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1.	Cruz, Raquel, et al. (författare) Novel genes and sex differences in COVID-19 severity 2022 Ingår i: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 31:22, s. 3789-3806 Tidskriftsartikel (refereegranskat)abstract Here, we describe the results of a genome-wide study conducted in 11 939 coronavirus disease 2019 (COVID-19) positive cases with an extensive clinical information that were recruited from 34 hospitals across Spain (SCOURGE consortium). In sex-disaggregated genome-wide association studies for COVID-19 hospitalization, genome-wide significance (P < 5 × 10−8) was crossed for variants in 3p21.31 and 21q22.11 loci only among males (P = 1.3 × 10−22 and P = 8.1 × 10−12, respectively), and for variants in 9q21.32 near TLE1 only among females (P = 4.4 × 10−8). In a second phase, results were combined with an independent Spanish cohort (1598 COVID-19 cases and 1068 population controls), revealing in the overall analysis two novel risk loci in 9p13.3 and 19q13.12, with fine-mapping prioritized variants functionally associated with AQP3 (P = 2.7 × 10−8) and ARHGAP33 (P = 1.3 × 10−8), respectively. The meta-analysis of both phases with four European studies stratified by sex from the Host Genetics Initiative (HGI) confirmed the association of the 3p21.31 and 21q22.11 loci predominantly in males and replicated a recently reported variant in 11p13 (ELF5, P = 4.1 × 10−8). Six of the COVID-19 HGI discovered loci were replicated and an HGI-based genetic risk score predicted the severity strata in SCOURGE. We also found more SNP-heritability and larger heritability differences by age (<60 or ≥60 years) among males than among females. Parallel genome-wide screening of inbreeding depression in SCOURGE also showed an effect of homozygosity in COVID-19 hospitalization and severity and this effect was stronger among older males. In summary, new candidate genes for COVID-19 severity and evidence supporting genetic disparities among sexes are provided.
2.	Klionsky, Daniel J, et al. (författare) Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). 2016 Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 12:1, s. 1-222 Tidskriftsartikel (refereegranskat)
3.	Carraminana, Albert, et al. (författare) Rationale and Study Design for an Individualized Perioperative Open Lung Ventilatory Strategy in Patients on One-Lung Ventilation (iPROVE-OLV) 2019 Ingår i: Journal of Cardiothoracic and Vascular Anesthesia. - : W B SAUNDERS CO-ELSEVIER INC. - 1053-0770 .- 1532-8422. ; 33:9, s. 2492-2502 Tidskriftsartikel (refereegranskat)abstract Objective: The aim of this clinical trial is to examine whether it is possible to reduce postoperative complications using an individualized perioperative ventilatory strategy versus using a standard lung-protective ventilation strategy in patients scheduled for thoracic surgery requiring one-lung ventilation. Design: International, multicenter, prospective, randomized controlled clinical trial. Setting: A network of university hospitals. Participants: The study comprises 1,380 patients scheduled for thoracic surgery. Interventions: The individualized group will receive intraoperative recruitment maneuvers followed by individualized positive end-expiratory pressure (open lung approach) during the intraoperative period plus postoperative ventilatory support with high-flow nasal cannula, whereas the control group will be managed with conventional lung-protective ventilation. Measurements and Main Results: Individual and total number of postoperative complications, including atelectasis, pneumothorax, pleural effusion, pneumonia, acute lung injury; unplanned readmission and reintubation; length of stay and death in the critical care unit and in the hospital will be analyzed for both groups. The authors hypothesize that the intraoperative application of an open lung approach followed by an individual indication of high-flow nasal cannula in the postoperative period will reduce pulmonary complications and length of hospital stay in high-risk surgical patients. (C) 2019 Published by Elsevier Inc.
4.	Bentham, James, et al. (författare) A century of trends in adult human height 2016 Ingår i: eLIFE. - 2050-084X. ; 5 Tidskriftsartikel (refereegranskat)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.
5.	Bentham, James, et al. (författare) A century of trends in adult human height 2016 Ingår i: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 5 Tidskriftsartikel (refereegranskat)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.
6.	Di Cesare, Mariachiara, et al. (författare) Trends in adult body-mass index in 200 countries from 1975 to 2014: A pooled analysis of 1698 population-based measurement studies with 19.2 million participants 2016 Ingår i: The Lancet. - : Lancet Publishing Group. - 0140-6736 .- 1474-547X. ; 387:10026, s. 1377-1396 Tidskriftsartikel (refereegranskat)
7.	Zamora, Juan Carlos, et al. (författare) Considerations and consequences of allowing DNA sequence data as types of fungal taxa 2018 Ingår i: IMA Fungus. - : INT MYCOLOGICAL ASSOC. - 2210-6340 .- 2210-6359. ; 9:1, s. 167-185 Tidskriftsartikel (refereegranskat)abstract Nomenclatural type definitions are one of the most important concepts in biological nomenclature. Being physical objects that can be re-studied by other researchers, types permanently link taxonomy (an artificial agreement to classify biological diversity) with nomenclature (an artificial agreement to name biological diversity). Two proposals to amend the International Code of Nomenclature for algae, fungi, and plants (ICN), allowing DNA sequences alone (of any region and extent) to serve as types of taxon names for voucherless fungi (mainly putative taxa from environmental DNA sequences), have been submitted to be voted on at the 11th International Mycological Congress (Puerto Rico, July 2018). We consider various genetic processes affecting the distribution of alleles among taxa and find that alleles may not consistently and uniquely represent the species within which they are contained. Should the proposals be accepted, the meaning of nomenclatural types would change in a fundamental way from physical objects as sources of data to the data themselves. Such changes are conducive to irreproducible science, the potential typification on artefactual data, and massive creation of names with low information content, ultimately causing nomenclatural instability and unnecessary work for future researchers that would stall future explorations of fungal diversity. We conclude that the acceptance of DNA sequences alone as types of names of taxa, under the terms used in the current proposals, is unnecessary and would not solve the problem of naming putative taxa known only from DNA sequences in a scientifically defensible way. As an alternative, we highlight the use of formulas for naming putative taxa (candidate taxa) that do not require any modification of the ICN.
8.	Ferrando, Carlos, et al. (författare) Effects of oxygen on post-surgical infections during an individualised perioperative open-lung ventilatory strategy : a randomised controlled trial 2020 Ingår i: British Journal of Anaesthesia. - : ELSEVIER SCI LTD. - 0007-0912 .- 1471-6771. ; 124:1, s. 110-120 Tidskriftsartikel (refereegranskat)abstract Background: We aimed to examine whether using a high fraction of inspired oxygen (FIO2) in the context of an individualised intra- and postoperative open-lung ventilation approach could decrease surgical site infection (SSI) in patients scheduled for abdominal surgery. Methods: We performed a multicentre, randomised controlled clinical trial in a network of 21 university hospitals from June 6, 2017 to July 19, 2018. Patients undergoing abdominal surgery were randomly assigned to receive a high (0.80) or conventional (0.3) FIO2 during the intraoperative period and during the first 3 postoperative hours. All patients were mechanically ventilated with an open-lung strategy, which included recruitment manoeuvres and individualised positive end-expiratory pressure for the best respiratory-system compliance, and individualised continuous postoperative airway pressure for adequate peripheral oxyhaemoglobin saturation. The primary outcome was the prevalence of SSI within the first 7 postoperative days. The secondary outcomes were composites of systemic complications, length of intensive care and hospital stay, and 6-month mortality. Results: We enrolled 740 subjects: 371 in the high FIO2 group and 369 in the low FIO2 group. Data from 717 subjects were available for final analysis. The rate of SSI during the first postoperative week did not differ between high (8.9%) and low (9.4%) FIO2 groups (relative risk [RR]: 0.94; 95% confidence interval [CI]: 0.59-1.50; P=0.90]). Secondary outcomes, such as atelectasis (7.7% vs 9.8%; RR: 0.77; 95% CI: 0.48-1.25; P=0.38) and myocardial ischaemia (0.6% [n=2] vs 0% [n=0]; P=0.47) did not differ between groups. Conclusions: An oxygenation strategy using high FIO2 compared with conventional FIO2 did not reduce postoperative SSIs in abdominal surgery. No differences in secondary outcomes or adverse events were found.
9.	Hudson, Lawrence N, et al. (författare) The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project 2017 Ingår i: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 7:1, s. 145-188 Tidskriftsartikel (refereegranskat)abstract The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.
