| 61. |
- Holme, Ingar, et al.
(författare)
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A risk score for predicting mortality in patients with asymptomatic mild to moderate aortic stenosis
- 2012
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Ingår i: Heart. - : BMJ Publishing Group Ltd & British Cardiovascular Society. - 1355-6037 .- 1468-201X. ; 98:5, s. 377-383
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Tidskriftsartikel (refereegranskat)abstract
- Background Prognostic information for asymptomatic patients with aortic stenosis (AS) from prospective studies is scarce and there is no risk score available to assess mortality. Objectives To develop an easily calculable score, from which clinicians could stratify patients into high and lower risk of mortality, using data from the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study. Method A search for significant prognostic factors (p < 0.01) among SEAS patients was made by a combined judgemental and statistical elimination procedure to derive a set of three factors (age, gender and smoking) that were forced into the model, and four additional factors captured by the data: left-ventricular mass index, bilirubin, heart rate and natural logarithm of C reactive protein. Calibration was done by comparing observed with calculated number of deaths by tenths of calculated risk using coefficients from the simvastatin + ezetimibe group on placebo group patients. Results Discrimination was good with ROC area of 0.76 for all patients. Estimated probabilities of death were categorised into thirds. An optimised split point of estimated 5-year risk was about 15% (close to the upper 14% tertile split point), with risk 4 times as high in the upper compared to the two lower thirds. The SEAS score performed better than another established high risk score developed for other purposes. Conclusion A new seven factor model for risk stratification of patients with mild to moderate asymptomatic AS identified a high risk group for total mortality with good discrimination properties. Trial registration number ClinicalTrials.gov, NCT 00092677.
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| 62. |
- Hung, Rayjean J, et al.
(författare)
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A susceptibility locus for lung cancer maps to nicotinic acetylcholine receptor subunit genes on 15q25
- 2008
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 452:7187, s. 633-637
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Tidskriftsartikel (refereegranskat)abstract
- Lung cancer is the most common cause of cancer death worldwide, with over one million cases annually. To identify genetic factors that modify disease risk, we conducted a genome-wide association study by analysing 317,139 single-nucleotide polymorphisms in 1,989 lung cancer cases and 2,625 controls from six central European countries. We identified a locus in chromosome region 15q25 that was strongly associated with lung cancer (P = 9 x 10(-10)). This locus was replicated in five separate lung cancer studies comprising an additional 2,513 lung cancer cases and 4,752 controls (P = 5 x 10(-20) overall), and it was found to account for 14% (attributable risk) of lung cancer cases. Statistically similar risks were observed irrespective of smoking status or propensity to smoke tobacco. The association region contains several genes, including three that encode nicotinic acetylcholine receptor subunits (CHRNA5, CHRNA3 and CHRNB4). Such subunits are expressed in neurons and other tissues, in particular alveolar epithelial cells, pulmonary neuroendocrine cells and lung cancer cell lines, and they bind to N'-nitrosonornicotine and potential lung carcinogens. A non-synonymous variant of CHRNA5 that induces an amino acid substitution (D398N) at a highly conserved site in the second intracellular loop of the protein is among the markers with the strongest disease associations. Our results provide compelling evidence of a locus at 15q25 predisposing to lung cancer, and reinforce interest in nicotinic acetylcholine receptors as potential disease candidates and chemopreventative targets.
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| 63. |
- Jabrah, Duaa, et al.
(författare)
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White blood cell subtypes and neutrophil extracellular traps content as biomarkers for stroke etiology in acute ischemic stroke clots retrieved by mechanical thrombectomy.
- 2024
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Ingår i: Thrombosis research. - 1879-2472. ; 234, s. 1-8
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Tidskriftsartikel (refereegranskat)abstract
- Lymphocytes, macrophages, neutrophils, and neutrophil extracellular traps (NETs) associate with stroke risk factors and form a thrombus through different mechanisms. We investigated the total WBCs, WBC subtypes and NETs composition in acute ischemic stroke (AIS) clots to identify possible etiological differences that could help us further understand the process of thrombosis that leads to AIS.AIS clots from 100 cases each of atherothrombotic (AT), cardioembolic (CE) and cryptogenic stroke etiology were collected per-pass as part of the CÚRAM RESTORE registry of AIS clots. Martius Scarlet Blue stain was used to identify the main histological components of the clots. Immunohistochemical staining was used to identify neutrophils, lymphocytes, macrophages, and NETs patterns. The cellular and histological components were quantified using Orbit Image Analysis software.AT clots were larger, with more red blood cells and fewer WBCs than CE clots. AT clots had more lymphocytes and cryptogenic clots had fewer macrophages than other etiologies. Most significantly, CE clots showed higher expression of neutrophils and extracellular web-like NETs compared to AT and cryptogenic clots. There was also a significantly higher distribution of web-like NETs around the periphery of the CE clots while a mixed distribution was observed in AT clots.The difference in neutrophil and NETs expression in clots from different etiologies may provide insight into the mechanism of clot formation.
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| 64. |
- Jander, Nikolaus, et al.
