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1.
  • 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.
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2.
  • 2019
  • Tidskriftsartikel (refereegranskat)
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3.
  • Backes, Claudia, et al. (författare)
  • Production and processing of graphene and related materials
  • 2020
  • Ingår i: 2D Materials. - : IOP Publishing. - 2053-1583. ; 7:2
  • Tidskriftsartikel (refereegranskat)abstract
    • We present an overview of the main techniques for production and processing of graphene and related materials (GRMs), as well as the key characterization procedures. We adopt a 'hands-on' approach, providing practical details and procedures as derived from literature as well as from the authors' experience, in order to enable the reader to reproduce the results. Section I is devoted to 'bottom up' approaches, whereby individual constituents are pieced together into more complex structures. We consider graphene nanoribbons (GNRs) produced either by solution processing or by on-surface synthesis in ultra high vacuum (UHV), as well carbon nanomembranes (CNM). Production of a variety of GNRs with tailored band gaps and edge shapes is now possible. CNMs can be tuned in terms of porosity, crystallinity and electronic behaviour. Section II covers 'top down' techniques. These rely on breaking down of a layered precursor, in the graphene case usually natural crystals like graphite or artificially synthesized materials, such as highly oriented pyrolythic graphite, monolayers or few layers (FL) flakes. The main focus of this section is on various exfoliation techniques in a liquid media, either intercalation or liquid phase exfoliation (LPE). The choice of precursor, exfoliation method, medium as well as the control of parameters such as time or temperature are crucial. A definite choice of parameters and conditions yields a particular material with specific properties that makes it more suitable for a targeted application. We cover protocols for the graphitic precursors to graphene oxide (GO). This is an important material for a range of applications in biomedicine, energy storage, nanocomposites, etc. Hummers' and modified Hummers' methods are used to make GO that subsequently can be reduced to obtain reduced graphene oxide (RGO) with a variety of strategies. GO flakes are also employed to prepare three-dimensional (3d) low density structures, such as sponges, foams, hydro- or aerogels. The assembly of flakes into 3d structures can provide improved mechanical properties. Aerogels with a highly open structure, with interconnected hierarchical pores, can enhance the accessibility to the whole surface area, as relevant for a number of applications, such as energy storage. The main recipes to yield graphite intercalation compounds (GICs) are also discussed. GICs are suitable precursors for covalent functionalization of graphene, but can also be used for the synthesis of uncharged graphene in solution. Degradation of the molecules intercalated in GICs can be triggered by high temperature treatment or microwave irradiation, creating a gas pressure surge in graphite and exfoliation. Electrochemical exfoliation by applying a voltage in an electrolyte to a graphite electrode can be tuned by varying precursors, electrolytes and potential. Graphite electrodes can be either negatively or positively intercalated to obtain GICs that are subsequently exfoliated. We also discuss the materials that can be amenable to exfoliation, by employing a theoretical data-mining approach. The exfoliation of LMs usually results in a heterogeneous dispersion of flakes with different lateral size and thickness. This is a critical bottleneck for applications, and hinders the full exploitation of GRMs produced by solution processing. The establishment of procedures to control the morphological properties of exfoliated GRMs, which also need to be industrially scalable, is one of the key needs. Section III deals with the processing of flakes. (Ultra)centrifugation techniques have thus far been the most investigated to sort GRMs following ultrasonication, shear mixing, ball milling, microfluidization, and wet-jet milling. It allows sorting by size and thickness. Inks formulated from GRM dispersions can be printed using a number of processes, from inkjet to screen printing. Each technique has specific rheological requirements, as well as geometrical constraints. The solvent choice is critical, not only for the GRM stability, but also in terms of optimizing printing on different substrates, such as glass, Si, plastic, paper, etc, all with different surface energies. Chemical modifications of such substrates is also a key step. Sections IV-VII are devoted to the growth of GRMs on various substrates and their processing after growth to place them on the surface of choice for specific applications. The substrate for graphene growth is a key determinant of the nature and quality of the resultant film. The lattice mismatch between graphene and substrate influences the resulting crystallinity. Growth on insulators, such as SiO2, typically results in films with small crystallites, whereas growth on the close-packed surfaces of metals yields highly crystalline films. Section IV outlines the growth of graphene on SiC substrates. This satisfies the requirements for electronic applications, with well-defined graphene-substrate interface, low trapped impurities and no need for transfer. It also allows graphene structures and devices to be measured directly on the growth substrate. The flatness of the substrate results in graphene with minimal strain and ripples on large areas, allowing spectroscopies and surface science to be performed. We also discuss the surface engineering by intercalation of the resulting graphene, its integration with Si-wafers and the production of nanostructures with the desired shape, with no need for patterning. Section V deals with chemical vapour deposition (CVD) onto various transition metals and on insulators. Growth on Ni results in graphitized polycrystalline films. While the thickness of these films can be optimized by controlling the deposition parameters, such as the type of hydrocarbon precursor and temperature, it is difficult to attain single layer graphene (SLG) across large areas, owing to the simultaneous nucleation/growth and solution/precipitation mechanisms. The differing characteristics of polycrystalline Ni films facilitate the growth of graphitic layers at different rates, resulting in regions with differing numbers of graphitic layers. High-quality films can be grown on Cu. Cu is available in a variety of shapes and forms, such as foils, bulks, foams, thin films on other materials and powders, making it attractive for industrial production of large area graphene films. The push to use CVD graphene in applications has also triggered a research line for the direct growth on insulators. The quality of the resulting films is lower than possible to date on metals, but enough, in terms of transmittance and resistivity, for many applications as described in section V. Transfer technologies are the focus of section VI. CVD synthesis of graphene on metals and bottom up molecular approaches require SLG to be transferred to the final target substrates. To have technological impact, the advances in production of high-quality large-area CVD graphene must be commensurate with those on transfer and placement on the final substrates. This is a prerequisite for most applications, such as touch panels, anticorrosion coatings, transparent electrodes and gas sensors etc. New strategies have improved the transferred graphene quality, making CVD graphene a feasible option for CMOS foundries. Methods based on complete etching of the metal substrate in suitable etchants, typically iron chloride, ammonium persulfate, or hydrogen chloride although reliable, are time- and resource-consuming, with damage to graphene and production of metal and etchant residues. Electrochemical delamination in a low-concentration aqueous solution is an alternative. In this case metallic substrates can be reused. Dry transfer is less detrimental for the SLG quality, enabling a deterministic transfer. There is a large range of layered materials (LMs) beyond graphite. Only few of them have been already exfoliated and fully characterized. Section VII deals with the growth of some of these materials. Amongst them, h-BN, transition metal tri- and di-chalcogenides are of paramount importance. The growth of h-BN is at present considered essential for the development of graphene in (opto) electronic applications, as h-BN is ideal as capping layer or substrate. The interesting optical and electronic properties of TMDs also require the development of scalable methods for their production. Large scale growth using chemical/physical vapour deposition or thermal assisted conversion has been thus far limited to a small set, such as h-BN or some TMDs. Heterostructures could also be directly grown. Section VIII discusses advances in GRM functionalization. A broad range of organic molecules can be anchored to the sp(2) basal plane by reductive functionalization. Negatively charged graphene can be prepared in liquid phase (e.g. via intercalation chemistry or electrochemically) and can react with electrophiles. This can be achieved both in dispersion or on substrate. The functional groups of GO can be further derivatized. Graphene can also be noncovalently functionalized, in particular with polycyclic aromatic hydrocarbons that assemble on the sp(2) carbon network by pi-pi stacking. In the liquid phase, this can enhance the colloidal stability of SLG/FLG. Approaches to achieve noncovalent on-substrate functionalization are also discussed, which can chemically dope graphene. Research efforts to derivatize CNMs are also summarized, as well as novel routes to selectively address defect sites. In dispersion, edges are the most dominant defects and can be covalently modified. This enhances colloidal stability without modifying the graphene basal plane. Basal plane point defects can also be modified, passivated and healed in ultra-high vacuum. The decoration of graphene with metal nanoparticles (NPs) has also received considerable attention, as it allows to exploit synergistic effects between NPs and graphene. Decoration can be either achieved chemically or in the gas phase. All LMs,
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4.
  • Antonell, Anna, et al. (författare)
  • Synaptic, axonal damage and inflammatory cerebrospinal fluid biomarkers in neurodegenerative dementias.
  • 2020
  • Ingår i: Alzheimer's & dementia : the journal of the Alzheimer's Association. - : Wiley. - 1552-5279. ; 16:2, s. 262-272
  • Tidskriftsartikel (refereegranskat)abstract
    • Synaptic damage, axonal neurodegeneration, and neuroinflammation are common features in Alzheimer's disease (AD), frontotemporal dementia (FTD), and Creutzfeldt-Jakob disease (CJD).Unicentric cohort of 353 participants included healthy control (HC) subjects, AD continuum stages, genetic AD and FTD, and FTD and CJD. We measured cerebrospinal fluid neurofilament light (NF-L), neurogranin (Ng), 14-3-3, and YKL-40 proteins.Biomarkers showed differences in HC subjects versus AD, FTD, and CJD. Disease groups differed between them except AD versus FTD for YKL-40. Only NF-L differed between all stages within the AD continuum. AD and FTD symptomatic mutation carriers presented differences with respect to HC subjects. Applying the AT(N) system, 96% subjects were positive for neurodegeneration if 14-3-3 was used, 94% if NF-L was used, 62% if Ng was used, and 53% if YKL-40 was used.Biomarkers of synapse and neurodegeneration differentiate HC subjects from neurodegenerative dementias and between AD, FTD, and CJD. NF-L and 14-3-3 performed similar to total tau when AT(N) system was applied.
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5.
  • Cirera, Lluís, et al. (författare)
  • Socioeconomic Effect of Education on Pancreatic Cancer Risk in Western Europe : An Update on the EPIC Cohorts Study
  • 2019
  • Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research (AACR). - 1055-9965 .- 1538-7755. ; 28:6, s. 1089-1092
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: To analyze the potential effect of social inequality on pancreatic cancer risk in Western Europe, by reassessing the association within the European Prospective Investigation into Cancer and Nutrition (EPIC) Study, including a larger number of cases and an extended follow-up.METHODS: Data on highest education attained were gathered for 459,170 participants (70% women) from 10 European countries. A relative index of inequality (RII) based on adult education was calculated for comparability across countries and generations. Cox regression models were applied to estimate relative inequality in pancreatic cancer risk, stratifying by age, gender, and center, and adjusting for known pancreatic cancer risk factors.RESULTS: A total of 1,223 incident pancreatic cancer cases were included after a mean follow-up of 13.9 (±4.0) years. An inverse social trend was found in models adjusted for age, sex, and center for both sexes [HR of RII, 1.27; 95% confidence interval (CI), 1.02-1.59], which was also significant among women (HR, 1.42; 95% CI, 1.05-1.92). Further adjusting by smoking intensity, alcohol consumption, body mass index, prevalent diabetes, and physical activity led to an attenuation of the RII risk and loss of statistical significance.CONCLUSIONS: The present reanalysis does not sustain the existence of an independent social inequality influence on pancreatic cancer risk in Western European women and men, using an index based on adult education, the most relevant social indicator linked to individual lifestyles, in a context of very low pancreatic cancer survival from (quasi) universal public health systems.IMPACT: The results do not support an association between education and risk of pancreatic cancer.
