| 1. |
- Thomas, HS, et al.
(författare)
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- 2019
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swepub:Mat__t
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| 2. |
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| 3. |
- Drake, TM, et al.
(författare)
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Surgical site infection after gastrointestinal surgery in children: an international, multicentre, prospective cohort study
- 2020
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Ingår i: BMJ global health. - : BMJ. - 2059-7908. ; 5:12
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Tidskriftsartikel (refereegranskat)abstract
- Surgical site infection (SSI) is one of the most common healthcare-associated infections (HAIs). However, there is a lack of data available about SSI in children worldwide, especially from low-income and middle-income countries. This study aimed to estimate the incidence of SSI in children and associations between SSI and morbidity across human development settings.MethodsA multicentre, international, prospective, validated cohort study of children aged under 16 years undergoing clean-contaminated, contaminated or dirty gastrointestinal surgery. Any hospital in the world providing paediatric surgery was eligible to contribute data between January and July 2016. The primary outcome was the incidence of SSI by 30 days. Relationships between explanatory variables and SSI were examined using multilevel logistic regression. Countries were stratified into high development, middle development and low development groups using the United Nations Human Development Index (HDI).ResultsOf 1159 children across 181 hospitals in 51 countries, 523 (45·1%) children were from high HDI, 397 (34·2%) from middle HDI and 239 (20·6%) from low HDI countries. The 30-day SSI rate was 6.3% (33/523) in high HDI, 12·8% (51/397) in middle HDI and 24·7% (59/239) in low HDI countries. SSI was associated with higher incidence of 30-day mortality, intervention, organ-space infection and other HAIs, with the highest rates seen in low HDI countries. Median length of stay in patients who had an SSI was longer (7.0 days), compared with 3.0 days in patients who did not have an SSI. Use of laparoscopy was associated with significantly lower SSI rates, even after accounting for HDI.ConclusionThe odds of SSI in children is nearly four times greater in low HDI compared with high HDI countries. Policies to reduce SSI should be prioritised as part of the wider global agenda.
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| 4. |
- Keppler, M., et al.
(författare)
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Discovery of a planetary-mass companion within the gap of the transition disk around PDS 70
- 2018
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 617
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Tidskriftsartikel (refereegranskat)abstract
- Context. Young circumstellar disks are the birthplaces of planets. Their study is of prime interest to understand the physical and chemical conditions under which planet formation takes place. Only very few detections of planet candidates within these disks exist, and most of them are currently suspected to be disk features.Aims. In this context, the transition disk around the young star PDS 70 is of particular interest, due to its large gap identified in previous observations, indicative of ongoing planet formation. We aim to search for the presence of an embedded young planet and search for disk structures that may be the result of disk-planet interactions and other evolutionary processes.Methods. We analyse new and archival near-infrared images of the transition disk PDS 70 obtained with the VLT/SPHERE, VLT/NaCo, and Gemini/NICI instruments in polarimetric differential imaging and angular differential imaging modes.Results. We detect a point source within the gap of the disk at about 195 mas (similar to 22 au) projected separation. The detection is confirmed at five different epochs, in three filter bands and using different instruments. The astrometry results in an object of bound nature, with high significance. The comparison of the measured magnitudes and colours to evolutionary tracks suggests that the detection is a companion of planetary mass. The luminosity of the detected object is consistent with that of an L-type dwarf, but its IR colours are redder, possibly indicating the presence of warm surrounding material. Further, we confirm the detection of a large gap of similar to 54 au in size within the disk in our scattered light images, and detect a signal from an inner disk component. We find that its spatial extent is very likely smaller than similar to 17 au in radius, and its position angle is consistent with that of the outer disk. The images of the outer disk show evidence of a complex azimuthal brightness distribution which is different at different wavelengths and may in part be explained by Rayleigh scattering from very small grains.Conclusions. The detection of a young protoplanet within the gap of the transition disk around PDS 70 opens the door to a so far observationally unexplored parameter space of planetary formation and evolution. Future observations of this system at different wavelengths and continuing astrometry will allow us to test theoretical predictions regarding planet-disk interactions, planetary atmospheres, and evolutionary models.
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| 5. |
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| 6. |
- Weigelt, G., et al.
(författare)
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VLTI-MATISSE chromatic aperture-synthesis imaging of eta Carinae's stellar wind across the Br alpha line Periastron passage observations in February 2020
- 2021
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 652
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Tidskriftsartikel (refereegranskat)abstract
- Context. Eta Carinae is a highly eccentric, massive binary system (semimajor axis similar to 15.5 au) with powerful stellar winds and a phase-dependent wind-wind collision (WWC) zone. The primary star, eta Car A, is a luminous blue variable (LBV); the secondary, eta Car B, is a Wolf-Rayet or O star with a faster but less dense wind. Aperture-synthesis imaging allows us to study the mass loss from the enigmatic LBV eta Car. Understanding LBVs is a crucial step toward improving our knowledge about massive stars and their evolution. Aims. Our aim is to study the intensity distribution and kinematics of eta Car's WWC zone. Methods. Using the VLTI-MATISSE mid-infrared interferometry instrument, we perform Br alpha imaging of eta Car's distorted wind. Results. We present the first VLTI-MATISSE aperture-synthesis images of eta Car A's stellar windin several spectral channels distributed across the Br alpha 4.052 mu m line (spectral resolving power R similar to 960). Our observations were performed close to periastron passage in February 2020 (orbital phase similar to 14.0022). The reconstructed iso-velocity images show the dependence of the primary stellar wind on wavelength or line-of-sight (LOS) velocity with a spatial resolution of 6 mas (similar to 14 au). The radius of the faintest outer wind regions is similar to 26 mas (similar to 60 au). At several negative LOS velocities, the primary stellar wind is less extended to the northwest than in other directions. This asymmetry is most likely caused by the WWC. Therefore, we see both the velocity field of the undisturbed primary wind and the WWC cavity. In continuum spectral channels, the primary star wind is more compact than in line channels. A fit of the observed continuum visibilities with the visibilities of a stellar wind CMFGEN model (CMFGEN is an atmosphere code developed to model the spectra of a variety of objects) provides a full width at half maximum fit diameter of the primary stellar wind of 2.84 +/- 0.06 mas (6.54 +/- 0.14 au). We comparethe derived intensity distributions with the CMFGEN stellar wind model and hydrodynamic WWC models.
