| 1. |
- Bonnet, Timothee, et al.
(författare)
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Genetic variance in fitness indicates rapid contemporary adaptive evolution in wild animals
- 2022
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 376:6596, s. 1012-1016
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Tidskriftsartikel (refereegranskat)abstract
- The rate of adaptive evolution, the contribution of selection to genetic changes that increase mean fitness, is determined by the additive genetic variance in individual relative fitness. To date, there are few robust estimates of this parameter for natural populations, and it is therefore unclear whether adaptive evolution can play a meaningful role in short-term population dynamics. We developed and applied quantitative genetic methods to long-term datasets from 19 wild bird and mammal populations and found that, while estimates vary between populations, additive genetic variance in relative fitness is often substantial and, on average, twice that of previous estimates. We show that these rates of contemporary adaptive evolution can affect population dynamics and hence that natural selection has the potential to partly mitigate effects of current environmental change.
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| 2. |
- Eggers, Kai M., 1962-, et al.
(författare)
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Diagnostic and prognostic performance of the ratio between high-sensitivity cardiac troponin I and troponin T in patients with chest pain
- 2022
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 17:11
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Tidskriftsartikel (refereegranskat)abstract
- Background Elevations of high-sensitivity cardiac troponin (hs-cTn) concentrations not related to type 1 myocardial infarction are common in chest pain patients presenting to emergency departments. The discrimination of these patients from those with type 1 myocardial infarction (MI) is challenging and resource-consuming. We aimed to investigate whether the hs-cTn I/T ratio might provide diagnostic and prognostic increment in this context.Methods We calculated the hs-cTn I/T ratio in 888 chest pain patients having hs-cTnI (Abbott Laboratories) or hs-cTnT (Roche Diagnostics) concentrations above the respective 99(th) percentile at 2 hours from presentation. All patients were followed for one year regarding mortality.Results The median hs-cTn I/T ratio was 3.45 (25(th), 75(th) percentiles 1.80-6.59) in type 1 MI patients (n = 408 (sic) 46.0%]), 1.18 (0.81-1.90) in type 2 MI patients (n = 56 (sic) 6.3%]) and 0.67 (0.39-1.12) in patients without MI. The hs-cTn I/T ratio provided good discrimination of type 1 MI from no type 1 MI (area under the receiver-operator characteristic curve 0.89 (sic) 95% confidence interval 0.86-0.91]), of type 1 MI from type 2 MI (area under the curve 0.81 (sic) 95% confidence interval 0.74-0.87]), and was associated with type 1 MI in adjusted analyses. The hs-cTn I/T ratio provided no consistent prognostic value.Conclusions The hs-cTn I/T ratio appears to be useful for early diagnosis of type 1 MI and its discrimination from type 2 MI in chest pain patients presenting with elevated hs-cTn. Differences in hs-cTn I/T ratio values may reflect variations in hs-cTn release mechanisms in response to different types of myocardial injury.
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| 3. |
- Eggers, Kai M., 1962-, et al.
(författare)
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Diagnostic and prognostic performance of the ratio between high-sensitivity cardiac troponin I and troponin T in patients with chest pain.
- 2022
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 17:11
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Tidskriftsartikel (refereegranskat)abstract
- Elevations of high-sensitivity cardiac troponin (hs-cTn) concentrations not related to type 1 myocardial infarction are common in chest pain patients presenting to emergency departments. The discrimination of these patients from those with type 1 myocardial infarction (MI) is challenging and resource-consuming. We aimed to investigate whether the hs-cTn I/T ratio might provide diagnostic and prognostic increment in this context.We calculated the hs-cTn I/T ratio in 888 chest pain patients having hs-cTnI (Abbott Laboratories) or hs-cTnT (Roche Diagnostics) concentrations above the respective 99th percentile at 2 hours from presentation. All patients were followed for one year regarding mortality.The median hs-cTn I/T ratio was 3.45 (25th, 75th percentiles 1.80-6.59) in type 1 MI patients (n = 408 ☯46.0%]), 1.18 (0.81-1.90) in type 2 MI patients (n = 56 ☯6.3%]) and 0.67 (0.39-1.12) in patients without MI. The hs-cTn I/T ratio provided good discrimination of type 1 MI from no type 1 MI (area under the receiver-operator characteristic curve 0.89 ☯95% confidence interval 0.86-0.91]), of type 1 MI from type 2 MI (area under the curve 0.81 ☯95% confidence interval 0.74-0.87]), and was associated with type 1 MI in adjusted analyses. The hs-cTn I/T ratio provided no consistent prognostic value.The hs-cTn I/T ratio appears to be useful for early diagnosis of type 1 MI and its discrimination from type 2 MI in chest pain patients presenting with elevated hs-cTn. Differences in hs-cTn I/T ratio values may reflect variations in hs-cTn release mechanisms in response to different types of myocardial injury.
