology. Previous research has revealed differences in larval phenology in different host-associated populations of the browntail moth, Euproctis chrysorrhoea (Lepidoptera: Erebidae). Here, sex pheromones among populations of this species are compared, and pheromone trapping data obtained is used in the field to build a phenological model that tests whether populations that feed on different plants differ in their adult flight period. The chemical and electrophysiological analyses revealed that two E. chrysorrhoea populations (on Prunus and on Arbutus unedo) use the same sex pheromone component for mate finding. Our trapping data, however, showed that males fly on average 25 days earlier in populations whose larvae feed on A. unedo compared to those whose larvae feed on Quercus species. Although the shifted phenology described here may underlie host-plant specialization in E. chrysorrhoea, and adults of this species are short-lived, the use of a common sexual pheromone and a large overlap in flight periods suggest that host race formation via allochronic isolation is unlikely in this moth.
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| 13. |
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| 14. |
- Lempiainen, H, et al.
(författare)
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Network analysis of coronary artery disease risk genes elucidates disease mechanisms and druggable targets
- 2018
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:1, s. 3434-
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Tidskriftsartikel (refereegranskat)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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| 15. |
- McGurnaghan, S. J., et al.
(författare)
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Development and validation of a cardiovascular risk prediction model in type 1 diabetes
- 2021
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 64, s. 2001-2011
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis We aimed to report current rates of CVD in type 1 diabetes and to develop a CVD risk prediction tool for type 1 diabetes. Methods A cohort of 27,527 people with type 1 diabetes without prior CVD was derived from the national register in Scotland. Incident CVD events during 199,552 person-years of follow-up were ascertained using hospital admissions and death registers. A Poisson regression model of CVD was developed and then validated in the Swedish National Diabetes Register (n = 33,183). We compared the percentage with a high 10 year CVD risk (i.e., >= 10%) using the model with the percentage eligible for statins using current guidelines by age. Results The age-standardised rate of CVD per 100,000 person-years was 4070 and 3429 in men and women, respectively, with type 1 diabetes in Scotland, and 4014 and 3956 in men and women in Sweden. The final model was well calibrated (Hosmer- Lemeshow test p > 0.05) and included a further 22 terms over a base model of age, sex and diabetes duration (C statistic 0.82; 95% CI 0.81, 0.83). The model increased the base model C statistic foam 0.66 to 0.80, from 0.60 to 0.75 and from 0.62 to 0.68 in those aged <40, 40-59 and >= 60 years, respectively (alp values <0.005). The model required minimal calibration in Sweden and had a C statistic of 0.85. Under current guidelines, >90% of those aged 20-39 years and 100% of those >= 40 years with type 1 diabetes were eligible for statins, but it was not until age 65 upwards that 100% had a modelled risk of CVD >= 10% in 10 years. Conclusions/interpretation A prediction tool such as that developed here can provide individualised risk predictions. This 10 year CVD risk prediction tool could facilitate patient discussions regarding appropriate statin prescribing. Apart from 10 year risk, such discussions may also consider longer-term CVD risk, the potential for greater benefits from early vs later statin intervention. the potential impact on quality of life of an early CVD event and evidence on safety, all of which could influence treatment decisions, particularly in younger people with type 1 diabetes.
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| 16. |
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| 17. |
- Ostergaard, H. B., et al.
