| 1. |
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Overview of the JET results
- 2015
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In: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 55:10
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Journal article (peer-reviewed)
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| 2. |
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| 3. |
- Mishra, A, et al.
(author)
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Diminishing benefits of urban living for children and adolescents' growth and development
- 2023
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 615:7954, s. 874-883
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Journal article (peer-reviewed)abstract
- Optimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1–6. Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5–19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was <1.1 kg m–2 in the vast majority of countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified.
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| 4. |
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- 2019
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Journal article (peer-reviewed)
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| 5. |
- Clark, Andrew G., et al.
(author)
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Evolution of genes and genomes on the Drosophila phylogeny
- 2007
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 450:7167, s. 203-218
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Journal article (peer-reviewed)abstract
- Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.
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| 6. |
- Bentham, James, et al.
(author)
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A century of trends in adult human height
- 2016
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In: eLIFE. - 2050-084X. ; 5
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Journal article (peer-reviewed)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.522.7) and 16.5 cm (13.319.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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| 7. |
- Bentham, James, et al.
(author)
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A century of trends in adult human height
- 2016
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In: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 5
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Journal article (peer-reviewed)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3– 19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8– 144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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| 8. |
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| 9. |
- Lakens, Daniel, et al.
(author)
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Justify your alpha
- 2018
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In: Nature Human Behaviour. - : Nature Publishing Group. - 2397-3374. ; 2:3, s. 168-171
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Journal article (peer-reviewed)abstract
- In response to recommendations to redefine statistical significance to P ≤ 0.005, we propose that researchers should transparently report and justify all choices they make when designing a study, including the alpha level.
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| 10. |
- Culina, Antica, et al.
(author)
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Connecting the data landscape of long-term ecological studies : The SPI-Birds data hub
- 2021
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In: Journal of Animal Ecology. - : John Wiley & Sons. - 0021-8790 .- 1365-2656. ; 90:9, s. 2147-2160
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Journal article (peer-reviewed)abstract
- The integration and synthesis of the data in different areas of science is drastically slowed and hindered by a lack of standards and networking programmes. Long-term studies of individually marked animals are not an exception. These studies are especially important as instrumental for understanding evolutionary and ecological processes in the wild. Furthermore, their number and global distribution provides a unique opportunity to assess the generality of patterns and to address broad-scale global issues (e.g. climate change). To solve data integration issues and enable a new scale of ecological and evolutionary research based on long-term studies of birds, we have created the SPI-Birds Network and Database ()-a large-scale initiative that connects data from, and researchers working on, studies of wild populations of individually recognizable (usually ringed) birds. Within year and a half since the establishment, SPI-Birds has recruited over 120 members, and currently hosts data on almost 1.5 million individual birds collected in 80 populations over 2,000 cumulative years, and counting. SPI-Birds acts as a data hub and a catalogue of studied populations. It prevents data loss, secures easy data finding, use and integration and thus facilitates collaboration and synthesis. We provide community-derived data and meta-data standards and improve data integrity guided by the principles of Findable, Accessible, Interoperable and Reusable (FAIR), and aligned with the existing metadata languages (e.g. ecological meta-data language). The encouraging community involvement stems from SPI-Bird's decentralized approach: research groups retain full control over data use and their way of data management, while SPI-Birds creates tailored pipelines to convert each unique data format into a standard format. We outline the lessons learned, so that other communities (e.g. those working on other taxa) can adapt our successful model. Creating community-specific hubs (such as ours, COMADRE for animal demography, etc.) will aid much-needed large-scale ecological data integration.
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| 11. |
- Danaei, Goodarz, et al.
(author)
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Effects of diabetes definition on global surveillance of diabetes prevalence and diagnosis: a pooled analysis of 96 population-based studies with 331288 participants
- 2015
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In: The Lancet Diabetes & Endocrinology. - 2213-8595 .- 2213-8587. ; 3:8, s. 624-637
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Journal article (peer-reviewed)abstract
- Background Diabetes has been defined on the basis of different biomarkers, including fasting plasma glucose (FPG), 2-h plasma glucose in an oral glucose tolerance test (2hOGTT), and HbA(1c). We assessed the effect of different diagnostic definitions on both the population prevalence of diabetes and the classification of previously undiagnosed individuals as having diabetes versus not having diabetes in a pooled analysis of data from population-based health examination surveys in different regions. Methods We used data from 96 population-based health examination surveys that had measured at least two of the biomarkers used for defining diabetes. Diabetes was defined using HbA(1c) (HbA(1c) >= 6 . 5% or history of diabetes diagnosis or using insulin or oral hypoglycaemic drugs) compared with either FPG only or FPG-or-2hOGTT definitions (FPG >= 7 . 0 mmol/L or 2hOGTT >= 11 . 1 mmol/L or history of diabetes or using insulin or oral hypoglycaemic drugs). We calculated diabetes prevalence, taking into account complex survey design and survey sample weights. We compared the prevalences of diabetes using different definitions graphically and by regression analyses. We calculated sensitivity and specificity of diabetes diagnosis based on HbA1c compared with diagnosis based on glucose among previously undiagnosed individuals (ie, excluding those with history of diabetes or using insulin or oral hypoglycaemic drugs). We calculated sensitivity and specificity in each survey, and then pooled results using a random-effects model. We assessed the sources of heterogeneity of sensitivity by meta-regressions for study characteristics selected a priori. Findings Population prevalence of diabetes based on FPG- or-2hOGTT was correlated with prevalence based on FPG alone (r= 0 . 98), but was higher by 2-6 percentage points at different prevalence levels. Prevalence based on HbA(1c) was lower than prevalence based on FPG in 42 . 8% of age-sex-survey groups and higher in another 41 . 6%; in the other 15 . 6%, the two definitions provided similar prevalence estimates. The variation across studies in the relation between glucose-based and HbA(1c)-based prevalences was partly related to participants' age, followed by natural logarithm of per person gross domestic product, the year of survey, mean BMI, and whether the survey population was national, subnational, or from specific communities. Diabetes defined as HbA(1c) 6 . 5% or more had a pooled sensitivity of 52 . 8% (95% CI 51 . 3-54 . 3%) and a pooled specificity of 99 . 74% (99 . 71-99 . 78%) compared with FPG 7 . 0 mmol/L or more for diagnosing previously undiagnosed participants; sensitivity compared with diabetes defined based on FPG-or-2hOGTT was 30 . 5% (28 . 7-32 . 3%). None of the preselected study-level characteristics explained the heterogeneity in the sensitivity of HbA(1c) versus FPG. Interpretation Different biomarkers and definitions for diabetes can provide different estimates of population prevalence of diabetes, and differentially identify people without previous diagnosis as having diabetes. Using an HbA(1c)-based definition alone in health surveys will not identify a substantial proportion of previously undiagnosed people who would be considered as having diabetes using a glucose-based test.
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| 12. |
- Patel, Riyaz S., et al.