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| 4. |
- Eichenlaub, Manuel, et al.
(författare)
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Comparator Data Characteristics and Testing Procedures for the Clinical Performance Evaluation of Continuous Glucose Monitoring Systems
- 2024
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Ingår i: Diabetes Technology & Therapeutics. - : Mary Ann Liebert. - 1520-9156 .- 1557-8593. ; 26:4, s. 263-275
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Tidskriftsartikel (refereegranskat)abstract
- Comparing the performance of different continuous glucose monitoring (CGM) systems is challenging due to the lack of comprehensive guidelines for clinical study design. In particular, the absence of concise requirements for the distribution of comparator (reference) blood glucose (BG) concentrations and their rate of change (RoC), that are used to evaluate CGM performance, impairs comparability. For this article, several experts in the field of CGM performance testing have collaborated to propose characteristics of the distribution of comparator measurements that should be collected during CGM performance testing. Specifically, it is proposed that at least 7.5% of comparator BG concentrations are <70 mg/dL (3.9 mmol/L) and >300 mg/dL (16.7 mmol/L), respectively and that at least 7.5% of BG-RoC combinations indicate fast BG changes with impending hypo- or hyperglycemia, respectively. These proposed characteristics of the comparator data can facilitate the harmonization of testing conditions across different studies and CGM systems and ensure that the most relevant scenarios representing real-life situations are established during performance testing. In addition, a study protocol and testing procedure for the manipulation of glucose levels is suggested that enables the collection of comparator data with these characteristics. This work is an important step towards establishing a future standard for the performance evaluation of CGM systems.
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| 5. |
- Hansson, Mari, et al.
(författare)
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On the Relationship between Molecular Hit Rates in High-Throughput Screening and Molecular Descriptors
- 2014
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Ingår i: Journal of Biomolecular Screening. - : Elsevier BV. - 1087-0571 .- 1552-454X. ; 19:5, s. 727-737
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Tidskriftsartikel (refereegranskat)abstract
- W High-throughput screening (HTS) is widely used in the pharmaceutical industry to identify novel chemical starting points for drug discovery projects. The current study focuses on the relationship between molecular hit rate in recent in-house HTS and four common molecular descriptors: lipophilicity (ClogP), size (heavy atom count, HEV), fraction of sp(3)-hybridized carbons (Fsp3), and fraction of molecular framework (f(MF)). The molecular hit rate is defined as the fraction of times the molecule has been assigned as active in the HTS campaigns where it has been screened. Beta-binomial statistical models were built to model the molecular hit rate as a function of these descriptors. The advantage of the beta-binomial statistical models is that the correlation between the descriptors is taken into account. Higher degree polynomial terms of the descriptors were also added into the beta-binomial statistic model to improve the model quality. The relative influence of different molecular descriptors on molecular hit rate has been estimated, taking into account that the descriptors are correlated to each other through applying beta-binomial statistical modeling. The results show that ClogP has the largest influence on the molecular hit rate, followed by Fsp3 and HEV. f(MF) has only a minor influence besides its correlation with the other molecular descriptors.
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| 6. |
- Masterson, Siobhán, et al.
(författare)
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Out-of-hospital cardiac arrest survival in international airports.
