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2.
  • Bousquet, Jean, et al. (författare)
  • Allergic Rhinitis and its Impact on Asthma (ARIA) Phase 4 (2018) : Change management in allergic rhinitis and asthma multimorbidity using mobile technology
  • 2019
  • Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier. - 0091-6749 .- 1097-6825. ; 143:3, s. 864-879
  • Tidskriftsartikel (refereegranskat)abstract
    • Allergic Rhinitis and its Impact on Asthma (ARIA) has evolved from a guideline by using the best approach to integrated care pathways using mobile technology in patients with allergic rhinitis (AR) and asthma multimorbidity. The proposed next phase of ARIA is change management, with the aim of providing an active and healthy life to patients with rhinitis and to those with asthma multimorbidity across the lifecycle irrespective of their sex or socioeconomic status to reduce health and social inequities incurred by the disease. ARIA has followed the 8-step model of Kotter to assess and implement the effect of rhinitis on asthma multimorbidity and to propose multimorbid guidelines. A second change management strategy is proposed by ARIA Phase 4 to increase self-medication and shared decision making in rhinitis and asthma multimorbidity. An innovation of ARIA has been the development and validation of information technology evidence-based tools (Mobile Airways Sentinel Network [MASK]) that can inform patient decisions on the basis of a self-care plan proposed by the health care professional.
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3.
  • Menditto, Enrica, et al. (författare)
  • Adherence to treatment in allergic rhinitis using mobile technology : The MASK Study
  • 2019
  • Ingår i: Clinical and Experimental Allergy. - : WILEY. - 0954-7894 .- 1365-2222. ; 49:4, s. 442-460
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Mobile technology may help to better understand the adherence to treatment. MASK-rhinitis (Mobile Airways Sentinel NetworK for allergic rhinitis) is a patient-centred ICT system. A mobile phone app (the Allergy Diary) central to MASK is available in 22 countries. Objectives: To assess the adherence to treatment in allergic rhinitis patients using the Allergy Diary App. Methods: An observational cross-sectional study was carried out on all users who filled in the Allergy Diary from 1 January 2016 to 1 August 2017. Secondary adherence was assessed by using the modified Medication Possession Ratio (MPR) and the Proportion of days covered (PDC) approach. Results: A total of 12143 users were registered. A total of 6949 users reported at least one VAS data recording. Among them, 1887 users reported >= 7 VAS data. About 1195 subjects were included in the analysis of adherence. One hundred and thirty-six (11.28%) users were adherent (MPR >= 70% and PDC <= 1.25), 51 (4.23%) were partly adherent (MPR >= 70% and PDC = 1.50) and 176 (14.60%) were switchers. On the other hand, 832 (69.05%) users were non-adherent to medications (MPR <70%). Of those, the largest group was non-adherent to medications and the time interval was increased in 442 (36.68%) users. Conclusion and clinical relevance: Adherence to treatment is low. The relative efficacy of continuous vs on-demand treatment for allergic rhinitis symptoms is still a matter of debate. This study shows an approach for measuring retrospective adherence based on a mobile app. This also represents a novel approach for analysing medication-taking behaviour in a real-world setting.
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5.
  • Loza, M. J., et al. (författare)
  • Validated and longitudinally stable asthma phenotypes based on cluster analysis of the ADEPT study
  • 2016
  • Ingår i: Respiratory Research. - : Springer Nature. - 1465-9921 .- 1465-993X. ; 17:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Asthma is a disease of varying severity and differing disease mechanisms. To date, studies aimed at stratifying asthma into clinically useful phenotypes have produced a number of phenotypes that have yet to be assessed for stability and to be validated in independent cohorts. The aim of this study was to define and validate, for the first time ever, clinically driven asthma phenotypes using two independent, severe asthma cohorts: ADEPT and U-BIOPRED. Methods: Fuzzy partition-around-medoid clustering was performed on pre-specified data from the ADEPT participants (n = 156) and independently on data from a subset of U-BIOPRED asthma participants (n = 82) for whom the same variables were available. Models for cluster classification probabilities were derived and applied to the 12-month longitudinal ADEPT data and to a larger subset of the U-BIOPRED asthma dataset (n = 397). High and low type-2 inflammation phenotypes were defined as high or low Th2 activity, indicated by endobronchial biopsies gene expression changes downstream of IL-4 or IL-13. Results: Four phenotypes were identified in the ADEPT (training) cohort, with distinct clinical and biomarker profiles. Phenotype 1 was "mild, good lung function, early onset", with a low-inflammatory, predominantly Type-2, phenotype. Phenotype 2 had a "moderate, hyper-responsive, eosinophilic" phenotype, with moderate asthma control, mild airflow obstruction and predominant Type-2 inflammation. Phenotype 3 had a "mixed severity, predominantly fixed obstructive, non-eosinophilic and neutrophilic" phenotype, with moderate asthma control and low Type-2 inflammation. Phenotype 4 had a "severe uncontrolled, severe reversible obstruction, mixed granulocytic" phenotype, with moderate Type-2 inflammation. These phenotypes had good longitudinal stability in the ADEPT cohort. They were reproduced and demonstrated high classification probability in two subsets of the U-BIOPRED asthma cohort. Conclusions: Focusing on the biology of the four clinical independently-validated easy-to-assess ADEPT asthma phenotypes will help understanding the unmet need and will aid in developing tailored therapies. Trial registration:NCT01274507(ADEPT), registered October 28, 2010 and NCT01982162(U-BIOPRED), registered October 30, 2013.