(author)
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Association of Chromosome 9p21 With Subsequent Coronary Heart Disease Events : A GENIUS-CHD Study of Individual Participant Data
- 2019
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In: Circulation. - 2574-8300. ; 12:4
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Journal article (peer-reviewed)abstract
- BACKGROUND: Genetic variation at chromosome 9p21 is a recognized risk factor for coronary heart disease (CHD). However, its effect on disease progression and subsequent events is unclear, raising questions about its value for stratification of residual risk.METHODS: A variant at chromosome 9p21 (rs1333049) was tested for association with subsequent events during follow-up in 103 357 Europeans with established CHD at baseline from the GENIUS-CHD (Genetics of Subsequent Coronary Heart Disease) Consortium (73.1% male, mean age 62.9 years). The primary outcome, subsequent CHD death or myocardial infarction (CHD death/myocardial infarction), occurred in 13 040 of the 93 115 participants with available outcome data. Effect estimates were compared with case/control risk obtained from the CARDIoGRAMplusC4D consortium (Coronary Artery Disease Genome-wide Replication and Meta-analysis [CARDIoGRAM] plus The Coronary Artery Disease [C4D] Genetics) including 47 222 CHD cases and 122 264 controls free of CHD.RESULTS: Meta-analyses revealed no significant association between chromosome 9p21 and the primary outcome of CHD death/myocardial infarction among those with established CHD at baseline (GENIUSCHD odds ratio, 1.02; 95% CI, 0.99-1.05). This contrasted with a strong association in CARDIoGRAMPlusC4D odds ratio 1.20; 95% CI, 1.18-1.22; P for interaction < 0.001 compared with the GENIUS-CHD estimate. Similarly, no clear associations were identified for additional subsequent outcomes, including all-cause death, although we found a modest positive association between chromosome 9p21 and subsequent revascularization (odds ratio, 1.07; 95% CI, 1.04-1.09).CONCLUSIONS: In contrast to studies comparing individuals with CHD to disease-free controls, we found no clear association between genetic variation at chromosome 9p21 and risk of subsequent acute CHD events when all individuals had CHD at baseline. However, the association with subsequent revascularization may support the postulated mechanism of chromosome 9p21 for promoting atheroma development.
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| 13. |
- Patel, Riyaz S., et al.
(author)
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Subsequent Event Risk in Individuals With Established Coronary Heart Disease : Design and Rationale of the GENIUS-CHD Consortium
- 2019
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In: Circulation. - 2574-8300. ; 12:4
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Journal article (peer-reviewed)abstract
- BACKGROUND: The Genetics of Subsequent Coronary Heart Disease (GENIUS-CHD) consortium was established to facilitate discovery and validation of genetic variants and biomarkers for risk of subsequent CHD events, in individuals with established CHD.METHODS: The consortium currently includes 57 studies from 18 countries, recruiting 185 614 participants with either acute coronary syndrome, stable CHD, or a mixture of both at baseline. All studies collected biological samples and followed-up study participants prospectively for subsequent events.RESULTS: Enrollment into the individual studies took place between 1985 to present day with a duration of follow-up ranging from 9 months to 15 years. Within each study, participants with CHD are predominantly of self-reported European descent (38%-100%), mostly male (44%-91%) with mean ages at recruitment ranging from 40 to 75 years. Initial feasibility analyses, using a federated analysis approach, yielded expected associations between age (hazard ratio, 1.15; 95% CI, 1.14-1.16) per 5-year increase, male sex (hazard ratio, 1.17; 95% CI, 1.13-1.21) and smoking (hazard ratio, 1.43; 95% CI, 1.35-1.51) with risk of subsequent CHD death or myocardial infarction and differing associations with other individual and composite cardiovascular endpoints.CONCLUSIONS: GENIUS-CHD is a global collaboration seeking to elucidate genetic and nongenetic determinants of subsequent event risk in individuals with established CHD, to improve residual risk prediction and identify novel drug targets for secondary prevention. Initial analyses demonstrate the feasibility and reliability of a federated analysis approach. The consortium now plans to initiate and test novel hypotheses as well as supporting replication and validation analyses for other investigators.
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| 14. |
- Vallée, Tanja C, et al.
(author)
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Wiskott-Aldrich Syndrome: A study on 577 patients defining the genotype as a predictive biomarker for disease severity.
- 2024
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In: Blood. - 1528-0020.
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Journal article (peer-reviewed)abstract
- WAS is a multifaceted monogenic disorder with a broad disease spectrum and variable disease severity and a variety of treatment options including allogeneic hematopoietic stem cell transplantation (HSCT) and gene therapy (GT). No reliable biomarker exists to predict disease course and outcome for individual patients. A total of 577 patients with a WAS variant from 26 countries and a median follow-up of 8.9 years (0.3-71.1), totaling 6118 patient-years, were included in this international retrospective study. Overall survival (OS) of the cohort (censored at HSCT or GT) was 82% (95% CI 78-87) at 15 years and 70% (61-80) at 30 years of age. The type of variant was predictive of outcome: patients with a missense variant in exons 1 or 2 or with the intronic hotspot variant c.559+5G>A (class I variants) had a 15-year OS of 93% (89-98) and a 30-year OS of 91% (86-97), compared to 71% (62-81) and 48% (34-68) in patients with any other variant (class II; p<0.0001). The cumulative incidence rates of disease-related complications such as severe bleeding (p=0.007), life-threatening infection (p<0.0001), and autoimmunity (p=0.004) occurred significantly later in patients with a class I variant. The cumulative incidence of malignancy (p=0.6) was not different between classes I and II. This study represents the largest cohort of WAS patients studied so far. It confirms the spectrum of disease severity and quantifies the risk for specific disease-related complications. The class of variant is a biomarker to predict the outcome for WAS patients.
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| 15. |
- Zhou, Bin, et al.
(author)
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Worldwide trends in diabetes since 1980: A pooled analysis of 751 population-based studies with 4.4 million participants
- 2016
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In: The Lancet. - : Elsevier B.V.. - 0140-6736 .- 1474-547X. ; 387:10027, s. 1513-1530
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Journal article (peer-reviewed)abstract
- Background: One of the global targets for non-communicable diseases is to halt, by 2025, the rise in the age standardised adult prevalence of diabetes at its 2010 levels. We aimed to estimate worldwide trends in diabetes, how likely it is for countries to achieve the global target, and how changes in prevalence, together with population growth and ageing, are aff ecting the number of adults with diabetes.Methods: We pooled data from population-based studies that had collected data on diabetes through measurement of its biomarkers. We used a Bayesian hierarchical model to estimate trends in diabetes prevalence-defined as fasting plasma glucose of 7.0 mmol/L or higher, or history of diagnosis with diabetes, or use of insulin or oral hypoglycaemic drugs-in 200 countries and territories in 21 regions, by sex and from 1980 to 2014. We also calculated the posterior probability of meeting the global diabetes target if post-2000 trends continue.Findings: We used data from 751 studies including 4372000 adults from 146 of the 200 countries we make estimates for. Global age-standardised diabetes prevalence increased from 4.3% (95% credible interval 2.4-17.0) in 1980 to 9.0% (7.2-11.1) in 2014 in men, and from 5.0% (2.9-7.9) to 7.9% (6.4-9.7) in women. The number of adults with diabetes in the world increased from 108 million in 1980 to 422 million in 2014 (28.5% due to the rise in prevalence, 39.7% due to population growth and ageing, and 31.8% due to interaction of these two factors). Age-standardised adult diabetes prevalence in 2014 was lowest in northwestern Europe, and highest in Polynesia and Micronesia, at nearly 25%, followed by Melanesia and the Middle East and north Africa. Between 1980 and 2014 there was little change in age-standardised diabetes prevalence in adult women in continental western Europe, although crude prevalence rose because of ageing of the population. By contrast, age-standardised adult prevalence rose by 15 percentage points in men and women in Polynesia and Micronesia. In 2014, American Samoa had the highest national prevalence of diabetes (>30% in both sexes), with age-standardised adult prevalence also higher than 25% in some other islands in Polynesia and Micronesia. If post-2000 trends continue, the probability of meeting the global target of halting the rise in the prevalence of diabetes by 2025 at the 2010 level worldwide is lower than 1% for men and is 1% for women. Only nine countries for men and 29 countries for women, mostly in western Europe, have a 50% or higher probability of meeting the global target.Interpretation: Since 1980, age-standardised diabetes prevalence in adults has increased, or at best remained unchanged, in every country. Together with population growth and ageing, this rise has led to a near quadrupling of the number of adults with diabetes worldwide. The burden of diabetes, both in terms of prevalence and number of adults aff ected, has increased faster in low-income and middle-income countries than in high-income countries.