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6.
  • Gutierrez-Gutierrez, Belen, et al. (författare)
  • Propensity Score and Desirability of Outcome Ranking Analysis of Ertapenem for Treatment of Nonsevere Bacteremic Urinary Tract Infections Due to Extended-Spectrum-Beta-Lactamase-Producing Enterobacterales in Kidney Transplant Recipients
  • 2021
  • Ingår i: Antimicrobial Agents and Chemotherapy. - : American Society for Microbiology. - 0066-4804 .- 1098-6596. ; 65:11
  • Tidskriftsartikel (refereegranskat)abstract
    • There are scarce data on the efficacy of ertapenem in the treatment of bacteremia due to extended-spectrum-beta-lactamase (ESBL)-producing Enterobacterales (ESBL-E) in kidney transplant (KT) recipients. We evaluated the association between treatment with ertapenem or meropenem and clinical cure in KT recipients with nonsevere bacteremic urinary tract infections (B-UTI) caused by ESBL-E. We performed a registered, retrospective, international (29 centers in 14 countries) cohort study (INCREMENT-SOT, NCT02852902). The association between targeted therapy with ertapenem versus meropenem and clinical cure at day 14 (the principal outcome) was studied by logistic regression. Propensity score matching and desirability of outcome ranking (DOOR) analyses were also performed. A total of 201 patients were included; only 1 patient (treated with meropenem) in the cohort died. Clinical cure at day 14 was reached in 45/100 (45%) and 51/101 (50.5%) of patients treated with ertapenem and meropenem, respectively (adjusted OR 1.29; 95% CI 0.51 to 3.22; P = 0.76); the propensity score-matched cohort included 55 pairs (adjusted OR for clinical cure at day 14, 1.18; 95% CI 0.43 to 3.29; P = 0.74). In this cohort, the proportion of cases treated with ertapenem with better DOOR than with meropenem was 49.7% (95% CI, 40.4 to 59.1%) when hospital stay was considered. It ranged from 59 to 67% in different scenarios of a modified (weights-based) DOOR sensitivity analysis when potential ecological advantage or cost was considered in addition to outcome. In conclusion, targeted therapy with ertapenem appears as effective as meropenem to treat nonsevere B-UTI due to ESBL-E in KT recipients and may have some advantages.
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7.
  • Merino, Jordi, et al. (författare)
  • Quality of dietary fat and genetic risk of type 2 diabetes : individual participant data meta-analysis
  • 2019
  • Ingår i: BMJ. British Medical Journal. - : BMJ Publishing Group Ltd. - 0959-8146 .- 0959-535X. ; 366
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE To investigate whether the genetic burden of type 2 diabetes modifies the association between the quality of dietary fat and the incidence of type 2 diabetes.DESIGN Individual participant data meta-analysis.DATA SOURCES Eligible prospective cohort studies were systematically sourced from studies published between January 1970 and February 2017 through electronic searches in major medical databases (Medline, Embase, and Scopus) and discussion with investigators.REVIEW METHODS Data from cohort studies or multicohort consortia with available genome-wide genetic data and information about the quality of dietary fat and the incidence of type 2 diabetes in participants of European descent was sought. Prospective cohorts that had accrued five or more years of follow-up were included. The type 2 diabetes genetic risk profile was characterized by a 68-variant polygenic risk score weighted by published effect sizes. Diet was recorded by using validated cohort-specific dietary assessment tools. Outcome measures were summary adjusted hazard ratios of incident type 2 diabetes for polygenic risk score, isocaloric replacement of carbohydrate (refined starch and sugars) with types of fat, and the interaction of types of fat with polygenic risk score.RESULTS Of 102 305 participants from 15 prospective cohort studies, 20 015 type 2 diabetes cases were documented after a median follow-up of 12 years (interquartile range 9.4-14.2). The hazard ratio of type 2 diabetes per increment of 10 risk alleles in the polygenic risk score was 1.64 (95% confidence interval 1.54 to 1.75, I-2 = 7.1%, tau(2) = 0.003). The increase of polyunsaturated fat and total omega 6 polyunsaturated fat intake in place of carbohydrate was associated with a lower risk of type 2 diabetes, with hazard ratios of 0.90 (0.82 to 0.98, I-2 = 18.0%, tau(2) = 0.006; per 5% of energy) and 0.99 (0.97 to 1.00, I-2 = 58.8%, tau(2) = 0.001; per increment of 1 g/d), respectively. Increasing monounsaturated fat in place of carbohydrate was associated with a higher risk of type 2 diabetes (hazard ratio 1.10, 95% confidence interval 1.01 to 1.19, I-2 = 25.9%, tau(2) = 0.006; per 5% of energy). Evidence of small study effects was detected for the overall association of polyunsaturated fat with the risk of type 2 diabetes, but not for the omega 6 polyunsaturated fat and monounsaturated fat associations. Significant interactions between dietary fat and polygenic risk score on the risk of type 2 diabetes (P>0.05 for interaction) were not observed.CONCLUSIONS These data indicate that genetic burden and the quality of dietary fat are each associated with the incidence of type 2 diabetes. The findings do not support tailoring recommendations on the quality of dietary fat to individual type 2 diabetes genetic risk profiles for the primary prevention of type 2 diabetes, and suggest that dietary fat is associated with the risk of type 2 diabetes across the spectrum of type 2 diabetes genetic risk.
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8.
  • Perez-Nadales, Elena, et al. (författare)
  • Predictors of mortality in solid organ transplant recipients with bloodstream infections due to carbapenemase-producing Enterobacterales : The impact of cytomegalovirus disease and lymphopenia
  • 2020
  • Ingår i: American Journal of Transplantation. - : WILEY. - 1600-6135 .- 1600-6143. ; 20:6, s. 1629-1641
  • Tidskriftsartikel (refereegranskat)abstract
    • Treatment of carbapenemase-producing Enterobacterales bloodstream infections in solid organ transplant recipients is challenging. The objective of this study was to develop a specific score to predict mortality in solid organ transplant recipients with carbapenemase-producing Enterobacterales bloodstream infections. A multinational, retrospective (2004-2016) cohort study (INCREMENT-SOT, ClinicalTrials.gov NCT02852902) was performed. The main outcome variable was 30-day all-cause mortality. The INCREMENT-SOT-CPE score was developed using logistic regression. The global cohort included 216 patients. The final logistic regression model included the following variables: INCREMENT-CPE mortality score >= 8 (8 points), no source control (3 points), inappropriate empirical therapy (2 points), cytomegalovirus disease (7 points), lymphopenia (4 points), and the interaction between INCREMENT-CPE score >= 8 and CMV disease (minus 7 points). This score showed an area under the receiver operating characteristic curve of 0.82 (95% confidence interval [CI] 0.76-0.88) and classified patients into 3 strata: 0-7 (low mortality), 8-11 (high mortality), and 12-17 (very-high mortality). We performed a stratified analysis of the effect of monotherapy vs combination therapy among 165 patients who received appropriate therapy. Monotherapy was associated with higher mortality only in the very-high (adjusted hazard ratio [HR] 2.82, 95% CI 1.13-7.06, P = .03) and high (HR 9.93, 95% CI 2.08-47.40, P = .004) mortality risk strata. A score-based algorithm is provided for therapy guidance.
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9.
  • Stepien, Magdalena, et al. (författare)
  • Pre-diagnostic copper and zinc biomarkers and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition cohort
  • 2017
  • Ingår i: Carcinogenesis. - : OXFORD UNIV PRESS. - 0143-3334 .- 1460-2180. ; 38:7, s. 699-707
  • Tidskriftsartikel (refereegranskat)abstract
    • Adequate intake of copper and zinc, two essential micronutrients, are important for antioxidant functions. Their imbalance may have implications for development of diseases like colorectal cancer (CRC), where oxidative stress is thought to be etiologically involved. As evidence from prospective epidemiologic studies is lacking, we conducted a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort to investigate the association between circulating levels of copper and zinc, and their calculated ratio, with risk of CRC development. Copper and zinc levels were measured by reflection X-ray fluorescence spectrometer in 966 cases and 966 matched controls. Multivariable adjusted odds ratios (OR) and 95% confidence intervals (CI) were calculated using conditional logistic regression and are presented for the fifth versus first quintile. Higher circulating concentration of copper was associated with a raised CRC risk (OR = 1.50; 95% CI: 1.06, 2.13; P-trend = 0.02) whereas an inverse association with cancer risk was observed for higher zinc levels (OR = 0.65; 95% CI: 0.43, 0.97; P-trend = 0.07). Consequently, the ratio of copper/zinc was positively associated with CRC (OR = 1.70; 95% CI: 1.20, 2.40; P-trend = 0.0005). In subgroup analyses by follow-up time, the associations remained statistically significant only in those diagnosed within 2 years of blood collection. In conclusion, these data suggest that copper or copper levels in relation to zinc (copper to zinc ratio) become imbalanced in the process of CRC development. Mechanistic studies into the underlying mechanisms of regulation and action are required to further examine a possible role for higher copper and copper/ zinc ratio levels in CRC development and progression.
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10.