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| 7. |
- Faries, B., et al.
(författare)
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Completion dissection or observation for sentinel-node metastasis in melanoma
- 2017
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Ingår i: New England Journal of Medicine. - 0028-4793. ; 376:23, s. 2211-2222
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Sentinel-lymph-node biopsy is associated with increased melanoma-specific survival (i.e., survival until death from melanoma) among patients with node-positive intermediatethickness melanomas (1.2 to 3.5 mm). The value of completion lymph-node dissection for patients with sentinel-node metastases is not clear. METHODS In an international trial, we randomly assigned patients with sentinel-node metastases detected by means of standard pathological assessment or a multimarker molecular assay to immediate completion lymph-node dissection (dissection group) or nodal observation with ultrasonography (observation group). The primary end point was melanoma-specific survival. Secondary end points included disease-free survival and the cumulative rate of nonsentinel-node metastasis. RESULTS Immediate completion lymph-node dissection was not associated with increased melanomaspecific survival among 1934 patients with data that could be evaluated in an intention-Totreat analysis or among 1755 patients in the per-protocol analysis. In the per-protocol analysis, the mean (-SE) 3-year rate of melanoma-specific survival was similar in the dissection group and the observation group (86-1.3% and 86-1.2%, respectively; P = 0.42 by the logrank test) at a median follow-up of 43 months. The rate of disease-free survival was slightly higher in the dissection group than in the observation group (68-1.7% and 63-1.7%, respectively; P = 0.05 by the log-rank test) at 3 years, based on an increased rate of disease control in the regional nodes at 3 years (92-1.0% vs. 77-1.5%; P<0.001 by the log-rank test); these results must be interpreted with caution. Nonsentinel-node metastases, identified in 11.5% of the patients in the dissection group, were a strong, independent prognostic factor for recurrence (hazard ratio, 1.78; P = 0.005). Lymphedema was observed in 24.1% of the patients in the dissection group and in 6.3% of those in the observation group. CONCLUSIONS Immediate completion lymph-node dissection increased the rate of regional disease control and provided prognostic information but did not increase melanoma-specific survival among patients with melanoma and sentinel-node metastases.
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| 8. |
- Muro-Arena, G. A., et al.
(författare)
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Shadowing and multiple rings in the protoplanetary disk of HD 139614
- 2020
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 635
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Tidskriftsartikel (refereegranskat)abstract
- Context. Shadows in scattered light images of protoplanetary disks are a common feature and support the presence of warps or misalignments between disk regions. These warps are possibly caused by an inclined (sub-)stellar companion embedded in the disk. Aims. We aim to study the morphology of the protoplanetary disk around the Herbig Ae star HD 139614 based on the first scattered light observations of this disk, which we model with the radiative transfer code MCMax3D. Methods. We obtained J- and H-band observations that show strong azimuthal asymmetries in polarized scattered light with VLT/SPHERE. In the outer disk, beyond similar to 30 au, a broad shadow spans a range of similar to 240 deg in position angle, in the east. A bright ring at similar to 16 au also shows an azimuthally asymmetric brightness, with the faintest side roughly coincidental with the brightest region of the outer disk. Additionally, two arcs are detected at similar to 34 and similar to 50 au. We created a simple four-zone approximation to a warped disk model of HD 139614 in order to qualitatively reproduce these features. The location and misalignment of the disk components were constrained from the shape and location of the shadows they cast. Results. We find that the shadow on the outer disk covers a range of position angles too wide to be explained by a single inner misaligned component. Our model requires a minimum of two separate misaligned zones - or a continuously warped region - to cast this broad shadow on the outer disk. A small misalignment of similar to 4 degrees between adjacent components can reproduce most of the observed shadow features. Conclusions. Multiple misaligned disk zones, potentially mimicking a warp, can explain the observed broad shadows in the HD 139614 disk. A planetary mass companion in the disk, located on an inclined orbit, could be responsible for such a feature and for the dust-depleted gap responsible for a dip in the SED.
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| 9. |
- Staubitz, J. I., et al.
