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| 2. |
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| 3. |
- Ament, A, et al.
(författare)
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Cost-Effectiveness of Pneumococcal Vaccination of Older People: A Study in 5 Western European Countries
- 2000
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Ingår i: Clinical infectious diseases. - : The University of Chicago Press. - 1537-6591 .- 1058-4838. ; 31:2, s. 444-450
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Tidskriftsartikel (refereegranskat)abstract
- Pneumococcal vaccination of older persons is thought to be cost-effective in preventing pneumococcal pneumonia, but evidence of clinical protection is uncertain. Because there is better evidence of vaccination effectiveness against invasive pneumococcal disease, we determined the cost-effectiveness of pneumococcal vaccination of persons aged ≥65 years in preventing hospital admission for both invasive pneumococcal disease and pneumococcal pneumonia in 5 western European countries. In the base case analyses, the cost-effectiveness ratios for preventing invasive disease varied from ∼11,000 to ∼33,000 European currency units (ecu) per quality-adjusted life year (QALY). Assuming a common incidence (50 cases per 100,000) and mortality rate (20%-40%) for invasive disease, the cost-effectiveness ratios were <12,000 ecu per QALY in all 5 countries. For preventing pneumococcal pneumonia, vaccinating all elderly persons would be highly cost-effective to cost saving. Public health authorities should consider policies for encouraging pneumococcal vaccination for all persons aged ≥65 years.
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| 4. |
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| 5. |
- Allerbring, E. B., et al.
(författare)
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Unexpected T-cell recognition of an altered peptide ligand is driven by reversed thermodynamics
- 2012
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Ingår i: European Journal of Immunology. - : Wiley. - 0014-2980 .- 1521-4141. ; 42:11, s. 2990-3000
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Tidskriftsartikel (refereegranskat)abstract
- The molecular basis underlying T-cell recognition of MHC molecules presenting altered peptide ligands is still not wellestablished. A hierarchy of T-cell activation by MHC class I-restricted altered peptide ligands has been defined using the T-cell receptor P14 specific for H-2Db in complex with the immunodominant lymphocytic choriomeningitis virus peptide gp33 (KAVYNFATM). While substitution of tyrosine to phenylalanine (Y4F) or serine (Y4S) abolished recognition by P14, the TCR unexpectedly recognized H-2Db in complex with the alanine-substituted semiagonist Y4A, which displayed the most significant structural modification. The observed functional hierarchy gp33 > Y4A > Y4S = Y4F was neither due to higher stabilization capacity nor to differences in structural conformation. However, thermodynamic analysis demonstrated that while recognition of the full agonist H-2Db/gp33 was strictly enthalpy driven, recognition of the weak agonist H-2Db/Y4A was instead entropy driven with a large reduction in the favorable enthalpy term. The fourfold larger negative heat capacity derived for the interaction of P14 with H-2Db/gp33 compared with H-2Db/Y4A can possibly be explained by higher water entrapment at the TCR/MHC interface, which is also consistent with the measured opposite entropy contributions for the interactions of P14 with both MHCs. In conclusion, this study demonstrates that P14 makes use of different strategies to adapt to structural modifications in the MHC/peptide complex.
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| 6. |
- Cadrin-Tourigny, Julia, et al.
(författare)
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A new prediction model for ventricular arrhythmias in arrhythmogenic right ventricular cardiomyopathy
- 2019
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 1522-9645 .- 0195-668X. ; 40:23, s. 1850-1858
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVC) is characterized by ventricular arrhythmias (VAs) and sudden cardiac death (SCD). We aimed to develop a model for individualized prediction of incident VA/SCD in ARVC patients. METHODS AND RESULTS: Five hundred and twenty-eight patients with a definite diagnosis and no history of sustained VAs/SCD at baseline, aged 38.2 ± 15.5 years, 44.7% male, were enrolled from five registries in North America and Europe. Over 4.83 (interquartile range 2.44-9.33) years of follow-up, 146 (27.7%) experienced sustained VA, defined as SCD, aborted SCD, sustained ventricular tachycardia, or appropriate implantable cardioverter-defibrillator (ICD) therapy. A prediction model estimating annual VA risk was developed using Cox regression with internal validation. Eight potential predictors were pre-specified: age, sex, cardiac syncope in the prior 6 months, non-sustained ventricular tachycardia, number of premature ventricular complexes in 24 h, number of leads with T-wave inversion, and right and left ventricular ejection fractions (LVEFs). All except LVEF were retained in the final model. The model accurately distinguished patients with and without events, with an optimism-corrected C-index of 0.77 [95% confidence interval (CI) 0.73-0.81] and minimal over-optimism [calibration slope of 0.93 (95% CI 0.92-0.95)]. By decision curve analysis, the clinical benefit of the model was superior to a current consensus-based ICD placement algorithm with a 20.6% reduction of ICD placements with the same proportion of protected patients (P < 0.001). CONCLUSION: Using the largest cohort of patients with ARVC and no prior VA, a prediction model using readily available clinical parameters was devised to estimate VA risk and guide decisions regarding primary prevention ICDs (www.arvcrisk.com).
