| 1. |
- 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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| 2. |
- 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
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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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| 3. |
- 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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| 4. |
- 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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| 5. |
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| 6. |
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| 7. |
- Bhat, N. D. R., et al.
(författare)
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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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Ingår i: Astrophysical Journal, Supplement Series. - : American Astronomical Society. - 1538-4365 .- 0067-0049. ; 238:1
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Tidskriftsartikel (refereegranskat)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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| 8. |
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| 9. |
- Fransson, P., et al.
(författare)
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Ultra-hypofractionated versus conventionally fractionated radiotherapy for prostate cancer (HYPO-RT-PC): patient-reported quality-of-life outcomes of a randomised, controlled, 3 trial
- 2021
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Ingår i: Lancet Oncology. - : Elsevier BV. - 1470-2045. ; 22:2, s. 235-245
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Tidskriftsartikel (refereegranskat)abstract
- Background The HYPO-RT-PC trial compared conventionally fractionated radiotherapy with ultra-hypofractionated radiotherapy in patients with localised prostate cancer. Ultra-hypofractionation was non-inferior to conventional fractionation regarding 5-year failure-free survival and toxicity. We aimed to assess whether patient-reported quality of life (QOL) differs between conventional fractionation and ultra-hypofractionation up to 6 years after treatment in the HYPO-RT-PC trial. Methods HYPO-RT-PC is a multicentre, open-label, randomised, controlled, non-inferiority, phase 3 trial done in 12 centres (seven university hospitals and five county hospitals) in Sweden and Denmark. Inclusion criteria were histologically verified intermediate-to-high-risk prostate cancer (defined as T1c-T3a with one or two of the following risk factors: stage T3a; Gleason score >= 7; and prostate-specific antigen 10-20 ng/mL with no evidence of lymph node involvement or distant metastases), age up to 75 years, and WHO performance status 0-2. Participants were randomly assigned (1:1) to conventional fractionation (78.0 Gy in 39 fractions, 5 days per week for 8 weeks) or ultra-hypofractionation (42.7 Gy in seven fractions, 3 days per week for 2.5 weeks) via a minimisation algorithm with stratification by trial centre, T-stage, Gleason score, and prostate-specific antigen. QOL was measured using the validated Prostate Cancer Symptom Scale (PCSS) and European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire (EORTC QLQ-C30) at baseline, the end of radiotherapy, months 3, 6, 12, and 24 after radiotherapy, every other year thereafter up to 10 years, and at 15 years. The primary endpoint (failure-free survival) has been reported elsewhere. Here we report QOL, a secondary endpoint analysed in the perprotocol population, up to 6 years after radiotherapy. The HYPO-RT-PC trial is registered with the ISRCTN registry, ISRCTN45905321. Findings Between July 1, 2005, and Nov 4, 2015, 1200 patients were enrolled and 1180 were randomly assigned (conventional fractionation n=591, ultra-hypofractionation n=589); 1165 patients (conventional fractionation n=582, ultra-hypofractionation n=583) were included in this QOL analysis. 158 (71%) of 223 patients in the conventional fractionation group and 146 (66%) of 220 in the ultra-hypofractionation group completed questionnaires at 6 years. The median follow-up was 48 months (IQR 25-72). In seven of ten bowel symptoms or problems the proportion of patients with clinically relevant deteriorations at the end of radiotherapy was significantly higher in the ultra-hypofractionation group than in the conventional fractionation group (stool frequency [p<0.0001], rush to toilet [p=0.0013], flatulence [p=0.0013], bowel cramp [p<0.0001], mucus [p=0.0014], blood in stool [p<0.0001], and limitation in daily activity [p=0.0014]). There were no statistically significant differences in the proportions of patients with clinically relevant acute urinary symptoms or problems (total 14 items) and sexual functioning between the two treatment groups at end of radiotherapy. Thereafter, there were no clinically relevant differences in urinary, bowel, or sexual functioning between the groups. At the 6-year followup there was no difference in the incidence of clinically relevant deterioration between the groups for overall urinary bother (43 [33%] of 132 for conventional fractionation vs 33 [28%] of 120 for ultra-hypofractionation; mean difference 5.1% [95% CI -4.4 to 14.6]; p=0.38), overall bowel bother (43 [33%] of 129 vs 34 [28%] of 123; 5.7% [-3.8 to 15.2]; p=0.33), overall sexual bother (75 [60%] of 126 vs 59 [50%] of 117; 9.1% [-1.4 to 19.6]; p=0.15), or global health/QOL (56 [42%] of 134 vs 46 [37%] of 125; 5.0% [-5.0 to 15.0]; p=0.41). Interpretation Although acute toxicity was higher for ultra-hypofractionation than conventional fractionation, this long-term patient-reported QOL analysis shows that ultra-hypofractionation was as well tolerated as conventional fractionation up to 6 years after completion of treatment. These findings support the use of ultra-hypofractionation radiotherapy for intermediate-to-high-risk prostate cancer.