(författare)
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Development and Validation of a Lifetime Risk Model for Kidney Failure and Treatment Benefit in Type 2 Diabetes 10-Year and Lifetime Risk Prediction Models
- 2022
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Ingår i: Clinical Journal of the American Society of Nephrology. - : Ovid Technologies (Wolters Kluwer Health). - 1555-9041 .- 1555-905X. ; 17:12, s. 1783-1791
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Tidskriftsartikel (refereegranskat)abstract
- Background and objectives: Individuals with type 2 diabetes are at a higher risk of developing kidney failure. The objective of this study was to develop and validate a decision support tool for estimating 10-year and lifetime risks of kidney failure in individuals with type 2 diabetes as well as estimating individual treatment effects of preventive medication. Design, setting, participants, & measurements: The prediction algorithm was developed in 707,077 individuals with prevalent and incident type 2 diabetes from the Swedish National Diabetes Register for 2002-2019. Two Cox proportional regression functions for kidney failure (first occurrence of kidney transplantation, long-term dialysis, or persistent eGFR < 15 ml/min per 1.73 m(2)) and all-cause mortality as respective end points were developed using routinely available predictors. These functions were combined into life tables to calculate the predicted survival without kidney failure while using all-cause mortality as the competing outcome. The model was externally validated in 256,265 individuals with incident type 2 diabetes from the Scottish Care Information Diabetes database between 2004 and 2019. Results: During a median follow-up of 6.8 years (interquartile range, 3.2-10.6), 8004 (1%) individuals with type 2 diabetes in the Swedish National Diabetes Register cohort developed kidney failure, and 202,078 (29%) died. The model performed well, with c statistics for kidney failure of 0.89 (95% confidence interval, 0.88 to 0.90) for internal validation and 0.74 (95% confidence interval, 0.73 to 0.76) for external validation. Calibration plots showed good agreement in observed versus predicted 10-year risk of kidney failure for both internal and external validation. Conclusions: This study derived and externally validated a prediction tool for estimating 10-year and lifetime risks of kidney failure as well as life years free of kidney failure gained with preventive treatment in individuals with type 2 diabetes using easily available clinical predictors.
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| 18. |
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| 19. |
- Bekkhus, Tove, et al.
(författare)
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Automated detection of vascular remodeling in human tumor draining lymph nodes by the deep learning tool HEV-finder
- 2022
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Ingår i: Journal of Pathology. - : John Wiley & Sons. - 0022-3417 .- 1096-9896. ; 258:1, s. 4-11
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Tidskriftsartikel (refereegranskat)abstract
- Vascular remodeling is common in human cancer and has potential as future biomarkers for prediction of disease progression and tumor immunity status. It can also affect metastatic sites, including the tumor-draining lymph nodes (TDLNs). Dilation of the high endothelial venules (HEVs) within TDLNs has been observed in several types of cancer. We recently demonstrated that it is a premetastatic effect that can be linked to tumor invasiveness in breast cancer. Manual visual assessment of changes in vascular morphology is a tedious and difficult task, limiting high-throughput analysis. Here we present a fully automated approach for detection and classification of HEV dilation. By using 12,524 manually classified HEVs, we trained a deep-learning model and created a graphical user interface for visualization of the results. The tool, named the HEV-finder, selectively analyses HEV dilation in specific regions of the lymph nodes. We evaluated the HEV-finder's ability to detect and classify HEV dilation in different types of breast cancer compared to manual annotations. Our results constitute a successful example of large-scale, fully automated, and user-independent, image-based quantitative assessment of vascular remodeling in human pathology and lay the ground for future exploration of HEV dilation in TDLNs as a biomarker.
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| 20. |
- Berkelmans, G. F. N., et al.
(författare)
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Population median imputation was noninferior to complex approaches for imputing missing values in cardiovascular prediction models in clinical practice
- 2022
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Ingår i: Journal of Clinical Epidemiology. - : Elsevier BV. - 0895-4356. ; 145, s. 70-80
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To compare the validity and robustness of five methods for handling missing characteristics when using cardiovascular disease risk prediction models for individual patients in a real-world clinical setting.& nbsp;Study design and setting: The performance of the missing data methods was assessed using data from the Swedish National Diabetes Registry (n = 419,533) with external validation using the Scottish Care Information ? diabetes database (n = 226,953). Five methods for handling missing data were compared. Two methods using submodels for each combination of available data, two imputation methods: conditional imputation and median imputation, and one alternative modeling method, called the naive approach, based on hazard ratios and populations statistics of known risk factors only. The validity was compared using calibration plots and c-statistics.& nbsp;Results: C-statistics were similar across methods in both development and validation data sets, that is, 0.82 (95% CI 0.82-0.83) in the Swedish National Diabetes Registry and 0.74 (95% CI 0.74-0.75) in Scottish Care Information-diabetes database. Differences were only observed after random introduction of missing data in the most important predictor variable (i.e., age).& nbsp;Conclusion: Validity and robustness of median imputation was not dissimilar to more complex methods for handling missing values, provided that the most important predictor variables, such as age, are not missing. (C)& nbsp;2022 Elsevier Inc. All rights reserved.