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6.
  • Bousquet, J. Jean, et al. (författare)
  • Next-generation ARIA care pathways for rhinitis and asthma : a model for multimorbid chronic diseases
  • 2019
  • Ingår i: Clinical and Translational Allergy. - : BMC. - 2045-7022. ; 9
  • Forskningsöversikt (refereegranskat)abstract
    • Background: In all societies, the burden and cost of allergic and chronic respiratory diseases are increasing rapidly. Most economies are struggling to deliver modern health care effectively. There is a need to support the transformation of the health care system into integrated care with organizational health literacy.Main body: As an example for chronic disease care, MASK (Mobile Airways Sentinel NetworK), a new project of the ARIA (Allergic Rhinitis and its Impact on Asthma) initiative, and POLLAR (Impact of Air POLLution on Asthma and Rhinitis, EIT Health), in collaboration with professional and patient organizations in the field of allergy and airway diseases, are proposing real-life ICPs centred around the patient with rhinitis, and using mHealth to monitor environmental exposure. Three aspects of care pathways are being developed: (i) Patient participation, health literacy and self-care through technology-assisted "patient activation", (ii) Implementation of care pathways by pharmacists and (iii) Next-generation guidelines assessing the recommendations of GRADE guidelines in rhinitis and asthma using real-world evidence (RWE) obtained through mobile technology. The EU and global political agendas are of great importance in supporting the digital transformation of health and care, and MASK has been recognized by DG Sante as a Good Practice in the field of digitally-enabled, integrated, person-centred care.Conclusion: In 20 years, ARIA has considerably evolved from the first multimorbidity guideline in respiratory diseases to the digital transformation of health and care with a strong political involvement.
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7.
  • Bousquet, Jean, et al. (författare)
  • ARIA digital anamorphosis : Digital transformation of health and care in airway diseases from research to practice
  • 2021
  • Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : John Wiley & Sons. - 0105-4538 .- 1398-9995. ; 76:1, s. 168-190
  • Forskningsöversikt (refereegranskat)abstract
    • Digital anamorphosis is used to define a distorted image of health and care that may be viewed correctly using digital tools and strategies. MASK digital anamorphosis represents the process used by MASK to develop the digital transformation of health and care in rhinitis. It strengthens the ARIA change management strategy in the prevention and management of airway disease. The MASK strategy is based on validated digital tools. Using the MASK digital tool and the CARAT online enhanced clinical framework, solutions for practical steps of digital enhancement of care are proposed.
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8.
  • Nguyen, Thanh N, et al. (författare)
  • Global Impact of the COVID-19 Pandemic on Stroke Volumes and Cerebrovascular Events: A 1-Year Follow-up.
  • 2023
  • Ingår i: Neurology. - 1526-632X. ; 100:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Declines in stroke admission, IV thrombolysis (IVT), and mechanical thrombectomy volumes were reported during the first wave of the COVID-19 pandemic. There is a paucity of data on the longer-term effect of the pandemic on stroke volumes over the course of a year and through the second wave of the pandemic. We sought to measure the effect of the COVID-19 pandemic on the volumes of stroke admissions, intracranial hemorrhage (ICH), IVT, and mechanical thrombectomy over a 1-year period at the onset of the pandemic (March 1, 2020, to February 28, 2021) compared with the immediately preceding year (March 1, 2019, to February 29, 2020).We conducted a longitudinal retrospective study across 6 continents, 56 countries, and 275 stroke centers. We collected volume data for COVID-19 admissions and 4 stroke metrics: ischemic stroke admissions, ICH admissions, IVT treatments, and mechanical thrombectomy procedures. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases.There were 148,895 stroke admissions in the 1 year immediately before compared with 138,453 admissions during the 1-year pandemic, representing a 7% decline (95% CI [95% CI 7.1-6.9]; p < 0.0001). ICH volumes declined from 29,585 to 28,156 (4.8% [5.1-4.6]; p < 0.0001) and IVT volume from 24,584 to 23,077 (6.1% [6.4-5.8]; p < 0.0001). Larger declines were observed at high-volume compared with low-volume centers (all p < 0.0001). There was no significant change in mechanical thrombectomy volumes (0.7% [0.6-0.9]; p = 0.49). Stroke was diagnosed in 1.3% [1.31-1.38] of 406,792 COVID-19 hospitalizations. SARS-CoV-2 infection was present in 2.9% ([2.82-2.97], 5,656/195,539) of all stroke hospitalizations.There was a global decline and shift to lower-volume centers of stroke admission volumes, ICH volumes, and IVT volumes during the 1st year of the COVID-19 pandemic compared with the prior year. Mechanical thrombectomy volumes were preserved. These results suggest preservation in the stroke care of higher severity of disease through the first pandemic year.This study is registered under NCT04934020.
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9.