(författare)
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EUROCRINE® : Nebennierenoperationen 2015 bis 2019 – überraschende erste Ergebnisse
- 2021
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Ingår i: Der Chirurg. - : Springer Science and Business Media LLC. - 0009-4722 .- 1433-0385. ; 92:5, s. 448-463
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Tidskriftsartikel (refereegranskat)abstract
- Background: Since 2015 operations performed in the field of endocrine surgery have been entered into the European registry EUROCRINE®. The aim of this analysis was a description of the current healthcare situation for adrenal surgery in a homogeneous healthcare environment corresponding to the German-speaking countries—or to the presence of the working group on surgical endocrinology (CAEK) of the German society for general and visceral surgery (DGAV)—and to assess the adherence to current international treatment guidelines. Methods: An analysis of the preoperative diagnostics, the applied operative techniques and the underlying histological entities was carried out for all operations on adrenal glands in Germany, Switzerland and Austria, which were registered in EUROCRINE® from 2015 to 2019. Results: In the total of 21 participating hospitals from the German-speaking EUROCRINE® countries, 658 operations on adrenal glands were performed. In 90% of cases unilateral adrenalectomy was performed, in 3% bilateral adrenalectomy and in 7% other resection procedures. In 41% the main histological diagnosis was an adrenocortical adenoma. In 15% malignant entities were detected on final histology, including 6% adrenocortical carcinoma (ACC) and 8% metastases to the adrenal glands. 23% of the operations were performed for pheochromocytoma. This entity was primarily resected using minimally invasive approaches (82%), whereas minimally invasive techniques were applied in 28% for ACC and in 66% for metastases to the adrenal glands. Conclusion: Surprisingly, following adrenocortical adenoma and pheochromocytoma, the third most common histological entity was metastasis of different extra-adrenal primary tumors to the adrenal gland. Of the operations for ACC 28% were scheduled for minimally invasive techniques, but conversion to open surgery was necessary in 20%. The analysis revealed discrepancies between treatment reality and international guideline recommendations that raise questions, which will be addressed by an updated version of the EUROCRINE® module for the documentation of adrenal surgery.
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| 10. |
- Chiavassa, A., et al.
(författare)
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The extended atmosphere and circumstellar environment of the cool evolved star VX Sagittarii as seen by MATISSE star
- 2022
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 658
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Tidskriftsartikel (refereegranskat)abstract
- Context. VX Sgr is a cool, evolved, and luminous red star whose stellar parameters are difficult to determine, which affects its classification.Aims. We aim to spatially resolve the photospheric extent as well as the circumstellar environment.Methods. We used interferometric observations obtained with the MATISSE instrument in the L (3-4 mu m), M (4.5-5 mu m), and N (8-13 mu m) bands. We reconstructed monochromatic images using the MIRA software. We used 3D radiation-hydrodynamics simulations carried out with (COBOLD)-B-5 and a uniform disc model to estimate the apparent diameter and interpret the stellar surface structures. Moreover, we employed the radiative transfer codes OPTIM3D and RADMC3D to compute the spectral energy distribution for the L, M, and N bands, respectively.Results. MATISSE observations unveil, for the first time, the morphology of VX Sgr across the L, M, and N bands. The reconstructed images show a complex morphology with brighter areas whose characteristics depend on the wavelength probed. We measured the angular diameter as a function of the wavelength and showed that the photospheric extent in the L and M bands depends on the opacity through the atmosphere. In addition to this, we also concluded that the observed photospheric inhomogeneities can be interpreted as convection-related surface structures. The comparison in the N band yielded a qualitative agreement between the N-band spectrum and simple dust radiative transfer simulations. However, it is not possible to firmly conclude on the interpretation of the current data because of the difficulty in constraing the model parameters using the limited accuracy of our absolute flux calibration.Conclusions. MATISSE observations and the derived reconstructed images unveil the appearance of VX Sgr's stellar surface and circumstellar environment across a very large spectral domain for the first time.
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| 11. |
- Paladini, C., et al.
(författare)
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The VLTI/MIDI view on the inner mass loss of evolved stars from the Herschel MESS sample
- 2017
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 600
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Tidskriftsartikel (refereegranskat)abstract
- Context. The mass-loss process from evolved stars is a key ingredient for our understanding of many fields of astrophysics, including stellar evolution and the chemical enrichment of the interstellar medium (ISM) via stellar yields. Nevertheless, many questions are still unsolved, one of which is the geometry of the mass-loss process. Aims. Taking advantage of the results from the Herschel Mass loss of Evolved StarS (MESS) programme, we initiated a coordinated effort to characterise the geometry of mass loss from evolved red giants at various spatial scales. Methods. For this purpose we used the MID-infrared interferometric Instrument (MIDI) to resolve the inner envelope of 14 asymptotic giant branch stars (AGBs) in the MESS sample. In this contribution we present an overview of the interferometric data collected within the frame of our Large Programme, and we also add archive data for completeness. We studied the geometry of the inner atmosphere by comparing the observations with predictions from different geometric models. Results. Asymmetries are detected for the following five stars: R Leo, RT Vir, ?1Gruis, omi Ori, and R Crt. All the objects are O-rich or S-type, suggesting that asymmetries in the N band are more common among stars with such chemistry. We speculate that this fact is related to the characteristics of the dust grains. Except for one star, no interferometric variability is detected, i.e. the changes in size of the shells of non-mira stars correspond to changes of the visibility of less than 10%. The observed spectral variability confirms previous findings from the literature. The detection of dust in our sample follows the location of the AGBs in the IRAS colour-colour diagram: More dust is detected around oxygen-rich stars in region II and in the carbon stars in region VII. The SiC dust feature does not appear in the visibility spectrum of the U Ant and S Sct, which are two carbon stars with detached shells. This finding has implications for the theory of SiC dust formation.
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| 12. |
- Akhmedov, A., et al.