10.	Kattge, Jens, et al. (författare) TRY plant trait database - enhanced coverage and open access 2020 Ingår i: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188 Tidskriftsartikel (refereegranskat)abstract Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
11.	Zhou, Bin, et al. (författare) Worldwide trends in diabetes since 1980: A pooled analysis of 751 population-based studies with 4.4 million participants 2016 Ingår i: The Lancet. - : Elsevier B.V.. - 0140-6736 .- 1474-547X. ; 387:10027, s. 1513-1530 Tidskriftsartikel (refereegranskat)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.
12.	Martínez-Sánchez, Noelia, et al. (författare) Hypothalamic AMPK-ER Stress-JNK1 Axis Mediates the Central Actions of Thyroid Hormones on Energy Balance 2017 Ingår i: Cell Metabolism. - Cambridge, MA, United States : Cell Press. - 1550-4131 .- 1932-7420. ; 26:1, s. 212-229.e12 Tidskriftsartikel (refereegranskat)abstract Thyroid hormones (THs) act in the brain to modulate energy balance. We show that central triiodothyronine (T3) regulates de novo lipogenesis in liver and lipid oxidation in brown adipose tissue (BAT) through the parasympathetic (PSNS) and sympathetic nervous system (SNS), respectively. Central T3 promotes hepatic lipogenesis with parallel stimulation of the thermogenic program in BAT. The action of T3 depends on AMP-activated protein kinase (AMPK)-induced regulation of two signaling pathways in the ventromedial nucleus of the hypothalamus (VMH): decreased ceramide-induced endoplasmic reticulum (ER) stress, which promotes BAT thermogenesis, and increased c-Jun N-terminal kinase (JNK) activation, which controls hepatic lipid metabolism. Of note, ablation of AMPKα1 in steroidogenic factor 1 (SF1) neurons of the VMH fully recapitulated the effect of central T3, pointing to this population in mediating the effect of central THs on metabolism. Overall, these findings uncover the underlying pathways through which central T3 modulates peripheral metabolism.
13.	Sartelli, Massimo, et al. (författare) Ten golden rules for optimal antibiotic use in hospital settings: the WARNING call to action 2023 Ingår i: WORLD JOURNAL OF EMERGENCY SURGERY. - 1749-7922. ; 18:1 Forskningsöversikt (refereegranskat)abstract Antibiotics are recognized widely for their benefits when used appropriately. However, they are often used inappropriately despite the importance of responsible use within good clinical practice. Effective antibiotic treatment is an essential component of universal healthcare, and it is a global responsibility to ensure appropriate use. Currently, pharmaceutical companies have little incentive to develop new antibiotics due to scientific, regulatory, and financial barriers, further emphasizing the importance of appropriate antibiotic use. To address this issue, the Global Alliance for Infections in Surgery established an international multidisciplinary task force of 295 experts from 115 countries with different backgrounds. The task force developed a position statement called WARNING (Worldwide Antimicrobial Resistance National/International Network Group) aimed at raising awareness of antimicrobial resistance and improving antibiotic prescribing practices worldwide. The statement outlined is 10 axioms, or "golden rules," for the appropriate use of antibiotics that all healthcare workers should consistently adhere in clinical practice.
14.	Abbasi, Rasha, et al. (författare) IceCube search for neutrinos from GRB 221009A 2023 Ingår i: Proceedings of 38th International Cosmic Ray Conference (ICRC 2023). - : Sissa Medialab Srl. Konferensbidrag (refereegranskat)abstract GRB 221009A is the brightest Gamma Ray Burst (GRB) ever observed. The observed extremelyhigh flux of high and very-high-energy photons provide a unique opportunity to probe the predictedneutrino counterpart to the electromagnetic emission. We have used a variety of methods to searchfor neutrinos in coincidence with the GRB over several time windows during the precursor, promptand afterglow phases of the GRB. MeV scale neutrinos are studied using photo-multiplier ratescalers which are normally used to search for galactic core-collapse supernovae neutrinos. GeVneutrinos are searched starting with DeepCore triggers. These events don’t have directionallocalization, but instead can indicate an excess in the rate of events. 10 GeV - 1 TeV and >TeVneutrinos are searched using traditional neutrino point source methods which take into accountthe direction and time of events with DeepCore and the entire IceCube detector respectively. The>TeV results include both a fast-response analysis conducted by IceCube in real-time with timewindows of T0 − 1 to T0 + 2 hours and T0 ± 1 day around the time of GRB 221009A, as well asan offline analysis with 3 new time windows up to a time window of T0 − 1 to T0 + 14 days, thelongest time period we consider. The combination of observations by IceCube covers 9 ordersof magnitude in neutrino energy, from MeV to PeV, placing upper limits across the range forpredicted neutrino emission.
15.	Donis, Daphne, et al. (författare) Stratification strength and light climate explain variation in chlorophyll a at the continental scale in a European multilake survey in a heatwave summer 2021 Ingår i: Limnology and Oceanography. - : John Wiley & Sons. - 0024-3590 .- 1939-5590. ; 66:12, s. 4314-4333 Tidskriftsartikel (refereegranskat)abstract To determine the drivers of phytoplankton biomass, we collected standardized morphometric, physical, and biological data in 230 lakes across the Mediterranean, Continental, and Boreal climatic zones of the European continent. Multilinear regression models tested on this snapshot of mostly eutrophic lakes (median total phosphorus [TP] = 0.06 and total nitrogen [TN] = 0.7 mg L-1), and its subsets (2 depth types and 3 climatic zones), show that light climate and stratification strength were the most significant explanatory variables for chlorophyll a (Chl a) variance. TN was a significant predictor for phytoplankton biomass for shallow and continental lakes, while TP never appeared as an explanatory variable, suggesting that under high TP, light, which partially controls stratification strength, becomes limiting for phytoplankton development. Mediterranean lakes were the warmest yet most weakly stratified and had significantly less Chl a than Boreal lakes, where the temperature anomaly from the long-term average, during a summer heatwave was the highest (+4 degrees C) and showed a significant, exponential relationship with stratification strength. This European survey represents a summer snapshot of phytoplankton biomass and its drivers, and lends support that light and stratification metrics, which are both affected by climate change, are better predictors for phytoplankton biomass in nutrient-rich lakes than nutrient concentrations and surface temperature.
16.	Mantzouki, Evanthia, et al. (författare) Temperature Effects Explain Continental Scale Distribution of Cyanobacterial Toxins 2018 Ingår i: Toxins. - : MDPI. - 2072-6651. ; 10:4 Tidskriftsartikel (refereegranskat)abstract Insight into how environmental change determines the production and distribution of cyanobacterial toxins is necessary for risk assessment. Management guidelines currently focus on hepatotoxins (microcystins). Increasing attention is given to other classes, such as neurotoxins (e.g., anatoxin-a) and cytotoxins (e.g., cylindrospermopsin) due to their potency. Most studies examine the relationship between individual toxin variants and environmental factors, such as nutrients, temperature and light. In summer 2015, we collected samples across Europe to investigate the effect of nutrient and temperature gradients on the variability of toxin production at a continental scale. Direct and indirect effects of temperature were the main drivers of the spatial distribution in the toxins produced by the cyanobacterial community, the toxin concentrations and toxin quota. Generalized linear models showed that a Toxin Diversity Index (TDI) increased with latitude, while it decreased with water stability. Increases in TDI were explained through a significant increase in toxin variants such as MC-YR, anatoxin and cylindrospermopsin, accompanied by a decreasing presence of MC-LR. While global warming continues, the direct and indirect effects of increased lake temperatures will drive changes in the distribution of cyanobacterial toxins in Europe, potentially promoting selection of a few highly toxic species or strains.
17.	2019 Tidskriftsartikel (refereegranskat)
18.	Bachi, Lorenzo, et al. (författare) ECG Modeling for Simulation of Arrhythmias in Time-Varying Conditions 2023 Ingår i: IEEE Transactions on Biomedical Engineering. - 0018-9294. ; 70:12, s. 3449-3460 Tidskriftsartikel (refereegranskat)abstract The present paper proposes an ECG simulator that advances modeling of arrhythmias and noise by introducing time-varying signal characteristics. The simulator is built around a discrete-time Markov chain model for simulating atrial and ventricular arrhythmias of particular relevance when analyzing atrial fibrillation (AF). Each state is associated with statistical information on episode duration and heartbeat characteristics. Statistical, time-varying modeling of muscle noise, motion artifacts, and the influence of respiration is introduced to increase the complexity of simulated ECGs, making the simulator well suited for data augmentation in machine learning. Modeling of how the PQ and QT intervals depend on heart rate is also introduced. The realism of simulated ECGs is assessed by three experienced doctors, showing that simulated ECGs are difficult to distinguish from real ECGs. Simulator usefulness is illustrated in terms of AF detection performance when either simulated or real ECGs are used to train a neural network for signal quality control. The results show that both types of training lead to similar performance.