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| 16. |
- Abbassi, Fariba, et al.
(author)
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Novel Benchmark Values for Redo Liver Transplantation Does the Outcome Justify the Effort?
- 2022
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In: Annals of Surgery. - : Lippincott Williams & Wilkins. - 0003-4932 .- 1528-1140. ; 276:5, s. 860-867
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Journal article (peer-reviewed)abstract
- Objective: To define benchmark cutoffs for redo liver transplantation (redo-LT). Background: In the era of organ shortage, redo-LT is frequently discussed in terms of expected poor outcome and wasteful resources. However, there is a lack of benchmark data to reliably evaluate outcomes after redo-LT. Methods: We collected data on redo-LT between January 2010 and December 2018 from 22 high-volume transplant centers. Benchmark cases were defined as recipients with model of end stage liver disease (MELD) score <= 25, absence of portal vein thrombosis, no mechanical ventilation at the time of surgery, receiving a graft from a donor after brain death. Also, high-urgent priority and early redo-LT including those for primary nonfunction (PNF) or hepatic artery thrombosis were excluded. Benchmark cutoffs were derived from the 75th percentile of the medians of all benchmark centers. Results: Of 1110 redo-LT, 373 (34%) cases qualified as benchmark cases. Among these cases, the rate of postoperative complications until discharge was 76%, and increased up to 87% at 1-year, respectively. One-year overall survival rate was excellent with 90%. Benchmark cutoffs included Comprehensive Complication Index CCI (R) at 1-year of <= 72, and in-hospital and 1-year mortality rates of <= 13% and <= 15%, respectively. In contrast, patients who received a redo-LT for PNF showed worse outcomes with some values dramatically outside the redoLT benchmarks. Conclusion: This study shows that redo-LT achieves good outcome when looking at benchmark scenarios. However, this figure changes in high-risk redo-LT, as for example in PNF. This analysis objectifies for the first-time results and efforts for redo-LT and can serve as a basis for discussion about the use of scarce resources.
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| 17. |
- Friedlein, Rainer, et al.
(author)
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Electronic structure of highly ordered films of self-assembled graphitic nanocolumns
- 2003
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In: Physical Review B. Condensed Matter and Materials Physics. - 1098-0121 .- 1550-235X. ; 68:19, s. 195414-
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Journal article (peer-reviewed)abstract
- Highly ordered, several nanometers thick films of alkylated large planar, polycyclic aromatic hydrocarbon (PAH) molecules have been grown on semi-metallic molybdenum disulfide substrates. The films are characterized by a two-dimensional lateral arrangement of columns standing at the surface on a macroscopic scale. The self-assembly of such insulated columns of face-to-face disks with surface-induced vertical alignment has been achieved directly from solution processing. Angle-resolved photoelectron spectra revealed a highly anisotropic quasi-one-dimensional electronic structure with an extended π-electronic wave function. An intermolecular dispersion of the highest occupied band of at least 0.15 eV along the stacking direction has been measured. A partial breakdown of the concept of quasimomentum due to the finite size of the nano-objects perpendicular to the stacks is observed.
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| 18. |
- Lambrechts, Marcel M., et al.
(author)
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The design of artificial nestboxes for the study of secondary hole-nesting birds: a review of methodological inconsistencies and potential biases
- 2010
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In: Acta Ornithologica. - 0001-6454 .- 1734-8471. ; 45:1, s. 1-26
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Journal article (peer-reviewed)abstract
- The widespread use of artificial nestboxes has led to significant advances in our knowledge of the ecology, behaviour and physiology of cavity nesting birds, especially small passerines Nestboxes have made it easier to perform routine monitoring and experimental manipulation of eggs or nestlings, and also repeatedly to capture, identify and manipulate the parents However, when comparing results across study sites the use of nestboxes may also Introduce a potentially significant confounding variable in the form of differences in nestbox design amongst studies, such as their physical dimensions, placement height, and the way in which they are constructed and maintained However, the use of nestboxes may also introduce an unconsidered and potentially significant confounding variable clue to differences in nestbox design amongst studies, such as their physical dimensions, placement height, and the way in which they are constructed and maintained Here we review to what extent the characteristics of artificial nestboxes (e g size, shape, construction material, colour) are documented in the 'methods' sections of publications involving hole-nesting passerine birds using natural or excavated cavities or artificial nestboxes for reproduction and roosting Despite explicit previous recommendations that authors describe in detail the characteristics of the nestboxes used, we found that the description of nestbox characteristics in most recent publications remains poor and insufficient We therefore list the types of descriptive data that should be included in the methods sections of relevant manuscripts and justify this by discussing how variation in nestbox characteristics can affect or confound conclusions from nestbox studies We also propose several recommendations to improve the reliability and usefulness of research based on long-term studies of any secondary hole-nesting species using artificial nestboxes for breeding or roosting.
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| 19. |
- Mahmoodi, Bakhtawar K., et al.
(author)
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Association of Factor V Leiden With Subsequent Atherothrombotic Events A GENIUS-CHD Study of Individual Participant Data
- 2020
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In: Circulation. - : Ovid Technologies (Wolters Kluwer Health). - 0009-7322 .- 1524-4539. ; 142:6, s. 546-555
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Journal article (peer-reviewed)abstract
- Background: Studies examining the role of factor V Leiden among patients at higher risk of atherothrombotic events, such as those with established coronary heart disease (CHD), are lacking. Given that coagulation is involved in the thrombus formation stage on atherosclerotic plaque rupture, we hypothesized that factor V Leiden may be a stronger risk factor for atherothrombotic events in patients with established CHD.Methods: We performed an individual-level meta-analysis including 25 prospective studies (18 cohorts, 3 case-cohorts, 4 randomized trials) from the GENIUS-CHD (Genetics of Subsequent Coronary Heart Disease) consortium involving patients with established CHD at baseline. Participating studies genotyped factor V Leiden status and shared risk estimates for the outcomes of interest using a centrally developed statistical code with harmonized definitions across studies. Cox proportional hazards regression models were used to obtain age- and sex-adjusted estimates. The obtained estimates were pooled using fixed-effect meta-analysis. The primary outcome was composite of myocardial infarction and CHD death. Secondary outcomes included any stroke, ischemic stroke, coronary revascularization, cardiovascular mortality, and all-cause mortality.Results: The studies included 69 681 individuals of whom 3190 (4.6%) were either heterozygous or homozygous (n=47) carriers of factor V Leiden. Median follow-up per study ranged from 1.0 to 10.6 years. A total of 20 studies with 61 147 participants and 6849 events contributed to analyses of the primary outcome. Factor V Leiden was not associated with the combined outcome of myocardial infarction and CHD death (hazard ratio, 1.03 [95% CI, 0.92-1.16];I-2=28%;P-heterogeneity=0.12). Subgroup analysis according to baseline characteristics or strata of traditional cardiovascular risk factors did not show relevant differences. Similarly, risk estimates for the secondary outcomes including stroke, coronary revascularization, cardiovascular mortality, and all-cause mortality were also close to identity.Conclusions: Factor V Leiden was not associated with increased risk of subsequent atherothrombotic events and mortality in high-risk participants with established and treated CHD. Routine assessment of factor V Leiden status is unlikely to improve atherothrombotic events risk stratification in this population.