(författare)
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Endothelial overexpression of LOX-1 increases plaque formation and promotes atherosclerosis in vivo
- 2014
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 35:40, s. 2839-2848
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Tidskriftsartikel (refereegranskat)abstract
- Aims Lectin-like oxLDL receptor-1 (LOX-1) mediates the uptake of oxidized low-density lipoprotein (oxLDL) in endothelial cells and macrophages. However, the different atherogenic potential of LOX-1-mediated endothelial and macrophage oxLDL uptake remains unclear. The present study was designed to investigate the in vivo role of endothelial LOX-1 in atherogenesis. Methods and results Endothelial-specific LOX-1 transgenic mice were generated using the Tie2 promoter (LOX-1TG). Oxidized low-density lipoprotein uptake was enhanced in cultured endothelial cells, but not in macrophages of LOX-1TG mice. Six-week-old male LOX-1TG and wild-type (WT) mice were fed a high-cholesterol diet (HCD) for 30 weeks. Increased reactive oxygen species production, impaired endothelial nitric oxide synthase activity and endothelial dysfunction were observed in LOX-1TG mice as compared with WT littermates. LOX-1 overexpression led to p38 phosphorylation, increased nuclear factor kappa B activity and subsequent up-regulation of vascular cell adhesion molecule-1, thereby favouring macrophage accumulation and aortic fatty streaks. Consistently, HCD-fed double-mutant LOX-1TG/ApoE(-/-) displayed oxidative stress and vascular inflammation with higher aortic plaques than ApoE(-/-) controls. Finally, bone marrow transplantation experiments showed that endothelial LOX-1 was sufficient for atherosclerosis development in vivo. Conclusions Endothelial-specific LOX-1 overexpression enhanced aortic oxLDL levels, thereby favouring endothelial dysfunction, vascular inflammation and plaque formation. Thus, LOX-1 may serve as a novel therapeutic target for atherosclerosis.
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| 13. |
- Reijers, S. J. M., et al.
(författare)
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Variation in response rates to isolated limb perfusion in different soft-tissue tumour subtypes: an international multi-centre study
- 2023
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Ingår i: European Journal of Cancer. - 0959-8049. ; 190
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of this study was to investigate the response rates of different extremity soft-tissue sarcoma subtypes (eSTS) after isolated limb perfusion (ILP), based on an international multi-centre study. Materials and methods: The retrospective cohort comprised eSTS patients from 17 specialised ILP centres that underwent melphalan-based ILP, with or without recombinant human tumour necrosis factor (rhTNF & alpha;) (TM-ILP and M-ILP, respectively). Response was measured on imaging (magnetic resonance imaging) and/or clinical response, for which M-ILPs were excluded. Results: A total of 1109 eSTS patients were included. The three most common histological subtypes were undifferentiated pleomorphic sarcoma (17%, n = 184), synovial sarcoma (16%, n = 175) and myxofibrosarcoma (8%, n = 87). rhTNF & alpha; was used in 93% (TM-ILP) and resulted in a significantly better overall response rate (ORR, p = 0.031) and complete responses (CR, p < 0.001) in comparison to M-ILP, without significant differences among histological subgroups. The ORR of TM-ILP was 68%, including 17% CR. Also, 80% showed progressive disease. Significantly higher response rates were shown for Kaposi sarcoma (KS) with 42% CR and 96% ORR (both p < 0.001), and significantly higher CR rates for angiosarcoma (AS, 45%, p < 0.001) and clear cell sarcoma (CCS, 31%, p = 0.049). ILP was followed by resection & LE; 6 months in 80% of the patients. The overall limb salvage rate was 88%, without significant differences among histological subgroups, but was significantly higher for ILP responders compared to non-responders (93% versus 76%, p < 0.001). Conclusion: ILP resulted in high response and LRS among all eSTS subtypes, however, with significant differences between subtypes with most promising results for KS, AS and CCS.
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| 14. |
- Rosenberg, T. M., et al.
(författare)
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Humid periods in southern Arabia : Windows of opportunity for modern human dispersal
- 2011
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Ingår i: Geology. - 0091-7613 .- 1943-2682. ; 39:12, s. 1115-1118
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Tidskriftsartikel (refereegranskat)abstract
- Arabia is a key area for the dispersal of anatomically modern humans (AMH, Homo sapiens) out of Africa. Given its modern hostile environment, the question of the timing of dispersal is also a question of climatic conditions. Fresh water and food were crucial factors facilitating AMH expansions into Arabia. By dating relict lake deposits, four periods of lake formation were identified: one during the early Holocene and three during the late Pleistocene centered ca. 80, ca. 100, and ca. 125 ka. Favorable environmental conditions during these periods allowed AMH to migrate across southern Arabia. Between ca. 75 and 10.5 ka, arid conditions prevailed and turned southern Arabia into a natural barrier for human dispersal. Thus, expansion of AMH through the southern corridor into Asia must have taken place before 75 ka, possibly in multiple dispersals.
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| 15. |
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| 16. |
- D'Hoore, A., et al.