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| 7. |
- Cadrin-Tourigny, Julia, et al.
(författare)
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A new prediction model for ventricular arrhythmias in arrhythmogenic right ventricular cardiomyopathy
- 2022
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 43:32, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVC) is characterized by ventricular arrhythmias (VAs) and sudden cardiac death (SCD). We aimed to develop a model for individualized prediction of incident VA/SCD in ARVC patients. Methods and results: Five hundred and twenty-eight patients with a definite diagnosis and no history of sustained VAs/SCD at baseline, aged 38.2 ± 15.5 years, 44.7% male, were enrolled from five registries in North America and Europe. Over 4.83 (interquartile range 2.44-9.33) years of follow-up, 146 (27.7%) experienced sustained VA, defined as SCD, aborted SCD, sustained ventricular tachycardia, or appropriate implantable cardioverter-defibrillator (ICD) therapy. A prediction model estimating annual VA risk was developed using Cox regression with internal validation. Eight potential predictors were pre-specified: Age, sex, cardiac syncope in the prior 6 months, non-sustained ventricular tachycardia, number of premature ventricular complexes in 24 h, number of leads with T-wave inversion, and right and left ventricular ejection fractions (LVEFs). All except LVEF were retained in the final model. The model accurately distinguished patients with and without events, with an optimism-corrected C-index of 0.77 [95% confidence interval (CI) 0.73-0.81] and minimal over-optimism [calibration slope of 0.93 (95% CI 0.92-0.95)]. By decision curve analysis, the clinical benefit of the model was superior to a current consensus-based ICD placement algorithm with a 20.3% reduction of ICD placements with the same proportion of protected patients (P < 0.001). Conclusion: Using the largest cohort of patients with ARVC and no prior VA, a prediction model using readily available clinical parameters was devised to estimate VA risk and guide decisions regarding primary prevention ICDs (www.arvcrisk.com).
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| 8. |
- Cadrin-Tourigny, Julia, et al.
(författare)
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Sudden Cardiac Death Prediction in Arrhythmogenic Right Ventricular Cardiomyopathy : A Multinational Collaboration
- 2021
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Ingår i: Circulation: Arrhythmia and Electrophysiology. - : Lippincott Williams & Wilkins. - 1941-3149 .- 1941-3084. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is associated with ventricular arrhythmias (VA) and sudden cardiac death (SCD). A model was recently developed to predict incident sustained VA in patients with ARVC. However, since this outcome may overestimate the risk for SCD, we aimed to specifically predict life-threatening VA (LTVA) as a closer surrogate for SCD. Methods: We assembled a retrospective cohort of definite ARVC cases from 15 centers in North America and Europe. Association of 8 prespecified clinical predictors with LTVA (SCD, aborted SCD, sustained, or implantable cardioverter-defibrillator treated ventricular tachycardia >250 beats per minute) in follow-up was assessed by Cox regression with backward selection. Candidate variables included age, sex, prior sustained VA (≥30s, hemodynamically unstable, or implantable cardioverter-defibrillator treated ventricular tachycardia; or aborted SCD), syncope, 24-hour premature ventricular complexes count, the number of anterior and inferior leads with T-wave inversion, left and right ventricular ejection fraction. The resulting model was internally validated using bootstrapping. Results: A total of 864 patients with definite ARVC (40±16 years; 53% male) were included. Over 5.75 years (interquartile range, 2.77-10.58) of follow-up, 93 (10.8%) patients experienced LTVA including 15 with SCD/aborted SCD (1.7%). Of the 8 prespecified clinical predictors, only 4 (younger age, male sex, premature ventricular complex count, and number of leads with T-wave inversion) were associated with LTVA. Notably, prior sustained VA did not predict subsequent LTVA (P=0.850). A model including only these 4 predictors had an optimism-corrected C-index of 0.74 (95% CI, 0.69-0.80) and calibration slope of 0.95 (95% CI, 0.94-0.98) indicating minimal over-optimism. Conclusions: LTVA events in patients with ARVC can be predicted by a novel simple prediction model using only 4 clinical predictors. Prior sustained VA and the extent of functional heart disease are not associated with subsequent LTVA events.