  • Stepien, Magdalena, et al. (författare)
  • Prediagnostic alterations in circulating bile acid profiles in the development of hepatocellular carcinoma
  • 2022
  • Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 150:8, s. 1255-1268
  • Tidskriftsartikel (refereegranskat)abstract
    • Bile acids (BAs) play different roles in cancer development. Some are carcinogenic and BA signaling is also involved in various metabolic, inflammatory and immune-related processes. The liver is the primary site of BA synthesis. Liver dysfunction and microbiome compositional changes, such as during hepatocellular carcinoma (HCC) development, may modulate BA metabolism increasing concentration of carcinogenic BAs. Observations from prospective cohorts are sparse. We conducted a study (233 HCC case-control pairs) nested within a large observational prospective cohort with blood samples taken at recruitment when healthy with follow-up over time for later cancer development. A targeted metabolomics method was used to quantify 17 BAs (primary/secondary/tertiary; conjugated/unconjugated) in prediagnostic plasma. Odd ratios (OR) for HCC risk associations were calculated by multivariable conditional logistic regression models. Positive HCC risk associations were observed for the molar sum of all BAs (ORdoubling = 2.30, 95% confidence intervals [CI]: 1.76-3.00), and choline- and taurine-conjugated BAs. Relative concentrations of BAs showed positive HCC risk associations for glycoholic acid and most taurine-conjugated BAs. We observe an association between increased HCC risk and higher levels of major circulating BAs, from several years prior to tumor diagnosis and after multivariable adjustment for confounders and liver functionality. Increase in BA concentration is accompanied by a shift in BA profile toward higher proportions of taurine-conjugated BAs, indicating early alterations of BA metabolism with HCC development. Future studies are needed to assess BA profiles for improved stratification of patients at high HCC risk and to determine whether supplementation with certain BAs may ameliorate liver dysfunction.
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14.
  • Vardas, Panos E., et al. (författare)
  • Orientações para pacing cardíaco e terapia deressincronização cardíaca
  • 2008
  • Ingår i: Revista portuguesa de cardiologia : orgão oficial da Sociedade Portuguesa de Cardiologia = Portuguese journal of cardiology : an official journal of the Portuguese Society of Cardiology. - 0870-2551. ; 27:5, s. 639-687
  • Tidskriftsartikel (refereegranskat)
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15.
  • Ageno, Walter, et al. (författare)
  • Managing reversal of direct oral anticoagulants in emergency situations Anticoagulation Education Task Force White Paper
  • 2016
  • Ingår i: Thrombosis and Haemostasis. - : SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN. - 0340-6245 .- 2567-689X. ; 116:6, s. 1003-1010
  • Tidskriftsartikel (refereegranskat)abstract
    • Anticoagulation is the cornerstone of prevention and treatment of venous thromboembolism (VTE) and stroke prevention in patients with atrial fibrillation (AF). However, the mechanisms by which anticoagulants confer therapeutic benefit also increase the risk of bleeding. As such, reversal strategies are critical. Until recently, the direct oral anticoagulants (DOACs) dabigatran, rivaroxaban, apixaban, and edoxaban lacked a specific reversal agent. This report is based on findings from the Anticoagulation Education Task Force, which brought together patient groups and professionals representing different medical specialties with an interest in patient safety and expertise in AF, VTE, stroke, anticoagulation, and reversal agents, to discuss the current status of anticoagulation reversal and fundamental changes in management of bleeding associated with DOACs occasioned by the approval of idarucizumab, a specific reversal agent for dabigatran, as well as recent clinical data on specific reversal agents for factor Xa inhibitors. Recommendations are given for when there is a definite need for a reversal agent (e.g. in cases of life-threatening bleeding, bleeding into a closed space or organ, persistent bleeding despite local haemostatic measures, and need for urgent interventions and/or interventions that carry a high risk for bleeding), when reversal agents may be helpful, and when a reversal agent is generally not needed. Key stakeholders who require 24-7/around-the-clock access to these agents vary among hospitals; however, from a practical perspective the emergency department is recommended as an appropriate location for these agents. Clearly, the advent of new agents requires standardised protocols for treating bleeding on an institutional level.
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16.
  • Batra, Gorav, et al. (författare)
  • Data standards for atrial fibrillation/flutter and catheter ablation : The European Unified Registries for Heart Care Evaluation and Randomized Trials (EuroHeart)
  • 2023
  • Ingår i: European Heart Journal - Quality of Care and Clinical Outcomes. - : Oxford University Press. - 2058-5225 .- 2058-1742. ; 9:6, s. 609-620
  • Tidskriftsartikel (refereegranskat)abstract
    • AIMS: Standardized data definitions are essential for monitoring and assessment of care and outcomes in observational studies and randomized controlled trials (RCTs). The European Unified Registries for Heart Care Evaluation and Randomized Trials (EuroHeart) project of the European Society of Cardiology aimed to develop contemporary data standards for atrial fibrillation/flutter (AF/AFL) and catheter ablation.METHODS AND RESULTS: We used the EuroHeart methodology for development of data standards and formed a Working Group comprising 23 experts in AF/AFL and catheter ablation registries, as well as representatives from the European Heart Rhythm Association and EuroHeart. We conducted a systematic literature review of AF/AFL and catheter ablation registries and data standard documents to generate candidate variables. We used a modified Delphi method to reach consensus on a final variable set. For each variable, the Working Group developed permissible values and definitions, and agreed as to whether the variable was mandatory (Level 1) or additional (Level 2). In total, 70 Level 1 and 92 Level 2 variables were selected and reviewed by a wider Reference Group of 42 experts from 24 countries. The Level 1 variables were implemented into the EuroHeart IT platform as the basis for continuous registration of individual patient data.CONCLUSION: By means of a structured process and working with international stakeholders, harmonized data standards for AF/AFL and catheter ablation for AF/AFL were developed. In context of the EuroHeart project, this will facilitate country-level quality of care improvement, international observational research, registry-based RCTs and post-marketing surveillance of devices and pharmacotherapies.
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17.
  • Berne, Olivier, et al. (författare)
  • PDRs4All : A JWST Early Release Science Program on Radiative Feedback from Massive Stars
  • 2022
  • Ingår i: Publications of the Astronomical Society of the Pacific. - : IOP Publishing. - 0004-6280 .- 1538-3873. ; 134:1035
  • Tidskriftsartikel (refereegranskat)abstract
    • Massive stars disrupt their natal molecular cloud material through radiative and mechanical feedback processes. These processes have profound effects on the evolution of interstellar matter in our Galaxy and throughout the universe, from the era of vigorous star formation at redshifts of 1-3 to the present day. The dominant feedback processes can be probed by observations of the Photo-Dissociation Regions (PDRs) where the far-ultraviolet photons of massive stars create warm regions of gas and dust in the neutral atomic and molecular gas. PDR emission provides a unique tool to study in detail the physical and chemical processes that are relevant for most of the mass in inter- and circumstellar media including diffuse clouds, proto-planetary disks, and molecular cloud surfaces, globules, planetary nebulae, and star-forming regions. PDR emission dominates the infrared (IR) spectra of star-forming galaxies. Most of the Galactic and extragalactic observations obtained with the James Webb Space Telescope (JWST) will therefore arise in PDR emission. In this paper we present an Early Release Science program using the MIRI, NIRSpec, and NIRCam instruments dedicated to the observations of an emblematic and nearby PDR: the Orion Bar. These early JWST observations will provide template data sets designed to identify key PDR characteristics in JWST observations. These data will serve to benchmark PDR models and extend them into the JWST era. We also present the Science-Enabling products that we will provide to the community. These template data sets and Science-Enabling products will guide the preparation of future proposals on star-forming regions in our Galaxy and beyond and will facilitate data analysis and interpretation of forthcoming JWST observations.
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18.
  • Berry, Sarah E., et al. (författare)
  • Human postprandial responses to food and potential for precision nutrition
  • 2020
  • Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 26:6, s. 964-973
  • Tidskriftsartikel (refereegranskat)abstract
    • Metabolic responses to food influence risk of cardiometabolic disease, but large-scale high-resolution studies are lacking. We recruited n = 1,002 twins and unrelated healthy adults in the United Kingdom to the PREDICT 1 study and assessed postprandial metabolic responses in a clinical setting and at home. We observed large inter-individual variability (as measured by the population coefficient of variation (s.d./mean, %)) in postprandial responses of blood triglyceride (103%), glucose (68%) and insulin (59%) following identical meals. Person-specific factors, such as gut microbiome, had a greater influence (7.1% of variance) than did meal macronutrients (3.6%) for postprandial lipemia, but not for postprandial glycemia (6.0% and 15.4%, respectively); genetic variants had a modest impact on predictions (9.5% for glucose, 0.8% for triglyceride, 0.2% for C-peptide). Findings were independently validated in a US cohort (n = 100 people). We developed a machine-learning model that predicted both triglyceride (r = 0.47) and glycemic (r = 0.77) responses to food intake. These findings may be informative for developing personalized diet strategies. The ClinicalTrials.gov registration identifier is NCT03479866.
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19.
  • Billings, Liana K., et al. (författare)
  • Increased Genetic Risk for b-Cell Failure Is Associated With b-Cell Function Decline in People With Prediabetes
  • 2024
  • Ingår i: Diabetes. - 0012-1797. ; 73:8, s. 1352-1360
  • Tidskriftsartikel (refereegranskat)abstract
    • Partitioned polygenic scores (pPS) have been developed to capture pathophysiologic processes underlying type 2 diabetes (T2D). We investigated the association of T2D pPS with diabetes-related traits and T2D incidence in the Diabetes Prevention Program. We generated five T2D pPS (b-cell, proinsulin, liver/lipid, obesity, lipodystrophy) in 2,647 participants randomized to intensive lifestyle, metformin, or placebo arms. Associations were tested with general linear models and Cox regression with adjustment for age, sex, and principal components. Sensitivity analyses included adjustment for BMI. Higher b-cell pPS was associated with lower insulinogenic index and corrected insulin response at 1-year follow-up with adjustment for baseline measures (effect per pPS SD 20.04, P = 9.6 × 1027, and 28.45 lU/mg, P = 5.6 × 1026, respec-tively) and with increased diabetes incidence with adjustment for BMI at nominal significance (hazard ratio 1.10 per SD, P = 0.035). The liver/lipid pPS was associated with reduced 1-year baseline-adjusted triglyceride levels (effect per SD 24.37, P = 0.001). There was no significant interaction between T2D pPS and randomized groups. The remaining pPS were associated with baseline measures only. We conclude that despite interventions for diabetes prevention, participants with a high genetic burden of the b-cell cluster pPS had worsening in measures of b-cell function.
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20.