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| 20. |
- Osikowicz, Wojciech, et al.
(author)
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A joint theoretical and experimental study on the electronic properties of phenyl-capped 3,4-ethylenedioxythiophene oligomers
- 2003
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In: Journal of Chemical Physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 119:19, s. 10415-10420
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Journal article (peer-reviewed)abstract
- The electronic structure of a series of phenyl-capped EDOT oligomers was studied using ultraviolet photoelectron spectroscopy, in combination with quantum-chemical methods. The bulk IP of the neutral PEDOT polymer was estimated to be 4.2 eV. The frontier band structue was predicted from the evolution of the spectral features in the studied series of oligomers.
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| 21. |
- Stankowska, Wiktoria, et al.
(author)
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Tumor Predisposing Post-Zygotic Chromosomal Alterations in Bladder Cancer-Insights from Histologically Normal Urothelium
- 2024
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In: Cancers. - : MDPI. - 2072-6694. ; 16:5
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Journal article (peer-reviewed)abstract
- Bladder urothelial carcinoma (BLCA) is the 10th most common cancer with a low survival rate and strong male bias. We studied the field cancerization in BLCA using multi-sample- and multi-tissue-per-patient protocol for sensitive detection of autosomal post-zygotic chromosomal alterations and loss of chromosome Y (LOY). We analysed 277 samples of histologically normal urothelium, 145 tumors and 63 blood samples from 52 males and 15 females, using the in-house adapted Mosaic Chromosomal Alterations (MoChA) pipeline. This approach allows identification of the early aberrations in urothelium from BLCA patients. Overall, 45% of patients exhibited at least one alteration in at least one normal urothelium sample. Recurrence analysis resulted in 16 hotspots composed of either gains and copy number neutral loss of heterozygosity (CN-LOH) or deletions and CN-LOH, encompassing well-known and new BLCA cancer driver genes. Conservative assessment of LOY showed 29%, 27% and 18% of LOY-cells in tumors, blood and normal urothelium, respectively. We provide a proof of principle that our approach can characterize the earliest alterations preconditioning normal urothelium to BLCA development. Frequent LOY in blood and urothelium-derived tissues suggest its involvement in BLCA.
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| 22. |
- Ahrendt, Wolfgang, 1967, et al.
(author)
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The KeY platform for verification and analysis of java programs
- 2014
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In: Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics). - Cham : Springer International Publishing. - 1611-3349 .- 0302-9743. ; 8471:8471, s. 55-71
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Conference paper (peer-reviewed)abstract
- The KeY system offers a platform of software analysis tools for sequential Java. Foremost, this includes full functional verification against contracts written in the Java Modeling Language. But the approach is general enough to provide a basis for other methods and purposes: (i) complementary validation techniques to formal verification such as testing and debugging, (ii) methods that reduce the complexity of verification such as modularization and abstract interpretation, (iii) analyses of non-functional properties such as information flowsecurity, and (iv) sound program transformation and code generation. We show that deductive technology that has been developed for full functional verification can be used as a basis and framework for other purposes than pure functional verification. We use the current release of the KeY system as an example to explain and prove this claim.
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| 23. |
- Anzt, Hartwig, et al.
(author)
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An environment for sustainable research software in Germany and beyond: current state, open challenges, and call for action
- 2020
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In: F1000 Research. - : F1000 Research Ltd. - 2046-1402. ; 9
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Journal article (peer-reviewed)abstract
- Research software has become a central asset in academic research. It optimizes existing and enables new research methods, implements and embeds research knowledge, and constitutes an essential research product in itself. Research software must be sustainable in order to understand, replicate, reproduce, and build upon existing research or conduct new research effectively. In other words, software must be available, discoverable, usable, and adaptable to new needs, both now and in the future. Research software therefore requires an environment that supports sustainability. Hence, a change is needed in the way research software development and maintenance are currently motivated, incentivized, funded, structurally and infrastructurally supported, and legally treated. Failing to do so will threaten the quality and validity of research. In this paper, we identify challenges for research software sustainability in Germany and beyond, in terms of motivation, selection, research software engineering personnel, funding, infrastructure, and legal aspects. Besides researchers, we specifically address political and academic decision-makers to increase awareness of the importance and needs of sustainable research software practices. In particular, we recommend strategies and measures to create an environment for sustainable research software, with the ultimate goal to ensure that software-driven research is valid, reproducible and sustainable, and that software is recognized as a first class citizen in research. This paper is the outcome of two workshops run in Germany in 2019, at deRSE19 - the first International Conference of Research Software Engineers in Germany - and a dedicated DFG-supported follow-up workshop in Berlin.
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| 24. |
- Balakrishnan, Anita, et al.
(author)
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Delivery of hepato-pancreato-biliary surgery during the COVID-19 pandemic : an European-African Hepato-Pancreato-Biliary Association (E-AHPBA) cross-sectional survey
- 2020
-
In: HPB. - : Elsevier BV. - 1365-182X. ; 22:8, s. 1128-1134
-
Journal article (peer-reviewed)abstract
- Background: The extent of the COVID-19 pandemic and the resulting response has varied globally. The European and African Hepato-Pancreato-Biliary Association (E-AHPBA), the premier representative body for practicing HPB surgeons in Europe and Africa, conducted this survey to assess the impact of COVID-19 on HPB surgery. Methods: An online survey was disseminated to all E-AHPBA members to assess the effects of the pandemic on unit capacity, management of HPB cancers, use of COVID-19 screening and other aspects of service delivery. Results: Overall, 145 (25%) members responded. Most units, particularly in COVID-high countries (>100,000 cases) reported insufficient critical care capacity and reduced HPB operating sessions compared to COVID-low countries. Delayed access to cancer surgery necessitated alternatives including increased neoadjuvant chemotherapy for pancreatic cancer and colorectal liver metastases, and locoregional treatments for hepatocellular carcinoma. Other aspects of service delivery including COVID-19 screening and personal protective equipment varied between units and countries. Conclusion: This study demonstrates that the COVID-19 pandemic has had a profound adverse impact on the delivery of HPB cancer care across the continents of Europe and Africa. The findings illustrate the need for safe resumption of cancer surgery in a “new” normal world with screening of patients and staff for COVID-19.
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| 25. |
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| 26. |
- Blomgren, Mats, et al.
(author)
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Idempotent transformations of finite groups
- 2013
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In: Advances in Mathematics. - : Elsevier BV. - 0001-8708 .- 1090-2082. ; 233:1, s. 56-86
-
Journal article (peer-reviewed)abstract
- We describe the action of idempotent transformations on finite groups. We show that finiteness is preserved by such transformations and enumerate all possible values such transformations can assign to a fixed finite simple group. This is done in terms of the first two homology groups. We prove for example that except special linear groups, such an orbit can have at most 7 elements. We also study the action of monomials of idempotent transformations on finite groups and show for example that orbits of this action are always finite.
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| 27. |
- Brunner, Fabian J., et al.