(författare)
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COMPRES : a prospective postmarketing evaluation of the compression anastomosis ring CAR 27/ColonRing
- 2015
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Ingår i: Colorectal Disease. - : Wiley. - 1462-8910 .- 1463-1318. ; 17:6, s. 522-529
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Tidskriftsartikel (refereegranskat)abstract
- AimPreclinical studies have suggested that nitinol-based compression anastomosis might be a viable solution to anastomotic leak following low anterior resection. A prospective multicentre open label study was therefore designed to evaluate the performance of the ColonRing in (low) colorectal anastomosis. MethodThe primary outcome measure was anastomotic leakage. Patients were recruited at 13 different colorectal surgical units in Europe, the United States and Israel. Institutional review board approval was obtained. ResultsBetween 21 March 2010 and 3 August 2011, 266 patients completed the study protocol. The overall anastomotic leakage rate was 5.3% for all anastomoses, including a rate of 3.1% for low anastomoses. Septic anastomotic complications occurred in 8.3% of all anastomoses and 8.2% of low anastomoses. ConclusionNitinol compression anastomosis is safe, effective and easy to use and may offer an advantage for low colorectal anastomosis. A prospective randomized trial comparing ColonRing with conventional stapling is needed.
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| 17. |
- Gnos, Edwin, et al.
(författare)
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Ash Shutbah: A possible impact structure in Saudi Arabia
- 2014
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Ingår i: Meteoritics and Planetary Science. - : Wiley. - 1086-9379. ; 49:10, s. 1902-1914
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Tidskriftsartikel (refereegranskat)abstract
- We have investigated the Ash Shutbah circular structure in central Saudi Arabia (21 degrees 37N 45 degrees 39E) using satellite imagery, field mapping, thin-section petrography, and X-ray diffraction of collected samples. The approximately 2.1km sized structure located in flat-lying Jurassic Tuwaiq Mountain Limestone has been nearly peneplained by erosional processes. Satellite and structural data show a central area consisting of Dhruma Formation sandstones with steep bedding and tight folds plunging radially outward. Open folding occurs in displaced, younger Tuwaiq Mountain Limestone Formation blocks surrounding the central area, but is absent outside the circular structure. An approximately 60cm thick, unique folded and disrupted orthoquartzitic sandstone marker bed occurring in the central area of the structure is found 140m deeper in undisturbed escarpment outcrops located a few hundred meters west of the structure. With exception of a possible concave shatter cone found in the orthoquartzite of the central area, other diagnostic shock features are lacking. Some quartz-rich sandstones from the central area show pervasive fracturing of quartz grains with common concussion fractures. This deformation was followed by an event of quartz dissolution and calcite precipitation consistent with local sea- or groundwater heating. The combination of central stratigraphic uplift of 140m, concussion features in discolored sandstone, outward-dipping concentric folds in the central area, deformation restricted to the rocks of the ring structure, a complex circular structure of 2.1km diameter that appears broadly consistent with what one would expect from an impact structure in sedimentary targets, and a possible shatter cone all point to an impact origin of the Ash Shutbah structure. In fact, the Ash Shutbah structure appears to be a textbook example of an eroded, complex impact crater located in flat-lying sedimentary rocks, where the undisturbed stratigraphic section can be studied in escarpment outcrops in the vicinity of the structure.
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| 18. |
- Lelièvre, E.C., et al.
(författare)
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Ptf1a/Rbpj complex inhibits ganglion cell fate and drives the specification of all horizontal cell subtypes in the chick retina
- 2011
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Ingår i: Developmental Biology. - : Elsevier BV. - 0012-1606 .- 1095-564X. ; 358:2, s. 296-308
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Tidskriftsartikel (refereegranskat)abstract
- During development, progenitor cells of the retina give rise to six principal classes of neurons and the Müller glial cells found within the adult retina. The pancreas transcription factor 1 subunit a (Ptf1a) encodes a basic-helix–loop–helix transcription factor necessary for the specification of horizontal cells and the majority of amacrine cell subtypes in the mouse retina. The Ptf1a-regulated genes and the regulation of Ptf1a activity by transcription cofactors during retinogenesis have been poorly investigated. Using a retrovirus-mediated gene transfer approach, we reported that Ptf1a was sufficient to promote the fates of amacrine and horizontal cells from retinal progenitors and inhibit retinal ganglion cell and photoreceptor differentiation in the chick retina. Both GABAergic H1 and non-GABAergic H3 horizontal cells were induced following the forced expression of Ptf1a. We describe Ptf1a as a strong, negative regulator of Atoh7 expression. Furthermore, the Rbpj-interacting domains of Ptf1a protein were required for its effects on cell fate specification. Together, these data provide a novel insight into the molecular basis of Ptf1a activity on early cell specification in the chick retina.
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| 19. |
- Nesti, Cedric, et al.