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| 21. |
- Bjornsdottir, H. H., et al.
(författare)
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A national observation study of cancer incidence and mortality risks in type 2 diabetes compared to the background population over time
- 2020
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- We examined changing patterns in cancer incidence and deaths in diabetes compared to the background population. A total of 457,473 patients with type 2 diabetes, included between 1998 and 2014, were matched on age, sex, and county to five controls from the population. Incidence, trends in incidence and post-cancer mortality for cancer were estimated with Cox regression and standardised incidence rates. Causes of death were estimated using logistic regression. Relative importance of risk factors was estimated using Heller's relative importance model. Type 2 diabetes had a higher risk for all cancer, HR 1.10 (95% CI 1.09-1.12), with highest HRs for liver (3.31), pancreas (2.19) and uterine cancer (1.78). There were lesser increases in risk for breast (1.05) and colorectal cancers (1.20). Type 2 diabetes patients experienced a higher HR 1.23 (1.21-1.25) of overall post-cancer mortality and mortality from prostate, breast, and colorectal cancers. By the year 2030 cancer could become the most common cause of death in type 2 diabetes. Persons with type 2 diabetes are at greater risk of developing cancer and lower chance of surviving it. Notably, hazards for specific cancers (e.g. liver, pancreas) in type 2 patients cannot be explained by obesity alone.
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| 22. |
- Dwibedi, Chinmay, 1987, et al.
(författare)
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Effect of self-managed lifestyle treatment on glycemic control in patients with type 2 diabetes
- 2022
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Ingår i: npj Digital Medicine. - : Nature Research. - 2398-6352. ; 5:1
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Tidskriftsartikel (refereegranskat)abstract
- The lack of effective, scalable solutions for lifestyle treatment is a global clinical problem, causing severe morbidity and mortality. We developed a method for lifestyle treatment that promotes self-reflection and iterative behavioral change, provided as a digital tool, and evaluated its effect in 370 patients with type 2 diabetes (ClinicalTrials.gov identifier: NCT04691973). Users of the tool had reduced blood glucose, both compared with randomized and matched controls (involving 158 and 204 users, respectively), as well as improved systolic blood pressure, body weight and insulin resistance. The improvement was sustained during the entire follow-up (average 730 days). A pathophysiological subgroup of obese insulin-resistant individuals had a pronounced glycemic response, enabling identification of those who would benefit in particular from lifestyle treatment. Natural language processing showed that the metabolic improvement was coupled with the self-reflective element of the tool. The treatment is cost-saving because of improved risk factor control for cardiovascular complications. The findings open an avenue for self-managed lifestyle treatment with long-term metabolic efficacy that is cost-saving and can reach large numbers of people. © 2022, The Author(s).
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| 23. |
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| 24. |
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| 25. |
- Freidle, M., et al.