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| 10. |
- Lange, S, et al.
(författare)
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The kinase domain of titin controls muscle gene expression and protein turnover
- 2005
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Ingår i: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 308:5728, s. 1599-1603
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Tidskriftsartikel (refereegranskat)abstract
- The giant sarcomeric protein titin contains a protein kinase domain (TK) ideally positioned to sense mechanical load. We identified a signaling complex where TK interacts with the zinc-finger protein nbr1 through a mechanically inducible conformation. Nbr1 targets the ubiquitin-associated p62/SQSTM1 to sarcomeres, and p62 in turn interacts with MuRF2, a muscle-specific RING-B-box E3 ligase and ligand of the transactivation domain of the serum response transcription factor (SRF). Nuclear translocation of MuRF2 was induced by mechanical inactivity and caused reduction of nuclear SRF and repression of transcription. A human mutation in the titin protein kinase domain causes hereditary muscle disease by disrupting this pathway.
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| 11. |
- Sun, B, et al.
(författare)
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Biophysical and physiological properties of a modified porcine surfactant enriched with surfactant protein A
- 1997
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Ingår i: The European respiratory journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 10:9, s. 1967-1974
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Tidskriftsartikel (refereegranskat)abstract
- Surfactant protein A (SP-A), a major protein component of natural pulmonary surfactant, is absent in exogenous surfactants currently used in clinical practice. We investigated the physical and physiological properties of one of these modified natural surfactants (Curosurf) after enrichment with 5% SP-A (SP-A-Curosurf). A pulsating bubble system was used for in vitro assessments and ventilated newborn rabbits for evaluation of in vivo effects. In the presence of various potential inhibitors (meconium 5 mg.mL-1, fibrinogen 5 mg.mL-1, albumin 25 mg.mL-1, or whole serum proteins 25 mg.mL-1), Curosurf at a concentration of 5 mg.mL-1 was inactivated while SP-A-Curosurf and natural porcine surfactant at the same concentration had normal maximum and minimum surface tension. This protective effect of SP-A was calcium dependent. In immature newborn rabbits, the improvement of lung-thorax compliance observed after treatment with 100 mg.kg-1 of SP-A-Curosurf was equivalent to that obtained with 200 mg.kg-1 of Curosurf. Similarly, in near-term newborn rabbits with respiratory failure induced by instillation of fibrinogen via the airways, the increase in compliance after administration of 100 mg.kg-1 of SP-A-Curosurf corresponded to that seen after treatment with 200 mg.kg-1 of Curosurf, whereas Curosurf at a dose of 100 mg.kg-1 had no substantial effect. Our data thus indicate that surfactant protein A increases the resistance of Curosurf to inactivation under in vivo conditions.
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| 12. |
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| 13. |
- Widmark, A., et al.