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| 9. |
- Carrick, Richard T., et al.
(författare)
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Implantable cardioverter defibrillator use in arrhythmogenic right ventricular cardiomyopathy in North America and Europe
- 2024
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Ingår i: European Heart Journal. - : OXFORD UNIV PRESS. - 0195-668X .- 1522-9645.
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Tidskriftsartikel (refereegranskat)abstract
- Background and Aims Implantable cardioverter-defibrillators (ICDs) are critical for preventing sudden cardiac death (SCD) in arrhythmogenic right ventricular cardiomyopathy (ARVC). This study aims to identify cross-continental differences in utilization of primary prevention ICDs and survival free from sustained ventricular arrhythmia (VA) in ARVC.Methods This was a retrospective analysis of ARVC patients without prior VA enrolled in clinical registries from 11 countries throughout Europe and North America. Patients were classified according to whether they received treatment in North America or Europe and were further stratified by baseline predicted VA risk into low- (<10%/5 years), intermediate- (10%-25%/5 years), and high-risk (>25%/5 years) groups. Differences in ICD implantation and survival free from sustained VA events (including appropriate ICD therapy) were assessed.Results One thousand ninety-eight patients were followed for a median of 5.1 years; 554 (50.5%) received a primary prevention ICD, and 286 (26.0%) experienced a first VA event. After adjusting for baseline risk factors, North Americans were more than three times as likely to receive ICDs {hazard ratio (HR) 3.1 [95% confidence interval (CI) 2.5, 3.8]} but had only mildly increased risk for incident sustained VA [HR 1.4 (95% CI 1.1, 1.8)]. North Americans without ICDs were at higher risk for incident sustained VA [HR 2.1 (95% CI 1.3, 3.4)] than Europeans.Conclusions North American ARVC patients were substantially more likely than Europeans to receive primary prevention ICDs across all arrhythmic risk strata. A lower rate of ICD implantation in Europe was not associated with a higher rate of VA events in those without ICDs.
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| 10. |
- Andrews, David J., et al.
(författare)
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Oblique reflections in the Mars Express MARSIS data set : Stable density structures in the Martian ionosphere
- 2014
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Ingår i: Journal of Geophysical Research-Space Physics. - 2169-9380. ; 119:5, s. 3944-3960
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Tidskriftsartikel (refereegranskat)abstract
- The Mars Advanced Radar for Subsurface and Ionospheric Sounding (MARSIS) onboard the European Space Agency's Mars Express (MEX) spacecraft routinely detects evidence of localized plasma density structures in the Martian dayside ionosphere. Such structures, likely taking the form of spatially extended elevations in the plasma density at a given altitude, give rise to oblique reflections in the Active Ionospheric Sounder data. These structures are likely related to the highly varied Martian crustal magnetic field. In this study we use the polar orbit of MEX to investigate the repeatability of the ionospheric structures producing these anomalous reflections, examining data taken in sequences of multiple orbits which pass over the same regions of the Martian surface under similar solar illuminations, within intervals lasting tens of days. Presenting three such examples, or case studies, we show for the first time that these oblique reflections are often incredibly stable, indicating that the underlying ionospheric structures are reliably reformed in the same locations and with qualitatively similar parameters. The visibility, or lack thereof, of a given oblique reflection on a single orbit can generally be attributed to variations in the crustal field within the ionosphere along the spacecraft trajectory. We show that, within these examples, oblique reflections are generally detected whenever the spacecraft passes over regions of intense near-radial crustal magnetic fields (i.e., with a cusp-like configuration). The apparent stability of these structures is an important feature that must be accounted for in models of their origin.