(författare)
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Behavioural and neuroplastic effects of a double-blind randomised controlled balance exercise trial in people with Parkinson's disease
- 2022
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Ingår i: Npj Parkinsons Disease. - : Springer Science and Business Media LLC. - 2373-8057. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Balance dysfunction is a disabling symptom in people with Parkinson's disease (PD). Evidence suggests that exercise can improve balance performance and induce neuroplastic effects. We hypothesised that a 10-week balance intervention (HiBalance) would improve balance, other motor and cognitive symptoms, and alter task-evoked brain activity in people with PD. We performed a double-blind randomised controlled trial (RCT) where 95 participants with PD were randomised to either HiBalance (n = 48) or a control group (n = 47). We found no significant group by time effect on balance performance (b = 0.4 95% CI [- 1, 1.9], p = 0.57) or on our secondary outcomes, including the measures of task-evoked brain activity. The findings of this well-powered, double-blind RCT contrast previous studies of the HiBalance programme but are congruent with other double-blind RCTs of physical exercise in PD. The divergent results raise important questions on how to optimise physical exercise interventions for people with PD.
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| 26. |
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| 27. |
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| 28. |
- Jones, Gregory T., et al.
(författare)
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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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Ingår i: Circulation Research. - 0009-7330 .- 1524-4571. ; 120:2, s. 341-
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Tidskriftsartikel (refereegranskat)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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| 29. |
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| 30. |
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| 31. |
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| 32. |
- Roblick, U J, et al.
(författare)
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Sequential proteome alterations during genesis and progression of colon cancer.
- 2004
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Ingår i: Cellular and Molecular Life Sciences (CMLS). - : Springer Science and Business Media LLC. - 1420-682X .- 1420-9071. ; 61:10
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Tidskriftsartikel (refereegranskat)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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| 33. |
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| 34. |
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| 35. |
- Akerblom, H., et al.
(författare)
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Association of Gastric Bypass Surgery With Risk of Developing Diabetic Retinopathy Among Patients With Obesity and Type 2 Diabetes in Sweden: An Observational Study
- 2021
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Ingår i: Jama Ophthalmology. - : American Medical Association (AMA). - 2168-6165 .- 2168-6173. ; 139:2, s. 200-205
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Knowledge of the incidence and progression of diabetic retinopathy (DR) after gastric bypass surgery (GBP) in patients with obesity and diabetes could guide the management of these patients. OBJECTIVE To investigate the incidence of diabetic ocular complications in patients with type 2 diabetes after GBP compared with the incidence of diabetic ocular complications in a matched cohort of patients with obesity and diabetes who have not undergone GBP. DESIGN, SETTING, AND PARTICIPANTS Data from 2 nationwide registers in Sweden, the Scandinavian Obesity Surgery Registry and the National Diabetes Register, were used for this cohort study. A total of 5321 patients with diabetes from the Scandinavian Obesity Surgery Registry who had undergone GBP from January 1, 2007, to December 31, 2013, were matched with 5321 patients with diabetes from the National Diabetes Register who had not undergone GBP, based on sex, age, body mass index (BMI), and calendar time (2007-2013). Follow-up data were obtained until December 31, 2015. Statistical analysis was performed from October 5, 2018, to September 30, 2019. EXPOSURE Gastric bypass surgery. MAIN OUTCOMES AND MEASURES Incidence of new DR and other diabetic ocular complications. RESULTS The study population consisted of 5321 patients who had undergone GBP (3223 women [60.6%]; mean [SD] age, 49.0 [9.5] years) and 5321 matched controls (3395 women [63.8%]; mean [SD] age, 47.1 [11.5] years). Mean (SD) follow-up was 4.5 (1.6) years. The mean (SD) BMI and hemoglobin A1c concentration at baseline were 42.0 (5.7) and 7.6%(1.5%), respectively, in the GBP group and 40.9 (7.3) and 7.5%(1.5%), respectively, in the control group. The mean (SD) duration of diabetes was 6.8 (6.3) years in the GBP group and 6.4 (6.4) years in the control group. The risk for new DR was reduced in the patients who underwent GBP (hazard ratio, 0.62 [95% CI, 0.49-0.78]; P <.001). The dominant risk factors for development of DR at baseline were diabetes duration, hemoglobin A1c concentration, use of insulin, glomerular filtration rate, and BMI. CONCLUSIONS AND RELEVANCE This nationwide matched cohort study suggests that there is a reduced risk of developing new DR associated with GBP, and no evidence of an increased risk of developing DR that threatened sight or required treatment. (c) 2021 American Medical Association. All rights reserved.