(författare)
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Ultra-hypofractionated versus conventionally fractionated radiotherapy for prostate cancer: 5-year outcomes of the HYPO-RT-PC randomised, non-inferiority, phase 3 trial
- 2019
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Ingår i: Lancet. - : Elsevier BV. - 0140-6736. ; 394:10196, s. 385-395
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Tidskriftsartikel (refereegranskat)abstract
- Background Hypofractionated radiotherapy for prostate cancer has gained increased attention due to its proposed high radiation-fraction sensitivity. Recent reports from studies comparing moderately hypofractionated and conventionally fractionated radiotherapy support the clinical use of moderate hypofractionation. To date, there are no published randomised studies on ultra-hypofractionated radiotherapy. Here, we report the outcomes of the Scandinavian HYPO-RTPC phase 3 trial with the aim to show non-inferiority of ultra-hypofractionation compared with conventional fractionation. Methods In this open-label, randomised, phase 3 non-inferiority trial done in 12 centres in Sweden and Denmark, we recruited men up to 75 years of age with intermediate-to-high-risk prostate cancer and a WHO performance status between 0 and 2. Patients were randomly assigned to ultra-hypofractionation (42.7 Gy in seven fractions, 3 days per week for 2.5 weeks) or conventional fractionated radiotherapy (78.0 Gy in 39 fractions, 5 days per week for 8 weeks). No androgen deprivation therapy was allowed. The primary endpoint was time to biochemical or clinical failure, analysed in the per-protocol population. The prespecified non-inferiority margin was 4% at 5 years, corresponding to a critical hazard ratio (HR) limit of 1.338. Physician-recorded toxicity was measured according to the Radiation Therapy Oncology Group (RTOG) morbidity scale and patient-reported outcome measurements with the Prostate Cancer Symptom Scale (PCSS) questionnaire. This trial is registered with the ISRCTN registry, number ISRCTN45905321. Findings Between July 1, 2005, and Nov 4, 2015, 1200 patients were randomly assigned to conventional fractionation (n=602) or ultra-hypofractionation (n=598), of whom 1180 (591 conventional fractionation and 589 ultra-hypofractionation) constituted the per-protocol population. 1054 (89%) participants were intermediate risk and 126 (11%) were high risk. Median follow-up time was 5.0 years (IQR 3.1-7.0). The estimated failure-free survival at 5 years was 84% (95% CI 80-87) in both treatment groups, with an adjusted HR of 1.002 (95% CI 0.758-1.325; log-rank p=0.99). There was weak evidence of an increased frequency of acute physician-reported RTOG grade 2 or worse urinary toxicity in the ultra-hypofractionation group at end of radiotherapy (158 [28%] of 569 patients vs 132 [23%] of 578 patients; p=0.057). There were no significant differences in grade 2 or worse urinary or bowel late toxicity between the two treatment groups at any point after radiotherapy, except for an increase in urinary toxicity in the ultra-hypofractionation group compared to the conventional fractionation group at 1-year follow-up (32 [6%] of 528 patients vs 13 [2%] of 529 patients; (p=0.0037). We observed no differences between groups in frequencies at 5 years of RTOG grade 2 or worse urinary toxicity (11 [5%] of 243 patients for the ultra-hypofractionation group vs 12 [5%] of 249 for the conventional fractionation group; p=1.00) and bowel toxicity (three [1%] of 244 patients vs nine [4%] of 249 patients; p=0.14). Patient-reported outcomes revealed significantly higher levels of acute urinary and bowel symptoms in the ultra-hypofractionation group compared with the conventional fractionation group but no significant increases in late symptoms were found, except for increased urinary symptoms at 1-year follow-up, consistent with the physician-evaluated toxicity. Interpretation Ultra-hypofractionated radiotherapy is non-inferior to conventionally fractionated radiotherapy for intermediate-to-high risk prostate cancer regarding failure-free survival. Early side-effects are more pronounced with ultra-hypofractionation compared with conventional fractionation whereas late toxicity is similar in both treatment groups. The results support the use of ultra-hypofractionation for radiotherapy of prostate cancer. Copyright (C) 2019 Elsevier Ltd. All rights reserved.
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| 14. |
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| 15. |
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| 18. |
- Bergendorff, O., et al.
(författare)
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Screening of some European medicinal plants for spasmolytic activity on isolated guinea-pig trachea
- 1995
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Ingår i: International Journal of Pharmacognosy. - 0925-1618. ; 33:4, s. 356-358
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Tidskriftsartikel (refereegranskat)abstract
- Eight European plants, used traditionally against diseases of the respiratory system, have been assayed for in vitro spasmolytic activity on guinea-pig trachea. The plants were collected or cultivated in the south of Sweden, and both water and 67% methanol extracts of the parts reported to be used in the traditional medicine were prepared and assayed. Five of the species did not show any significant activity at concentrations up to 0.6 mg extract per ml organ bath, the methanol extracts of 2 species (Glechoma hederacea and Hyssopus officinale) showed weak activity, while 0.6 mg/ml of the methanol extract of the aerial parts of Artemisia abrotanum relaxed the tone induced by 0.1 μmol/l carbachol almost (80%) as effectively as 2.2 mmol/l terbutaline.