19.	Barack, Leor, et al. (författare) Black holes, gravitational waves and fundamental physics : a roadmap 2019 Ingår i: Classical and quantum gravity. - : IOP Publishing. - 0264-9381 .- 1361-6382. ; 36:14 Forskningsöversikt (refereegranskat)abstract The grand challenges of contemporary fundamental physics dark matter, dark energy, vacuum energy, inflation and early universe cosmology, singularities and the hierarchy problem all involve gravity as a key component. And of all gravitational phenomena, black holes stand out in their elegant simplicity, while harbouring some of the most remarkable predictions of General Relativity: event horizons, singularities and ergoregions. The hitherto invisible landscape of the gravitational Universe is being unveiled before our eyes: the historical direct detection of gravitational waves by the LIGO-Virgo collaboration marks the dawn of a new era of scientific exploration. Gravitational-wave astronomy will allow us to test models of black hole formation, growth and evolution, as well as models of gravitational-wave generation and propagation. It will provide evidence for event horizons and ergoregions, test the theory of General Relativity itself, and may reveal the existence of new fundamental fields. The synthesis of these results has the potential to radically reshape our understanding of the cosmos and of the laws of Nature. The purpose of this work is to present a concise, yet comprehensive overview of the state of the art in the relevant fields of research, summarize important open problems, and lay out a roadmap for future progress. This write-up is an initiative taken within the framework of the European Action on 'Black holes, Gravitational waves and Fundamental Physics'.
20.	Barquero-Perez, Oscar, et al. (författare) On the influence of heart rate and coupling interval prematurity on heart rate turbulence 2017 Ingår i: IEEE Transactions on Biomedical Engineering. - 1558-2531. ; 64:2, s. 302-309 Tidskriftsartikel (refereegranskat)abstract Objective: Heart rate turbulence (HRT) has been successfully explored for cardiac risk stratification. While HRT is known to be influenced by the heart rate (HR) and the coupling interval (CI), nonconcordant results have been reported on how the CI influences HRT. The purpose of this study is to investigate HRT changes in terms of CI and HR by means of an especially designed protocol. Methods: A dataset was acquired from 11 patients with structurally normal hearts for which CI was altered by different pacing trains and HR by isoproterenol during electrophysiological study (EPS). The protocol was designed so that, first, the effect of HR changes on HRT and, second, the combined effect of HR and CI could be explored. As a complement to the EPS dataset, a database of 24-h Holters from 61 acute myocardial infarction (AMI) patients was studied for the purpose of assessing risk. Data analysis was performed by using different nonlinear ridge regression models, and the relevance of model variables was assessed using resampling methods. The EPS subjects, with and without isoproterenol, were analyzed separately. Results: The proposed nonlinear regression models were found to account for the influence of HR and CI on HRT, both in patients undergoing EPS without isoproterenol and in low-risk AMI patients, whereas this influence was absent in high-risk AMI patients. Moreover, model coefficients related to CI were not statistically significant, p > 0.05, on EPS subjects with isoproterenol. Conclusion: The observed relationship between CI and HRT, being in agreement with the baroreflex hypothesis, was statistically significant (p < 0.05), when decoupling the effect of HR and normalizing the CI by the HR. Significance: The results of this study can help to provide new risk indicators that take into account physiological influence on HRT, as well as to model how this influence changes in different cardiac conditions.
21.	Beal, Jacob, et al. (författare) Robust estimation of bacterial cell count from optical density 2020 Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1 Tidskriftsartikel (refereegranskat)abstract Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
22.	Bousquet, Jean, et al. (författare) ARIA digital anamorphosis : Digital transformation of health and care in airway diseases from research to practice 2021 Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : John Wiley & Sons. - 0105-4538 .- 1398-9995. ; 76:1, s. 168-190 Forskningsöversikt (refereegranskat)abstract Digital anamorphosis is used to define a distorted image of health and care that may be viewed correctly using digital tools and strategies. MASK digital anamorphosis represents the process used by MASK to develop the digital transformation of health and care in rhinitis. It strengthens the ARIA change management strategy in the prevention and management of airway disease. The MASK strategy is based on validated digital tools. Using the MASK digital tool and the CARAT online enhanced clinical framework, solutions for practical steps of digital enhancement of care are proposed.
23.	Culina, Antica, et al. (författare) Connecting the data landscape of long-term ecological studies : The SPI-Birds data hub 2021 Ingår i: Journal of Animal Ecology. - : John Wiley & Sons. - 0021-8790 .- 1365-2656. ; 90:9, s. 2147-2160 Tidskriftsartikel (refereegranskat)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.
24.	Demidova, Marina, et al. (författare) T wave alternans in experimental myocardial infarction: Time course and predictive value for the assessment of myocardial damage. 2013 Ingår i: Journal of Electrocardiology. - : Elsevier BV. - 1532-8430 .- 0022-0736. ; 46:3, s. 263-269 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: T-wave alternans (TWA) is associated with prognosis after myocardial infarction (MI), however its link to the extent of ischemic injury has not been clarified. We analyzed the course of TWA and its relation to myocardial damage in experimental myocardial infarction. METHODS: In 21 pigs, infarction was induced by 40-minute long balloon inflation in LAD under continuous 12-lead ECG monitoring. TWA was assessed in a 32-beat sliding window, using periodic component analysis and the Laplacian Likelihood Ratio method. Myocardium at risk (MaR) and infarct size (IS) were evaluated by SPECT and magnetic resonance imaging respectively. RESULTS: TWA appeared at 7.2±4.5minutes of occlusion, reached its maximum at 12.7±6.3 and lasted until 26.5±9.2minutes. The maximal level of TWA was associated with both MaR (r=0.499, p=0.035) and IS (r=0.65, p=0.004). CONCLUSION: TWA magnitude is associated with both MaR and IS in experiment, which encourages further studies in clinical settings.
25.	Demidova, Marina, et al. (författare) Transient and rapid QRS widening associated with J-wave pattern predicts impending ventricular fibrillation in experimental myocardial infarction. 2014 Ingår i: Heart Rhythm. - : Elsevier BV. - 1547-5271. ; 11:7, s. 1195-1201 Tidskriftsartikel (refereegranskat)abstract Certain types of the early repolarization (ER) phenomenon, previously considered to be benign, have been reported to be associated with ventricular fibrillation (VF), both in population-based studies and in the myocardial infarction (MI) settings.
26.	Gil, Eduardo, et al. (författare) Heart Rate Turbulence Analysis Based on Photoplethysmography 2013 Ingår i: IEEE Transactions on Biomedical Engineering. - 1558-2531. ; 60:11, s. 3149-3155 Tidskriftsartikel (refereegranskat)abstract The goal of this paper is to determine whether the photoplethysmography (PPG) can replace the ECG-based detection of heart rate turbulence. Using the PPG, classification of ventricular premature beats (VPBs) is accomplished with a linear classifier. The two conventional parameters turbulence onset and slope are studied together with a recently introduced parameter characterizing turbulence shape. Performance is studied on a dataset with 4131 VPBs, recorded from a total of 27 patients in different clinical contexts (hemodialysis treatment, intensive care monitoring, and electrophysiological study). The sensitivity/specificity of VPB classification was found to be 90.5/99.9%, with an accuracy of 99.3%, suggesting that classification of VPBs can be reliable made from the PPG. The main difference between the two types of turbulence analysis stems from the fact that the pulse transit time varies largely immediately after the VPB. Out of the 22 patients which had a sufficient number of VPBs, the outcome of the ECG-and PPG-based analysis was identical in 21. It is concluded that the PPG may serve as a surrogate technique for the ECG in turbulence analysis.
27.	Gomez, Neurys, et al. (författare) Changes in T-Peak-to-T-End Morphology Measured by Time-Warping are Associated with Ischemia-Induced Ventricular Fibrillation in a Porcine Model 2023 Ingår i: Computing in Cardiology, CinC 2023. - 2325-8861 .- 2325-887X. - 9798350382525 Konferensbidrag (refereegranskat)abstract In this work, we use a time-warping-based morphology variation index, d_{w}, computed between the peak and the end of the T-wave, and assess its association with the occurrence of ventricular fibrillation (VF) episodes in ischemic conditions. ECG recordings from 26 pigs under-going a 40-minute coronary occlusion were analyzed. The d_{w} series was obtained by quantifying the morphological differences between the final part of the T wave at different stages of the occlusion and a reference T wave in the control recording. During control recordings, d_{w} remained stationary with a median value along each recording of 1.76 ms, IQR of 1.80, while during artery occlusion followed a well-marked gradual increasing trend as ischemia progressed, with median of 15.47 ms, IQR of 18.53. At the 20-to-25 min period from occlusion onset (and during 5 min prior to VF episode) dw averages in the VF group was significantly higher than in the non-VF group with median values of 40.0 (and 34.4) vs 7.8 (and 7.7) ms, with p-values of 0.002 (and 0.001), respectively. In conclusion, dynamic increases of the d_{w} index during ischaemia progression in pigs are associated with VF occurrence.