(författare)
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Hemicolectomy versus appendectomy for patients with appendiceal neuroendocrine tumours 1-2 cm in size : a retrospective, Europe-wide, pooled cohort study
- 2023
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Ingår i: The Lancet Oncology. - : Elsevier. - 1470-2045 .- 1474-5488. ; 24:2, s. 187-194
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundAwareness of the potential global overtreatment of patients with appendiceal neuroendocrine tumours (NETs) of 1–2 cm in size by performing oncological resections is increasing, but the rarity of this tumour has impeded clear recommendations to date. We aimed to assess the malignant potential of appendiceal NETs of 1–2 cm in size in patients with or without right-sided hemicolectomy.MethodsIn this retrospective cohort study, we pooled data from 40 hospitals in 15 European countries for patients of any age and Eastern Cooperative Oncology Group performance status with a histopathologically confirmed appendiceal NET of 1–2 cm in size who had a complete resection of the primary tumour between Jan 1, 2000, and Dec 31, 2010. Patients either had an appendectomy only or an appendectomy with oncological right-sided hemicolectomy or ileocecal resection. Predefined primary outcomes were the frequency of distant metastases and tumour-related mortality. Secondary outcomes included the frequency of regional lymph node metastases, the association between regional lymph node metastases and histopathological risk factors, and overall survival with or without right-sided hemicolectomy. Cox proportional hazards regression was used to estimate the relative all-cause mortality hazard associated with right-sided hemicolectomy compared with appendectomy alone. This study is registered with ClinicalTrials.gov, NCT03852693.Findings282 patients with suspected appendiceal tumours were identified, of whom 278 with an appendiceal NET of 1–2 cm in size were included. 163 (59%) had an appendectomy and 115 (41%) had a right-sided hemicolectomy, 110 (40%) were men, 168 (60%) were women, and mean age at initial surgery was 36·0 years (SD 18·2). Median follow-up was 13·0 years (IQR 11·0–15·6). After centralised histopathological review, appendiceal NETs were classified as a possible or probable primary tumour in two (1%) of 278 patients with distant peritoneal metastases and in two (1%) 278 patients with distant metastases in the liver. All metastases were diagnosed synchronously with no tumour-related deaths during follow-up. Regional lymph node metastases were found in 22 (20%) of 112 patients with right-sided hemicolectomy with available data. On the basis of histopathological risk factors, we estimated that 12·8% (95% CI 6·5 –21·1) of patients undergoing appendectomy probably had residual regional lymph node metastases. Overall survival was similar between patients with appendectomy and right-sided hemicolectomy (adjusted hazard ratio 0·88 [95% CI 0·36–2·17]; p=0·71).InterpretationThis study provides evidence that right-sided hemicolectomy is not indicated after complete resection of an appendiceal NET of 1–2 cm in size by appendectomy, that regional lymph node metastases of appendiceal NETs are clinically irrelevant, and that an additional postoperative exclusion of metastases and histopathological evaluation of risk factors is not supported by the presented results. These findings should inform consensus best practice guidelines for this patient cohort.
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| 20. |
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| 21. |
- Anton, KA, et al.
(författare)
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PKA-regulated VASP phosphorylation promotes extrusion of transformed cells from the epithelium
- 2014
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Ingår i: Journal of cell science. - : The Company of Biologists. - 1477-9137 .- 0021-9533. ; 127:16Pt 16, s. 3425-3433
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Tidskriftsartikel (refereegranskat)abstract
- At the early stages of carcinogenesis, transformation occurs in single cells within tissues. In an epithelial monolayer, such mutated cells are recognized by their normal neighbors and are often apically extruded. The apical extrusion requires cytoskeletal reorganization and cell shape changes, but it is poorly understood what molecular switches are involved in regulation of these processes. Here, using SILAC-based quantitative mass spectrometry we have identified proteins that are modulated in transformed cells upon their interaction with normal cells. Phosphorylation of VASP at serine 239 is specifically upregulated in RasV12-transformed cells when they are surrounded by normal cells. VASP phosphorylation is required for the cell shape changes and apical extrusion of Ras-transformed cells. Furthermore, PKA is activated in Ras-transformed cells surrounded by normal cells, leading to VASP phosphorylation. These results indicate that the PKA/VASP pathway is a crucial regulator for tumor cell extrusion from the epithelium and shed light on the events occurring at the early stage of carcinogenesis.
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| 22. |
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| 23. |
- Danchin, Nicolas, et al.
(författare)
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Use, patient selection and outcomes of P2Y12 receptor inhibitor treatment in patients with STEMI based on contemporary European registries
- 2016
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Ingår i: European Heart Journal - Cardiovascular Pharmacotherapy. - : Oxford University Press (OUP). - 2055-6837 .- 2055-6845. ; 2:3, s. 152-167
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Tidskriftsartikel (refereegranskat)abstract
- Aims Among acute coronary syndromes (ACS), ST-segment elevation myocardial infarction (STEMI) has the most severe early clinical course. We aimed to describe the effectiveness and safety of P2Y12 receptor inhibitors in patients with STEMI based on the data from contemporary European ACS registries. Methods and results Twelve registries provided data in a systematic manner on outcomes in STEMI patients overall, and seven of these also provided data for P2Y12 receptor inhibitor-based dual antiplatelet therapy. The registrieswere heterogeneous in terms of site, patient, and treatment selection, as well as in definition of endpoints (e.g. bleeding events). All-cause death rates based on the data from 84 299 patients (9612 patients on prasugrel, 11 492 on ticagrelor, and 27 824 on clopidogrel) ranged between 0.49 and 6.68% in-hospital, between 3.07 and 7.95% at 30 days (reported in 6 registries), between 8.15 and 9.13% at 180 days, and between 2.41 and 9.58% at 1 year (5 registries). Major bleeding rates were 0.09-3.55% inhospital (8 registries), 0.09-1.65% at 30 days, and 1.96% at 1 year (only 1 registry). Fatal/life-Threatening bleeding was rare occurring between 0.08 and 0.13% in-hospital (4 registries) and 1.96% at 1 year (1 registry). Conclusions Real-world evidence from European contemporary registries shows that death, ischaemic events, and bleeding rates are lower than those reported in Phase III studies of P2Y12 inhibitors. Regarding individual P2Y12 inhibitors, patients on prasugrel, and, to a lesser degree, ticagrelor, had fewer ischaemic and bleeding events at all time points than clopidogrel-Treated patients. These findings are partly related to the fact that the newer agents are used in younger and less ill patients.
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| 24. |
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| 25. |
- Lettino, Maddalena, et al.