  • Boriani, Giuseppe, et al. (författare)
  • Safety and efficacy of dronedarone from clinical trials to real-world evidence : implications for its use in atrial fibrillation
  • 2019
  • Ingår i: Europace. - : Oxford University Press. - 1099-5129 .- 1532-2092. ; 21:12, s. 1764-1775
  • Tidskriftsartikel (refereegranskat)abstract
    • Efficacy and safety of dronedarone was shown in the ATHENA trial for paroxysmal or persistent atrial fibrillation (AF) patients. Further trials revealed safety concerns in patients with heart failure and permanent AF. This review summarizes insights from recent real-world studies and meta-analyses, including reports on efficacy, with focus on liver safety, mortality risk in patients with paroxysmal/persistent AF, and interactions of dronedarone with direct oral anticoagulants. Reports of rapidly progressing liver failure in dronedarone-prescribed patients in 2011 led to regulatory cautions about potential liver toxicity. Recent real-world evidence suggests dronedarone liver safety profile is similar to other antiarrhythmics and liver toxicity could be equally common with many Class III antiarrhythmics. Dronedarone safety concerns (increased mortality in patients with permanent AF) were raised based on randomized controlled trials (RCT) (ANDROMEDA and PALLAS), but comedication with digoxin may have increased the mortality rates in PALLAS, considering the dronedarone-digoxin pharmacokinetic (PK) interaction. Real-world data on apixaban-dronedarone interactions and edoxaban RCT observations suggest no significant safety risks for these drug combinations. Median trough plasma concentrations of dabigatran 110 mg during concomitant use with dronedarone are at acceptable levels, while PK data on the rivaroxaban-dronedarone interaction are unavailable. In RCTs and real-world studies, dronedarone significantly reduces AF burden and cardiovascular hospitalizations, and demonstrates a low risk for proarrhythmia in patients with paroxysmal or persistent AF. The concerns on liver safety must be balanced against the significant reduction in hospitalizations in patients with non-permanent AF and low risk for proarrhythmias following dronedarone treatment.
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21.
  • Bradbury, Kathryn E., et al. (författare)
  • Circulating insulin-like growth factor I in relation to melanoma risk in the European prospective investigation into cancer and nutrition
  • 2019
  • Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 144:5, s. 957-966
  • Tidskriftsartikel (refereegranskat)abstract
    • Insulin-like growth factor-I (IGF-I) regulates cell proliferation and apoptosis, and is thought to play a role in tumour development. Previous prospective studies have shown that higher circulating concentrations of IGF-I are associated with a higher risk of cancers at specific sites, including breast and prostate. No prospective study has examined the association between circulating IGF-I concentrations and melanoma risk. A nested case-control study of 1,221 melanoma cases and 1,221 controls was performed in the European Prospective Investigation into Cancer and Nutrition cohort, a prospective cohort of 520,000 participants recruited from 10 European countries. Conditional logistic regression was used to estimate odds ratios (ORs) for incident melanoma in relation to circulating IGF-I concentrations, measured by immunoassay. Analyses were conditioned on the matching factors and further adjusted for age at blood collection, education, height, BMI, smoking status, alcohol intake, marital status, physical activity and in women only, use of menopausal hormone therapy. There was no significant association between circulating IGF-I concentration and melanoma risk (OR for highest vs lowest fifth = 0.93 [95% confidence interval [CI]: 0.71 to 1.22]). There was no significant heterogeneity in the association between IGF-I concentrations and melanoma risk when subdivided by gender, age at blood collection, BMI, height, age at diagnosis, time between blood collection and diagnosis, or by anatomical site or histological subtype of the tumour (Pheterogeneity≥0.078). We found no evidence for an association between circulating concentrations of IGF-I measured in adulthood and the risk of melanoma.
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22.
  • Camm, A. John, et al. (författare)
  • AIM-AF : A Physician Survey in the United States and Europe
  • 2022
  • Ingår i: Journal of the American Heart Association. - : Ovid Technologies (Wolters Kluwer Health). - 2047-9980. ; 11:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Guideline recommendations are the accepted reference for selection of therapies for rhythm control of atrial fibrillation (AF). This study was designed to understand physicians' treatment practices and adherence to guidelines.Methods and Results: The AIM-AF (Antiarrhythmic Medication for Atrial Fibrillation) study was an online survey of clinical cardiologists and electrophysiologists that was conducted in the United States and Europe (N=629). Respondents actively treated >= 30 patients with AF who received drug therapy, and had received or were referred for ablation every 3 months. The survey comprised 96 questions on physician demographics, AF types, and treatment practices. Overall, 54% of respondents considered guidelines to be the most important nonpatient factor influencing treatment choice. Across most queried comorbidities, amiodarone was selected by 60% to 80% of respondents. Other nonadherent usage included sotalol by 21% in patients with renal impairment; dofetilide initiation (16%, United States only) outside of hospital; class Ic agents by 6% in coronary artery disease; and dronedarone by 8% in patients with heart failure with reduced ejection fraction. Additionally, rhythm control strategies were frequently chosen in asymptomatic AF (antiarrhythmic drugs [AADs], 35%; ablation, 8%) and subclinical AF (AADs, 38%; ablation, 13%). Despite guideline algorithms emphasizing safety first, efficacy (48%) was selected as the most important consideration for AAD choice, followed by safety (34%).Conclusions: Despite surveyed clinicians recognizing the importance of guidelines, nonadherence was frequently observed. While deviation may be reasonable in selected patients, in general, nonadherence has the potential to compromise patient safety. These findings highlight an underappreciation of the safe use of AADs, emphasizing the need for interventions to support optimal AAD selection.
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23.
  • Cercos-Pita, Jose Luis, et al. (författare)
  • The role of time integration in energy conservation in Smoothed Particle Hydrodynamics fluid dynamics simulations
  • 2023
  • Ingår i: European journal of mechanics. B, Fluids. - : Elsevier. - 0997-7546 .- 1873-7390. ; 97, s. 78-92
  • Tidskriftsartikel (refereegranskat)abstract
    • The choice of a time integration scheme is a crucial aspect of any transient fluid simulation, and Smoothed-Particle Hydrodynamics (SPH) is no exception. The influence of the time integration scheme on energy balance is here addressed. To do so, explicit expressions allowing to compute the deviations from the energy balance, induced by the time integration scheme, are provided. These expressions, computed a posteriori, are valid for different integration methods. Besides, a new formulation that improves energy conservation by enhancing stability, based on an implicit integration scheme, is proposed. Such formulation is tested with the simulation of a two-dimensional non-viscous impact of two jets, with no artificial dissipation terms. To the best of our knowledge, this is the first stable simulation of a non-dissipative system with a weakly-compressible SPH method. A viscous case, the Taylor-Green vortex, has also been simulated. Results show that an implicit time integration scheme also behaves better in a viscous context.(c) 2022 Elsevier Masson SAS. All rights reserved.
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24.
  • Chown, Ryan, et al. (författare)
  • PDRs4All: IV. An embarrassment of riches: Aromatic infrared bands in the Orion Bar
  • 2024
  • Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 685
  • Tidskriftsartikel (refereegranskat)abstract
    • Context. Mid-infrared observations of photodissociation regions (PDRs) are dominated by strong emission features called aromatic infrared bands (AIBs). The most prominent AIBs are found at 3.3, 6.2, 7.7, 8.6, and 11.2 µm. The most sensitive, highest-resolution infrared spectral imaging data ever taken of the prototypical PDR, the Orion Bar, have been captured by JWST. These high-quality data allow for an unprecedentedly detailed view of AIBs. Aims. We provide an inventory of the AIBs found in the Orion Bar, along with mid-IR template spectra from five distinct regions in the Bar: the molecular PDR (i.e. the three H2 dissociation fronts), the atomic PDR, and the H II region. Methods. We used JWST NIRSpec IFU and MIRI MRS observations of the Orion Bar from the JWST Early Release Science Program, PDRs4All (ID: 1288). We extracted five template spectra to represent the morphology and environment of the Orion Bar PDR. We investigated and characterised the AIBs in these template spectra. We describe the variations among them here. Results. The superb sensitivity and the spectral and spatial resolution of these JWST observations reveal many details of the AIB emission and enable an improved characterization of their detailed profile shapes and sub-components. The Orion Bar spectra are dominated by the well-known AIBs at 3.3, 6.2, 7.7, 8.6, 11.2, and 12.7 µm with well-defined profiles. In addition, the spectra display a wealth of weaker features and sub-components. The widths of many AIBs show clear and systematic variations, being narrowest in the atomic PDR template, but showing a clear broadening in the H II region template while the broadest bands are found in the three dissociation front templates. In addition, the relative strengths of AIB (sub-)components vary among the template spectra as well. All AIB profiles are characteristic of class A sources as designated by Peeters (2022, A&A, 390, 1089), except for the 11.2 µm AIB profile deep in the molecular zone, which belongs to class B11.2. Furthermore, the observations show that the sub-components that contribute to the 5.75, 7.7, and 11.2 µm AIBs become much weaker in the PDR surface layers. We attribute this to the presence of small, more labile carriers in the deeper PDR layers that are photolysed away in the harsh radiation field near the surface. The 3.3/11.2 AIB intensity ratio decreases by about 40% between the dissociation fronts and the H II region, indicating a shift in the polycyclic aromatic hydrocarbon (PAH) size distribution to larger PAHs in the PDR surface layers, also likely due to the effects of photochemistry. The observed broadening of the bands in the molecular PDR is consistent with an enhanced importance of smaller PAHs since smaller PAHs attain a higher internal excitation energy at a fixed photon energy. Conclusions. Spectral-imaging observations of the Orion Bar using JWST yield key insights into the photochemical evolution of PAHs, such as the evolution responsible for the shift of 11.2 µm AIB emission from class B11.2 in the molecular PDR to class A11.2 in the PDR surface layers. This photochemical evolution is driven by the increased importance of FUV processing in the PDR surface layers, resulting in a “weeding out” of the weakest links of the PAH family in these layers. For now, these JWST observations are consistent with a model in which the underlying PAH family is composed of a few species: the so-called ‘grandPAHs’.
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25.
  • Connolly, Stuart J, et al. (författare)
  • Dronedarone in High-Risk Permanent Atrial Fibrillation
  • 2011
  • Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 365:24, s. 2268-2276
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Dronedarone restores sinus rhythm and reduces hospitalization or death in intermittent atrial fibrillation. It also lowers heart rate and blood pressure and has antiadrenergic and potential ventricular anti-arrhythmic effects. We hypothesized that dronedarone would reduce major vascular events in high-risk permanent atrial fibrillation. Methods We assigned patients who were at least 65 years of age with at least a 6-month history of permanent atrial fibrillation and risk factors for major vascular events to receive dronedarone or placebo. The first coprimary outcome was stroke, myocardial infarction, systemic embolism, or death from cardiovascular causes. The second coprimary outcome was unplanned hospitalization for a cardiovascular cause or death. Results After the enrollment of 3236 patients, the study was stopped for safety reasons. The first coprimary outcome occurred in 43 patients receiving dronedarone and 19 receiving placebo (hazard ratio, 2.29; 95% confidence interval [CI], 1.34 to 3.94; P=0.002). There were 21 deaths from cardiovascular causes in the dronedarone group and 10 in the placebo group (hazard ratio, 2.11; 95% CI, 1.00 to 4.49; P=0.046), including death from arrhythmia in 13 patients and 4 patients, respectively (hazard ratio, 3.26; 95% CI, 1.06 to 10.00; P=0.03). Stroke occurred in 23 patients in the dronedarone group and 10 in the placebo group (hazard ratio, 2.32; 95% CI, 1.11 to 4.88; P=0.02). Hospitalization for heart failure occurred in 43 patients in the dronedarone group and 24 in the placebo group (hazard ratio, 1.81; 95% CI, 1.10 to 2.99; P=0.02). Conclusions Dronedarone increased rates of heart failure, stroke, and death from cardiovascular causes in patients with permanent atrial fibrillation who were at risk for major vascular events. Our data show that this drug should not be used in such patients.