28.	Gomez, Neurys, et al. (författare) T-wave Peak-to-End Changes Quantified by Time-Warping Predicts Ventricular Fibrillation in a Porcine Myocardial Infarction Model 2024 Ingår i: IEEE Transactions on Biomedical Engineering. - 0018-9294. ; , s. 1-10 Tidskriftsartikel (refereegranskat)abstract Background: The T-peak-to-T-end ($\mathrm{T}_{pe}$) interval has shown potential in predicting ventricular arrhythmic risk. It is an appealing index to be measured during ischemia since it is less influenced by ST-segment changes than the early part of the T wave. A time-warping-based index, derived from a spatially transformed PCA lead, $d^{{\kern0.28436pt}\text{PCA}}_{w,{\scriptscriptstyle \mathrm{T}_{pe}}}$, quantifying changes in the $\mathrm{T}_{pe}$ morphology, has previously demonstrated utility in tracking repolarization changes induced by a 5-minute ischemia model in humans. The value of $d^{{\kern0.28436pt}\text{PCA}}_{w,{\scriptscriptstyle \mathrm{T}_{pe}}}$ as a predictor of ventricular fibrillation (VF) episodes is assessed in a porcine model of myocardial ischemia with ischemia maintained for 40 minutes. Methods: From 32 pigs undergoing a coronary occlusion, pre-occlusion and occlusion ECG recordings from 10 pigs suffering a VF episode after 10 min of occlusion (Delayed VF) and 16 that did not had any episode during the recording were analyzed. The $d^{{\kern0.28436pt}\text{PCA}}_{w,{\scriptscriptstyle \mathrm{T}_{pe}}}$ series was measured by comparing $\mathrm{T}_{pe}$ morphologies at different stages of the occlusion relative to the peak-to-end morphology of a baseline T-wave. Results: During baseline, $d^{{\kern0.28436pt}\text{PCA}}_{w,{\scriptscriptstyle \mathrm{T}_{pe}}}$ remained stationary with an intra-recording median [IQR] value of 1.60 [1.33] ms. During artery occlusion, $d^{{\kern0.28436pt}\text{PCA}}_{w,{\scriptscriptstyle \mathrm{T}_{pe}}}$ followed a well-marked gradual increasing trend as ischemia progressed, reaching a median of 14.58 [17.72] ms. $d^{{\kern0.28436pt}\text{PCA}}_{w,{\scriptscriptstyle \mathrm{T}_{pe}}}$ averages were significantly higher (${p< 0.05}$) in the VF group than in the Non-VF group at time intervals 0-5, 5-10, 10-15, 15-20, 20-25 min after occlusion onset and at 10-15, 5-10 and 5-0 minutes prior to VF episode, with median values of 12.5, 18.8, 26.8, 24.0, 31.0, 18.6, 25.0 and 28.8 vs 6.3, 7.6, 8.0, 7.8, 7.8, 8.5, 7.2 and 6.0 ms, respectively. The $\mathrm{T}_{pe}^{\text{PCA}}$ interval was also significantly higher in the VF group at all analyzed time periods, but with a lower significance level. Pigs with maximum $d^{{\kern0.28436pt}\text{PCA}}_{w,{\scriptscriptstyle \mathrm{T}_{pe}}}$ $\geq$ 20.0 ms and $\mathrm{T}_{pe}^{\text{PCA}}$ $\geq$ 85.4 ms had significantly higher risk for VF occurring in the early 5-10 minutes interval, with 90.0%/75.0% and 80.0%/69.0% sensitivity/specificity, respectively. Univariate Cox analysis yielded hazard ratios of 12.5 for $d^{{\kern0.28436pt}\text{PCA}}_{w,{\scriptscriptstyle \mathrm{T}_{pe}}}$ vs 5.5 for $\mathrm{T}_{pe}^{\text{PCA}}$. Conclusions and Significance: The time-warping-based index, $d^{{\kern0.28436pt}\text{PCA}}_{w,{\scriptscriptstyle \mathrm{T}_{pe}}}$, is a stronger VF predictor than $\mathrm{T}_{pe}^{\text{PCA}}$ during ischemia in a porcine model, advising for further clinical exploration studies in humans.
29.	Jansen, Iris E, et al. (författare) Genome-wide meta-analysis for Alzheimer's disease cerebrospinal fluid biomarkers. 2022 Ingår i: Acta neuropathologica. - : Springer Science and Business Media LLC. - 1432-0533 .- 0001-6322. ; 144:5, s. 821-842 Tidskriftsartikel (refereegranskat)abstract Amyloid-beta 42 (Aβ42) and phosphorylated tau (pTau) levels in cerebrospinal fluid (CSF) reflect core features of the pathogenesis of Alzheimer's disease (AD) more directly than clinical diagnosis. Initiated by the European Alzheimer & Dementia Biobank (EADB), the largest collaborative effort on genetics underlying CSF biomarkers was established, including 31 cohorts with a total of 13,116 individuals (discovery n=8074; replication n=5042 individuals). Besides the APOE locus, novel associations with two other well-established AD risk loci were observed; CR1 was shown a locus for Aβ42 and BIN1 for pTau. GMNC and C16orf95 were further identified as loci for pTau, of which the latter is novel. Clustering methods exploring the influence of all known AD risk loci on the CSF protein levels, revealed 4 biological categories suggesting multiple Aβ42 and pTau related biological pathways involved in the etiology of AD. In functional follow-up analyses, GMNC and C16orf95 both associated with lateral ventricular volume, implying an overlap in genetic etiology for tau levels and brain ventricular volume.
30.	Jansen, Willemijn J, et al. (författare) Prevalence Estimates of Amyloid Abnormality Across the Alzheimer Disease Clinical Spectrum. 2022 Ingår i: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 79:3, s. 228-243 Tidskriftsartikel (refereegranskat)abstract One characteristic histopathological event in Alzheimer disease (AD) is cerebral amyloid aggregation, which can be detected by biomarkers in cerebrospinal fluid (CSF) and on positron emission tomography (PET) scans. Prevalence estimates of amyloid pathology are important for health care planning and clinical trial design.To estimate the prevalence of amyloid abnormality in persons with normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia and to examine the potential implications of cutoff methods, biomarker modality (CSF or PET), age, sex, APOE genotype, educational level, geographical region, and dementia severity for these estimates.This cross-sectional, individual-participant pooled study included participants from 85 Amyloid Biomarker Study cohorts. Data collection was performed from January 1, 2013, to December 31, 2020. Participants had normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia. Normal cognition and subjective cognitive decline were defined by normal scores on cognitive tests, with the presence of cognitive complaints defining subjective cognitive decline. Mild cognitive impairment and clinical AD dementia were diagnosed according to published criteria.Alzheimer disease biomarkers detected on PET or in CSF.Amyloid measurements were dichotomized as normal or abnormal using cohort-provided cutoffs for CSF or PET or by visual reading for PET. Adjusted data-driven cutoffs for abnormal amyloid were calculated using gaussian mixture modeling. Prevalence of amyloid abnormality was estimated according to age, sex, cognitive status, biomarker modality, APOE carrier status, educational level, geographical location, and dementia severity using generalized estimating equations.Among the 19097 participants (mean [SD] age, 69.1 [9.8] years; 10148 women [53.1%]) included, 10139 (53.1%) underwent an amyloid PET scan and 8958 (46.9%) had an amyloid CSF measurement. Using cohort-provided cutoffs, amyloid abnormality prevalences were similar to 2015 estimates for individuals without dementia and were similar across PET- and CSF-based estimates (24%; 95% CI, 21%-28%) in participants with normal cognition, 27% (95% CI, 21%-33%) in participants with subjective cognitive decline, and 51% (95% CI, 46%-56%) in participants with mild cognitive impairment, whereas for clinical AD dementia the estimates were higher for PET than CSF (87% vs 79%; mean difference, 8%; 95% CI, 0%-16%; P=.04). Gaussian mixture modeling-based cutoffs for amyloid measures on PET scans were similar to cohort-provided cutoffs and were not adjusted. Adjusted CSF cutoffs resulted in a 10% higher amyloid abnormality prevalence than PET-based estimates in persons with normal cognition (mean difference, 9%; 95% CI, 3%-15%; P=.004), subjective cognitive decline (9%; 95% CI, 3%-15%; P=.005), and mild cognitive impairment (10%; 95% CI, 3%-17%; P=.004), whereas the estimates were comparable in persons with clinical AD dementia (mean difference, 4%; 95% CI, -2% to 9%; P=.18).This study found that CSF-based estimates using adjusted data-driven cutoffs were up to 10% higher than PET-based estimates in people without dementia, whereas the results were similar among people with dementia. This finding suggests that preclinical and prodromal AD may be more prevalent than previously estimated, which has important implications for clinical trial recruitment strategies and health care planning policies.