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| 19. |
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| 20. |
- 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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| 21. |
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| 22. |
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| 23. |
- Förlin, Lars, 1950, et al.
(författare)
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Effektscreening –Biologisk effektövervakning i förorenade områdenlängs Sveriges kust2017–2018
- 2019
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Undersökningarna visar att samtliga metoder inklusive undersökningar av hälsotillståndet hos fisk, fortplantning och biomarkörer hos vitmärla, lysosomal membranstabilitet hos mussla och imposex hos snäckor med få undantag visade på tydliga effekter i de åtta undersökta och förorenade områdena längs Sveriges kuster. En jämförelse mellan de olika metoderna visar, med undantag för området i Uddevalla/Byfjorden, en tydlig påverkan i resterande undersökta områdena. I Byfjorden noterades mindre stressade musslor och endast låga stadier av imposex hos snäckor medan fiskhälsan kunde konstateras vara påverkad. Utöver Byfjorden gjordes undersökningar med mer än en av metoderna även i Sundsvallsfjärden, Norrsundet, Bråviken, Ronnebyåns mynning och Landskrona. I dessa områden visar jämförelsen mellan metoderna att samtliga indikerar en tydlig påverkan. Att samtliga metoder ger utslag beror sannolikt på att alla valda undersökningsområden har en mycket komplex och ganska påtaglig föroreningsbelastning vilket innebär att det kan förväntas att de flesta organismer som lever i dessa områden kan uppvisa effekter som kan härledas till påverkan av miljöstörande ämnen. I Sverige är den nationella effektbaserade miljöövervakningen i marin miljö väsentligen inriktad på att undersöka effekter av miljögifter i referensområden. Sådana områden karakteriseras av att de ska ligga på stort avstånd från större befolkningscentra och industrier, eller till exempel inte ligga nära stora flodmynningar. Resultaten från denna studie kompletterar den ordinarie miljöövervakningen i referensområden och visar med stor tydlighet att de undersökta områdena är källor för miljöstörande ämnen till vattenmiljön. Undersökningarna visar också att det är önskvärt att kontinuerlig biologisk effektövervakning kommer igång i något eller några påverkade områden inom ramen för den nationella miljöövervakningen för att parallellt följa förändringar i miljön nära eller en bit från påtagliga, mer eller mindre kontinuerliga föroreningskällor i vårt samhälle. Detta skulle också komplettera Sveriges internationella rapportering av miljödata genom att förutom att rapportera effektdata från referensområden även kunna rapportera data från påverkade/förorenade områden.
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| 25. |
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| 26. |
- Pasternak, B., et al.
(författare)
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Use of sodium-glucose co-transporter 2 inhibitors and risk of serious renal events: Scandinavian cohort study
- 2020
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Ingår i: Bmj-British Medical Journal. - : BMJ. - 1756-1833. ; 369
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE To assess the association between use of sodium-glucose co-transporter 2 (SGLT2) inhibitors and risk of serious renal events in data from routine clinical practice. DESIGN Cohort study using an active comparator, new user design and nationwide register data. SETTING Sweden, Denmark, and Norway, 2013-18. PARTICIPANTS Cohort of 29 887 new users of SGLT2 inhibitors (follow-up time: dapagliflozin 66.1%; empagliflozin 32.6%; canagliflozin 1.3%) and 29 887 new users of an active comparator, dipeptidyl peptidase-4 inhibitors, matched 1:1 on the basis of a propensity score with 57 variables. Mean follow-up time was 1.7 (SD 1.0) years. EXPOSURES SGLT2 inhibitors versus dipeptidyl peptidase-4 inhibitors, defined by filled prescriptions and analysed according to intention to treat. MAIN OUTCOME MEASURES The main outcome was serious renal events, a composite including renal replacement therapy, death from renal causes, and hospital admission for renal events. Secondary outcomes were the individual components of the main outcome. RESULTS The mean age of the study population was 61.3 (SD 10.5) years; 11 108 (19%) had cardiovascular disease, and 1974 (3%) had chronic kidney disease. Use of SGLT2 inhibitors, compared with dipeptidyl peptidase-4 inhibitors, was associated with a reduced risk of serious renal events (2.6 events per 1000 person years versus 6.2 events per 1000 person years; hazard ratio 0.42 (95% confidence interval 0.34 to 0.53); absolute difference -3.6 (-4.4 to -2.8) events per 1000 person years). In secondary outcome analyses, the hazard ratio for use of SGLT2 inhibitors versus dipeptidyl peptidase-4 inhibitors was 0.32 (0.22 to 0.47) for renal replacement therapy, 0.41 (0.32 to 0.52) for hospital admission for renal events, and 0.77 (0.26 to 2.23) for death from renal causes. In sensitivity analyses in each of the Swedish and Danish parts of the cohort, the model was further adjusted for glycated haemoglobin and estimated glomerular filtration rate (Sweden and Denmark) and for blood pressure, body mass index, and smoking (Sweden only); in these analyses, the hazard ratio moved from 0.41 (0.26 to 0.66) to 0.50 (0.31 to 0.81) in Sweden and from 0.42 (0.32 to 0.56) to 0.55 (0.41 to 0.74) in Denmark. CONCLUSIONS In this analysis using nationwide data from three countries, use of SGLT2 inhibitors, compared with dipeptidyl peptidase-4 inhibitors, was associated with a significantly reduced risk of serious renal events.