  • Cruz, Raquel, et al. (författare)
  • Novel genes and sex differences in COVID-19 severity
  • 2022
  • Ingår i: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 31:22, s. 3789-3806
  • Tidskriftsartikel (refereegranskat)abstract
    • Here, we describe the results of a genome-wide study conducted in 11 939 coronavirus disease 2019 (COVID-19) positive cases with an extensive clinical information that were recruited from 34 hospitals across Spain (SCOURGE consortium). In sex-disaggregated genome-wide association studies for COVID-19 hospitalization, genome-wide significance (P < 5 × 10−8) was crossed for variants in 3p21.31 and 21q22.11 loci only among males (P = 1.3 × 10−22 and P = 8.1 × 10−12, respectively), and for variants in 9q21.32 near TLE1 only among females (P = 4.4 × 10−8). In a second phase, results were combined with an independent Spanish cohort (1598 COVID-19 cases and 1068 population controls), revealing in the overall analysis two novel risk loci in 9p13.3 and 19q13.12, with fine-mapping prioritized variants functionally associated with AQP3 (P = 2.7 × 10−8) and ARHGAP33 (P = 1.3 × 10−8), respectively. The meta-analysis of both phases with four European studies stratified by sex from the Host Genetics Initiative (HGI) confirmed the association of the 3p21.31 and 21q22.11 loci predominantly in males and replicated a recently reported variant in 11p13 (ELF5, P = 4.1 × 10−8). Six of the COVID-19 HGI discovered loci were replicated and an HGI-based genetic risk score predicted the severity strata in SCOURGE. We also found more SNP-heritability and larger heritability differences by age (<60 or ≥60 years) among males than among females. Parallel genome-wide screening of inbreeding depression in SCOURGE also showed an effect of homozygosity in COVID-19 hospitalization and severity and this effect was stronger among older males. In summary, new candidate genes for COVID-19 severity and evidence supporting genetic disparities among sexes are provided.
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10.
  • Bruneau, Anne, et al. (författare)
  • Advances in Legume Systematics 14. Classification of Caesalpinioideae. Part 2: Higher-level classification
  • 2024
  • Ingår i: PhytoKeys. - Sofia : Pensoft Publishers. - 1314-2011 .- 1314-2003. ; 240, s. 1-552
  • Tidskriftsartikel (refereegranskat)abstract
    • Caesalpinioideae is the second largest subfamily of legumes (Leguminosae) with ca. 4680 species and 163 genera. It is an ecologically and economically important group formed of mostly woody perennials that range from large canopy emergent trees to functionally herbaceous geoxyles, lianas and shrubs, and which has a global distribution, occurring on every continent except Antarctica. Following the recent re-circumscription of 15 Caesalpinioideae genera as presented in Advances in Legume Systematics 14, Part 1, and using as a basis a phylogenomic analysis of 997 nuclear gene sequences for 420 species and all but five of the genera currently recognised in the subfamily, we present a new higher-level classification for the subfamily. The new classification of Caesalpinioideae comprises eleven tribes, all of which are either new, reinstated or re-circumscribed at this rank: Caesalpinieae Rchb. (27 genera / ca. 223 species), Campsiandreae LPWG (2 / 5-22), Cassieae Bronn (7 / 695), Cera-tonieae Rchb. (4 / 6), Dimorphandreae Benth. (4 / 35), Erythrophleeae LPWG (2 /13), Gleditsieae Nakai (3 / 20), Mimoseae Bronn (100 / ca. 3510), Pterogyneae LPWG (1 / 1), Schizolobieae Nakai (8 / 42-43), Sclerolobieae Benth. & Hook. f. (5 / ca. 113). Although many of these lineages have been recognised and named in the past, either as tribes or informal generic groups, their circumscriptions have varied widely and changed over the past decades, such that all the tribes described here differ in generic membership from those previously recognised. Importantly, the approximately 3500 species and 100 genera of the former subfamily Mimosoideae are now placed in the reinstated, but newly circumscribed, tribe Mimoseae. Because of the large size and ecological importance of the tribe, we also provide a clade-based classification system for Mimoseae that includes 17 named lower-level clades. Fourteen of the 100 Mimoseae genera remain unplaced in these lower-level clades: eight are resolved in two grades and six are phylogenetically isolated monogeneric lineages. In addition to the new classification, we provide a key to genera, morphological descriptions and notes for all 163 genera, all tribes, and all named clades. The diversity of growth forms, foliage, flowers and fruits are illustrated for all genera, and for each genus we also provide a distribution map, based on quality-controlled herbarium specimen localities. A glossary for specialised terms used in legume morphology is provided. This new phylogenetically based classification of Caesalpinioideae provides a solid system for communication and a framework for downstream analyses of biogeography, trait evolution and diversification, as well as for taxonomic revision of still understudied genera.
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11.