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26.
  • De Putte, Dries Van, et al. (författare)
  • PDRs4All VIII. Mid-infrared emission line inventory of the Orion Bar
  • 2024
  • Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 687
  • Tidskriftsartikel (refereegranskat)abstract
    • Context . Mid-infrared emission features are important probes of the properties of ionized gas and hot or warm molecular gas, which are difficult to probe at other wavelengths. The Orion Bar photodissociation region (PDR) is a bright, nearby, and frequently studied target containing large amounts of gas under these conditions. Under the “PDRs4All” Early Release Science Program for JWST, a part of the Orion Bar was observed with MIRI integral field unit (IFU) spectroscopy, and these high-sensitivity IR spectroscopic images of very high angular resolution (0.2′′) provide a rich observational inventory of the mid-infrared (MIR) emission lines, while resolving the H II region, the ionization front, and multiple dissociation fronts. Aims . We list, identify, and measure the most prominent gas emission lines in the Orion Bar using the new MIRI IFU data. An initial analysis summarizes the physical conditions of the gas and demonstrates the potential of these new data and future IFU observations with JWST. Methods. The MIRI IFU mosaic spatially resolves the substructure of the PDR, its footprint cutting perpendicularly across the ionization front and three dissociation fronts. We performed an up-to-date data reduction, and extracted five spectra that represent the ionized, atomic, and molecular gas layers. We identified the observed lines through a comparison with theoretical line lists derived from atomic data and simulated PDR models. The identified species and transitions are summarized in the main table of this work, with measurements of the line intensities and central wavelengths. Results . We identified around 100 lines and report an additional 18 lines that remain unidentified. The majority consists of H I recombination lines arising from the ionized gas layer bordering the PDR. The H I line ratios are well matched by emissivity coefficients from H recombination theory, but deviate by up to 10% because of contamination by He I lines. We report the observed emission lines of various ionization stages of Ne, P, S, Cl, Ar, Fe, and Ni. We show how the Ne III/Ne II, S IV/S III, and Ar III/Ar II ratios trace the conditions in the ionized layer bordering the PDR, while Fe III/Fe II and Ni III/Ni II exhibit a different behavior, as there are significant contributions to Fe II and Ni II from the neutral PDR gas. We observe the pure-rotational H2 lines in the vibrational ground state from 0–0 S(1) to 0–0 S(8), and in the first vibrationally excited state from 1–1 S(5) to 1–1 S(9). We derive H2 excitation diagrams, and for the three observed dissociation fronts, the rotational excitation can be approximated with one thermal (∼700 K) component representative of an average gas temperature, and one nonthermal component (∼2700 K) probing the effect of UV pumping. We compare these results to an existing model of the Orion Bar PDR, and find that the predicted excitation matches the data qualitatively, while adjustments to the parameters of the PDR model are required to reproduce the intensity of the 0–0 S(6) to S(8) lines.
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27.
  • Fabritz, Larissa, et al. (författare)
  • Dynamic risk assessment to improve quality of care in patients with atrial fibrillation : the 7th AFNET/EHRA Consensus Conference
  • 2021
  • Ingår i: Europace. - : Oxford University Press. - 1099-5129 .- 1532-2092. ; 23:3, s. 329-344
  • Tidskriftsartikel (refereegranskat)abstract
    • AimsThe risk of developing atrial fibrillation (AF) and its complications continues to increase, despite good progress in preventing AF-related strokes.Methods and resultsThis article summarizes the outcomes of the 7th Consensus Conference of the Atrial Fibrillation NETwork (AFNET) and the European Heart Rhythm Association (EHRA) held in Lisbon in March 2019. Sixty-five international AF specialists met to present new data and find consensus on pressing issues in AF prevention, management and future research to improve care for patients with AF and prevent AF-related complications. This article is the main outcome of an interactive, iterative discussion between breakout specialist groups and the meeting plenary. AF patients have dynamic risk profiles requiring repeated assessment and risk-based therapy stratification to optimize quality of care. Interrogation of deeply phenotyped datasets with outcomes will lead to a better understanding of the cardiac and systemic effects of AF, interacting with comorbidities and predisposing factors, enabling stratified therapy. New proposals include an algorithm for the acute management of patients with AF and heart failure, a call for a refined, data-driven assessment of stroke risk, suggestions for anticoagulation use in special populations, and a call for rhythm control therapy selection based on risk of AF recurrence.ConclusionThe remaining morbidity and mortality in patients with AF needs better characterization. Likely drivers of the remaining AF-related problems are AF burden, potentially treatable by rhythm control therapy, and concomitant conditions, potentially treatable by treating these conditions. Identifying the drivers of AF-related complications holds promise for stratified therapy.
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28.
  • Fico, Giuseppe, et al. (författare)
  • What do healthcare professionals need to turn risk models for type 2 diabetes into usable computerized clinical decision support systems? Lessons learned from the MOSAIC project
  • 2019
  • Ingår i: BMC Medical Informatics and Decision Making. - : Springer Science and Business Media LLC. - 1472-6947. ; 19
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: To understand user needs, system requirements and organizational conditions towards successful design and adoption of Clinical Decision Support Systems for Type 2 Diabetes (T2D) care built on top of computerized risk models. Methods: The holistic and evidence-based CEHRES Roadmap, used to create eHealth solutions through participatory development approach, persuasive design techniques and business modelling, was adopted in the MOSAIC project to define the sequence of multidisciplinary methods organized in three phases, user needs, implementation and evaluation. The research was qualitative, the total number of participants was ninety, about five-seventeen involved in each round of experiment. Results: Prediction models for the onset of T2D are built on clinical studies, while for T2D care are derived from healthcare registries. Accordingly, two set of DSSs were defined: the first, T2D Screening, introduces a novel routine; in the second case, T2D Care, DSSs can support managers at population level, and daily practitioners at individual level. In the user needs phase, T2D Screening and solution T2D Care at population level share similar priorities, as both deal with risk-stratification. End-users of T2D Screening and solution T2D Care at individual level prioritize easiness of use and satisfaction, while managers prefer the tools to be available every time and everywhere. In the implementation phase, three Use Cases were defined for T2D Screening, adapting the tool to different settings and granularity of information. Two Use Cases were defined around solutions T2D Care at population and T2D Care at individual, to be used in primary or secondary care. Suitable filtering options were equipped with "attractive" visual analytics to focus the attention of end-users on specific parameters and events. In the evaluation phase, good levels of user experience versus bad level of usability suggest that end-users of T2D Screening perceived the potential, but they are worried about complexity. Usability and user experience were above acceptable thresholds for T2D Care at population and T2D Care at individual. Conclusions: By using a holistic approach, we have been able to understand user needs, behaviours and interactions and give new insights in the definition of effective Decision Support Systems to deal with the complexity of T2D care.
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29.
  • Habart, Emilie, et al. (författare)
  • PDRs4All II. JWST’s NIR and MIR imaging view of the Orion Nebula
  • 2024
  • Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 685
  • Tidskriftsartikel (refereegranskat)abstract
    • Context. The James Webb Space Telescope (JWST) has captured the most detailed and sharpest infrared (IR) images ever taken of the inner region of the Orion Nebula, the nearest massive star formation region, and a prototypical highly irradiated dense photo-dissociation region (PDR). Aims. We investigate the fundamental interaction of far-ultraviolet (FUV) photons with molecular clouds. The transitions across the ionization front (IF), dissociation front (DF), and the molecular cloud are studied at high-angular resolution. These transitions are relevant to understanding the effects of radiative feedback from massive stars and the dominant physical and chemical processes that lead to the IR emission that JWST will detect in many Galactic and extragalactic environments. Methods. We utilized NIRCam and MIRI to obtain sub-arcsecond images over ∼150′′ and 42′′ in key gas phase lines (e.g., Pa α, Br α, [FeII] 1.64 µm, H2 1–0 S(1) 2.12 µm, 0–0 S(9) 4.69 µm), aromatic and aliphatic infrared bands (aromatic infrared bands at 3.3–3.4 µm, 7.7, and 11.3 µm), dust emission, and scattered light. Their emission are powerful tracers of the IF and DF, FUV radiation field and density distribution. Using NIRSpec observations the fractional contributions of lines, AIBs, and continuum emission to our NIRCam images were estimated. A very good agreement is found for the distribution and intensity of lines and AIBs between the NIRCam and NIRSpec observations. Results. Due to the proximity of the Orion Nebula and the unprecedented angular resolution of JWST, these data reveal that the molecular cloud borders are hyper structured at small angular scales of ∼0.1–1′′ (∼0.0002–0.002 pc or ∼40–400 au at 414 pc). A diverse set of features are observed such as ridges, waves, globules and photoevaporated protoplanetary disks. At the PDR atomic to molecular transition, several bright features are detected that are associated with the highly irradiated surroundings of the dense molecular condensations and embedded young star. Toward the Orion Bar PDR, a highly sculpted interface is detected with sharp edges and density increases near the IF and DF. This was predicted by previous modeling studies, but the fronts were unresolved in most tracers. The spatial distribution of the AIBs reveals that the PDR edge is steep and is followed by an extensive warm atomic layer up to the DF with multiple ridges. A complex, structured, and folded H0/H2 DF surface was traced by the H2 lines. This dataset was used to revisit the commonly adopted 2D PDR structure of the Orion Bar as our observations show that a 3D “terraced” geometry is required to explain the JWST observations. JWST provides us with a complete view of the PDR, all the way from the PDR edge to the substructured dense region, and this allowed us to determine, in detail, where the emission of the atomic and molecular lines, aromatic bands, and dust originate. Conclusions. This study offers an unprecedented dataset to benchmark and transform PDR physico-chemical and dynamical models for the JWST era. A fundamental step forward in our understanding of the interaction of FUV photons with molecular clouds and the role of FUV irradiation along the star formation sequence is provided.