(författare)
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Diabetic patients with acute coronary syndromes in contemporary European registries : Characteristics and outcomes
- 2017
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Ingår i: European Heart Journal - Cardiovascular Pharmacotherapy. - : Oxford University Press (OUP). - 2055-6837 .- 2055-6845. ; 3:4, s. 198-213
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Tidskriftsartikel (refereegranskat)abstract
- Aims Among patients with acute coronary syndromes (ACS), those with diabetes mellitus (DM) are at particularly high risk of recurrent cardiovascular events and premature death. We aimed to provide a descriptive overview of unadjusted analyses of patient characteristics, ACS management, and outcomes up to 1 year after hospital admission for an ACS/index-ACS event, in patients with DM in contemporary registries in Europe. Methods and results A total of 10 registries provided data in a systematic manner on ACS patients with DM (total n =28 899), and without DM (total n= 97 505). In the DM population, the proportion of patients with ST-Segment Elevation Myocardial Infarction (STEMI) ranged from 22.1% to 64.6% (other patients had non-ST-Segment Elevation Myocardial Infarction (NSTEMI-ACS) or unstable angina). All-cause mortality in the registries ranged from 1.4% to 9.4% in-hospital; 2.8% to 7.9% at 30 days post-discharge; 5.1% to 10.7% at 180 days post-discharge; and 3.3% to 10.5% at 1 year post-discharge. Major bleeding events were reported in up to 3.8% of patients while in hospital (8 registries); up to 1.3% at 30 days (data from two registries only), and 2.0% at 1 year (one registry only). Registries differed substantially in terms of study setting, site, patient selection, definition and schedule of endpoints, and use of various P2Y12 inhibitors. In most, but not all, registries, event rates in DM patients were higher than in patients without DM. Pooled risk ratios comparing cohorts with DM vs. no DM were in-hospital significantly higher in DM for all-cause death (1.66; 95% CI 1.42-1.94), for cardiovascular death (2.33; 1.78 - 3.03), and for major bleeding (1.35; 1.21-1.52). Conclusion These registry data from real-life clinical practice confirm a high risk for recurrent events among DM patients with ACS, with great variation across the different registries.
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| 26. |
- Osto, E., et al.
(författare)
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c-Jun N-terminal kinase 2 deficiency protects against hypercholesterolemia-induced endothelial dysfunction and oxidative stress
- 2008
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Ingår i: Circulation. - 0009-7322. ; 118:20, s. 2073-80
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Tidskriftsartikel (refereegranskat)abstract
- Background— Hypercholesterolemia-induced endothelial dysfunction due to excessive production of reactive oxygen species is a major trigger of atherogenesis. The c-Jun-N-terminal kinases (JNKs) are activated by oxidative stress and play a key role in atherogenesis and inflammation. We investigated whether JNK2 deletion protects from hypercholesterolemia-induced endothelial dysfunction and oxidative stress. Methods and Results— Male JNK2 knockout (JNK2−/−) and wild-type (WT) mice (8 weeks old) were fed either a high-cholesterol diet (HCD; 1.25% total cholesterol) or a normal diet for 14 weeks. Aortic lysates of WT mice fed a HCD showed an increase in JNK phosphorylation compared with WT mice fed a normal diet (P<0.05). Endothelium-dependent relaxations to acetylcholine were impaired in WT HCD mice (P<0.05 versus WT normal diet). In contrast, JNK2−/− HCD mice did not exhibit endothelial dysfunction (96±5% maximal relaxation in response to acetylcholine; P<0.05 versus WT HCD). Endothelium-independent relaxations were identical in all groups. A hypercholesterolemia-induced decrease in nitric oxide (NO) release of endothelial cells was found in WT but not in JNK2−/− mice. In parallel, endothelial NO synthase expression was upregulated only in JNK2−/− HCD animals, whereas the expression of antioxidant defense systems such as extracellular superoxide dismutase and manganese superoxide dismutase was decreased in WT but not in JNK2−/− HCD mice. In contrast to JNK2−/− mice, WT HCD displayed an increase in O2− and ONOO− concentrations as well as nitrotyrosine staining and peroxidation.
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| 27. |
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| 28. |
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| 29. |
- Ricci, R., et al.
(författare)
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Requirement of JNK2 for scavenger receptor A-mediated foam cell formation in atherogenesis
- 2004
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Ingår i: Science. - 1095-9203. ; 306:5701, s. 1558-61
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Tidskriftsartikel (refereegranskat)abstract
- In vitro studies suggest a role for c-Jun N-terminal kinases (JNKs) in proatherogenic cellular processes. We show that atherosclerosis-prone ApoE-/- mice simultaneously lacking JNK2 (ApoE-/- JNK2-/- mice), but not ApoE-/- JNK1-/- mice, developed less atherosclerosis than do ApoE-/- mice. Pharmacological inhibition of JNK activity efficiently reduced plaque formation. Macrophages lacking JNK2 displayed suppressed foam cell formation caused by defective uptake and degradation of modified lipoproteins and showed increased amounts of the modified lipoprotein-binding and -internalizing scavenger receptor A (SR-A), whose phosphorylation was markedly decreased. Macrophage-restricted deletion of JNK2 was sufficient to decrease atherogenesis. Thus, JNK2-dependent phosphorylation of SR-A promotes uptake of lipids in macrophages, thereby regulating foam cell formation, a critical step in atherogenesis.
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| 30. |
- Robinson, Adam H., et al.