  • Gorasso, Vanessa, et al. (författare)
  • Burden of disease attributable to risk factors in European countries: a scoping literature review
  • 2023
  • Ingår i: Archives of Public Health. - 0778-7367 .- 2049-3258. ; 81:1
  • Forskningsöversikt (refereegranskat)abstract
    • Objectives: Within the framework of the burden of disease (BoD) approach, disease and injury burden estimates attributable to risk factors are a useful guide for policy formulation and priority setting in disease prevention. Considering the important differences in methods, and their impact on burden estimates, we conducted a scoping literature review to: (1) map the BoD assessments including risk factors performed across Europe; and (2) identify the methodological choices in comparative risk assessment (CRA) and risk assessment methods. Methods: We searched multiple literature databases, including grey literature websites and targeted public health agencies websites. Results: A total of 113 studies were included in the synthesis and further divided into independent BoD assessments (54 studies) and studies linked to the Global Burden of Disease (59 papers). Our results showed that the methods used to perform CRA varied substantially across independent European BoD studies. While there were some methodological choices that were more common than others, we did not observe patterns in terms of country, year or risk factor. Each methodological choice can affect the comparability of estimates between and within countries and/or risk factors, since they might significantly influence the quantification of the attributable burden. From our analysis we observed that the use of CRA was less common for some types of risk factors and outcomes. These included environmental and occupational risk factors, which are more likely to use bottom-up approaches for health outcomes where disease envelopes may not be available. Conclusions: Our review also highlighted misreporting, the lack of uncertainty analysis and the under-investigation of causal relationships in BoD studies. Development and use of guidelines for performing and reporting BoD studies will help understand differences, avoid misinterpretations thus improving comparability among estimates.
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12.
  • Nordlund, Lina Mtwana, et al. (författare)
  • One hundred priority questions for advancing seagrass conservation in Europe
  • 2024
  • Ingår i: PLANTS PEOPLE PLANET. - 2572-2611.
  • Tidskriftsartikel (refereegranskat)abstract
    • Societal Impact StatementSeagrass ecosystems are of fundamental importance to our planet and wellbeing. Seagrasses are marine flowering plants, which engineer ecosystems that provide a multitude of ecosystem services, for example, blue foods and carbon sequestration. Seagrass ecosystems have largely been degraded across much of their global range. There is now increasing interest in the conservation and restoration of these systems, particularly in the context of the climate emergency and the biodiversity crisis. The collation of 100 questions from experts across Europe could, if answered, improve our ability to conserve and restore these systems by facilitating a fundamental shift in the success of such work.SummarySeagrass meadows provide numerous ecosystem services including biodiversity, coastal protection, and carbon sequestration. In Europe, seagrasses can be found in shallow sheltered waters along coastlines, in estuaries & lagoons, and around islands, but their distribution has declined. Factors such as poor water quality, coastal modification, mechanical damage, overfishing, land-sea interactions, climate change and disease have reduced the coverage of Europe's seagrasses necessitating their recovery. Research, monitoring and conservation efforts on seagrass ecosystems in Europe are mostly uncoordinated and biased towards certain species and regions, resulting in inadequate delivery of critical information for their management. Here, we aim to identify the 100 priority questions, that if addressed would strongly advance seagrass monitoring, research and conservation in Europe. Using a Delphi method, researchers, practitioners, and policymakers with seagrass experience from across Europe and with diverse seagrass expertise participated in the process that involved the formulation of research questions, a voting process and an online workshop to identify the final list of the 100 questions. The final list of questions covers areas across nine themes: Biodiversity & Ecology; Ecosystem services; Blue carbon; Fishery support; Drivers, Threats, Resilience & Response; Monitoring & Assessment; Conservation & Restoration; Governance, Policy & Management; and Communication. Answering these questions will fill current knowledge gaps and place European seagrass onto a positive trajectory of recovery. Seagrass ecosystems are of fundamental importance to our planet and wellbeing. Seagrasses are marine flowering plants which engineer ecosystems that provide a multitude of ecosystem services, for example, blue foods and carbon sequestration. Seagrass ecosystems have largely been degraded across much of their global range. There is now increasing interest in the conservation and restoration of these systems, particularly in the context of the climate emergency and the biodiversity crisis. The collation of 100 questions from experts across Europe could, if answered, improve our ability to conserve and restore these systems by facilitating a fundamental shift in the success of such work. image
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13.
  • Plugge, Caroline M., et al. (författare)
  • Syngas as Electron Donor for Sulfate and Thiosulfate Reducing Haloalkaliphilic Microorganisms in a Gas-Lift Bioreactor
  • 2020
  • Ingår i: Microorganisms. - : MDPI. - 2076-2607. ; 8:9, s. 1-18
  • Tidskriftsartikel (refereegranskat)abstract
    • Biodesulfurization processes remove toxic and corrosive hydrogen sulfide from gas streams (e.g., natural gas, biogas, or syngas). To improve the efficiency of these processes under haloalkaline conditions, a sulfate and thiosulfate reduction step can be included. The use of H-2/CO mixtures (as in syngas) instead of pure H-2 was tested to investigate the potential cost reduction of the electron donor required. Syngas is produced in the gas-reforming process and consists mainly of H-2, carbon monoxide (CO), and carbon dioxide (CO2). Purification of syngas to obtain pure H-2 implies higher costs because of additional post-treatment. Therefore, the use of syngas has merit in the biodesulfurization process. Initially, CO inhibited hydrogen-dependent sulfate reduction. However, after 30 days the biomass was adapted and both H-2 and CO were used as electron donors. First, formate was produced, followed by sulfate and thiosulfate reduction, and later in the reactor run acetate and methane were detected. Sulfide production rates with sulfate and thiosulfate after adaptation were comparable with previously described rates with only hydrogen. The addition of CO marginally affected the microbial community in which Tindallia sp. was dominant. Over time, acetate production increased and acetogenesis became the dominant process in the bioreactor. Around 50% of H-2/CO was converted to acetate. Acetate supported biomass growth and higher biomass concentrations were reached compared to bioreactors without CO feed. Finally, CO addition resulted in the formation of small, compact microbial aggregates. This suggests that CO or syngas can be used to stimulate aggregation in haloalkaline biodesulfurization systems.