(author)
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Application of non-HDL cholesterol for population-based cardiovascular risk stratification : results from the Multinational Cardiovascular Risk Consortium
- 2019
-
In: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 394:10215, s. 2173-2183
-
Journal article (peer-reviewed)abstract
- Background: The relevance of blood lipid concentrations to long-term incidence of cardiovascular disease and the relevance of lipid-lowering therapy for cardiovascular disease outcomes is unclear. We investigated the cardiovascular disease risk associated with the full spectrum of bloodstream non-HDL cholesterol concentrations. We also created an easy-to-use tool to estimate the long-term probabilities for a cardiovascular disease event associated with non-HDL cholesterol and modelled its risk reduction by lipid-lowering treatment.Methods: In this risk-evaluation and risk-modelling study, we used Multinational Cardiovascular Risk Consortium data from 19 countries across Europe, Australia, and North America. Individuals without prevalent cardiovascular disease at baseline and with robust available data on cardiovascular disease outcomes were included. The primary composite endpoint of atherosclerotic cardiovascular disease was defined as the occurrence of the coronary heart disease event or ischaemic stroke. Sex-specific multivariable analyses were computed using non-HDL cholesterol categories according to the European guideline thresholds, adjusted for age, sex, cohort, and classical modifiable cardiovascular risk factors. In a derivation and validation design, we created a tool to estimate the probabilities of a cardiovascular disease event by the age of 75 years, dependent on age, sex, and risk factors, and the associated modelled risk reduction, assuming a 50% reduction of non-HDL cholesterol.Findings: Of the 524 444 individuals in the 44 cohorts in the Consortium database, we identified 398 846 individuals belonging to 38 cohorts (184 055 [48·7%] women; median age 51·0 years [IQR 40·7–59·7]). 199 415 individuals were included in the derivation cohort (91 786 [48·4%] women) and 199 431 (92 269 [49·1%] women) in the validation cohort. During a maximum follow-up of 43·6 years (median 13·5 years, IQR 7·0–20·1), 54 542 cardiovascular endpoints occurred. Incidence curve analyses showed progressively higher 30-year cardiovascular disease event-rates for increasing non-HDL cholesterol categories (from 7·7% for non-HDL cholesterol <2·6 mmol/L to 33·7% for ≥5·7 mmol/L in women and from 12·8% to 43·6% in men; p<0·0001). Multivariable adjusted Cox models with non-HDL cholesterol lower than 2·6 mmol/L as reference showed an increase in the association between non-HDL cholesterol concentration and cardiovascular disease for both sexes (from hazard ratio 1·1, 95% CI 1·0–1·3 for non-HDL cholesterol 2·6 to <3·7 mmol/L to 1·9, 1·6–2·2 for ≥5·7 mmol/L in women and from 1·1, 1·0–1·3 to 2·3, 2·0–2·5 in men). The derived tool allowed the estimation of cardiovascular disease event probabilities specific for non-HDL cholesterol with high comparability between the derivation and validation cohorts as reflected by smooth calibration curves analyses and a root mean square error lower than 1% for the estimated probabilities of cardiovascular disease. A 50% reduction of non-HDL cholesterol concentrations was associated with reduced risk of a cardiovascular disease event by the age of 75 years, and this risk reduction was greater the earlier cholesterol concentrations were reduced.Interpretation: Non-HDL cholesterol concentrations in blood are strongly associated with long-term risk of atherosclerotic cardiovascular disease. We provide a simple tool for individual long-term risk assessment and the potential benefit of early lipid-lowering intervention. These data could be useful for physician–patient communication about primary prevention strategies.
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| 28. |
- Chachólski, Wojciech, et al.
(author)
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Cellular covers of divisible abelian groups
- 2009
-
In: ALPINE PERSPECTIVES ON ALGEBRAIC TOPOLOGY. - 9780821848395 ; , s. 77-97
-
Conference paper (peer-reviewed)abstract
- We determine all the possible values of the cellular approximation functor c(A) : cell(A)E -> E, where A is an arbitrary group and E is a divisible abelian group.
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| 29. |
- Chacholski, Wojciech, et al.
(author)
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Cellular generators
- 2004
-
In: Proceedings of the American Mathematical Society. - 0002-9939 .- 1088-6826. ; 132:11, s. 3397-3409
-
Journal article (peer-reviewed)abstract
- The aim of this paper is twofold. On the one hand, we show that the kernelof the Bousfield periodization functor P-A is cellularly generated by a space B, i.e., we construct a space B such that the smallest closed class C( B) containing B is exactly C( A). On the other hand, we show that the partial order (Spaces, much greater than) is a complete lattice, where B much greater than A if B is an element of C(A). Finally, as a corollary we obtain Bousfield's theorem, which states that (Spaces, >) is a complete lattice, where B > A if B is an element of.
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| 30. |
- Chacholski, Wojciech, et al.
(author)
-
The A-core and A-cover of a group
- 2009
-
In: Journal of Algebra. - : Elsevier BV. - 0021-8693 .- 1090-266X. ; 321:2, s. 631-666
-
Journal article (peer-reviewed)abstract
- This paper provides a comprehensive investigation of the cellular approximation functor cell(A) G, in the category of groups. approximating a group G by a group A. We also study related notions such as A-injection, A-generation and A-constructibility of a group G and we find several interesting connections with the Schur multiplier H-2(G, Z). Our constructions are direct and are given in a slow and detailed manner.
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| 31. |
- Corino, Valentina D. A., et al.
(author)
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Association between Atrial Fibrillatory Rate and Heart Rate Variability in Patients with Atrial Fibrillation and Congestive Heart Failure
- 2013
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In: Annals of Noninvasive Electrocardiology. - : Wiley. - 1082-720X. ; 18:1, s. 41-50
-
Journal article (peer-reviewed)abstract
- Background Even if atrial fibrillatory rate (AFR) has been related to clinical outcome in patients with atrial fibrillation (AF), its relation with ventricular response has not been deeply studied. The aim of this study was to investigate the relation between AFR and RR series variability in patients with AF. Methods Twenty-minute electrocardiograms in orthogonal leads were processed to extract AFR, using spatiotemporal QRST cancellation and time frequency analysis, and RR series in 127 patients (age 69 +/- 11 years) with congestive heart failure (NYHA IIIII) enrolled in the MUSIC study (MUerte Subita en Insufficiencia Cardiaca). Heart rate variability and irregularity were assessed by time domain parameters and entropy-based indices, respectively and their correlation with AFR investigated. Results Variability measures seem not to be related to AFR, while irregularity measures do. A significant correlation between AFR and variability parameters of heart rate variability during AF was found only in patients not treated with antiarrhythmics drugs (correlation = 0.56 P < 0.05 for pNN50), while this correlation was lost in patients taking rate- or rhythm-control drugs. A significant positive correlation between AFR and indices of RR irregularity was found, showing that a higher AFR is related to a less organized RR series (correlation = 0.33 P < 0.05 for regularity index for all patients, correlation increased in subgroups of patients treated with the same drug). Conclusions These results suggest that a higher AFR is associated with a higher degree of irregularity of ventricular response that is observed regardless of the use of rate-controlling drugs. Ann Noninvasive Electrocardiol 2013;18(1):41-50
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| 32. |
- Cwikiel, Wojciech, et al.
(author)
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Non-traumatic vascular emergencies: imaging and intervention in acute arterial conditions
- 2002
-
In: European Radiology. - : Springer Science and Business Media LLC. - 0938-7994 .- 1432-1084. ; 12:11, s. 2619-2626
-
Journal article (peer-reviewed)abstract
- Methods of imaging and intervention in acute non-traumatic vascular arterial conditions has changed substantially during recent years. Computed tomography, MRI angiography and, more recently, intravascular ultrasonography (IVUS) have replaced to a large extent conventional diagnostic angiography. An increasing number of patients are treated by endovascular interventions and numerous new treatment methods have been evaluated. Technical development of new equipment and instruments, increasing skill of interventional radiologists and better understanding of events following interventions improve continuously results of the treatment. Radiologic diagnosis and intervention have important roles in the treatment of acute non-traumatic vascular arterial conditions.