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| 28. |
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| 29. |
- Thunes, KH, et al.
(författare)
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The arthropod community of Scots pine (Pinus sylvestris L.) canopies in Norway
- 2004
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Ingår i: Entomologica Fennica. - 0785-8760. ; 15:2, s. 65-90
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Forskningsöversikt (refereegranskat)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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| 32. |
- Alaiya, A, et al.
(författare)
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Polypeptide expression in prostate hyperplasia and prostate adenocarcinoma
- 2000
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Ingår i: Analytical cellular pathology : the journal of the European Society for Analytical Cellular Pathology. - : Hindawi Limited. - 0921-8912. ; 21:1, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- Cells were collected from prostate hyperplasias (n=6) and prostate carcinomas (n=6) and subjected to two‐dimensional gel electrophoresis (2‐DE). The resulting polypeptide patterns were analysed with the PDQUEST computer software. Malignant tumors showed significant increases in the level of expression of proliferating cell nuclear antigen (PCNA), calreticulin, HSP 90 and pHSP 60, oncoprotein 18(v), elongation factor 2, glutathione‐S‐transferaseπ(GST‐π), superoxide dismutase and triose phosphate isomerase. In addition, decreases in the levels of tropomyosin‐1 and 2 and cytokeratin 18 were observed in prostate carcinomas compared to prostate hyperplasias. This pattern of alterations is similar to that observed in other carcinomas in our previous studies. All malignant tumors showed simultaneous alterations in 5 or more of 9 markers studied, whereas only one case of benign hyperplasia showed alterations in 5 markers. The EST‐data base for prostate tumors available from NCI (CGAP) was searched for the expression of the mRNAs corresponding to proteins identified in our gels. Large differences in the relative expression of mRNAs and proteins were observed. Our data show alterations in the pattern of polypeptide expression in prostate carcinomas which are similar to those observed in other carcinomas.
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| 33. |
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| 34. |
- Albrecht, Franziska, et al.
(författare)
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Effects of a Highly Challenging Balance Training Program on Motor Function and Brain Structure in Parkinson's Disease
- 2021
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Ingår i: Journal of Parkinson's Disease. - : IOS Press. - 1877-7171 .- 1877-718X. ; 11:4, s. 2057-2071
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Tidskriftsartikel (refereegranskat)abstract
- Background: Parkinson's disease (PD) is characterized by motor deficits and brain alterations having a detrimental impact on balance, gait, and cognition. Intensive physical exercise can induce changes in the neural system, potentially counteracting neurodegeneration in PD and improving clinical symptoms. Objective: This randomized controlled trial investigated effects of a highly challenging, cognitively demanding, balance and gait training (HiBalance) program in participants with PD on brain structure. Methods: 95 participants were assigned to either the HiBalance or an active control speech training program. The group-based interventions were performed in 1-hour sessions, twice per week over a 10-week period. Participants underwent balance, gait, cognitive function, and structural magnetic resonance imaging assessments before and after the interventions. Voxel-based morphometry was analyzed in 34 HiBalance and 31 active controls. Additionally, structural covariance networks were assessed. Results: There was no significant time by group interaction between the HiBalance and control training in balance, gait, or brain volume. Within-HiBalance-group analyses showed higher left putamen volumes post-training. In repeated measures correlation a positive linear, non-significant relationship between gait speed and putamen volume was revealed. In the HiBalance group we found community structure changes and stronger thalamic-cerebellar connectivity in structural covariance networks. Neither brain volume changes nor topology changes were found for the active controls after the training. Conclusion: Thus, subtle structural brain changes occur after balance and gait training. Future studies need to determine whether training modifications or other assessment methods lead to stronger effects.