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14.
  • Sánchez Van Kammen, Mayte, et al. (författare)
  • Characteristics and Outcomes of Patients with Cerebral Venous Sinus Thrombosis in SARS-CoV-2 Vaccine-Induced Immune Thrombotic Thrombocytopenia
  • 2021
  • Ingår i: JAMA Neurology. - : American Medical Association. - 2168-6149 .- 2168-6157. ; 78:11, s. 1314-1323
  • Tidskriftsartikel (refereegranskat)abstract
    • Importance: Thrombosis with thrombocytopenia syndrome (TTS) has been reported after vaccination with the SARS-CoV-2 vaccines ChAdOx1 nCov-19 (Oxford-AstraZeneca) and Ad26.COV2.S (Janssen/Johnson & Johnson).Objective: To describe the clinical characteristics and outcome of patients with cerebral venous sinus thrombosis (CVST) after SARS-CoV-2 vaccination with and without TTS.Design, Setting, and Participants: This cohort study used data from an international registry of consecutive patients with CVST within 28 days of SARS-CoV-2 vaccination included between March 29 and June 18, 2021, from 81 hospitals in 19 countries. For reference, data from patients with CVST between 2015 and 2018 were derived from an existing international registry. Clinical characteristics and mortality rate were described for adults with (1) CVST in the setting of SARS-CoV-2 vaccine-induced immune thrombotic thrombocytopenia, (2) CVST after SARS-CoV-2 vaccination not fulling criteria for TTS, and (3) CVST unrelated to SARS-CoV-2 vaccination.Exposures: Patients were classified as having TTS if they had new-onset thrombocytopenia without recent exposure to heparin, in accordance with the Brighton Collaboration interim criteria.Main Outcomes and Measures: Clinical characteristics and mortality rate.Results: Of 116 patients with postvaccination CVST, 78 (67.2%) had TTS, of whom 76 had been vaccinated with ChAdOx1 nCov-19; 38 (32.8%) had no indication of TTS. The control group included 207 patients with CVST before the COVID-19 pandemic. A total of 63 of 78 (81%), 30 of 38 (79%), and 145 of 207 (70.0%) patients, respectively, were female, and the mean (SD) age was 45 (14), 55 (20), and 42 (16) years, respectively. Concomitant thromboembolism occurred in 25 of 70 patients (36%) in the TTS group, 2 of 35 (6%) in the no TTS group, and 10 of 206 (4.9%) in the control group, and in-hospital mortality rates were 47% (36 of 76; 95% CI, 37-58), 5% (2 of 37; 95% CI, 1-18), and 3.9% (8 of 207; 95% CI, 2.0-7.4), respectively. The mortality rate was 61% (14 of 23) among patients in the TTS group diagnosed before the condition garnered attention in the scientific community and 42% (22 of 53) among patients diagnosed later.Conclusions and Relevance: In this cohort study of patients with CVST, a distinct clinical profile and high mortality rate was observed in patients meeting criteria for TTS after SARS-CoV-2 vaccination..
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15.
  • Scutelnic, Adrian, et al. (författare)
  • Management of Cerebral Venous Thrombosis Due to Adenoviral COVID-19 Vaccination.
  • 2022
  • Ingår i: Annals of neurology. - : Wiley. - 1531-8249 .- 0364-5134. ; 92:4, s. 562-573
  • Tidskriftsartikel (refereegranskat)abstract
    • Cerebral venous thrombosis (CVT) caused by vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare adverse effect of adenovirus-based severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) vaccines. In March 2021, after autoimmune pathogenesis of VITT was discovered, treatment recommendations were developed. These comprised immunomodulation, non-heparin anticoagulants, and avoidance of platelet transfusion. The aim of this study was to evaluate adherence to these recommendations and its association with mortality.We used data from an international prospective registry of patients with CVT after the adenovirus-based SARS-CoV-2 vaccination. We analyzed possible, probable, or definite VITT-CVT cases included until January 18, 2022. Immunomodulation entailed administration of intravenous immunoglobulins and/or plasmapheresis.Ninety-nine patients with VITT-CVT from 71 hospitals in 17 countries were analyzed. Five of 38 (13%), 11 of 24 (46%), and 28 of 37 (76%) of the patients diagnosed in March, April, and from May onward, respectively, were treated in-line with VITT recommendations (p<0.001). Overall, treatment according to recommendations had no statistically significant influence on mortality (14/44 [32%] vs 29/55 [52%], adjusted odds ratio [OR]=0.43, 95% confidence interval [CI]=0.16-1.19). However, patients who received immunomodulation had lower mortality (19/65 [29%] vs 24/34 [70%], adjusted OR=0.19, 95% CI=0.06-0.58). Treatment with non-heparin anticoagulants instead of heparins was not associated with lower mortality (17/51 [33%] vs 13/35 [37%], adjusted OR=0.70, 95% CI=0.24-2.04). Mortality was also not significantly influenced by platelet transfusion (17/27 [63%] vs 26/72 [36%], adjusted OR=2.19, 95% CI=0.74-6.54).In patients with VITT-CVT, adherence to VITT treatment recommendations improved over time. Immunomodulation seems crucial for reducing mortality of VITT-CVT. ANN NEUROL 2022;92:562-573.