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30.
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31.
  • Jayasekara, Harindra, et al. (författare)
  • Lifetime alcohol intake, drinking patterns over time and risk of stomach cancer : A pooled analysis of data from two prospective cohort studies
  • 2021
  • Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 148:11, s. 2759-2773
  • Tidskriftsartikel (refereegranskat)abstract
    • Alcohol consumption is causally linked to several cancers but the evidence for stomach cancer is inconclusive. In our study, the association between long-term alcohol intake and risk of stomach cancer and its subtypes was evaluated. We performed a pooled analysis of data collected at baseline from 491 714 participants in the European Prospective Investigation into Cancer and Nutrition and the Melbourne Collaborative Cohort Study. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for incident stomach cancer in relation to lifetime alcohol intake and group-based life course intake trajectories, adjusted for potential confounders including Helicobacter pylori infection. In all, 1225 incident stomach cancers (78% noncardia) were diagnosed over 7 094 637 person-years; 984 in 382 957 study participants with lifetime alcohol intake data (5 455 507 person-years). Although lifetime alcohol intake was not associated with overall stomach cancer risk, we observed a weak positive association with noncardia cancer (HR = 1.03, 95% CI: 1.00-1.06 per 10 g/d increment), with a HR of 1.50 (95% CI: 1.08-2.09) for ≥60 g/d compared to 0.1 to 4.9 g/d. A weak inverse association with cardia cancer (HR = 0.93, 95% CI: 0.87-1.00) was also observed. HRs of 1.48 (95% CI: 1.10-1.99) for noncardia and 0.51 (95% CI: 0.26-1.03) for cardia cancer were observed for a life course trajectory characterized by heavy decreasing intake compared to light stable intake (Phomogeneity =.02). These associations did not differ appreciably by smoking or H pylori infection status. Limiting alcohol use during lifetime, particularly avoiding heavy use during early adulthood, might help prevent noncardia stomach cancer. Heterogeneous associations observed for cardia and noncardia cancers may indicate etiologic differences.
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32.
  • Li, Zhen, et al. (författare)
  • Single-Copy Genes as Molecular Markers for Phylogenomic Studies in Seed Plants
  • 2017
  • Ingår i: Genome Biology and Evolution. - : Oxford University Press. - 1759-6653. ; 9:5, s. 1130-1147
  • Tidskriftsartikel (refereegranskat)abstract
    • Phylogenetic relationships among seed plant taxa, especially within the gymnosperms, remain contested. In contrast to angio-sperms, for which several genomic, transcriptomic and phylogenetic resources are available, there are few, if any, molecular markers that allow broad comparisons among gymnosperm species. With few gymnosperm genomes available, recently obtained transcriptomes in gymnosperms are a great addition to identifying single-copy gene families as molecular markers for phylogenomic analysis in seed plants. Taking advantage of an increasing number of available genomes and transcriptomes, we identified single-copy genes in a broad collection of seed plants and used these to infer phylogenetic relationships between major seed plant taxa. This study aims at extending the current phylogenetic toolkit for seed plants, assessing its ability for resolving seed plant phylogeny, and discussing potential factors affecting phylogenetic reconstruction. In total, we identified 3,072 single-copy genes in 31 gymnosperms and 2,156 single-copy genes in 34 angiosperms. All studied seed plants shared 1,469 single-copy genes, which are generally involved in functions like DNA metabolism, cell cycle, and photosynthesis. A selected set of 106 single-copy genes provided good resolution for the seed plant phylogeny except for gnetophytes. Although some of our analyses support a sister relationship between gnetophytes and other gymnosperms, phylogenetic trees from concatenated alignments without 3rd codon positions and amino acid alignments under the CAT + GTR model, support gnetophytes as a sister group to Pinaceae. Our phylogenomic analyses demonstrate that, in general, single-copy genes can uncover both recent and deep divergences of seed plant phylogeny.
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33.
  • Linz, Dominik, et al. (författare)
  • Longer and better lives for patients with atrial fibrillation : the 9th AFNET/EHRA consensus conference
  • 2024
  • Ingår i: Europace. - : Oxford University Press. - 1099-5129 .- 1532-2092. ; 26:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims: Recent trial data demonstrate beneficial effects of active rhythm management in patients with atrial fibrillation (AF) and support the concept that a low arrhythmia burden is associated with a low risk of AF-related complications. The aim of this document is to summarize the key outcomes of the 9th AFNET/EHRA Consensus Conference of the Atrial Fibrillation NETwork (AFNET) and the European Heart Rhythm Association (EHRA).Methods and results: Eighty-three international experts met in Munster for 2 days in September 2023. Key findings are as follows: (i) Active rhythm management should be part of the default initial treatment for all suitable patients with AF. (ii) Patients with device-detected AF have a low burden of AF and a low risk of stroke. Anticoagulation prevents some strokes and also increases major but non-lethal bleeding. (iii) More research is needed to improve stroke risk prediction in patients with AF, especially in those with a low AF burden. Biomolecules, genetics, and imaging can support this. (iv) The presence of AF should trigger systematic workup and comprehensive treatment of concomitant cardiovascular conditions. (v) Machine learning algorithms have been used to improve detection or likely development of AF. Cooperation between clinicians and data scientists is needed to leverage the potential of data science applications for patients with AF.Conclusions: Patients with AF and a low arrhythmia burden have a lower risk of stroke and other cardiovascular events than those with a high arrhythmia burden. Combining active rhythm control, anticoagulation, rate control, and therapy of concomitant cardiovascular conditions can improve the lives of patients with AF. Graphical Abstract
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34.
  • López-Merino, Lourdes, et al. (författare)
  • Reconstructing the impact of human activities in a NW Iberian Roman mining landscape for the last 2500 years
  • 2014
  • Ingår i: Journal of Archaeological Science. - : Elsevier. - 0305-4403 .- 1095-9238. ; 50, s. 208-218
  • Tidskriftsartikel (refereegranskat)abstract
    • Little is known about the impact of human activities during Roman times on NW Iberian mining landscapes beyond the geomorphological transformations brought about by the use of hydraulic power for gold extraction. We present the high-resolution pollen record of La Molina mire, located in an area intensely used for gold mining (Asturias, NW Spain), combined with other proxy data from the same peat core to identify different human activities, evaluate the strategies followed for the management of the resources and describe the landscape response to human disturbances. We reconstructed the timing and synchronicity of landscape changes of varying intensity and form occurred before, during and after Roman times. An open landscape was prevalent during the local Late Iron Age, a period of relatively environmental stability. During the Early Roman Empire more significant vegetation shifts took place, reflected by changes in both forest (Corylus and Quercus) and heathland cover, as mining/metallurgy peaked and grazing and cultivation increased. In the Late Roman Empire, the influence of mining/metallurgy on landscape change started to disappear. This decoupling was further consolidated in the Germanic period (i.e., Visigothic and Sueve domination of the region), with a sharp decrease in mining/metallurgy but continued grazing. Although human impact was intense in some periods, mostly during the Early Roman Empire, forest regeneration occurred afterwards: clearances were local and short-lived. However, the Roman mining landscape turned into an agrarian one at the onset of the Middle Ages, characterized by a profound deforestation at a regional level due to a myriad of human activities that resulted in an irreversible openness of the landscape.
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35.
  • Merino, Jordi, et al. (författare)
  • Interaction Between Type 2 Diabetes Prevention Strategies and Genetic Determinants of Coronary Artery Disease on Cardiometabolic Risk Factors
  • 2020
  • Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 69:1, s. 112-120
  • Tidskriftsartikel (refereegranskat)abstract
    • Coronary artery disease (CAD) is more frequent among individuals with dysglycemia. Preventive interventions for diabetes can improve cardiometabolic risk factors (CRFs), but it is unclear whether the benefits on CRFs are similar for individuals at different genetic risk for CAD. We built a 201-variant polygenic risk score (PRS) for CAD and tested for interaction with diabetes prevention strategies on 1-year changes in CRFs in 2,658 Diabetes Prevention Program (DPP) participants. We also examined whether separate lifestyle behaviors interact with PRS and affect changes in CRFs in each intervention group. Participants in both the lifestyle and metformin interventions had greater improvement in the majority of recognized CRFs compared with placebo (P < 0.001) irrespective of CAD genetic risk (Pinteraction > 0.05). We detected nominal significant interactions between PRS and dietary quality and physical activity on 1-year change in BMI, fasting glucose, triglycerides, and HDL cholesterol in individuals randomized to metformin or placebo, but none of them achieved the multiple-testing correction for significance. This study confirms that diabetes preventive interventions improve CRFs regardless of CAD genetic risk and delivers hypothesis-generating data on the varying benefit of increasing physical activity and improving diet on intermediate cardiovascular risk factors depending on individual CAD genetic risk profile.
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36.
  • Merino, Jordi, et al. (författare)
  • Polygenic scores, diet quality, and type 2 diabetes risk : An observational study among 35,759 adults from 3 US cohorts
  • 2022
  • Ingår i: PLoS Medicine. - : Public Library of Science (PLoS). - 1549-1277 .- 1549-1676. ; 19:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Bothgenetic and lifestyle factors contribute to the risk of type 2 diabetes, but the extent to which there is a synergistic effect of the 2 factors is unclear. The aim of this study was to examine the joint associations of genetic risk and diet quality with incident type 2 diabetes. Methods and findings We analyzed data from 35,759 men and women in the United States participating in the Nurses’ Health Study (NHS) I (1986 to 2016) and II (1991 to 2017) and the Health Professionals Follow-up Study (HPFS; 1986 to 2016) with available genetic data and who did not have diabetes, cardiovascular disease, or cancer at baseline. Genetic risk was characterized using both a global polygenic score capturing overall genetic risk and pathway-specific polygenic scores denoting distinct pathophysiological mechanisms. Diet quality was assessed using the Alternate Healthy Eating Index (AHEI). Cox models were used to calculate hazard ratios (HRs) for type 2 diabetes after adjusting for potential confounders. WAU ith: Pleas over 902,386 person-years of follow-up, 4,433 participants were diagnosed with type 2 diabetes. The relative risk of type 2 diabetes was 1.29 (95% confidence interval [CI] 1.25, 1.32; P < 0.001) per standard deviation (SD) increase in global polygenic score and 1.13 (1.09, 1.17; P < 0.001) per 10-unit decrease in AHEI. Irrespective of genetic risk, low diet quality, as compared to high diet quality, was associated with approximately 30% increased risk of type 2 diabetes (Pinteraction = 0.69). The joint association of low diet quality and increased genetic risk was similar to the sum of the risk associated with each factor alone (Pinteraction = 0.30). Limitations of this study include the self-report of diet information and possible bias resulting from inclusion of highly educated participants with available genetic data. Conclusions These data provide evidence for the independent associations of genetic risk and diet quality with incident type 2 diabetes and suggest that a healthy diet is associated with lower diabetes risk across all levels of genetic risk.