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| 35. |
- 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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| 36. |
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| 37. |
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| 38. |
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| 39. |
- Anguelova, M., et al.
(författare)
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Conservation laws and unidentifiability of rate expressions in biochemical models
- 2007
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Ingår i: IET SYSTEMS BIOLOGY. - : Institution of Engineering and Technology (IET). - 1751-8849 .- 1751-8857. ; 1:4, s. 230-237
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Tidskriftsartikel (refereegranskat)abstract
- New experimental techniques in bioscience provide us with high-quality data allowing quantitative mathematical modelling. Parameter estimation is often necessary and, in connection with this, it is important to know whether all parameters can be uniquely estimated from available data, (i.e. whether the model is identifiable). Dealing essentially with models for metabolism, we show how the assumption of an algebraic relation between concentrations may cause parameters to be unidentifiable. If a sufficient data set is available, the problem with unidentifiability arises locally in individual rate expressions. A general method for reparameterisation to identifiable rate expressions is provided, together with a Mathematica code to help with the calculations. The general results are exemplified by four well-cited models for glycolysis.
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| 40. |
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| 41. |
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| 42. |
- Atteia, A., et al.
(författare)
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Structure, organization and expression of the genes encoding mitochondrial cytochrome c1 and the Rieske iron-sulfur protein in Chlamydomonas reinhardtii
- 2003
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Ingår i: Molecular Genetics and Genomics. - : Springer Verlag. - 1617-4615 .- 1617-4623. ; 268:5, s. 637-644
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Tidskriftsartikel (refereegranskat)abstract
- The sequence and organization of the Chlamydomonas reinhardtii genes encoding cytochrome c 1 ( Cyc1) and the Rieske-type iron-sulfur protein ( Isp), two key nucleus-encoded subunits of the mitochondrial cytochrome bc 1 complex, are presented. Southern hybridization analysis indicates that both Cyc1 and Isp are present as single-copy genes in C. reinhardtii. The Cyc1 gene spans 6404 bp and contains six introns, ranging from 178 to 1134 bp in size. The Isp gene spans 1238 bp and contains four smaller introns, ranging in length from 83 to 167 bp. In both genes, the intron/exon junctions follow the GT/AG rule. Internal conserved sequences were identified in only some of the introns in the Cyc1 gene. The levels of expression of Isp and Cyc1 genes are comparable in wild-type C. reinhardtii cells and in a mutant strain carrying a deletion in the mitochondrial gene for cytochrome b (dum-1). Nevertheless, no accumulation of the nucleus-encoded cytochrome c 1 or of core proteins I and II was observed in the membranes of the respiratory mutant. These data show that, in the green alga C. reinhardtii, the subunits of the cytochrome bc1 complex fail to assemble properly in the absence of cytochrome b.
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| 43. |
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| 44. |
- Axelsson, Kristian F, 1973, et al.