(författare)
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Indexing aortic valve area by body surface area increases the prevalence of severe aortic stenosis
- 2014
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Ingår i: Heart. - : BMJ. - 1355-6037 .- 1468-201X. ; 100:1, s. 28-33
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Tidskriftsartikel (refereegranskat)abstract
- Background To account for differences in body size in patients with aortic stenosis, aortic valve area (AVA) is divided by body surface area (BSA) to calculate indexed AVA (AVA(index)). Cut-off values for severe stenosis are <1.0cm(2) for AVA and <0.6cm(2)/m(2) for AVA(index). Objective To investigate the influence of indexation on the prevalence of severe aortic stenosis and on the predictive accuracy regarding clinical outcome. Methods Echocardiographic and anthropometric data from a retrospective cohort of 2843 patients with aortic stenosis (jet velocity >2.5m/s) and from 1525 patients prospectively followed in the simvastatin and ezetimibe in aortic stenosis (SEAS) trial were analysed. Results The prevalence of severe stenosis increased with the AVA(index) criterion compared to AVA from 71% to 80% in the retrospective cohort, and from 29% to 44% in SEAS (both p<0.001). Overall, the predictive accuracy for aortic valve events was virtually identical for AVA and AVA(index) in the SEAS population (mean follow-up of 46months; area under the receiver operating characteristic curve: 0.67 (95% CI 0.64 to 0.70) vs 0.68 (CI 0.65 to 0.71) (NS). However, 213 patients additionally categorised as severe by AVA(index) experienced significantly less valve related events than those fulfilling only the AVA criterion (p<0.001). Conclusions Indexing AVA by BSA (AVA(index)) significantly increases the prevalence of patients with criteria for severe stenosis by including patients with a milder degree of the disease without improving the predictive accuracy for aortic valve related events.
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| 65. |
- Jander, Nikolaus, et al.
(författare)
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Outcome of Patients With Low-Gradient "Severe" Aortic Stenosis and Preserved Ejection Fraction
- 2011
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Ingår i: Circulation. - 1524-4539 .- 0009-7322. ; 123:8, s. 887-895
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Tidskriftsartikel (refereegranskat)abstract
- Background-Retrospective studies have suggested that patients with a low transvalvular gradient in the presence of an aortic valve area <1.0 cm(2) and normal ejection fraction may represent a subgroup with an advanced stage of aortic valve disease, reduced stroke volume, and poor prognosis requiring early surgery. We therefore evaluated the outcome of patients with low-gradient "severe" stenosis (defined as aortic valve area < 1.0 cm(2) and mean gradient <= 40 mm Hg) in the prospective Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study. Methods and Results-Outcome in patients with low-gradient "severe" aortic stenosis was compared with outcome in patients with moderate stenosis (aortic valve area 1.0 to 1.5 cm(2); mean gradient 25 to 40 mm Hg). The primary end point of aortic valve events included death from cardiovascular causes, aortic valve replacement, and heart failure due to aortic stenosis. Secondary end points were major cardiovascular events and cardiovascular death. In 1525 asymptomatic patients (mean age, 67 +/- 10 years; ejection fraction, >= 55%), baseline echocardiography revealed low-gradient severe stenosis in 435 patients (29%) and moderate stenosis in 184 (12%). Left ventricular mass was lower in patients with low-gradient severe stenosis than in those with moderate stenosis (182 +/- 64 versus 212 +/- 68 g; P < 0.01). During 46 months of follow-up, aortic valve events occurred in 48.5% versus 44.6%, respectively (P=0.37; major cardiovascular events, 50.9% versus 48.5%, P=0.58; cardiovascular death, 7.8% versus 4.9%, P=0.19). Low-gradient severe stenosis patients with reduced stroke volume index (<= 35 mL/m(2); n=223) had aortic valve events comparable to those in patients with normal stroke volume index (46.2% versus 50.9%; P=0.53). Conclusions-Patients with low-gradient "severe" aortic stenosis and normal ejection fraction have an outcome similar to that in patients with moderate stenosis. (Circulation. 2011;123:887-895.)
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| 66. |
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| 67. |
- Jander, Nikolaus, et al.