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16.
  • Sousa, João A. B., et al. (författare)
  • Immobilization of sulfate and thiosulfate-reducing biomass on sand under haloalkaline conditions
  • 2020
  • Ingår i: Science of the Total Environment. - : Elsevier. - 0048-9697 .- 1879-1026. ; 745, s. 1-8
  • Tidskriftsartikel (refereegranskat)abstract
    • Biological sulfate and thiosulfate reduction under haloalkaline conditions can be applied to treat waste streams from biodesulfurization systems. However, the lack of microbial aggregation under haloalkaline conditions limits the volumetric rates of sulfate and thiosulfate reducing bioreactors. As biomass retention in haloalkaline bioreactors has not been studied before, sand was chosen as a biomass carrier material to increase cell retention and consequently raise the volumetric rates. The results showed that similar to 10 fold higher biomass concentrations could be achieved with sand, compared to previous studies without carrier addition. The volumetric rates of sulfate/thiosulfate reduction increased approximately 4.5 times. Biomass attachment to the sand was restricted to cavities within the sand particles. Acetate produced by acetogenic bacteria from H-2 and CO2 was used as carbon source for biomass growth, while formate that was also produced from H-2 and CO2 enhanced sulfate reduction. The microbial community composition was analyzed by 165 rRNA gene amplicon sequencing, and Tindallia related bacteria were probably responsible for formate formation from hydrogen. The community attached to the sand particles was similar to the suspended fraction, but the relative abundance of sequences most closely related to Desuljohalobiaceae was much higher in the attached fraction compared to the suspended fraction (30% and 13%, respectively). The results indicated that even though the biomass attachment to sand was poor, it still increased the biomass concentration and consequently the sulfate and thiosulfate reduction volumetric rates. (C) 2020 The Authors. Published by Elsevier B.V.
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17.
  • Sousa-Pinto, Bernardo, et al. (författare)
  • Comparison of rhinitis treatments using MASK-air® data and considering the minimal important difference
  • 2022
  • Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : John Wiley & Sons. - 0105-4538 .- 1398-9995. ; 77:10, s. 3002-3014
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Different treatments exist for allergic rhinitis (AR), including pharmacotherapy and allergen immunotherapy (AIT), but they have not been compared using direct patient data (i.e., “real-world data”). We aimed to compare AR pharmacological treatments on (i) daily symptoms, (ii) frequency of use in co-medication, (iii) visual analogue scales (VASs) on allergy symptom control considering the minimal important difference (MID) and (iv) the effect of AIT.Methods: We assessed the MASK-air® app data (May 2015–December 2020) by users self-reporting AR (16–90 years). We compared eight AR medication schemes on reported VAS of allergy symptoms, clustering data by the patient and controlling for confounding factors. We compared (i) allergy symptoms between patients with and without AIT and (ii) different drug classes used in co-medication.Results: We analysed 269,837 days from 10,860 users. Most days (52.7%) involved medication use. Median VAS levels were significantly higher in co-medication than in monotherapy (including the fixed combination azelastine-fluticasone) schemes. In adjusted models, azelastine-fluticasone was associated with lower average VAS global allergy symptoms than all other medication schemes, while the contrary was observed for oral corticosteroids. AIT was associated with a decrease in allergy symptoms in some medication schemes. A difference larger than the MID compared to no treatment was observed for oral steroids. Azelastine-fluticasone was the drug class with the lowest chance of being used in co-medication (adjusted OR = 0.75; 95% CI = 0.71–0.80).Conclusion: Median VAS levels were higher in co-medication than in monotherapy. Patients with more severe symptoms report a higher treatment, which is currently not reflected in guidelines.
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18.
  • Sousa-Pinto, Bernardo, et al. (författare)
  • Consistent trajectories of rhinitis control and treatment in 16,177 weeks : the MASK-air® longitudinal study
  • 2023
  • Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : John Wiley & Sons. - 0105-4538 .- 1398-9995. ; 78:4, s. 968-983
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Data from mHealth apps can provide valuable information on rhinitis control and treatment patterns. However, in MASK-air®, these data have only been analyzed cross-sectionally, without considering the changes of symptoms over time. We analyzed data from MASK-air® longitudinally, clustering weeks according to reported rhinitis symptoms. Methods: We analyzed MASK-air® data, assessing the weeks for which patients had answered a rhinitis daily questionnaire on all 7 days. We firstly used k-means clustering algorithms for longitudinal data to define clusters of weeks according to the trajectories of reported daily rhinitis symptoms. Clustering was applied separately for weeks when medication was reported or not. We compared obtained clusters on symptoms and rhinitis medication patterns. We then used the latent class mixture model to assess the robustness of results. Results: We analyzed 113,239 days (16,177 complete weeks) from 2590 patients (mean age ± SD = 39.1 ± 13.7 years). The first clustering algorithm identified ten clusters among weeks with medication use: seven with low variability in rhinitis control during the week and three with highly-variable control. Clusters with poorly-controlled rhinitis displayed a higher frequency of rhinitis co-medication, a more frequent change of medication schemes and more pronounced seasonal patterns. Six clusters were identified in weeks when no rhinitis medication was used, displaying similar control patterns. The second clustering method provided similar results. Moreover, patients displayed consistent levels of rhinitis control, reporting several weeks with similar levels of control. Conclusions: We identified 16 patterns of weekly rhinitis control. Co-medication and medication change schemes were common in uncontrolled weeks, reinforcing the hypothesis that patients treat themselves according to their symptoms.