31.	Kassebaum, Nicholas J., et al. (författare) Global, regional, and national disability-adjusted life-years (DALYs) for 315 diseases and injuries and healthy life expectancy (HALE), 1990-2015 : a systematic analysis for the Global Burden of Disease Study 2015 2016 Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 388:10053, s. 1603-1658 Tidskriftsartikel (refereegranskat)abstract Background Healthy life expectancy (HALE) and disability-adjusted life-years (DALYs) provide summary measures of health across geographies and time that can inform assessments of epidemiological patterns and health system performance, help to prioritise investments in research and development, and monitor progress toward the Sustainable Development Goals (SDGs). We aimed to provide updated HALE and DALYs for geographies worldwide and evaluate how disease burden changes with development. Methods We used results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015) for all-cause mortality, cause-specific mortality, and non-fatal disease burden to derive HALE and DALYs by sex for 195 countries and territories from 1990 to 2015. We calculated DALYs by summing years of life lost (YLLs) and years of life lived with disability (YLDs) for each geography, age group, sex, and year. We estimated HALE using the Sullivan method, which draws from age-specific death rates and YLDs per capita. We then assessed how observed levels of DALYs and HALE differed from expected trends calculated with the Socio-demographic Index (SDI), a composite indicator constructed from measures of income per capita, average years of schooling, and total fertility rate. Findings Total global DALYs remained largely unchanged from 1990 to 2015, with decreases in communicable, neonatal, maternal, and nutritional (Group 1) disease DALYs off set by increased DALYs due to non-communicable diseases (NCDs). Much of this epidemiological transition was caused by changes in population growth and ageing, but it was accelerated by widespread improvements in SDI that also correlated strongly with the increasing importance of NCDs. Both total DALYs and age-standardised DALY rates due to most Group 1 causes significantly decreased by 2015, and although total burden climbed for the majority of NCDs, age-standardised DALY rates due to NCDs declined. Nonetheless, age-standardised DALY rates due to several high-burden NCDs (including osteoarthritis, drug use disorders, depression, diabetes, congenital birth defects, and skin, oral, and sense organ diseases) either increased or remained unchanged, leading to increases in their relative ranking in many geographies. From 2005 to 2015, HALE at birth increased by an average of 2.9 years (95% uncertainty interval 2.9-3.0) for men and 3.5 years (3.4-3.7) for women, while HALE at age 65 years improved by 0.85 years (0.78-0.92) and 1.2 years (1.1-1.3), respectively. Rising SDI was associated with consistently higher HALE and a somewhat smaller proportion of life spent with functional health loss; however, rising SDI was related to increases in total disability. Many countries and territories in central America and eastern sub-Saharan Africa had increasingly lower rates of disease burden than expected given their SDI. At the same time, a subset of geographies recorded a growing gap between observed and expected levels of DALYs, a trend driven mainly by rising burden due to war, interpersonal violence, and various NCDs. Interpretation Health is improving globally, but this means more populations are spending more time with functional health loss, an absolute expansion of morbidity. The proportion of life spent in ill health decreases somewhat with increasing SDI, a relative compression of morbidity, which supports continued efforts to elevate personal income, improve education, and limit fertility. Our analysis of DALYs and HALE and their relationship to SDI represents a robust framework on which to benchmark geography-specific health performance and SDG progress. Country-specific drivers of disease burden, particularly for causes with higher-than-expected DALYs, should inform financial and research investments, prevention efforts, health policies, and health system improvement initiatives for all countries along the development continuum.
32.	Manzano-Nunez, Ramiro, et al. (författare) Could resuscitative endovascular balloon occlusion of the aorta improve survival among severely injured patients with post-intubation hypotension? 2018 Ingår i: European Journal of Trauma and Emergency Surgery. - : Springer Berlin/Heidelberg. - 1863-9933 .- 1863-9941. ; 44:4, s. 527-533 Forskningsöversikt (refereegranskat)abstract Current literature shows the association of post-intubation hypotension and increased odds of mortality in critically ill non-trauma and trauma populations. However, there is a lack of research on potential interventions that can prevent or ameliorate the consequences of endotracheal intubation and thus improve the prognosis of trauma patients with post-intubation hypotension. This review paper hypothesizes that the deployment of REBOA among trauma patients with PIH, by its physiologic effects, will reduce the odds of mortality in this population. The objective of this paper is to review the current literature on REBOA and post-intubation hypotension, and, furthermore, to provide a rational hypothesis on the potential role of REBOA in severely injured patients with post-intubation hypotension.
33.	Martinez, Juan Pablo, et al. (författare) Assessment of QT-measurement accuracy using the 12-lead electrocardiogram derived from EASI leads 2007 Ingår i: Journal of Electrocardiology. - : Elsevier BV. - 1532-8430 .- 0022-0736. ; 40:2, s. 172-179 Tidskriftsartikel (refereegranskat)abstract The purpose of the present study is to assess QT-interval measurements from the EASI 12-lead electrocardiogram (ECG) as compared with the standard 12-lead ECG. The QT interval was automatically determined in simultaneously recorded standard and EASI 12-lead ECGs, using a validated wavelet-based delineator. The agreement between the 2 sets of measurements was quantified both on a lead-by-lead basis and a multilead basis with global definitions of QRS onset and T-wave end. The results show that the agreement between QT-interval measurements from the 2 lead systems is acceptable, with negligible mean differences and with correlation coefficients ranging from 0.91 to 0.98 depending on the lead studied. Although the SD shows a clear dependence on the selected lead (ranging from 9.2 to 26.4 milliseconds), differences are within the accepted tolerances for automatic delineation. In a few patients, large differences were found, mainly because of changes in morphology present in both lead systems. QT intervals measured by the multilead approach were considerably more stable than single-lead measurements and resulted in a much better agreement between the 2 lead systems (correlation coefficient, 0.98; QT difference, 1.1 +/- 9.8 milliseconds). Thus, the EASI 12-lead ECG may be used for reliable QT monitoring when the multilead delineation approach is adopted. (c) 2007 Elsevier Inc. All rights reserved.
34.	Martínez, Juan Pablo, et al. (författare) The STAFF III Database : ECGs recorded during acutely induced myocardial ischemia 2017 Ingår i: Computing in Cardiology. - 2325-8861. ; 44 Tidskriftsartikel (refereegranskat)abstract The STAFF III database was acquired with the aim of better understanding the ECG signatures observed during acute ischemia, with special focus on high-frequency QRS components. The database contains recordings from 104 patients undergoing elective balloon percutaneous coronary intervention. The database has not only been analyzed in numerous clinical studies, but also turned out to be an excellent tool for methodological development. Its use has, by far, exceeded the original aim. Inspired by this fact, the database has now been made publicly available at Physionet.
35.	Pablo Martinez, Juan, et al. (författare) Detection Performance and Risk Stratification Using a Model-Based Shape Index Characterizing Heart Rate Turbulence 2010 Ingår i: Annals of Biomedical Engineering. - : Springer Science and Business Media LLC. - 1573-9686 .- 0090-6964. ; 38:10, s. 3173-3184 Tidskriftsartikel (refereegranskat)abstract A detection-theoretic approach to quantify heart rate turbulence (HRT) following a ventricular premature beat is proposed and validated using an extended integral pulse frequency modulation (IPFM) model which accounts for HRT. The modulating signal of the extended IPFM model is projected into a three-dimensional subspace spanned by the Karhunen-Loeve basis functions, characterizing HRT shape. The presence or absence of HRT is decided by means of a likelihood ratio test, the Neyman-Pearson detector, resulting in a quadratic detection statistic. Using a labeled dataset built from different interbeat interval series, detection performance is assessed and found to outperform the two widely used indices: turbulence onset (TO) and turbulence slope (TS). The ability of the proposed method to predict the risk of cardiac death is evaluated in a population of patients (n = 90) with ischemic cardiomyopathy and mild-to-moderate congestive heart failure. While both TS and the novel HRT index differ significantly in survivors and cardiac death patients, mortality analysis shows that the latter index exhibits much stronger association with risk of cardiac death (hazard ratio = 2.8, CI = 1.32-5.97, p = 0.008). It is also shown that the model-based shape indices, but not TO and TS, remain predictive of cardiac death in our population when computed from 4-h instead of 24-h ambulatory ECGs.