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37.
  • Merino, Jordi, et al. (författare)
  • Validity of continuous glucose monitoring for categorizing glycemic responses to diet : Implications for use in personalized nutrition
  • 2022
  • Ingår i: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165. ; 115:6, s. 1569-1576
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Continuous glucose monitor (CGM) devices enable characterization of individuals' glycemic variation. However, there are concerns about their reliability for categorizing glycemic responses to foods that would limit their potential application in personalized nutrition recommendations. Objectives: We aimed to evaluate the concordance of 2 simultaneously worn CGM devices in measuring postprandial glycemic responses. Methods: Within ZOE PREDICT (Personalised Responses to Dietary Composition Trial) 1, 394 participants wore 2 CGM devices simultaneously [n = 360 participants with 2 Abbott Freestyle Libre Pro (FSL) devices; n = 34 participants with both FSL and Dexcom G6] for ≤14 d while consuming standardized (n = 4457) and ad libitum (n = 5738) meals. We examined the CV and correlation of the incremental area under the glucose curve at 2 h (glucoseiAUC0-2 h). Within-subject meal ranking was assessed using Kendall τ rank correlation. Concordance between paired devices in time in range according to the American Diabetes Association cutoffs (TIRADA) and glucose variability (glucose CV) was also investigated. Results: The CV of glucoseiAUC0-2 h for standardized meals was 3.7% (IQR: 1.7%-7.1%) for intrabrand device and 12.5% (IQR: 5.1%-24.8%) for interbrand device comparisons. Similar estimates were observed for ad libitum meals, with intrabrand and interbrand device CVs of glucoseiAUC0-2 h of 4.1% (IQR: 1.8%-7.1%) and 16.6% (IQR: 5.5%-30.7%), respectively. Kendall τ rank correlation showed glucoseiAUC0-2h-derived meal rankings were agreeable between paired CGM devices (intrabrand: 0.9; IQR: 0.8-0.9; interbrand: 0.7; IQR: 0.5-0.8). Paired CGMs also showed strong concordance for TIRADA with a intrabrand device CV of 4.8% (IQR: 1.9%-9.8%) and an interbrand device CV of 3.2% (IQR: 1.1%-6.2%). Conclusions: Our data demonstrate strong concordance of CGM devices in monitoring glycemic responses and suggest their potential use in personalized nutrition.
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38.
  • Merino, Luis, et al. (författare)
  • Single and Multi-UAV Relative Position Estimation Based on Natural Landmarks
  • 2007
  • Ingår i: Advances in Unmanned Aerial Vehicles. - Netherlands : Springer. - 9781402061134 - 9781402061141 ; , s. 267-307
  • Bokkapitel (populärvet., debatt m.m.)abstract
    • This Chapter presents a vision-based method for unmanned aerial vehicle (UAV) motion estimation that uses as input an image motion field obtained from matches of point-like features. The Chapter enhances visionbased techniques developed for single UAV localization and demonstrates how they can be modified to deal with the problem of multi-UAV relative position estimation. The proposed approach is built upon the assumption that if different UAVs identify, using their cameras, common objects in a scene, the relative pose displacement between the UAVs can be computed from these correspondences under certain assumptions. However, although point-like features are suitable for local UAV motion estimation, finding matches between images collected using different cameras is a difficult task that may be overcome using blob features. Results justify the proposed approach.
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39.
  • Merino, Luis, et al. (författare)
  • Vision-Based Multi-UAV Position Estimation
  • 2006
  • Ingår i: IEEE Robotics & Automation Magazine. - 1070-9932. ; 13:3, s. 53-62
  • Tidskriftsartikel (refereegranskat)abstract
    • This paper describes a method for vision-based unmanned aerial vehicle (UAV) motion estimation from multiple planar homographies. The paper also describes the determination of the relative displacement between different UAVs employing techniques for blob feature extraction and matching. It then presents and shows experimental results of the application of the proposed technique to multi-UAV detection of forest fires.  
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40.
  • Ollero, Anibal, et al. (författare)
  • Multiple Eyes in the Skies
  • 2005
  • Ingår i: IEEE robotics & automation magazine. - 1070-9932 .- 1558-223X. ; 12:2, s. 46-57
  • Tidskriftsartikel (refereegranskat)abstract
    • The management of environmental and industrial disasters, search and rescue operations, surveillance of natural scenarios, environmental monitoring, and many other field robotics applications require high mobility and the need to reach locations that are difficult to access with ground vehicles. In many cases, the use of aerial vehicles is the best way to approach the objective to get information or to deploy instrumentation. Unmanned air vehicles (UAVs) have significantly increased their flight performance and autonomous onboard processing capabilities in the last ten years. But a single aerial vehicle equipped with a large array of different sensors of various modalities is limited at any time to a single viewpoint. A team of aerial vehicles, however, can simultaneously collect information from multiple locations and exploit the information derived from multiple disparate points. Furthermore, having a team with multiple heterogeneous aerial vehicles offers additional advantages due to the possibility of beneficial complementarities of the vehicles.
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41.
  • Peeters, Els, et al. (författare)
  • PDRs4All: III. JWST's NIR spectroscopic view of the Orion Bar
  • 2024
  • Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 685
  • Tidskriftsartikel (refereegranskat)abstract
    • Context. JWST has taken the sharpest and most sensitive infrared (IR) spectral imaging observations ever of the Orion Bar photodis-sociation region (PDR), which is part of the nearest massive star-forming region the Orion Nebula, and often considered to be the 'prototypical'strongly illuminated PDR. Aims. We investigate the impact of radiative feedback from massive stars on their natal cloud and focus on the transition from the H II region to the atomic PDR -crossing the ionisation front (IF) -, and the subsequent transition to the molecular PDR -crossing the dissociation front (DF). Given the prevalence of PDRs in the interstellar medium and their dominant contribution to IR radiation, understanding the response of the PDR gas to far-ultraviolet (FUV) photons and the associated physical and chemical processes is fundamental to our understanding of star and planet formation and for the interpretation of any unresolved PDR as seen by JWST. Methods. We used high-resolution near-IR integral field spectroscopic data from NIRSpec on JWST to observe the Orion Bar PDR as part of the PDRs4All JWST Early Release Science programme. We constructed a 3″ × 25″ spatio-spectral mosaic covering 0.97-5.27 μm at a spectral resolution R of ~2700 and an angular resolution of 0.075″-0.173″. To study the properties of key regions captured in this mosaic, we extracted five template spectra in apertures centred on the three H2 dissociation fronts, the atomic PDR, and the H II region. This wealth of detailed spatial-spectral information was analysed in terms of variations in the physical conditions-incident UV field, density, and temperature -of the PDR gas. Results. The NIRSpec data reveal a forest of lines including, but not limited to, He I, H I, and C I recombination lines; ionic lines (e.g. Fe III and Fe II); O I and N I fluorescence lines; aromatic infrared bands (AIBs, including aromatic CH, aliphatic CH, and their CD counterparts); pure rotational and ro-vibrational lines from H2; and ro-vibrational lines from HD, CO, and CH+, with most of them having been detected for the first time towards a PDR. Their spatial distribution resolves the H and He ionisation structure in the Huygens region, gives insight into the geometry of the Bar, and confirms the large-scale stratification of PDRs. In addition, we observed numerous smaller-scale structures whose typical size decreases with distance from θ1 Ori C and IR lines from C I, if solely arising from radiative recombination and cascade, reveal very high gas temperatures (a few 1000 K) consistent with the hot irradiated surface of small-scale dense clumps inside the PDR. The morphology of the Bar, in particular that of the H2 lines, reveals multiple prominent filaments that exhibit different characteristics. This leaves the impression of a 'terraced'transition from the predominantly atomic surface region to the CO-rich molecular zone deeper in. We attribute the different characteristics of the H2 filaments to their varying depth into the PDR and, in some cases, not reaching the C+/C/CO transition. These observations thus reveal what local conditions are required to drive the physical and chemical processes needed to explain the different characteristics of the DFs and the photochemical evolution of the AIB carriers. Conclusions. This study showcases the discovery space created by JWST to further our understanding of the impact radiation from young stars has on their natal molecular cloud and proto-planetary disk, which touches on star and planet formation as well as galaxy evolution.
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42.
  • Pierrotti, Ligia C., et al. (författare)
  • Efficacy of beta-lactam/beta-lactamase inhibitors to treat extended-spectrum beta-lactamase-producing Enterobacterales bacteremia secondary to urinary tract infection in kidney transplant recipients (INCREMENT-SOT Project)
  • 2021
  • Ingår i: Transplant Infectious Disease. - : John Wiley & Sons. - 1398-2273 .- 1399-3062. ; 23:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Whether active therapy with beta-lactam/beta-lactamase inhibitors (BLBLI) is as affective as carbapenems for extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E) bloodstream infection (BSI) secondary to urinary tract infection (UTI) in kidney transplant recipients (KTRs) remains unclear. Methods We retrospectively evaluated 306 KTR admitted to 30 centers from January 2014 to October 2016. Therapeutic failure (lack of cure or clinical improvement and/or death from any cause) at days 7 and 30 from ESBL-E BSI onset was the primary and secondary study outcomes, respectively. Results Therapeutic failure at days 7 and 30 occurred in 8.2% (25/306) and 13.4% (41/306) of patients. Hospital-acquired BSI (adjusted OR [aOR]: 4.10; 95% confidence interval [CI]: 1.50-11.20) and Pitt score (aOR: 1.47; 95% CI: 1.21-1.77) were independently associated with therapeutic failure at day 7. Age-adjusted Charlson Index (aOR: 1.25; 95% CI: 1.05-1.48), Pitt score (aOR: 1.72; 95% CI: 1.35-2.17), and lymphocyte count <= 500 cells/mu L at presentation (aOR: 3.16; 95% CI: 1.42-7.06) predicted therapeutic failure at day 30. Carbapenem monotherapy (68.6%, primarily meropenem) was the most frequent active therapy, followed by BLBLI monotherapy (10.8%, mostly piperacillin-tazobactam). Propensity score (PS)-adjusted models revealed no significant impact of the choice of active therapy (carbapenem-containing vs any other regimen, BLBLI- vs carbapenem-based monotherapy) within the first 72 hours on any of the study outcomes. Conclusions Our data suggest that active therapy based on BLBLI may be as effective as carbapenem-containing regimens for ESBL-E BSI secondary to UTI in the specific population of KTR. Potential residual confounding and unpowered sample size cannot be excluded (ClinicalTrials.gov identifier: NCT02852902).