- 2018
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Ingår i: Resuscitation. - : Elsevier BV. - 0300-9572 .- 1873-1570. ; 127, s. 58-62
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The highest achievable survival rate following out-of-hospital cardiac arrest is unknown. Data from airports serving international destinations (international airports) provide the opportunity to evaluate the success of pre-hospital resuscitation in a relatively controlled but real-life environment.METHODS: This retrospective cohort study included all cases of out-of-hospital cardiac arrest at international airports with resuscitation attempted between January 1st, 2013 and December 31st, 2015. Crude incidence, patient, event characteristics and survival to hospital discharge/survival to 30 days (survival) were calculated. Mixed effect logistic regression analyses were performed to identify predictors of survival. Variability in survival between airports/countries was quantified using the median odds ratio.RESULTS: There were 800 cases identified, with an average of 40 per airport. Incidence was 0.024/100,000 passengers per year. Percentage survival for all patients was 32%, and 58% for patients with an initial shockable heart rhythm. In adjusted analyses, initial shockable heart rhythm was the strongest predictor of survival (odds ratio, 36.7; 95% confidence interval [CI], 15.5-87.0). In the bystander-witnessed subgroup, delivery of a defibrillation shock by a bystander was a strong predictor of survival (odds ratio 4.8; 95% CI, 3.0-7.8). Grouping of cases was significant at country level and survival varied between countries.CONCLUSIONS: In international airports, 32% of patients survived an out-of-hospital cardiac arrest, substantially more than in the general population. Our analysis suggested similarity between airports within countries, but differences between countries. Systematic data collection and reporting are essential to ensure international airports continually maximise activities to increase survival.
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| 7. |
- Neumann, Johannes Tobias, et al.
(författare)
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Personalized diagnosis in suspected myocardial infarction
- 2023
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Ingår i: Clinical Research in Cardiology. - : Springer. - 1861-0684 .- 1861-0692. ; 112, s. 1288-1301
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Tidskriftsartikel (refereegranskat)abstract
- Background: In suspected myocardial infarction (MI), guidelines recommend using high-sensitivity cardiac troponin (hscTn)- based approaches. These require fixed assay-specific thresholds and timepoints, without directly integrating clinical information. Using machine-learning techniques including hs-cTn and clinical routine variables, we aimed to build a digital tool to directly estimate the individual probability of MI, allowing for numerous hs-cTn assays.Methods: In 2,575 patients presenting to the emergency department with suspected MI, two ensembles of machine-learning models using single or serial concentrations of six different hs-cTn assays were derived to estimate the individual MI probability ( ARTEMIS model). Discriminative performance of the models was assessed using area under the receiver operating characteristic curve (AUC) and logLoss. Model performance was validated in an external cohort with 1688 patients and tested for global generalizability in 13 international cohorts with 23,411 patients.Results: Eleven routinely available variables including age, sex, cardiovascular risk factors, electrocardiography, and hs-cTn were included in the ARTEMIS models. In the validation and generalization cohorts, excellent discriminative performance was confirmed, superior to hs-cTn only. For the serial hs-cTn measurement model, AUC ranged from 0.92 to 0.98. Good calibration was observed. Using a single hs-cTn measurement, the ARTEMIS model allowed direct rule-out of MI with very high and similar safety but up to tripled efficiency compared to the guideline- recommended strategy.Conclusion We developed and validated diagnostic models to accurately estimate the individual probability of MI, which allow for variable hs-cTn use and flexible timing of resampling. Their digital application may provide rapid, safe and efficient personalized patient care.
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| 8. |
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| 9. |
- Pemberton, Hugh G., et al.
(författare)
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Automated quantitative MRI volumetry reports support diagnostic interpretation in dementia : a multi-rater, clinical accuracy study
- 2021
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Ingår i: European Radiology. - : Springer. - 0938-7994 .- 1432-1084. ; 31:7, s. 5312-5323
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Tidskriftsartikel (refereegranskat)abstract
- Objectives We examined whether providing a quantitative report (QReport) of regional brain volumes improves radiologists' accuracy and confidence in detecting volume loss, and in differentiating Alzheimer's disease (AD) and frontotemporal dementia (FTD), compared with visual assessment alone. Methods Our forced-choice multi-rater clinical accuracy study used MRI from 16 AD patients, 14 FTD patients, and 15 healthy controls; age range 52-81. Our QReport was presented to raters with regional grey matter volumes plotted as percentiles against data from a normative population (n = 461). Nine raters with varying radiological experience (3 each: consultants, registrars, 'non-clinical image analysts') assessed each case twice (with and without the QReport). Raters were blinded to clinical and demographic information; they classified scans as 'normal' or 'abnormal' and if 'abnormal' as 'AD' or 'FTD'. Results The QReport improved sensitivity for detecting volume loss and AD across all raters combined (p = 0.015* and p = 0.002*, respectively). Only the consultant group's accuracy increased significantly when using the QReport (p = 0.02*). Overall, raters' agreement (Cohen's kappa) with the 'gold standard' was not significantly affected by the QReport; only the consultant group improved significantly (kappa(s) 0.41 -> 0.55, p = 0.04*). Cronbach's alpha for interrater agreement improved from 0.886 to 0.925, corresponding to an improvement from 'good' to 'excellent'. Conclusion Our QReport referencing single-subject results to normative data alongside visual assessment improved sensitivity, accuracy, and interrater agreement for detecting volume loss. The QReport was most effective in the consultants, suggesting that experience is needed to fully benefit from the additional information provided by quantitative analyses.