(författare)
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Risk of fracture in adults with type 2 diabetes in Sweden: A national cohort study
- 2023
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Ingår i: Plos Medicine. - : Public Library of Science (PLoS). - 1549-1277 .- 1549-1676. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- Author summary Why was this study done? Type 2 diabetes mellitus (T2DM) is considered a risk factor for fracture but the evidence regarding the impact of T2DM on fracture risk is conflicting.We sought to determine if patients with T2DM had increased fracture risk and if so, to identify T2DM-related risk factors. What did the researchers do and find? We used a national register covering nearly all adult patients with T2DM in Sweden to compare the risk of fracture between T2DM patients ( = 580,127) and population controls ( = 580,127) without T2DM.In general, the risk of fracture was only marginally increased (by 1% for major osteoporotic fracture (MOF) and by 6% for hip fracture) for patients with T2DM compared to controls, but for patients with presence of risk factors, such as low BMI, long T2DM duration, insulin treatment, and/or low physical activity, the risk increase was more substantial (20% or higher) and potentially clinically relevant. What do these findings mean? Our findings suggest that T2DM per se should not be considered an important risk factor for fracture.Special consideration of the T2DM-related risk factors can be used to identify T2DM patients with a clinically relevant increased fracture risk.Further studies are needed to develop fracture risk calculators for different settings and populations for T2DM patients specifically. BackgroundType 2 diabetes mellitus (T2DM) is considered a risk factor for fracture but the evidence regarding the impact of T2DM on fracture risk is conflicting. The objective of the study was to determine if patients with T2DM have increased fracture risk and if T2DM-related risk factors could be identified. Methods and findingsIn this national cohort study in Sweden, we investigated the risk of fracture in 580,127 T2DM patients, identified through the national diabetes register including from both primary care and hospitals, and an equal number of population-based controls without diabetes matched for age, sex, and county from 2007 to 2017. The mean age at entry was 66.7 years and 43.6% were women. During a median follow-up time of 6.6 (interquartile range (IQR) 3.1 to 9.8) years, patients with T2DM had a marginally but significantly increased risk of major osteoporotic fracture (MOF) (hazard ratio (HR) 1.01 (95% confidence interval [CI] 1.00 to 1.03)) and hip fracture (HR 1.06 (95% CI 1.04 to 1.08)) compared to controls, associations that were only minimally affected (HR 1.05 (95% CI 1.03 to 1.06) and HR 1.11 (95% CI 1.09 to 1.14), respectively) by multivariable adjustment (age, sex, marital status, and an additional 20 variables related to general morbidity, cardiovascular status, risk of falls, and fracture). In a multivariable-adjusted Cox model, the proportion of the risk for all fracture outcomes (Heller's R2) explained by T2DM was below 0.1%. Among the T2DM patients, important risk factors for fracture were a low BMI (<25 kg/m(2)), long diabetes duration (>= 15 years), insulin treatment, and low physical activity. In total, 55% of the T2DM patients had none of these risk factors and a significantly lower fracture risk than their respective controls. The relatively short mean duration of T2DM and lack of bone density data, constitute limitations of the analysis. ConclusionIn this study, we observed only a marginally increased fracture risk in T2DM, a condition that explained less than 0.1% of the fracture risk. Consideration of the herein identified T2DM-related risk factors could be used to stratify T2DM patients according to fracture risk.
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| 45. |
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| 46. |
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| 47. |
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| 48. |
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| 49. |
- Bjerg, L., et al.
(författare)
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Duration of diabetes-related complications and mortality in type 1 diabetes: a national cohort study
- 2021
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Ingår i: International Journal of Epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 50:4, s. 1250-1259
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Tidskriftsartikel (refereegranskat)abstract
- Background: People with type 1 diabetes often live for many years with different combinations of diabetes-related complications. We aimed to quantify how complication duration and total complication burden affect mortality, using data from national registers. Methods: This study included 33 396 individuals with type 1 diabetes, registered in the Swedish National Diabetes Register at any time between 2001 and 2012. Each individual was followed and classified according to their time-updated diabetes-related complication status. The main outcomes were all-cause mortality, cardiovascular (CV) mortality and non-CV mortality. Poisson models were used to estimate the rate of these outcomes as a function of the time-updated complication duration. Results: Overall, 1748 of the 33 396 individuals died during 198 872 person-years of follow-up. Overall, the time-updated all-cause mortality rate ratio (MRR) was 2.25 [95% confidence interval (CI): 1.99-2.54] for patients with diabetic kidney disease, 0.98 (0.82-1.18) for patients with retinopathy and 4.00 (3.56-4.50) for patients with cardiovascular disease relative to individuals without complications. The excess rate was highest in the first period after a diagnosis of CVD, with an 8-fold higher mortality rate, and stabilized after some 5 years. After diagnosis of diabetic kidney disease, we observed an increase in all-cause mortality with an MRR of around 2 compared with individuals without diabetic kidney disease, which stabilized after few years. Conclusions: In this cohort we show that duration of diabetes-related complications is an important determinant of mortality in type 1 diabetes, for example the MRR associated with CVD is highest in the first period after diagnosis of CVD. A stronger focus on time-updated information and thorough consideration of complication duration may improve risk stratification in routine clinical practice.
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| 50. |
- Bjermer, Leif, et al.
(författare)
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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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Ingår i: European Respiratory Journal. - 1399-3003. ; 5:7, s. 785-790
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Tidskriftsartikel (refereegranskat)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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