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| 33. |
- de Jong, Michel P, et al.
(author)
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The electronic structure of n- and p-doped phenyl-capped 3,4-ethylenedioxythiophene trimer
- 2003
-
In: Journal of Chemical Physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 118:14, s. 6495-6502
-
Journal article (peer-reviewed)abstract
- A study was conducted on the effects of chemical doping on the chemical and electronic structure of condensed molecular solid films of the ethylenedioxythiophene (EDOT) trimer using ultraviolet photoelectron spectroscopy (UPS) and x-ray photoelectron spectroscopy (XPS). Phenyl-capped EDOT oligomers were potential candidates for molecular electronics applications and serve as model molecules for PEDOT. By combining UPS, XPS, and NEXAFS, a clear picture of the doping induced changes in the electronic structure of phenyl-capped EDOT-trimer was obtained.
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| 34. |
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| 35. |
- Fryknäs, Mårten, et al.
(author)
-
Iron chelators target both proliferating and quiescent cancer cells
- 2016
-
In: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 6
-
Journal article (peer-reviewed)abstract
- Poorly vascularized areas of solid tumors contain quiescent cell populations that are resistant to cell cycle-active cancer drugs. The compound VLX600 was recently identified to target quiescent tumor cells and to inhibit mitochondrial respiration. We here performed gene expression analysis in order to characterize the cellular response to VLX600. The compound-specific signature of VLX600 revealed a striking similarity to signatures generated by compounds known to chelate iron. Validation experiments including addition of ferrous and ferric iron in excess, EXAFS measurements, and structure activity relationship analyses showed that VLX600 chelates iron and supported the hypothesis that the biological effects of this compound is due to iron chelation. Compounds that chelate iron possess anti-cancer activity, an effect largely attributed to inhibition of ribonucleotide reductase in proliferating cells. Here we show that iron chelators decrease mitochondrial energy production, an effect poorly tolerated by metabolically stressed tumor cells. These pleiotropic features make iron chelators an attractive option for the treatment of solid tumors containing heterogeneous populations of proliferating and quiescent cells.
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| 36. |
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| 37. |
- Hess, Georg, et al.
(author)
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Health-related quality of life data from a phase 3, international, randomized, open-label, multicenter study in patients with previously treated mantle cell lymphoma treated with ibrutinib versus temsirolimus
- 2017
-
In: Leukemia and Lymphoma. - : Informa UK Limited. - 1042-8194 .- 1029-2403. ; 58:12, s. 2824-2832
-
Journal article (peer-reviewed)abstract
- Mantle cell lymphoma (MCL) is a rare, aggressive, incurable B-cell malignancy. Ibrutinib has been shown to be highly active for patients with relapsed/refractory (R/R) MCL. The RAY trial (MCL3001) was a phase 3, randomized, open-label, multicenter study that compared ibrutinib with temsirolimus in patients with R/R MCL. Active disease is frequently associated with impaired functional status and reduced well-being. Therefore, the current study employed two patient-reported outcome instruments, the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) and the EQ-5D-5L, to assess symptoms, well-being, health status, and health-related quality of life of patients on treatment within the RAY trial. We found that patients on ibrutinib had substantial improvement in FACT-Lym subscale and total scores, and had improvement in EQ-5D-5L utility and VAS scores compared with temsirolimus patients, indicating a superior well-being. These improvements in well-being correlated with clinical response, indicating that better health-related quality of life was associated with decreased disease burden.
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| 38. |
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| 39. |
- Jacobs, Rita, et al.
(author)
-
Fluid Management, Intra-Abdominal Hypertension and the Abdominal Compartment Syndrome : A Narrative Review
- 2022
-
In: Life. - : MDPI AG. - 0024-3019 .- 2075-1729. ; 12:9
-
Research review (peer-reviewed)abstract
- Background: General pathophysiological mechanisms regarding associations between fluid administration and intra-abdominal hypertension (IAH) are evident, but specific effects of type, amount, and timing of fluids are less clear. Objectives: This review aims to summarize current knowledge on associations between fluid administration and intra-abdominal pressure (IAP) and fluid management in patients at risk of intra-abdominal hypertension and abdominal compartment syndrome (ACS). Methods: We performed a structured literature search from 1950 until May 2021 to identify evidence of associations between fluid management and intra-abdominal pressure not limited to any specific study or patient population. Findings were summarized based on the following information: general concepts of fluid management, physiology of fluid movement in patients with intra-abdominal hypertension, and data on associations between fluid administration and IAH. Results: We identified three randomized controlled trials (RCTs), 38 prospective observational studies, 29 retrospective studies, 18 case reports in adults, two observational studies and 10 case reports in children, and three animal studies that addressed associations between fluid administration and IAH. Associations between fluid resuscitation and IAH were confirmed in most studies. Fluid resuscitation contributes to the development of IAH. However, patients with IAH receive more fluids to manage the effect of IAH on other organ systems, thereby causing a vicious cycle. Timing and approach to de-resuscitation are of utmost importance, but clear indicators to guide this decision-making process are lacking. In selected cases, only surgical decompression of the abdomen can stop deterioration and prevent further morbidity and mortality. Conclusions: Current evidence confirms an association between fluid resuscitation and secondary IAH, but optimal fluid management strategies for patients with IAH remain controversial.
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| 40. |
- Janusek, D., et al.
(author)
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The roles of mid-myocardial and epicardial cells in T-wave alternans development : a simulation study
- 2018
-
In: Biomedical engineering online. - : Springer Science and Business Media LLC. - 1475-925X. ; 17
-
Journal article (peer-reviewed)abstract
- Background: The occurrence of T-wave alternans in electrocardiographic signals was recently linked to susceptibility to ventricular arrhythmias and sudden cardiac death. Thus, by detecting and comprehending the origins of T-wave alternans, it might be possible to prevent such events.Results: Here, we simulated T-wave alternans in a computer-generated human heart model by modulating the action potential duration and amplitude during the first part of the repolarization phase. We hypothesized that changes in the intracardiac alternans patterns of action potential properties would differentially influence T-wave alternans measurements at the body surface. Specifically, changes were simulated globally in the whole left and right ventricles to simulate concordant T-wave alternans, and locally in selected regions to simulate discordant and regional discordant, hereinafter referred to as “regional”, T-wave alternans. Body surface potential maps and 12-lead electrocardiographic signals were then computed. In depth discrimination, the influence of epicardial layers on T-wave alternans development was significantly higher than that of mid-myocardial cells. Meanwhile, spatial discrimination revealed that discordant and regional action potential property changes had a higher influence on T-wave alternans amplitude than concordant changes. Notably, varying T-wave alternans sources yielded distinct body surface potential map patterns for T-wave alternans amplitude, which can be used for location of regions within hearts exhibiting impaired repolarization. The highest ability for T-wave alternans detection was achieved in lead V1. Ultimately, we proposed new parameters Vector Magnitude Alternans and Vector Angle Alternans, with higher ability for T-wave alternans detection when using multi-lead electrocardiographic signals processing than for single leads. Finally, QT alternans was found to be associated with the process of T-wave alternans generation.Conclusions: The distributions of the body surface T-wave alternans amplitude have been shown to have unique patterns depending on the type of alternans (concordant, discordant or regional) and the location of the disturbance in the heart. The influence of epicardial cells on T-wave alternans development is significantly higher than that of mid-myocardial cells, among which the sub-endocardial layer exerted the highest influence. QT interval alternans is identified as a phenomenon that correlate with T-wave alternans.
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| 41. |
- Jung, Christian, et al.