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- Albrecht, F., et al.
(författare)
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Unraveling Parkinson's disease heterogeneity using subtypes based on multimodal data
- 2022
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Ingår i: Parkinsonism and Related Disorders. - : Elsevier BV. - 1353-8020 .- 1873-5126. ; 102, s. 19-29
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Tidskriftsartikel (refereegranskat)abstract
- Background: Parkinson's disease (PD) is a clinically and neuroanatomically heterogeneous neurodegenerative disease characterized by different subtypes. To this date, no studies have used multimodal data that combines clinical, motor, cognitive and neuroimaging assessments to identify these subtypes, which may provide complementary, clinically relevant information. To address this limitation, we subtyped participants with mild-moderate PD based on a rich, multimodal dataset of clinical, cognitive, motor, and neuroimaging variables. Methods: Cross-sectional data from 95 PD participants from our randomized EXPANd (EXercise in PArkinson's disease and Neuroplasticity) controlled trial were included. Participants were subtyped using clinical, motor, and cognitive assessments as well as structural and resting-state MRI data. Subtyping was done by random forest clustering. We extracted information about the subtypes by inspecting their neuroimaging profiles and descriptive statistics. Results: Our multimodal subtyping analysis yielded three PD subtypes: a motor-cognitive subtype characterized by widespread alterations in brain structure and function as well as impairment in motor and cognitive abilities; a cognitive dominant subtype mainly impaired in cognitive function that showed frontoparietal structural and functional changes; and a motor dominant subtype impaired in motor variables without any brain alterations. Motor variables were most important for the subtyping, followed by gray matter volume in the right medial postcentral gyrus. Conclusions: Three distinct PD subtypes were identified in our multimodal dataset. The most important features to subtype PD participants were motor variables in addition to structural MRI in the sensorimotor region. These findings have the potential to improve our understanding of PD heterogeneity, which in turn can lead to personalized interventions and rehabilitation.
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- Askling, J., et al.
(författare)
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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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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 75:10, s. 1789-1796
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Tidskriftsartikel (refereegranskat)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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- Atroshi, I, et al.
(författare)
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Quality of life after hip revision with impaction bone grafting on a par with that 4 years after primary cemented arthroplasty
- 2004
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Ingår i: Acta Orthopaedica Scandinavica. - : Medical Journals Sweden AB. - 0001-6470. ; 75:6, s. 677-683
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Tidskriftsartikel (refereegranskat)abstract
- Background There have been few studies evaluating patient-reported quality of life outcomes after hip revision with impaction bone grafting. Patients and methods The inclusion criteria were aseptic loosening after primary arthroplasty performed for osteoarthrosis, and first-time revision with impacted morselized allograft bone and cemented Exeter stem. During a 4-year period, 35 patients were eligible and all were included. The Nottingham Health Profile (NHP) was completed by the patients and the Charnley hip scores recorded by the examining surgeon preoperatively, after 6 months and yearly up to 4 years (28 patients) postoperatively. For comparison, 35 osteoarthrotic patients completed the NHP 4 years after cemented Exeter primary arthroplasty. Results At 4 years, the NHP scores for the revision patients did not differ significantly from those recorded in the primary arthroplasty group. Among the revision patients, mixed model analysis showed improvement in NHP pain (p < 0.001) and physical mobility scores (p = 0.002). The effect size at 4 years was large for pain (1.2) and moderate for physical mobility (0.6). The major improvement was recorded at 6 months, with no further substantial change observed. The correlations between the NHP and Charnley scores were weak or moderate (r, -0.15 to -0.67). Interpretation Hip revision with impaction bone grafting leads to substantially improved quality of life, similar to that 4 years after primary arthroplasty.