36.	Perez, Cristina, et al. (författare) Evaluation of a QT Adaptation Time Estimator for ECG Exercise Stress Test in Controlled Simulation 2023 Ingår i: Computing in Cardiology, CinC 2023. - 2325-887X .- 2325-8861. - 9798350382525 Konferensbidrag (refereegranskat)abstract Slowed adaptation of the QT interval to sudden abrupt heart rate (HR) changes has been identified as a marker of ventricular arrhythmic risk. However, abrupt HR changes are difficult to induce in patients. Quantifying the QT adaptation time in gradual HR changes, as observed in ECGs recording during an exercise stress test, has been recently proposed. The time lag between the QT series and an instantaneous memoryless HR-dependent QT series along stress test was computed as QT memory. Here, this method was evaluated in a control scenario using simulated exercise stress test ECG signals presenting different QT adaptation times. The method robustness was studied by contaminating the ECGs with muscular noise (MN) signals with different Signal-to-Noise ratio (SNR) values, either synthetic or extracted from real recordings. We found that delineation of the T-wave end point in the first transformed lead from Periodic Component Analysis offers the best performance for low SNR. Moreover, we confirmed that the estimator provides an unbiased estimate of the QT memory introduced in the simulations for the studied range of SNR values (25 to 50 dB).
37.	Sandberg, Frida, et al. (författare) Prediction of hypotension in hemodialysis patients 2014 Ingår i: Physiological Measurement. - : IOP Publishing. - 0967-3334 .- 1361-6579. ; 35:9, s. 1885-1898 Tidskriftsartikel (refereegranskat)abstract Intradialytic hypotension (IDH) is the most common adverse complication during hemodialysis. Its early prediction and prevention will dramatically improve the quality of life for patients with an end stage renal disease. In a recent study, changes in the normalized envelope of the test statistic of the photoplethysmograpic (PPG) signal were found to predict acute symptomatic IDH. In the present study, the PPG-based predictor is generalized to include a patient-dependent threshold which incorporates on-line information on heart rate variability and heart rate turbulence. From datasets with patients prone and resistant to IDH, the results show that symptomatic IDH could be correctly predicted in 9 out of 14 cases, while 5 out of 24 were falsely predicted. In a subset of the data containing only patients prone to IDH, acute symptomatic IDH could be correctly predicted in 5 out of 5 cases, with one false prediction out of 14. When testing the robustness of the predictor, no significant changes were observed in the test statistic when controlled changes occurred in dialysis fluid temperature, ultrafiltration rate and body position.
38.	Sandberg, Frida, et al. (författare) Prediction of intradialytic hypotension using PPG and ECG 2013 Ingår i: 2013 Computing in Cardiology. - 9781479908844 ; 40, s. 1227-1230 Konferensbidrag (refereegranskat)abstract Intradialytic hypotension (IDH) is the most common complication during hemodialysis; early prediction and prevention of IDH would dramatically improve the living conditions for patients with end stage renal disease. A recently published study suggests that a decrease in the envelope of the photoplethysmograpy (PPG) signal can be used for predicting acute symptomatic IDH. In the present study, the PPG based method is extended by introducing a patient dependent detection threshold, which involves information on heart rate variability (HRV) and heart rate turbulence (HRT) from the current dialysis session. This is motivated since several studies have found significant differences in HRV and HRT between hypotension-prone and hypotension-resistant patients. Recordings from 15 patients during 38 hemodialysis sessions were used to evaluate the method. Symptomatic IDH was correctly predicted in 9 out of 14 cases, while 5 out of 24 cases were falsely predicted. The performance was better for acute symptomatic IDH, 5 out of 5 cases were correctly predicted. The present method represents a novel approach to combining information derived from ECG and PPG signals.
39.	Smith, Danny, et al. (författare) Model-Based Detection of Heart Rate Turbulence Using Mean Shape Information 2010 Ingår i: IEEE Transactions on Biomedical Engineering. - 1558-2531. ; 57:2, s. 334-342 Tidskriftsartikel (refereegranskat)abstract A generalized likelihood ratio test (GLRT) statistic is proposed for detection of heart rate turbulence (HRT), where a set of Karhunen-Loeve basis functions models HRT. The detector structure is based on the extended integral pulse frequency modulation model that accounts for the presence of ectopic beats and HRT. This new test statistic takes a priori information regarding HRT shape into account, whereas our previously presented GLRT detector relied solely on the energy contained in the signal subspace. The spectral relationship between heart rate variability (HRV) and HRT is investigated for the purpose of modeling HRV "noise" present during the turbulence period, the results suggesting that the white noise assumption is feasible to pursue. The performance was studied for both simulated and real data, leading to results which show that the new GLRT detector is superior to the original one as well as to the commonly used parameter turbulence slope (TS) on both types of data. Averaging ten ventricular ectopic beats, the estimated detection probability of the new detector, the previous detector, and TS were found to be 0.83, 0.35, and 0.41, respectively, when the false alarm probability was held fixed at 0.1.
40.	Solem, Kristian, et al. (författare) Model-based detection of heart rate turbulence. 2008 Ingår i: IEEE Transactions on Biomedical Engineering. - 1558-2531. ; 55:12, s. 2712-2722 Tidskriftsartikel (refereegranskat)abstract In this study, the integral pulse frequency modulation model is extended to account for the presence of ectopic beats and heart rate turbulence (HRT). Based on this model, a new statistical approach to the detection and characterization of HRT is presented. The detector structure involves a set of Karhunen-LoEve basis functions and a generalized likelihood ratio test statistic T(x) . The three most significant basis functions reflect the difference in heart rate prior to a ventricular ectopic beat (VEB) compared to after HRT, the "average" HRT, and a delayed contribution to HRT, respectively. Detector performance was studied on both simulated and ECG signals. Three different simulations were performed for the purpose of studying the influence of SNR, QRS jitter, and ECG sampling rate. The results show that the HRT test statistic T(x) performs better in all simulations than do the commonly used parameters known as turbulence onset (TO) and turbulence slope (TS). In order to attain the same performance as T(x), TS needs at least twice the amount of VEBs for averaging, and TO at least four times. The detector performance was also studied on ECGs acquired from eight patients who underwent hemodialysis treatment with the goal to discriminate between patients considered to be hypotension-resistant (HtR) and hypotension-prone (HtP). The results show that T(x) exhibits larger mean values in HtR patients than in HtP, suggesting that HRT is mostly present in HtR patients. The overlap between the two groups was larger for TO and TS than for T(x).
41.	Trenkwalder, Claudia, et al. (författare) Expert Consensus Group report on the use of apomorphine in the treatment of Parkinson's disease - Clinical practice recommendations 2015 Ingår i: Parkinsonism & Related Disorders. - : Elsevier BV. - 1873-5126 .- 1353-8020. ; 21:9, s. 1023-1030 Forskningsöversikt (refereegranskat)abstract Extensive published evidence supports the use of subcutaneously-administered apomorphine as an effective therapy for Parkinson's disease (PD) but to date no consensus recommendations have been available to guide healthcare professionals in the optimal application of apomorphine therapy in clinical practice. This document outlines best-practice recommendations for selecting appropriate candidates for apomorphine intermittent injection (the pen-injection formulation) or apomorphine continuousinfusion (the pump formulation), for initiating patients onto therapy and for managing their ongoing treatment. Apomorphine is a suitable therapeutic option for PD patients who experience troublesome 'off periods despite optimized treatment with oral PD medications. Due to its speed of onset, apomorphine injection is particularly suited to those patients requiring rapid, reliable relief of both unpredictable and predictable 'off' periods, those who require reliable and fast relief when anticipating an 'off', those with levodopa absorption or gastric emptying problems resulting in delayed or failed 'on', or for rapid relief of early morning dystonia or akinesia. Apomorphine infusionl is suited for patients whose 'off periods can no longer be adequately controlled by standard oral PD treatment or for those in whom rescue doses of apomorphine injection are effective but either needed too frequently (more than 4-6 times per day), or are associated with increasing dyskinesia. In addition to treating motor fluctuations, there is evidence that apomorphine infusion may be effective for the management of specific non-motor symptoms of PD associated with 'off' periods. Apomorphine infusion is less invasive than other non-oral treatment options for advancing disease, intrajejunal levodopa infusion and deep-brain stimulation. (C) 2015 Elsevier Ltd. All rights reserved.