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| 11. |
- Edberg, Niklas, et al.
(författare)
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Rosetta and Mars Express observations of the influence of high solar wind pressure on the Martian plasma environment
- 2009
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Ingår i: Annales Geophysicae. - : Copernicus GmbH. - 0992-7689 .- 1432-0576. ; 27:12, s. 4533-4545
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Tidskriftsartikel (refereegranskat)abstract
- We report on new simultaneous in-situ observations at Mars from Rosetta and Mars Express (MEX) on how the Martian plasma environment is affected by high pressure solar wind. A significant sharp increase in solar wind density, magnetic field strength and turbulence followed by a gradual increase in solar wind velocity is observed during similar to 24 h in the combined data set from both spacecraft after Rosetta's closest approach to Mars on 25 February 2007. The bow shock and magnetic pileup boundary are coincidently observed by MEX to become asymmetric in their shapes. The fortunate orbit of MEX at this time allows a study of the inbound boundary crossings on one side of the planet and the outbound crossings on almost the opposite side, both very close to the terminator plane. The solar wind and interplanetary magnetic field (IMF) downstream of Mars are monitored through simultaneous measurements provided by Rosetta. Possible explanations for the asymmetries are discussed, such as crustal magnetic fields and IMF direction. In the same interval, during the high solar wind pressure pulse, MEX observations show an increased amount of escaping planetary ions from the polar region of Mars. We link the high pressure solar wind with the observed simultaneous ion outflow and discuss how the pressure pulse could also be associated with the observed boundary shape asymmetry.
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| 12. |
- Sandoval-Castellanos, Edson, et al.
(författare)
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Ancient mitogenomes from Pre-Pottery Neolithic Central Anatolia and the effects of a Late Neolithic bottleneck in sheep (Ovis aries)
- 2024
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Ingår i: SCIENCE ADVANCES. - 2375-2548. ; 10:15
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Tidskriftsartikel (refereegranskat)abstract
- Occupied between similar to 10,300 and 9300 years ago, the Pre-Pottery Neolithic site of Asikli Hoyuk in Central Anatolia went through early phases of sheep domestication. Analysis of 629 mitochondrial genomes from this and numerous sites in Anatolia, southwest Asia, Europe, and Africa produced a phylogenetic tree with excessive coalescences (nodes) around the Neolithic, a potential signature of a domestication bottleneck. This is consistent with archeological evidence of sheep management at Asikli Hoyuk which transitioned from residential stabling to open pasturing over a millennium of site occupation. However, unexpectedly, we detected high genetic diversity throughout Asikli Hoyuk's occupation rather than a bottleneck. Instead, we detected a tenfold demographic bottleneck later in the Neolithic, which caused the fixation of mitochondrial haplogroup B in southwestern Anatolia. The mitochondrial genetic makeup that emerged was carried from the core region of early Neolithic sheep management into Europe and dominates the matrilineal diversity of both its ancient and the billion-strong modern sheep populations.
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| 15. |
- Opgenoorth, Hermann J., et al.
(författare)
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Mars ionospheric response to solar wind variability
- 2013
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Ingår i: Journal of Geophysical Research: Space Physics. - : American Geophysical Union (AGU). - 2169-9380. ; 118:10, s. 6558-6587
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Tidskriftsartikel (refereegranskat)abstract
- At planets with induced magnetospheres, the coupling between the ionosphere, the weak draped magnetosphere, and the solar wind is very direct in comparison to Earth. The weak induced magnetosphere itself is created by the prevailing Solar wind conditions and therefore in its shape and strength dynamically depending on it. In early 2010, Mars was located behind Earth in the Solar wind; thus, we can use coordinated data from multiple near-Earth spacecraft (Stereo, Wind) to evaluate what kind of Solar wind disturbances have passed by Earth and might consecutively hit Mars, and when. We employ plasma data from the ESA Mars-Express mission, the ASPERA-3 particle instrument, and the MARSIS Active Ionospheric Sounder (AIS) to investigate, for a number of isolated events in March and April 2010, how the ionosphere and the induced magnetosphere at Mars develop and decay in response to Solar wind variability in the magnetic field, density, and velocity. In a dedicated campaign mode, we use frequent long-duration MARSIS AIS operations for several consecutive orbits, to monitor for the first time the long-term development of the Martian plasma environment during solar wind disturbances. We find that the magnetosphere and ionosphere of Mars can become considerably compressed by solar wind dynamic pressure variations, which usually are also associated with changes in the magnetic draping of the interplanetary magnetic field around the planet. These are typically associated with corotating interaction regions and coronal mass ejections, and can last for several days. During such episodes of compression, we see signatures of increased plasma transport over the terminator and enhanced ion outflow from the upper atmosphere.