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19.
  • Tomaz, Kaira C P, et al. (författare)
  • Identification of potential inhibitors of casein kinase 2 alpha of Plasmodium falciparum with potent in vitro activity.
  • 2023
  • Ingår i: Antimicrobial Agents and Chemotherapy. - 0066-4804. ; 67:11
  • Tidskriftsartikel (refereegranskat)abstract
    • Drug resistance to commercially available antimalarials is a major obstacle in malaria control and elimination, creating the need to find new antiparasitic compounds with novel mechanisms of action. The success of kinase inhibitors for oncological treatments has paved the way for the exploitation of protein kinases as drug targets in various diseases, including malaria. Casein kinases are ubiquitous serine/threonine kinases involved in a wide range of cellular processes such as mitotic checkpoint signaling, DNA damage response, and circadian rhythm. In Plasmodium, it is suggested that these protein kinases are essential for both asexual and sexual blood-stage parasites, reinforcing their potential as targets for multi-stage antimalarials. To identify new putative PfCK2α inhibitors, we utilized an in silico chemogenomic strategy involving virtual screening with docking simulations and quantitative structure-activity relationship predictions. Our investigation resulted in the discovery of a new quinazoline molecule (542), which exhibited potent activity against asexual blood stages and a high selectivity index (>100). Subsequently, we conducted chemical-genetic interaction analysis on yeasts with mutations in casein kinases. Our chemical-genetic interaction results are consistent with the hypothesis that 542 inhibits yeast Cka1, which has a hinge region with high similarity to PfCK2α. This finding is in agreement with our in silico results suggesting that 542 inhibits PfCK2α via hinge region interaction.
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20.
  • Chen, Gongbo, et al. (författare)
  • Mortality risk attributable to wildfire-related PM2·5 pollution : a global time series study in 749 locations
  • 2021
  • Ingår i: The Lancet Planetary Health. - : Elsevier. - 2542-5196. ; 5:9, s. e579-e587
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Many regions of the world are now facing more frequent and unprecedentedly large wildfires. However, the association between wildfire-related PM2·5 and mortality has not been well characterised. We aimed to comprehensively assess the association between short-term exposure to wildfire-related PM2·5 and mortality across various regions of the world.METHODS: For this time series study, data on daily counts of deaths for all causes, cardiovascular causes, and respiratory causes were collected from 749 cities in 43 countries and regions during 2000-16. Daily concentrations of wildfire-related PM2·5 were estimated using the three-dimensional chemical transport model GEOS-Chem at a 0·25° × 0·25° resolution. The association between wildfire-related PM2·5 exposure and mortality was examined using a quasi-Poisson time series model in each city considering both the current-day and lag effects, and the effect estimates were then pooled using a random-effects meta-analysis. Based on these pooled effect estimates, the population attributable fraction and relative risk (RR) of annual mortality due to acute wildfire-related PM2·5 exposure was calculated.FINDINGS: 65·6 million all-cause deaths, 15·1 million cardiovascular deaths, and 6·8 million respiratory deaths were included in our analyses. The pooled RRs of mortality associated with each 10 μg/m3 increase in the 3-day moving average (lag 0-2 days) of wildfire-related PM2·5 exposure were 1·019 (95% CI 1·016-1·022) for all-cause mortality, 1·017 (1·012-1·021) for cardiovascular mortality, and 1·019 (1·013-1·025) for respiratory mortality. Overall, 0·62% (95% CI 0·48-0·75) of all-cause deaths, 0·55% (0·43-0·67) of cardiovascular deaths, and 0·64% (0·50-0·78) of respiratory deaths were annually attributable to the acute impacts of wildfire-related PM2·5 exposure during the study period.INTERPRETATION: Short-term exposure to wildfire-related PM2·5 was associated with increased risk of mortality. Urgent action is needed to reduce health risks from the increasing wildfires.
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21.
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22.
  • de Lemos, Rogerio, et al. (författare)
  • Software Engineering for Self-Adaptive Systems : A Second Research Roadmap
  • 2013
  • Ingår i: Software Engineering for Self-Adaptive Systems II. - Berlin, Heidelberg : Springer. - 9783642358128 ; , s. 1-32
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • The goal of this roadmap paper is to summarize the state-of-the-art and identify research challenges when developing, deploying and managing self-adaptive software systems. Instead of dealing with a wide range of topics associated with the field, we focus on four essential topics of self-adaptation: design space for self-adaptive solutions, software engineering processes for self-adaptive systems, from centralized to decentralized control, and practical run-time verification & validation for self-adaptive systems. For each topic, we present an overview, suggest future directions, and focus on selected challenges. This paper complements and extends a previous roadmap on software engineering for self-adaptive systems published in 2009 covering a different set of topics, and reflecting in part on the previous paper. This roadmap is one of the many results of the Dagstuhl Seminar 10431 on Software Engineering for Self-Adaptive Systems, which took place in October 2010.
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23.
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24.