42.	Wang, Haidong, et al. (författare) Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015 : a systematic analysis for the Global Burden of Disease Study 2015 2016 Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 388:10053, s. 1459-1544 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Improving survival and extending the longevity of life for all populations requires timely, robust evidence on local mortality levels and trends. The Global Burden of Disease 2015 Study (GBD 2015) provides a comprehensive assessment of all-cause and cause-specific mortality for 249 causes in 195 countries and territories from 1980 to 2015. These results informed an in-depth investigation of observed and expected mortality patterns based on sociodemographic measures.METHODS: We estimated all-cause mortality by age, sex, geography, and year using an improved analytical approach originally developed for GBD 2013 and GBD 2010. Improvements included refinements to the estimation of child and adult mortality and corresponding uncertainty, parameter selection for under-5 mortality synthesis by spatiotemporal Gaussian process regression, and sibling history data processing. We also expanded the database of vital registration, survey, and census data to 14 294 geography-year datapoints. For GBD 2015, eight causes, including Ebola virus disease, were added to the previous GBD cause list for mortality. We used six modelling approaches to assess cause-specific mortality, with the Cause of Death Ensemble Model (CODEm) generating estimates for most causes. We used a series of novel analyses to systematically quantify the drivers of trends in mortality across geographies. First, we assessed observed and expected levels and trends of cause-specific mortality as they relate to the Socio-demographic Index (SDI), a summary indicator derived from measures of income per capita, educational attainment, and fertility. Second, we examined factors affecting total mortality patterns through a series of counterfactual scenarios, testing the magnitude by which population growth, population age structures, and epidemiological changes contributed to shifts in mortality. Finally, we attributed changes in life expectancy to changes in cause of death. We documented each step of the GBD 2015 estimation processes, as well as data sources, in accordance with Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER).FINDINGS: Globally, life expectancy from birth increased from 61·7 years (95% uncertainty interval 61·4-61·9) in 1980 to 71·8 years (71·5-72·2) in 2015. Several countries in sub-Saharan Africa had very large gains in life expectancy from 2005 to 2015, rebounding from an era of exceedingly high loss of life due to HIV/AIDS. At the same time, many geographies saw life expectancy stagnate or decline, particularly for men and in countries with rising mortality from war or interpersonal violence. From 2005 to 2015, male life expectancy in Syria dropped by 11·3 years (3·7-17·4), to 62·6 years (56·5-70·2). Total deaths increased by 4·1% (2·6-5·6) from 2005 to 2015, rising to 55·8 million (54·9 million to 56·6 million) in 2015, but age-standardised death rates fell by 17·0% (15·8-18·1) during this time, underscoring changes in population growth and shifts in global age structures. The result was similar for non-communicable diseases (NCDs), with total deaths from these causes increasing by 14·1% (12·6-16·0) to 39·8 million (39·2 million to 40·5 million) in 2015, whereas age-standardised rates decreased by 13·1% (11·9-14·3). Globally, this mortality pattern emerged for several NCDs, including several types of cancer, ischaemic heart disease, cirrhosis, and Alzheimer's disease and other dementias. By contrast, both total deaths and age-standardised death rates due to communicable, maternal, neonatal, and nutritional conditions significantly declined from 2005 to 2015, gains largely attributable to decreases in mortality rates due to HIV/AIDS (42·1%, 39·1-44·6), malaria (43·1%, 34·7-51·8), neonatal preterm birth complications (29·8%, 24·8-34·9), and maternal disorders (29·1%, 19·3-37·1). Progress was slower for several causes, such as lower respiratory infections and nutritional deficiencies, whereas deaths increased for others, including dengue and drug use disorders. Age-standardised death rates due to injuries significantly declined from 2005 to 2015, yet interpersonal violence and war claimed increasingly more lives in some regions, particularly in the Middle East. In 2015, rotaviral enteritis (rotavirus) was the leading cause of under-5 deaths due to diarrhoea (146 000 deaths, 118 000-183 000) and pneumococcal pneumonia was the leading cause of under-5 deaths due to lower respiratory infections (393 000 deaths, 228 000-532 000), although pathogen-specific mortality varied by region. Globally, the effects of population growth, ageing, and changes in age-standardised death rates substantially differed by cause. Our analyses on the expected associations between cause-specific mortality and SDI show the regular shifts in cause of death composition and population age structure with rising SDI. Country patterns of premature mortality (measured as years of life lost [YLLs]) and how they differ from the level expected on the basis of SDI alone revealed distinct but highly heterogeneous patterns by region and country or territory. Ischaemic heart disease, stroke, and diabetes were among the leading causes of YLLs in most regions, but in many cases, intraregional results sharply diverged for ratios of observed and expected YLLs based on SDI. Communicable, maternal, neonatal, and nutritional diseases caused the most YLLs throughout sub-Saharan Africa, with observed YLLs far exceeding expected YLLs for countries in which malaria or HIV/AIDS remained the leading causes of early death.INTERPRETATION: At the global scale, age-specific mortality has steadily improved over the past 35 years; this pattern of general progress continued in the past decade. Progress has been faster in most countries than expected on the basis of development measured by the SDI. Against this background of progress, some countries have seen falls in life expectancy, and age-standardised death rates for some causes are increasing. Despite progress in reducing age-standardised death rates, population growth and ageing mean that the number of deaths from most non-communicable causes are increasing in most countries, putting increased demands on health systems.
43.	Alcolea, Daniel, et al. (författare) Feasibility of Lumbar Puncture in the Study of Cerebrospinal Fluid Biomarkers for Alzheimer's Disease: A Multicenter Study in Spain. 2014 Ingår i: Journal of Alzheimer's disease : JAD. - 1875-8908. ; 39:4, s. 719-726 Tidskriftsartikel (refereegranskat)abstract Lumbar puncture (LP) is increasingly performed in memory units due to the usefulness of cerebrospinal fluid (CSF) biomarkers in the diagnosis of Alzheimer's disease. The feasibility of this procedure in this context, however, is controversial.
44.	Algaba, Juan-Carlos, et al. (författare) Broadband Multi-wavelength Properties of M87 during the 2017 Event Horizon Telescope Campaign 2021 Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 911:1 Forskningsöversikt (refereegranskat)abstract In 2017, the Event Horizon Telescope (EHT) Collaboration succeeded in capturing the first direct image of the center of the M87 galaxy. The asymmetric ring morphology and size are consistent with theoretical expectations for a weakly accreting supermassive black hole of mass ∼6.5 × 109 M o˙. The EHTC also partnered with several international facilities in space and on the ground, to arrange an extensive, quasi-simultaneous multi-wavelength campaign. This Letter presents the results and analysis of this campaign, as well as the multi-wavelength data as a legacy data repository. We captured M87 in a historically low state, and the core flux dominates over HST-1 at high energies, making it possible to combine core flux constraints with the more spatially precise very long baseline interferometry data. We present the most complete simultaneous multi-wavelength spectrum of the active nucleus to date, and discuss the complexity and caveats of combining data from different spatial scales into one broadband spectrum. We apply two heuristic, isotropic leptonic single-zone models to provide insight into the basic source properties, but conclude that a structured jet is necessary to explain M87's spectrum. We can exclude that the simultaneous γ-ray emission is produced via inverse Compton emission in the same region producing the EHT mm-band emission, and further conclude that the γ-rays can only be produced in the inner jets (inward of HST-1) if there are strongly particle-dominated regions. Direct synchrotron emission from accelerated protons and secondaries cannot yet be excluded.
45.	Breznau, Nate, et al. (författare) Observing many researchers using the same data and hypothesis reveals a hidden universe of uncertainty 2022 Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 119:44 Tidskriftsartikel (refereegranskat)abstract This study explores how researchers analytical choices affect the reliability of scientific findings. Most discussions of reliability problems in science focus on systematic biases. We broaden the lens to emphasize the idiosyncrasy of conscious and unconscious decisions that researchers make during data analysis. We coordinated 161 researchers in 73 research teams and observed their research decisions as they used the same data to independently test the same prominent social science hypothesis: that greater immigration reduces support for social policies among the public. In this typical case of social science research, research teams reported both widely diverging numerical findings and substantive conclusions despite identical start conditions. Researchers expertise, prior beliefs, and expectations barely predict the wide variation in research outcomes. More than 95% of the total variance in numerical results remains unexplained even after qualitative coding of all identifiable decisions in each teams workflow. This reveals a universe of uncertainty that remains hidden when considering a single study in isolation. The idiosyncratic nature of how researchers results and conclusions varied is a previously underappreciated explanation for why many scientific hypotheses remain contested. These results call for greater epistemic humility and clarity in reporting scientific findings.