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- Axelsson, Lisa, 1984, et al.
(författare)
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Jatropha cultivation in southern India: assessing farmers experiences
- 2012
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Ingår i: Biofuels, Bioproducts and Biorefining. - : John Wiley and Sons. - 1932-104X .- 1932-1031. ; 6:3, s. 246-256
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Tidskriftsartikel (refereegranskat)abstract
- Together with 106 farmers who started growing Jatropha (Jatropha curcas L.) in 20042006, this research sought to increase the knowledge around the real-life experience of Jatropha farming in the southern India states of Tamil Nadu and Andhra Pradesh. Launched as an alternative for diesel in India, Jatropha has been promoted as a non-edible plant that could grow on poor soils, yield oil-rich seeds for production of bio-diesel, and not compete directly with food production. Through interviews with the farmers, information was gathered regarding their socio-economic situation, the implementation and performance of their Jatropha plantations, and their reasons for continuing or discontinuing Jatropha cultivation. Results reveal that 82% of the farmers had substituted former cropland for their Jatropha cultivation. By 2010, 85% (n = 90) of the farmers who cultivated Jatropha in 2004 had stopped. Cultivating the crop did not give the economic returns the farmers anticipated, mainly due to a lack of information about the crop and its maintenance during cultivation and due to water scarcity. A majority of the farmers irrigated and applied fertilizer, and even pesticides. Many problems experienced by the farmers were due to limited knowledge about cultivating Jatropha caused by poor planning and implementation of the national Jatropha program. Extension services, subsidies, and other support were not provided as promised. The farmers who continued cultivation had means of income other than Jatropha and held hopes of a future Jatropha market. The lack of market structures, such as purchase agreements and buyers, as well as a low retail price for the seeds, were frequently stated as barriers to Jatropha cultivation. For Jatropha biodiesel to perform well, efforts are needed to improve yield levels and stability through genetic improvements and drought tolerance, as well as agriculture extension services to support adoption of the crop. Government programs will -probably be more effective if implementing biodiesel production is conjoined with stimulating the demand for Jatropha biodiesel. To avoid food-biofuel competition, additional measures may be needed such as land-use restrictions for Jatropha producers and taxes on biofuels or biofuel feedstocks to improve the competitiveness of the food sector compared to the bioenergy sector.
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| 44. |
- Axelsson, Lisa, et al.
(författare)
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Performance of Jatropha biodiesel production and its environmental and socio-economic impact – A case study in Southern India
- 2011
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Ingår i: World Renewable Energy Congress 2011. - Linköping : Linköping University Electronic Press. - 9789173930703 ; , s. 2470-2477
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Konferensbidrag (refereegranskat)abstract
- In India expectations have been high on production of biodiesel from the oil-crop Jatropha. Jatropha is promoted as a drought- and pest-resistant crop, with the potential to grow on degraded soil with a low amount of inputs. These characteristics encourage hope for positive environmental and socio-economic impacts from Jatropha biodiesel production. The purpose of this study was to explore the performance of Jatropha biodiesel production in Southern India, to identify motivational factors for continued Jatropha cultivation, and to assess environmental and socio-economic impacts of the Jatropha biodiesel production. 106 farmers who have or have had Jatropha plantations were visited and interviewed regarding their opinion of Jatropha cultivation. The result indicates that 85 percent of the farmers have discontinued cultivation of Jatropha. The main barriers to continued cultivation derive from ecological problems, economic losses, and problems in the development and execution of the governmental implementation of the Jatropha programme. The Jatropha characteristics were overrated, and the plantations failed to provide income to the farmer. A common factor for the farmers who continued Jatropha cultivation was that they had the economic means to maintain non-profitable plantations. As the Jatropha programme was not as successful as expected, the expected positive environmental and socio-economic impacts have not been realized.
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- Bekkhus, Tove, et al.