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| 10. |
- Pickering, John W., et al.
(författare)
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Rapid Rule-out of Acute Myocardial Infarction With a Single High-Sensitivity Cardiac Troponin T Measurement Below the Limit of Detection A Collaborative Meta-analysis
- 2017
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Ingår i: Annals of Internal Medicine. - 0003-4819 .- 1539-3704. ; 166:10, s. 715-724
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Tidskriftsartikel (refereegranskat)abstract
- Background: High-sensitivity assays for cardiac troponin T (hs-cTnT) are sometimes used to rapidly rule out acute myocardial infarction (AMI). Purpose: To estimate the ability of a single hs-cTnT concentration below the limit of detection (<0.005 mu g/L) and a nonischemic electrocardiogram (ECG) to rule out AMI in adults presenting to the emergency department (ED) with chest pain. Data Sources: EMBASE and MEDLINE without language restrictions (1 January 2008 to 14 December 2016). Study Selection: Cohort studies involving adults presenting to the ED with possible acute coronary syndrome in whom an ECG and hs-cTnT measurements were obtained and AMI outcomes adjudicated during initial hospitalization. Data Extraction: Investigators of studies provided data on the number of low-risk patients (no new ischemia on ECG and hs-cTnT measurements <0.005 mu g/L) and the number who had AMI during hospitalization (primary outcome) or a major adverse cardiac event (MACE) or death within 30 days (secondary outcomes), by risk classification (low or not low risk). Two independent epidemiologists rated risk of bias of studies. Data Synthesis: Of 9241 patients in 11 cohort studies, 2825 (30.6%) were classified as low risk. Fourteen (0.5%) low-risk patients had AMI. Sensitivity of the risk classification for AMI ranged from 87.5% to 100% in individual studies. Pooled estimated sensitivity was 98.7% (95% CI, 96.6% to 99.5%). Sensitivity for 30-day MACEs ranged from 87.9% to 100%; pooled sensitivity was 98.0% (CI, 94.7% to 99.3%). No low-risk patients died. Limitation: Few studies, variation in timing and methods of reference standard troponin tests, and heterogeneity of risk and prevalence of AMI across studies. Conclusion: A single hs-cTnT concentration below the limit of detection in combination with a nonischemic ECG may successfully rule out AMI in patients presenting to EDs with possible emergency acute coronary syndrome.
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| 11. |
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| 12. |
- Skeoch, S., et al.
(författare)
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Imaging atherosclerosis in rheumatoid arthritis: evidence for increased prevalence, altered phenotype and a link between systemic and localised plaque inflammation
- 2017
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322 .- 2045-2322. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- In rheumatoid arthritis (RA), chronic inflammation is thought to drive increased cardiovascular risk through accelerated atherosclerosis. It may also lead to a more high-risk plaque phenotype. We sought to investigate carotid plaque phenotype in RA patients using Dynamic Contrast-Enhanced MRI (DCEMRI) and Fludeoxyglucose Positron Emission Tomography(FDG-PET). In this pilot study, RA patients and age/sex-matched controls were evaluated for cardiovascular risk factors and carotid plaque on ultrasound. Subjects with plaque >2 mm thick underwent DCE-MRI, and a subgroup of patients had FDG-PET. Comparison of MRI findings between groups and correlation between clinical, serological markers and imaging findings was undertaken. 130 patients and 62 controls were recruited. Plaque was more prevalent in the RA group (53.1% vs 37.0%, p = 0.038) and was independently associated with IL6 levels (HR[95% CI]: 2.03 [1.26, 3.26] per quartile). DCE-MRI data were available in 15 patients and 5 controls. Higher prevalence of plaque calcification was noted in RA, despite similar plaque size (73.3% vs 20%, p = 0.04). FDG-PET detected plaque inflammation in 12/13 patients scanned and degree of inflammation correlated with hs-CRP (r = 0.58, p = 0.04). This study confirms increased prevalence of atherosclerosis in RA and provides data to support the hypothesis that patients have a high-risk plaque phenotype.
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