(författare)
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Velocity ratio predicts outcomes in patients with low gradient severe aortic stenosis and preserved EF
- 2014
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Ingår i: Heart. - : BMJ. - 1355-6037 .- 1468-201X. ; 100:24, s. 1946-1953
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Tidskriftsartikel (refereegranskat)abstract
- Objective To evaluate the usefulness of velocity ratio (VR) in patients with low gradient severe aortic stenosis (LGSAS) and preserved EF.Background LGSAS despite preserved EF represents a clinically challenging entity. Reliance on mean pressure gradient (MPG) may underestimate stenosis severity as has been reported in the context of paradoxical low flow, LGSAS. On the other hand, grading of stenosis severity by aortic valve area (AVA) may overrate stenosis severity due to erroneous underestimation of LV outflow tract (LVOT) diameter, small body size or inconsistencies in cut-off values for severe stenosis. We hypothesised that VR may have conceptual advantages over MPG and AVA, predict clinical outcomes and thereby be useful in the management of patients with LGSAS.Methods Patients from the prospective Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study with an AVA<1.0 cm(2), MPG <= 40 mm Hg and EF >= 55% and asymptomatic at baseline were stratified according to VR with a cut-off value of 0.25. Outcomes were evaluated according to aortic valve-related events and cardiovascular death.Results Of 435 patients with LGSAS, 197 (45%) had VR<0.25 suggesting severe and 238 (55%) had VR >= 0.25 suggesting non-severe stenosis. Aortic valve-related events (mean follow-up 42 +/- 14 months) were more frequent in patients with VR<0.25 (57% vs 41%; p<0.001) as was cardiovascular death within the first 24 months (p<0.05). In multivariable Cox regression analysis, MPG was the strongest independent predictor of aortic valve events (p<0.001) followed by VR (p<0.02). Adjusting AVA by VR increased predictive accuracy for aortic valve events (area under the receiver operating curve 0.62 (95% CI 0.57 to 0.67) vs 0.56 (95% CI 0.51 to 0.61) for AVA, p=0.02) with net reclassification improvement calculated at 0.36 (95% CI 0.17 to 0.54, p<0.001). VR did not improve the prediction of clinical events by MPG.Conclusions In the difficult setting of LGSAS, VR shows a strong association with valve-related events and - although not outperforming MPG-may be particularly useful in guiding clinical management.
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| 68. |
- Jarvis, Erich D., et al.
(författare)
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Whole-genome analyses resolve early branches in the tree of life of modern birds
- 2014
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 346:6215, s. 1320-1331
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Tidskriftsartikel (refereegranskat)abstract
- To better determine the history of modern birds, we performed a genome-scale phylogenetic analysis of 48 species representing all orders of Neoaves using phylogenomic methods created to handle genome-scale data. We recovered a highly resolved tree that confirms previously controversial sister or close relationships. We identified the first divergence in Neoaves, two groups we named Passerea and Columbea, representing independent lineages of diverse and convergently evolved land and water bird species. Among Passerea, we infer the common ancestor of core landbirds to have been an apex predator and confirm independent gains of vocal learning. Among Columbea, we identify pigeons and flamingoes as belonging to sister clades. Even with whole genomes, some of the earliest branches in Neoaves proved challenging to resolve, which was best explained by massive protein-coding sequence convergence and high levels of incomplete lineage sorting that occurred during a rapid radiation after the Cretaceous-Paleogene mass extinction event about 66 million years ago.
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| 69. |
- Karoly, Janik, et al.
(författare)
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The JCMT BISTRO Survey: Studying the Complex Magnetic Field of L43
- 2023
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Ingår i: Astrophysical Journal. - 1538-4357 .- 0004-637X. ; 952:1
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Tidskriftsartikel (refereegranskat)abstract
- We present observations of polarized dust emission at 850 mu m from the L43 molecular cloud, which sits in the Ophiuchus cloud complex. The data were taken using SCUBA-2/POL-2 on the James Clerk Maxwell Telescope as a part of the BISTRO large program. L43 is a dense (N-H2 similar to 10(22) - 10(23) cm(-2)) complex molecular cloud with a submillimeter-bright starless core and two protostellar sources. There appears to be an evolutionary gradient along the isolated filament that L43 is embedded within, with the most evolved source closest to the Sco OB2 association. One of the protostars drives a CO outflow that has created a cavity to the southeast. We see a magnetic field that appears to be aligned with the cavity walls of the outflow, suggesting interaction with the outflow. We also find a magnetic field strength of up to similar to 160 +/- 30 mu G in the main starless core and up to similar to 90 +/- 40 mu G in the more diffuse, extended region. These field strengths give magnetically super- and subcritical values, respectively, and both are found to be roughly trans-Alfvenic. We also present a new method of data reduction for these denser but fainter objects like starless cores.
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| 70. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes
- 2008
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Ingår i: Autophagy. - : Landes Bioscience. - 1554-8627 .- 1554-8635. ; 4:2, s. 151-175
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Forskningsöversikt (refereegranskat)abstract
- Research in autophagy continues to accelerate,1 and as a result many new scientists are entering the field. Accordingly, it is important to establish a standard set of criteria for monitoring macroautophagy in different organisms. Recent reviews have described the range of assays that have been used for this purpose.2,3 There are many useful and convenient methods that can be used to monitor macroautophagy in yeast, but relatively few in other model systems, and there is much confusion regarding acceptable methods to measure macroautophagy in higher eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers of autophagosomes versus those that measure flux through the autophagy pathway; thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from fully functional autophagy that includes delivery to, and degradation within, lysosomes (in most higher eukaryotes) or the vacuole (in plants and fungi). Here, we present a set of guidelines for the selection and interpretation of the methods that can be used by investigators who are attempting to examine macroautophagy and related processes, as well as by reviewers who need to provide realistic and reasonable critiques of papers that investigate these processes. This set of guidelines is not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to verify an autophagic response.
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