(författare)
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Remodeling of the Lymph Node High Endothelial Venules Reflects Tumor Invasiveness in Breast Cancer and is Associated with Dysregulation of Perivascular Stromal Cells
- 2021
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 13:2
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Tidskriftsartikel (refereegranskat)abstract
- Simple Summary Tumor draining lymph nodes (TDLNs) are the most common metastatic sites in human cancer but are also essential sites for induction of tumor immunity. How different types of primary tumors affect the anti-tumor immune response in the LNs is not fully understood. By analyzing biobank tissue from breast cancer patients, we demonstrate that invasive breast cancer induce dramatic pre-metastatic LN changes affecting the structure and function of the specialized LN vasculature and associated stromal cells, required for recruitment of T-lymphocytes into the LNs. These changes could not be seen in patients with non-invasive breast cancer and provide new insights of how invasive tumors can disrupt essential functions within the immune system. The data also shows promise of LN stromal and vascular changes as possible future biomarkers for prediction of disease progression in human cancer. The tumor-draining lymph nodes (TDLNs) are primary sites for induction of tumor immunity. They are also common sites of metastasis, suggesting that tumor-induced mechanisms can subvert anti-tumor immune responses and promote metastatic seeding. The high endothelial venules (HEVs) together with CCL21-expressing fibroblastic reticular cells (FRCs) are essential for lymphocyte recruitment into the LNs. We established multicolor antibody panels for evaluation of HEVs and FRCs in TDLNs from breast cancer (BC) patients. Our data show that patients with invasive BC display extensive structural and molecular remodeling of the HEVs, including vessel dilation, thinning of the endothelium and discontinuous expression of the HEV-marker PNAd. Remodeling of the HEVs was associated with dysregulation of CCL21 in perivascular FRCs and with accumulation of CCL21-saturated lymphocytes, which we link to loss of CCL21-binding heparan sulfate in FRCs. These changes were rare or absent in LNs from patients with non-invasive BC and cancer-free organ donors and were observed independent of nodal metastasis. Thus, pre-metastatic dysregulation of core stromal and vascular functions within TDLNs reflect the primary tumor invasiveness in BC. This adds to the understanding of cancer-induced perturbation of the immune response and opens for prospects of vascular and stromal changes in TDLNs as potential biomarkers.
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- Bjorkstrom, K., et al.
(författare)
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Risk Factors for Severe Liver Disease in Patients With Type 2 Diabetes
- 2019
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Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier BV. - 1542-3565. ; 17:13, s. 2769-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: Type 2 diabetes is a risk factor for development of cirrhosis and hepatocellular carcinoma. However, risk factors that identify persons with the highest risk for these outcomes are missing from unselected, population-based cohorts. METHODS: The National Diabetes Register contains data on about 90% of persons in Sweden with type 2 diabetes. In this cohort study, persons with type 2 diabetes listed in the National Diabetes Register were compared with 5 individuals from the general population (controls), matched for age, sex, and county. In total, 406 770 persons with type 2 diabetes and 2 033 850 controls were included and followed for 21 596 934 person-years. We used population-based registers to determine the incidence of severe liver disease, defined as a diagnosis of hepatocellular carcinoma, cirrhosis, decompensation, liver failure and/or death due to liver disease during follow up. Cox regression was performed to estimate the risk of severe liver disease and to examine risk factors in persons with type 2 diabetes. RESULTS: Risk for severe liver disease was increased in patients with type 2 diabetes compared to controls (hazard ratio, 2.28; 95% CI, 2.21-2.36). Risk factors associated with severe liver disease in persons with type 2 diabetes were higher age, male sex, hypertension, higher body mass index, lower glomerular filtration rate, microalbuminuria, and smoking. Statins were associated with a decreased risk of severe liver disease. CONCLUSIONS: Persons with type 2 diabetes have an increased risk for severe liver disease. Knowledge of risk factors can be helpful in identifying persons with type 2 diabetes who have a high risk for severe liver disease.
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