46.	Chaudhuri, K. Ray, et al. (författare) Economic Burden of Parkinson’s Disease : A Multinational, Real-World, Cost-of-Illness Study Ingår i: Drugs - Real World Outcomes. - 2199-1154. Tidskriftsartikel (refereegranskat)abstract Background: Parkinson’s disease is now one of the fastest-growing neurodegenerative disorders in the developed world, with an increasing prevalence and associated socioeconomic costs. Progression of the disease leads to a gradual deterioration in patients’ quality of life, despite optimal treatment, and both medical and societal needs increase, often with the assistance of paid and/or unpaid caregivers. Objective: We aimed to quantify the incremental economic burden of Parkinson’s disease by disease severity in a real-world setting across differing geographic regions. Methods: Demographics, clinical characteristics, health status, patient quality of life, caregiver burden, and healthcare resource utilization data were drawn from the Adelphi Parkinson’s Disease Specific Program™, conducted in the USA, five European countries, and Japan. Results: A total of 563 neurologists provided data for 5299 individuals with Parkinson’s disease; 61% were male, with a mean age of 64 years. Approximately 15% of individuals were deemed to have advanced disease, with significantly more comorbidities, and a poorer quality of life, than those with non-advanced disease. Overall, the mean annual healthcare resource utilization increased significantly with advancing disease, and resulted in a three-fold difference in the USA and Europe. The main drivers behind the high economic burden included hospitalizations, prescription medications, and indirect costs. Conclusions: People with Parkinson’s disease, and their caregivers, incur a higher economic burden as their disease progresses. Future interventions that can control symptoms or slow disease progression could reduce the burden on people with Parkinson’s disease and their caregivers, whilst also substantially impacting societal costs.
47.	Chavez-Rodriguez, Mauro F., et al. (författare) Fuel saving strategies in the Andes : long-term impacts for Peru, Colombia and Ecuador 2018 Ingår i: Energy Strategy Reviews. - : Elsevier. - 2211-467X .- 2211-4688. ; 20, s. 35-48 Tidskriftsartikel (refereegranskat)abstract Crude oil exports and imports play a crucial role in the trade balance of Peru, Colombia and Ecuador. These countries are looking into fossil fuel saving measures as a way to deal with increasing demands and decreasing oil production rates. However, studies about the long-term effects of these measures is lacking. Using a combination of energy simulation technics, 17 fuel saving strategies ranging from fuel switching to the investment in underground transport and hydropower capacity expansion were modelled and assessed to evaluate their long-term effect on fossil fuels demand reduction. Our results show that the full implementation of strategies can account for cumulative oil savings of over 550 million barrels of oil by 2030. Findings also point out that Ecuador and Colombia could face the transition from net oil-exporters to importers as soon as the end of the next decade.
48.	De Groot, Natasja M.S., et al. (författare) Critical appraisal of technologies to assess electrical activity during atrial fibrillation : a position paper from the European Heart Rhythm Association and European Society of Cardiology Working Group on eCardiology in collaboration with the Heart Rhythm Society, Asia Pacific Heart Rhythm Society, Latin American Heart Rhythm Society and Computing in Cardiology 2022 Ingår i: Europace. - : Oxford University Press (OUP). - 1099-5129. ; 24:2, s. 313-330 Forskningsöversikt (refereegranskat)abstract We aim to provide a critical appraisal of basic concepts underlying signal recording and processing technologies applied for (i) atrial fibrillation (AF) mapping to unravel AF mechanisms and/or identifying target sites for AF therapy and (ii) AF detection, to optimize usage of technologies, stimulate research aimed at closing knowledge gaps, and developing ideal AF recording and processing technologies. Recording and processing techniques for assessment of electrical activity during AF essential for diagnosis and guiding ablative therapy including body surface electrocardiograms (ECG) and endo- or epicardial electrograms (EGM) are evaluated. Discussion of (i) differences in uni-, bi-, and multi-polar (omnipolar/Laplacian) recording modes, (ii) impact of recording technologies on EGM morphology, (iii) global or local mapping using various types of EGM involving signal processing techniques including isochronal-, voltage- fractionation-, dipole density-, and rotor mapping, enabling derivation of parameters like atrial rate, entropy, conduction velocity/direction, (iv) value of epicardial and optical mapping, (v) AF detection by cardiac implantable electronic devices containing various detection algorithms applicable to stored EGMs, (vi) contribution of machine learning (ML) to further improvement of signals processing technologies. Recording and processing of EGM (or ECG) are the cornerstones of (body surface) mapping of AF. Currently available AF recording and processing technologies are mainly restricted to specific applications or have technological limitations. Improvements in AF mapping by obtaining highest fidelity source signals (e.g. catheter-electrode combinations) for signal processing (e.g. filtering, digitization, and noise elimination) is of utmost importance. Novel acquisition instruments (multi-polar catheters combined with improved physical modelling and ML techniques) will enable enhanced and automated interpretation of EGM recordings in the near future.
49.	Delgado-Lista, Javier, et al. (författare) Top Single Nucleotide Polymorphisms Affecting Carbohydrate Metabolism in Metabolic Syndrome : From the LIPGENE Study 2014 Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 99:2, s. E384-E389 Tidskriftsartikel (refereegranskat)abstract Rationale: Metabolic syndrome (MetS) is a high-prevalence condition characterized by altered energy metabolism, insulin resistance, and elevated cardiovascular risk. Objectives: Although many individual single nucleotide polymorphisms (SNPs) have been linked to certain MetS features, there are few studies analyzing the influence of SNPs on carbohydrate metabolism in MetS. Methods: A total of 904 SNPs (tag SNPs and functional SNPs) were tested for influence on 8 fasting and dynamic markers of carbohydrate metabolism, by performance of an intravenous glucose tolerance test in 450 participants in the LIPGENE study. Findings: From 382 initial gene-phenotype associations between SNPs and any phenotypic variables, 61 (16% of the preselected variables) remained significant after bootstrapping. Top SNPs affecting glucose metabolism variables were as follows: fasting glucose, rs26125 (PPARGC1B); fasting insulin, rs4759277 (LRP1); C-peptide, rs4759277 (LRP1); homeostasis assessment of insulin resistance, rs4759277 (LRP1); quantitative insulin sensitivity check index, rs184003 (AGER); sensitivity index, rs7301876 (ABCC9), acute insulin response to glucose, rs290481 (TCF7L2); and disposition index, rs12691 (CEBPA). Conclusions: We describe here the top SNPs linked to phenotypic features in carbohydrate metabolism among approximately 1000 candidate gene variations in fasting and postprandial samples of 450 patients with MetS from the LIPGENE study.
50.	Demidova, Marina M, et al. (författare) QRS broadening due to terminal distortion is associated with the size of myocardial injury in experimental myocardial infarction 2016 Ingår i: Journal of Electrocardiology. - : Elsevier BV. - 1532-8430 .- 0022-0736. ; 49:3, s. 300-306 Tidskriftsartikel (refereegranskat)abstract INTRODUCTION: Not only repolarization, but also depolarization ECG indexes reflect the progression of ischemic injury. The aim was to assess the QRS duration and morphology dynamics during the prolonged coronary occlusion and their association with the myocardial area at risk (MaR) and final infarct size (IS).METHODS: In pigs, myocardial infarction was induced by inflation of an angioplasty balloon in the left descending artery (LAD), and ECG was continuously recorded. QRS duration was calculated on a beat-to-beat basis during the occlusion period. Single photon emission computed tomography (SPECT) was performed for the assessment of MaR, and IS was assessed by magnetic resonance imaging (MRI).RESULTS: All animals developed an anteroseptal infarction with MaR 40±9% and IS 23±7%. Two peaks of QRS widening were found in all animals: the early peak immediately after LAD occlusion and the late one 17.7±4.1min later. No association was found between MaR and IS and either QRS width or the degree of QRS widening at the early peak. QRS duration on the late peak correlated with both MaR (r=0.61; p=0.007) and IS (r=0.55; p=0.018).CONCLUSION: The QRS widening at the late peak, but not at the early peak, is associated with the size of myocardial injury, suggesting different underlying mechanisms.

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