(author)
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A comparison of very old patients admitted to intensive care unit after acute versus elective surgery or intervention
- 2019
-
In: Journal of critical care. - : W B SAUNDERS CO-ELSEVIER INC. - 0883-9441 .- 1557-8615. ; 52, s. 141-148
-
Journal article (peer-reviewed)abstract
- Background: We aimed to evaluate differences in outcome between patients admitted to intensive care unit (ICU) after elective versus acute surgery in a multinational cohort of very old patients (80 years; VIP). Predictors of mortality, with special emphasis on frailty, were assessed.Methods: In total, 5063 VIPs were induded in this analysis, 922 were admitted after elective surgery or intervention, 4141 acutely, with 402 after acute surgery. Differences were calculated using Mann-Whitney-U test and Wilcoxon test. Univariate and multivariable logistic regression were used to assess associations with mortality.Results: Compared patients admitted after acute surgery, patients admitted after elective surgery suffered less often from frailty as defined as CFS (28% vs 46%; p < 0.001), evidenced lower SOFA scores (4 +/- 5 vs 7 +/- 7; p < 0.001). Presence of frailty (CFS >4) was associated with significantly increased mortality both in elective surgery patients (7% vs 12%; p = 0.01), in acute surgery (7% vs 12%; p = 0.02).Conclusions: VIPs admitted to ICU after elective surgery evidenced favorable outcome over patients after acute surgery even after correction for relevant confounders. Frailty might be used to guide clinicians in risk stratification in both patients admitted after elective and acute surgery.
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| 42. |
- Kaneberg, Elvira Ruiz, et al.
(author)
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Defence organizations in emergency networks : the early response to COVID-19 in Europe
- 2023
-
In: Journal of Humanitarian Logistics and Supply Chain Management. - : Emerald Group Publishing Limited. - 2042-6747 .- 2042-6755. ; 13:1, s. 91-105
-
Journal article (peer-reviewed)abstract
- Purpose – The purpose of this study is to analyse the crisis network response of European countries and the role played by defence organizations(DOs) during the early response phase of the pandemic, here set to encompass 75 days.Design/methodology/approach – Published materials – reports, news and communications – provided by authorities and DOs were used. Some ofthe authors actively participated in national pandemic response networks. An exploratory approach and qualitative content analysis were applied.The data were collected in national languages from 13 European countries, and they were coded and analysed using the actors, resources andactivities (ARA) framework.Findings – This study identified three main categories of activity structures in which the DOs interacted with civilian members of response networks,health-related services, logistics services and public support services. These networks among actors were found within formal response systems andemergent networks. The DOs engaged as actors that provided a range of services when civil authorities could not cope with the huge demand forspecific services and when resources were scarce in the initial response phase.Originality/value – This study contributes by filling an important research gap with regard to the civil-military relations associated with the use ofDO resources in the civil response to the pandemic crisis in Europe, which is described as an untraditional response. The ARA network approachprovides a framework for arranging ARA and extends the wider civil-military network to expand the formal networks of the early crisis response. Thestudy lays knowledge about the co-operation between civilian and military actors in different contexts and provides a broader understanding of theroles that DOs played in the response operations.
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| 43. |
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| 44. |
- Kubica, Jacek, et al.
(author)
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Prolonged antithrombotic therapy in patients after acute coronary syndrome : A critical appraisal of current European Society of Cardiology guidelines
- 2020
-
In: CARDIOLOGY JOURNAL. - : VM Media SP. zo.o VM Group SK. - 1897-5593 .- 1898-018X. ; 27:6, s. 661-676
-
Journal article (peer-reviewed)abstract
- The increased risk of non-cardiovascular death in patients receiving clopidogrel or prasugrel in comparison with the placebo group in the Dual Antiplatelet Therapy (DAPT) trial in contrast to the decreased risk of cardiovascular death and all-cause death seen in patients treated with low-dose ticagrelor in the EU label population of the PEGASUS-TIMI 54 trial, resulted in inclusion in the 2020 ESC NSTE-ACS guidelines the recommendation for use of clopidogrel or prasugrel only if the patient is not eligible for treatment with ticagrelor. The prevalence of the primary outcome composed of cardiovascular death, stroke, or myocardial infarction was lower in the low-dose rivaroxaban and acetylsalicylic acid (ASA) group than in the ASA-alone group in the COMPASS trial. Moreover, all-cause mortality and cardiovascular mortality rates were lower in the rivaroxaban-plus-ASA group. Comparison of the PEGASUS-TIMI 54 and COMPASS trial patient characteristics clearly shows that each of these treatment strategies should be addressed at different groups of patients. A greater benefit in post-acute coronary syndrome (ACS) patients with a high risk of ischemic events and without high bleeding risk may be expected with ASA and ticagrelor 60 mg b.i.d. when the therapy is continued without interruption or with short interruption only after ACS. On the other hand, ASA and rivaroxaban 2.5 mg b.i.d. seems to be a better option when indications for dual antithrombotic therapy (DATT) appear after a longer time from ACS (more than 2 years) and/or from cessation of DAPT (more than 1 year) and in patients with multiple vascular bed atherosclerosis. Thus, both options of DATTs complement each other rather than compete, as can be presumed from the recommendations. However, a direct comparison between these strategies should be tested in future clinical trials.
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| 45. |
- Mann, Stefan A., et al.
(author)
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Convergence of models of human ventricular myocyte electrophysiology after global optimization to recapitulate clinical long QT phenotypes
- 2016
-
In: Journal of Molecular and Cellular Cardiology. - : Elsevier BV. - 0022-2828 .- 1095-8584. ; 100, s. 25-34
-
Journal article (peer-reviewed)abstract
- In-silico models of human cardiac electrophysiology are now being considered for prediction of cardiotoxicity as part of the preclinical assessment phase of all new drugs. We ask the question whether any of the available models are actually fit for this purpose. We tested three models of the human ventricular action potential, the O'hara-Rudy (ORD11), the Grandi-Bers (GB10) and the Ten Tusscher (TT06) models. We extracted clinical QT data for LQTS1 and LQTS2 patients with nonsense mutations that would be predicted to cause 50% loss of function in I-Ks and I-Kr respectively. We also obtained clinical QT data for LQTS3 patients. We then used a global optimization approach to improve the existing in silico models so that they reproduced all three clinical data sets more closely. We also examined the effects of adrenergic stimulation in the different LQTS subsets. All models, in their original form, produce markedly different and unrealistic predictions of QT prolongation for LQTS1, 2 and 3. After global optimization of the maximum conductances for membrane channels, all models have similar current densities during the action potential, despite differences in kinetic properties of the channels in the different models, and more closely reproduce the prolongation of repolarization seen in all LQTS subtypes. In-silico models of cardiac electrophysiology have the potential to be tremendously useful in complementing traditional preclinical drug testing studies. However, our results demonstrate they should be carefully validated and optimized to clinical data before they can be used for this purpose.
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| 46. |
- Moller, Anders Pape, et al.