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| 19. |
- Sork, Helena, et al.
(författare)
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Lipid-based Transfection Reagents Exhibit Cryo-induced Increase in Transfection Efficiency
- 2016
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Ingår i: Molecular Therapy Nucleic Acids. - : Elsevier BV. - 2162-2531. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- The advantages of lipid-based transfection reagents have permitted their widespread use in molecular biology and gene therapy. This study outlines the effect of cryo-manipulation of a cationic lipid-based formulation, Lipofectamine 2000, which, after being frozen and thawed, showed orders of magnitude higher plasmid delivery efficiency throughout eight different cell lines, without compromising cell viability. Increased transfection efficiency with the freeze-thawed reagent was also seen with 2'-O-methyl phosphorothioate oligonucleotide delivery and in a splice-correction assay. Most importantly, a log-scale improvement in gene delivery using the freeze-thawed reagent was seen in vivo. Using three different methods, we detected considerable differences in the polydispersity of the different nucleic acid complexes as well as observed a clear difference in their surface spreading and sedimentation, with the freeze-thawed ones displaying substantially higher rate of dispersion and deposition on the glass surface. This hitherto overlooked elevated potency of the freeze-thawed reagent facilitates the targeting of hard-to-transfect cells, accomplishes higher transfection rates, and decreases the overall amount of reagent needed for delivery. Additionally, as we also saw a slight increase in plasmid delivery using other freeze-thawed transfection reagents, we postulate that freeze-thawing might prove to be useful for an even wider variety of transfection reagents.
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| 20. |
- Uttervall, K., et al.
(författare)
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The Use of Novel Drugs Can Effectively Improve Response, Delay Relapse and Enhance Overall Survival in Multiple Myeloma Patients with Renal Impairment
- 2014
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 9:7
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Tidskriftsartikel (refereegranskat)abstract
- Background: Renal impairment is a common feature in multiple myeloma and is considered a poor prognostic factor. Aim: To determine the impact of novel drugs (i.e. bortezomib, lenalidomide and thalidomide) in the treatment of myeloma patients with renal impairment. The primary endpoint was overall survival and secondary endpoints were time to next treatment and response. Methods: The study population included all patients diagnosed with treatment-demanding multiple myeloma January 2000 to June 2011 at 15 Swedish hospitals. Renal impairment was defined as an estimated glomerular filtration rate under 60 mL/min/1.73 m(2). Result: The study population consisted of 1538 patients, of which 680 had renal impairment at diagnosis. The median overall survival in patients with renal impairment was 33 months, which was significantly shorter than 52 months in patients with normal renal function (P<0.001). Novel agents in first line improved overall survival (median 60 months) in non-high-dose treated patients with renal impairment (n = 143) as compared to those treated with conventional cytotoxic drugs (n = 411) (median 27 months) (P<0.001). In the multivariate analysis up front treatment with bortezomib was an independent factor for better overall survival in non-high-dose treated renally impaired patients. High-dose treated renally impaired patients had significantly better median overall survival than non-high-dose ones (74 versus 26 months) and novel drugs did not significantly improve survival further in these patients. Patients with renal impairment had both a shorter median time to next treatment and a lower response rate than those with normal renal function. However, novel drugs and high dose treatment lead to a significantly longer time to next treatment and the use of novel agents significantly improved the response rate of these patients. Conclusion: High dose treatment and novel drugs, especially bortezomib, can effectively overcome the negative impact of renal impairment in patients with multiple myeloma.
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