(författare)
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Multiscale characterisation of chimneys/pipes : Fluid escape structures within sedimentary basins
- 2021
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Ingår i: International Journal of Greenhouse Gas Control. - : Elsevier BV. - 1750-5836 .- 1878-0148. ; 106
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Tidskriftsartikel (refereegranskat)abstract
- Evaluation of seismic reflection data has identified the presence of fluid escape structures cross-cutting overburden stratigraphy within sedimentary basins globally. Seismically-imaged chimneys/pipes are considered to be possible pathways for fluid flow, which may hydraulically connect deeper strata to the seabed. The properties of fluid migration pathways through the overburden must be constrained to enable secure, long-term subsurface carbon dioxide (CO2) storage. We have investigated a site of natural active fluid escape in the North Sea, the Scanner pockmark complex, to determine the physical characteristics of focused fluid conduits, and how they control fluid flow. Here we show that a multi-scale, multi-disciplinary experimental approach is required for complete characterisation of fluid escape structures. Geophysical techniques are necessary to resolve fracture geometry and subsurface structure (e.g., multi-frequency seismics) and physical parameters of sediments (e.g., controlled source electromagnetics) across a wide range of length scales (m to km). At smaller (mm to cm) scales, sediment cores were sampled directly and their physical and chemical properties assessed using laboratory-based methods. Numerical modelling approaches bridge the resolution gap, though their validity is dependent on calibration and constraint from field and laboratory experimental data. Further, time-lapse seismic and acoustic methods capable of resolving temporal changes are key for determining fluid flux. Future optimisation of experiment resource use may be facilitated by the installation of permanent seabed infrastructure, and replacement of manual data processing with automated workflows. This study can be used to inform measurement, monitoring and verification workflows that will assist policymaking, regulation, and best practice for CO2 subsurface storage operations.
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| 31. |
- Rosenberg, Thomas M., et al.
(författare)
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Middle and Late Pleistocene humid periods recorded in palaeolake deposits of the Nafud desert, Saudi Arabia
- 2013
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Ingår i: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791 .- 1873-457X. ; 70, s. 109-123
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Tidskriftsartikel (refereegranskat)abstract
- Present climate in the Nafud desert of northern Saudi Arabia is hyper-arid and moisture brought by north-westerly winds scarcely reaches the region. The existence of abundant palaeolake sediments provides evidence for a considerably wetter climate in the past. However, the existing chronological framework of these deposits is solely based on radiocarbon dating of questionable reliability, due to potential post-depositional contamination with younger C-14. By using luminescence dating, we show that the lake deposits were not formed between 40 and 20 ka as suggested previously, but approximately ca 410 ka, 320 ka, 200 ka, 125 ka, and 100 ka ago. All of these humid phases are in good agreement with those recorded in lake sediments and speleothems from southern Arabia. Surprisingly, no Holocene lake deposits were identified. Geological characteristics of the deposits and diatom analysis suggest that a single, perennial lake covered the entire south-western Nafud ca 320 ka ago. In contrast, lakes of the 200 ka, 125 ka, and 100 ka humid intervals were smaller and restricted to interdune depressions of a preexisting dune relief. The concurrent occurrence of humid phases in the Nafud, southern Arabia and the eastern Mediterranean suggests that moisture in northern Arabia originated either from the Mediterranean due to more frequent frontal depression systems or from stronger Indian monsoon circulation, respectively. However, based on previously published climate model simulations and palaecolimate evidence from central Arabia and the Negev desert, we argue that humid climate conditions in the Nafud were probably caused by a stronger African monsoon and a distinct change in zonal atmospheric circulation.
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| 32. |
- Zeymer, Uwe, et al.
(författare)
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P2Y12 receptor inhibitors in patients with non-STelevation acute coronary syndrome in the real world : Use, patient selection, and outcomes from contemporary European registries
- 2016
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Ingår i: European Heart Journal - Cardiovascular Pharmacotherapy. - : Oxford University Press (OUP). - 2055-6837 .- 2055-6845. ; 2:4, s. 229-243
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Tidskriftsartikel (refereegranskat)abstract
- Aims Non-ST-elevation acute coronary syndrome (NSTE-ACS) is present in about 60-70% of patients admitted with acute coronary syndromes in clinical practice. This study provides a 'real-life' overview of NSTE-ACS patient characteristics, dual antiplatelet therapy clinical practice, and outcomes at both the time of discharge from hospital and up to 1-year post-discharge. Methods and results A total of 10 registries (documenting 84 054 NSTE-ACS patients) provided data in a systematic manner on patient characteristics and outcomes for NSTE-ACS in general, and 6 of these (with 52 173 NSTE-ACS patients) also provided more specific data according to P2Y12 receptor inhibitor used. Unadjusted analyses were performed at the study level, and no formal meta-Analysis was performed due to large heterogeneity between studies in the settings, patient characteristics, and outcome definitions. All-cause death rates across registries ranged from 0.76 to 4.79% in-hospital, from 1.61 to 6.65% at 30 days, from 3.66 to 7.16% at 180 days, and from 3.14 to 9.73% at 1 year. Major bleeding events were reported in up to 2.77% of patients while in hospital (in seven registries), up to 1.08% at 30 days (data from one registry only), and 2.06% at 1 year (one registry). Conclusions There were substantial differences in the use of and patient selection for clopidogrel, prasugrel, and ticagrelor, which were associated with differences in short-And long-Term ischaemic and bleeding events. In future registries, data collection should be performed in a more standardized way with respect to endpoints, definitions, and time points.
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