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43.
  • Pistor, Paul, et al. (författare)
  • Structure reinvestigation of α-, β- And γ-In2S3
  • 2016
  • Ingår i: Acta Crystallographica. Section B: Structural Science, Crystal Engineering and Materials. - 2052-5192. ; 72, s. 410-415
  • Tidskriftsartikel (refereegranskat)abstract
    • Semiconducting indium sulfide (In2S3) has recently attracted considerable attention as a buffer material in the field of thin film photovoltaics. Compared with this growing interest, however, detailed characterizations of the crystal structure of this material are rather scarce and controversial. In order to close this gap, we have carried out a reinvestigation of the crystal structure of this material with an in situ X-ray diffraction study as a function of temperature using monochromatic synchrotron radiation. For the purpose of this study, high quality polycrystalline In2S3 material with nominally stoichiometric composition was synthesized at high temperatures. We found three modifications of In2S3 in the temperature range between 300 and 1300 K, with structural phase transitions at temperatures of 717 K and above 1049 K. By Rietveld refinement we extracted the crystal structure data and the temperature coefficients of the lattice constants for all three phases, including a high-temperature trigonal γ-In2S3 modification.
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44.
  • Reiffel, James A., et al. (författare)
  • Real-world utilization of the pill-in-the-pocket method for terminating episodes of atrial fibrillation : data from the multinational Antiarrhythmic Interventions for Managing Atrial Fibrillation (AIM-AF) survey
  • 2023
  • Ingår i: Europace. - : Oxford University Press. - 1099-5129 .- 1532-2092. ; 25:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims: Atrial fibrillation (AF) is the most common sustained arrhythmia encountered in clinical practice. Episodes may stop spontaneously (paroxysmal AF); may terminate only via intervention (persistent AF); or may persist indefinitely (permanent AF) (see European and American guidelines, referenced below, for more precise definitions). Recently, there has been renewed interest in an approach to terminate AF acutely referred to as 'pill-in-the-pocket' (PITP). The PITP is recognized in both the US and European guidelines as an effective option using an oral antiarrhythmic drug for acute conversion of acute/recent-onset AF. However, how PITP is currently used has not been systematically evaluated.Methods and results: The recently published Antiarrhythmic Interventions for Managing Atrial Fibrillation (AIM-AF) survey included questions regarding current PITP usage, stratified by US vs. European countries surveyed, by representative countries within Europe, and by cardiologists vs. electrophysiologists. This manuscript presents the data from this planned sub-study. Our survey revealed that clinicians in both the USA and Europe consider PITP in about a quarter of their patients, mostly for recent-onset AF with minimal or no structural heart disease (guideline appropriate). However, significant deviations exist. See the Graphical abstract for a summary of the data.Conclusion: Our findings highlight the frequent use of PITP and the need for further physician education about appropriate and optimal use of this strategy.
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45.
  • Santangelo, James S., et al. (författare)
  • Global urban environmental change drives adaptation in white clover
  • 2022
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 375
  • Tidskriftsartikel (refereegranskat)abstract
    • Urbanization transforms environments in ways that alter biological evolution. We examined whether urban environmental change drives parallel evolution by sampling 110,019 white clover plants from 6169 populations in 160 cities globally. Plants were assayed for a Mendelian antiherbivore defense that also affects tolerance to abiotic stressors. Urban-rural gradients were associated with the evolution of clines in defense in 47% of cities throughout the world. Variation in the strength of clines was explained by environmental changes in drought stress and vegetation cover that varied among cities. Sequencing 2074 genomes from 26 cities revealed that the evolution of urban-rural dines was best explained by adaptive evolution, but the degree of parallel adaptation varied among cities. Our results demonstrate that urbanization leads to adaptation at a global scale.
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46.
  • Schnabel, Renate B, et al. (författare)
  • Early diagnosis and better rhythm management to improve outcomes in patients with atrial fibrillation : the 8th AFNET/EHRA consensus conference
  • 2023
  • Ingår i: Europace. - : Oxford University Press. - 1099-5129 .- 1532-2092. ; 25:1, s. 6-27
  • Tidskriftsartikel (refereegranskat)abstract
    • Despite marked progress in the management of atrial fibrillation (AF), detecting AF remains difficult and AF-related complications cause unacceptable morbidity and mortality even on optimal current therapy. This document summarizes the key outcomes of the 8th AFNET/EHRA Consensus Conference of the Atrial Fibrillation NETwork (AFNET) and the European Heart Rhythm Association (EHRA). Eighty-three international experts met in Hamburg for 2 days in October 2021. Results of the interdisciplinary, hybrid discussions in breakout groups and the plenary based on recently published and unpublished observations are summarized in this consensus paper to support improved care for patients with AF by guiding prevention, individualized management, and research strategies. The main outcomes are (i) new evidence supports a simple, scalable, and pragmatic population-based AF screening pathway; (ii) rhythm management is evolving from therapy aimed at improving symptoms to an integrated domain in the prevention of AF-related outcomes, especially in patients with recently diagnosed AF; (iii) improved characterization of atrial cardiomyopathy may help to identify patients in need for therapy; (iv) standardized assessment of cognitive function in patients with AF could lead to improvement in patient outcomes; and (v) artificial intelligence (AI) can support all of the above aims, but requires advanced interdisciplinary knowledge and collaboration as well as a better medico-legal framework. Implementation of new evidence-based approaches to AF screening and rhythm management can improve outcomes in patients with AF. Additional benefits are possible with further efforts to identify and target atrial cardiomyopathy and cognitive impairment, which can be facilitated by AI.
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47.
  • Tobias, Deirdre K, et al. (författare)
  • Second international consensus report on gaps and opportunities for the clinical translation of precision diabetes medicine
  • 2023
  • Ingår i: Nature Medicine. - 1546-170X. ; 29:10, s. 2438-2457
  • Forskningsöversikt (refereegranskat)abstract
    • Precision medicine is part of the logical evolution of contemporary evidence-based medicine that seeks to reduce errors and optimize outcomes when making medical decisions and health recommendations. Diabetes affects hundreds of millions of people worldwide, many of whom will develop life-threatening complications and die prematurely. Precision medicine can potentially address this enormous problem by accounting for heterogeneity in the etiology, clinical presentation and pathogenesis of common forms of diabetes and risks of complications. This second international consensus report on precision diabetes medicine summarizes the findings from a systematic evidence review across the key pillars of precision medicine (prevention, diagnosis, treatment, prognosis) in four recognized forms of diabetes (monogenic, gestational, type 1, type 2). These reviews address key questions about the translation of precision medicine research into practice. Although not complete, owing to the vast literature on this topic, they revealed opportunities for the immediate or near-term clinical implementation of precision diabetes medicine; furthermore, we expose important gaps in knowledge, focusing on the need to obtain new clinically relevant evidence. Gaps include the need for common standards for clinical readiness, including consideration of cost-effectiveness, health equity, predictive accuracy, liability and accessibility. Key milestones are outlined for the broad clinical implementation of precision diabetes medicine.
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48.
  • Zamora-Ros, Raul, et al. (författare)
  • Consumption of fish is not associated with risk of differentiated thyroid carcinoma in the European prospective investigation into cancer and nutrition (EPIC) study
  • 2017
  • Ingår i: Journal of Nutrition. - : Elsevier BV. - 0022-3166 .- 1541-6100. ; 147:7, s. 1366-1373
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Differentiated thyroid cancer (TC) is the most common endocrine cancer. Fish can be an important source of iodine and other micronutrients and contaminants that may affect the thyroid gland and TC risk. Objective: We prospectively evaluated the relations between the consumption of total fish and different fish types and shellfish and TC risk in the EPIC (European Prospective Investigation into Cancer and Nutrition) study. Methods: EPIC is a cohort of > 500,000 men and women, mostly aged 35-70 y, who were recruited in 10 European countries. After a mean follow-up of 14 y, 748 primary differentiated TC cases were diagnosed; 666 were in women and 601 were papillary TC. Data on intakes of lean fish, fatty fish, fish products, and shellfish were collected by using countryspecific validated dietary questionnaires at recruitment. Multivariable Cox regression was used to calculate HRs and 95% CIs adjusted for many potential confounders, including dietary and nondietary factors. Results: No significant association was observed between total fish consumption and differentiated TC risk for the highest compared with the lowest quartile (HR: 1.03; 95% CI: 0.81, 1.32; P-trend = 0.67). Likewise, no significant association was observed with the intake of any specific type of fish, fish product, or shellfish. No significant heterogeneity was found by TC subtype (papillary or follicular tumors), by sex, or between countries with low and high TC incidence. Conclusion: This large study shows that the intake of fish and shellfish was not associated with differentiated TC risk in Europe, a region in which iodine deficiency or excess is rare.
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49.
  • Zamora-Ros, Raul, et al. (författare)
  • Dietary flavonoid intake and colorectal cancer risk in the European prospective investigation into cancer and nutrition (EPIC) cohort
  • 2017
  • Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 140:8, s. 1836-1844
  • Tidskriftsartikel (refereegranskat)abstract
    • Flavonoids have been shown to inhibit colon cancer cell proliferation in vitro and protect against colorectal carcinogenesis in animal models. However, epidemiological evidence on the potential role of flavonoid intake in colorectal cancer (CRC) development remains sparse and inconsistent. We evaluated the association between dietary intakes of total flavonoids and their subclasses and risk of development of CRC, within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. A cohort of 477,312 adult men and women were recruited in 10 European countries. At baseline, dietary intakes of total flavonoids and individual subclasses were estimated using centre-specific validated dietary questionnaires and composition data from the Phenol-Explorer database. During an average of 11 years of follow-up, 4,517 new cases of primary CRC were identified, of which 2,869 were colon (proximal = 1,298 and distal = 1,266) and 1,648 rectal tumours. No association was found between total flavonoid intake and the risk of overall CRC (HR for comparison of extreme quintiles 1.05, 95% CI 0.93–1.18; p-trend = 0.58) or any CRC subtype. No association was also observed with any intake of individual flavonoid subclasses. Similar results were observed for flavonoid intake expressed as glycosides or aglycone equivalents. Intake of total flavonoids and flavonoid subclasses, as estimated from dietary questionnaires, did not show any association with risk of CRC development.
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