(author)
-
Clutch-size variation in Western Palaearctic secondary hole-nesting passerine birds in relation to nest box design
- 2014
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In: Methods in Ecology and Evolution. - 2041-210X. ; 5:4, s. 353-362
-
Journal article (peer-reviewed)abstract
- Secondary hole-nesting birds that do not construct nest holes themselves and hence regularly breed in nest boxes constitute important model systems for field studies in many biological disciplines with hundreds of scientists and amateurs involved. Those research groups are spread over wide geographic areas that experience considerable variation in environmental conditions, and researchers provide nest boxes of varying designs that may inadvertently introduce spatial and temporal variation in reproductive parameters. We quantified the relationship between mean clutch size and nest box size and material after controlling for a range of environmental variables in four of the most widely used model species in the Western Palaearctic: great tit Parus major, blue tit Cyanistes caeruleus, pied flycatcher Ficedula hypoleuca and collared flycatcher F.albicollis from 365 populations and 79610 clutches. Nest floor area and nest box material varied non-randomly across latitudes and longitudes, showing that scientists did not adopt a random box design. Clutch size increased with nest floor area in great tits, but not in blue tits and flycatchers. Clutch size of blue tits was larger in wooden than in concrete nest boxes. These findings demonstrate that the size of nest boxes and material used to construct nest boxes can differentially affect clutch size in different species. The findings also suggest that the nest box design may affect not only focal species, but also indirectly other species through the effects of nest box design on productivity and therefore potentially population density and hence interspecific competition.
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| 47. |
- Müezzinler, Aysel, et al.
(author)
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Smoking and All-cause Mortality in Older Adults : Results From the CHANCES Consortium
- 2015
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In: American Journal of Preventive Medicine. - : Elsevier BV. - 0749-3797 .- 1873-2607. ; 49:5, s. e53-e63
-
Journal article (peer-reviewed)abstract
- INTRODUCTION: Smoking is known to be a major cause of death among middle-aged adults, but evidence on its impact and the benefits of smoking cessation among older adults has remained limited. Therefore, we aimed to estimate the influence of smoking and smoking cessation on all-cause mortality in people aged ≥60 years.METHODS: Relative mortality and mortality rate advancement periods (RAPs) were estimated by Cox proportional hazards models for the population-based prospective cohort studies from Europe and the U.S. (CHANCES [Consortium on Health and Ageing: Network of Cohorts in Europe and the U.S.]), and subsequently pooled by individual participant meta-analysis. Statistical analyses were performed from June 2013 to March 2014.RESULTS: A total of 489,056 participants aged ≥60 years at baseline from 22 population-based cohort studies were included. Overall, 99,298 deaths were recorded. Current smokers had 2-fold and former smokers had 1.3-fold increased mortality compared with never smokers. These increases in mortality translated to RAPs of 6.4 (95% CI=4.8, 7.9) and 2.4 (95% CI=1.5, 3.4) years, respectively. A clear positive dose-response relationship was observed between number of currently smoked cigarettes and mortality. For former smokers, excess mortality and RAPs decreased with time since cessation, with RAPs of 3.9 (95% CI=3.0, 4.7), 2.7 (95% CI=1.8, 3.6), and 0.7 (95% CI=0.2, 1.1) for those who had quit <10, 10 to 19, and ≥20 years ago, respectively.CONCLUSIONS: Smoking remains as a strong risk factor for premature mortality in older individuals and cessation remains beneficial even at advanced ages. Efforts to support smoking abstinence at all ages should be a public health priority.
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| 48. |
- Nazir, Madiha, et al.
(author)
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Targeting tumor cells based on Phosphodiesterase 3A expression
- 2017
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In: Experimental Cell Research. - : Elsevier BV. - 0014-4827 .- 1090-2422. ; 361:2, s. 308-315
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Journal article (peer-reviewed)abstract
- We and others have previously reported a correlation between high phosphodiesterase 3 A (PDE3A) expression and selective sensitivity to phosphodiesterase (PDE) inhibitors. This indicates that PDE3A could serve both as a drug target and a biomarker of sensitivity to PDE3 inhibition. In this report, we explored publicly available mRNA gene expression data to identify cell lines with different PDE3A expression. Cell lines with high PDE3A expression showed marked in vitro sensitivity to PDE inhibitors zardaverine and quazinone, when compared with those having low PDE3A expression. Immunofluorescence and immunohistochemical stainings were in agreement with PDE3A mRNA expression, providing suitable alternatives for biomarker analysis of clinical tissue specimens. Moreover, we here demonstrate that tumor cells from patients with ovarian carcinoma show great variability in PDE3A protein expression and that level of PDE3A expression is correlated with sensitivity to PDE inhibition. Finally, we demonstrate that PDE3A is highly expressed in subsets of patient tumor cell samples from different solid cancer diagnoses and expressed at exceptional levels in gastrointestinal stromal tumor (GIST) specimens. Importantly, vulnerability to PDE3 inhibitors has recently been associated with co-expression of PDE3A and Schlafen family member 12 (SLFN12). We here demonstrate that high expression of PDE3A in clinical specimens, at least on the mRNA level, seems to be frequently associated with high SLFIV12 expression. In conclusion, PDE3A seems to be both a promising biomarker and drug target for individualized drug treatment of various cancers.
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| 49. |
- Pérez-Granados, Cristian, et al.
(author)
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European scenarios for future biological invasions
- 2024
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In: People and Nature. - 2575-8314. ; 6:1, s. 245-259
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Journal article (peer-reviewed)abstract
- Invasive alien species are one of the major threats to global biodiversity, ecosystem integrity, nature's contributions to people and human health. While scenarios about potential future developments have been available for other global change drivers for quite some time, we largely lack an understanding of how biological invasions might unfold in the future across spatial scales.Based on previous work on global invasion scenarios, we developed a workflow to downscale global scenarios to a regional and policy-relevant context. We applied this workflow at the European scale to create four European scenarios of biological invasions until 2050 that consider different environmental, socio-economic and socio-cultural trajectories, namely the European Alien Species Narratives (Eur-ASNs).We compared the Eur-ASNs with their previously published global counterparts (Global-ASNs), assessing changes in 26 scenario variables. This assessment showed a high consistency between global and European scenarios in the logic and assumptions of the scenario variables. However, several discrepancies in scenario variable trends were detected that could be attributed to scale differences. This suggests that the workflow is able to capture scale-dependent differences across scenarios.We also compared the Global- and Eur-ASNs with the widely used Global and European Shared Socioeconomic Pathways (SSPs), a set of scenarios developed in the context of climate change to capture different future socio-economic trends. Our comparison showed considerable divergences in the scenario space occupied by the different scenarios, with overall larger differences between the ASNs and SSPs than across scales (global vs. European) within the scenario initiatives.Given the differences between the ASNs and SSPs, it seems that the SSPs do not adequately capture the scenario space relevant to understanding the complex future of biological invasions. This underlines the importance of developing independent but complementary scenarios focussed on biological invasions. The downscaling workflow we implemented and presented here provides a tool to develop such scenarios across different regions and contexts. This is a major step towards an improved understanding of all major drivers of global change, including biological invasions.
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| 50. |
- Roura-Pascual, Nuria, et al.
(author)
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A scenario-guided strategy for the future management of biological invasions
- 2024
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In: Frontiers in Ecology and the Environment. - 1540-9295 .- 1540-9309.
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Research review (peer-reviewed)abstract
- Future dynamics of biological invasions are highly uncertain because they depend on multiple social-ecological drivers. We used a scenario-based approach to explore potential management options for invasive species in Europe. During two workshops involving a multidisciplinary team of experts, we developed a management strategy arranged into 19 goals relating to policy, research, public awareness, and biosecurity. We conceived solutions for achieving these goals under different plausible future scenarios, and identified four interrelated recommendations around which any long-term strategy for managing invasive species can be structured: (1) a European biosecurity regime, (2) a dedicated communication strategy, (3) data standardization and management tools, and (4) a monitoring and assessment system. Finally, we assessed the feasibility of the management strategy and found substantial differences among scenarios. Collectively, our results indicate that it is time for a new strategy for managing biological invasions in Europe, one that is based on a more integrative approach across socioeconomic sectors and countries.
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