  • Roman, Pawel, et al. (författare)
  • Selection and Application of Sulfide Oxidizing Microorganisms Able to Withstand Thiols in Gas Biodesulfurization Systems
  • 2016
  • Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 50:23, s. 12808-12815
  • Tidskriftsartikel (refereegranskat)abstract
    • After the first commercial applications of a new biological process for the removal of hydrogen sulfide (H2S) from low pressure biogas, the need arose to broaden the operating window to also enable the removal of organosulfur compounds from high pressure sour gases. In this study we have selected microorganisms from a full-scale biodesulfurization system that are capable of withstanding the presence of thiols. This full-scale unit has been in stable operation for more than 10 years. We investigated the microbial community by using high-throughput sequencing of 16S rRNA gene amplicons which showed that methanethiol gave a competitive advantage to bacteria belonging to the genera Thioalkalibacter (Halothiobacillaceae family) and Alkalilimnicola (Ectothiorhosdospiraceae family). The sulfide-oxidizing potential of the acclimatized population was investigated under elevated thiol loading rates (4.5–9.1 mM d–1), consisting of a mix of methanethiol, ethanethiol, and propanethiol. With this biomass, it was possible to achieve a stable bioreactor operation at which 80% of the supplied H2S (61 mM d–1) was biologically oxidized to elemental sulfur. The remainder was chemically produced thiosulfate. Moreover, we found that a conventionally applied method for controlling the oxygen supply to the bioreactor, that is, by maintaining a redox potential set-point value, appeared to be ineffective in the presence of thiols.
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25.
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26.
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27.
  • Sousa-Pinto, Bernardo, et al. (författare)
  • Development and validation of combined symptom-medication scores for allergic rhinitis*
  • 2022
  • Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : John Wiley & Sons. - 0105-4538 .- 1398-9995. ; 77:7, s. 2147-2162
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Validated combined symptom-medication scores (CSMSs) are needed to investigate the effects of allergic rhinitis treatments. This study aimed to use real-life data from the MASK-air® app to generate and validate hypothesis- and data-driven CSMSs.Methods: We used MASK-air® data to assess the concurrent validity, test-retest reliability and responsiveness of one hypothesis-driven CSMS (modified CSMS: mCSMS), one mixed hypothesis- and data-driven score (mixed score), and several data-driven CSMSs. The latter were generated with MASK-air® data following cluster analysis and regression models or factor analysis. These CSMSs were compared with scales measuring (i) the impact of rhinitis on work productivity (visual analogue scale [VAS] of work of MASK-air®, and Work Productivity and Activity Impairment: Allergy Specific [WPAI-AS]), (ii) quality-of-life (EQ-5D VAS) and (iii) control of allergic diseases (Control of Allergic Rhinitis and Asthma Test [CARAT]).Results: We assessed 317,176 days of MASK-air® use from 17,780 users aged 16-90 years, in 25 countries. The mCSMS and the factor analyses-based CSMSs displayed poorer validity and responsiveness compared to the remaining CSMSs. The latter displayed moderate-to-strong correlations with the tested comparators, high test-retest reliability and moderate-to-large responsiveness. Among data-driven CSMSs, a better performance was observed for cluster analyses-based CSMSs. High accuracy (capacity of discriminating different levels of rhinitis control) was observed for the latter (AUC-ROC = 0.904) and for the mixed CSMS (AUC-ROC = 0.820).Conclusion: The mixed CSMS and the cluster-based CSMSs presented medium-high validity, reliability and accuracy, rendering them as candidates for primary endpoints in future rhinitis trials.
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28.
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29.
  • Brito de Figueiredo, Maria Clea, et al. (författare)
  • Reducing the impact of irrigated crops on freshwater availability : the case of Brazilian yellow melons
  • 2014
  • Ingår i: The International Journal of Life Cycle Assessment. - : Springer Science and Business Media LLC. - 0948-3349 .- 1614-7502. ; 19:2, s. 437-448
  • Tidskriftsartikel (refereegranskat)abstract
    • This study quantifies freshwater consumption throughout the life cycle of Brazilian exported yellow melons and assesses the resulting impact on freshwater availability. Results are used to identify improvement options. Moreover, the study explores the further impact of variations in irrigation volume, yield, and production location. The product system boundary encompasses production of seeds, seedlings, and melon plants; melon packing; disposal of solid farm waste; and farm input and melon transportation to European ports. The primary data in the study were collected from farmers in order to quantify freshwater consumption related to packing and to production of seeds, seedlings, and melons. Open-field melon irrigation was also estimated, considering the region's climate and soil characteristics. Estimated and current water consumptions were compared in order to identify impact reduction opportunities. Sensitivity analysis was used to evaluate variations in the impact because of changes in melon field irrigation, yield, and farm location. This study shows that the average impact on freshwater availability of 1 kg of exported Brazilian yellow melons is 135 l H2O-e, with a range from 17 to 224 l H2O-e depending on the growing season's production period. Irrigation during plant production accounts for 98 % of this impact. Current melon field water consumption in the Low Jaguaribe and A double dagger u region is at least 39 % higher than necessary, which affects the quality of fruits and yield. The impact of melon production in other world regions on freshwater availability may range from 0.3 l H2O-e/kg in Costa Rica to 466 l H2O-e/kg in the USA. The impact of temporary crops, such as melons, on water availability should be presented in ranges, instead of as an average, since regional consumptive water and water stress variations occur in different growing season periods. Current and estimated water consumption for irrigation may also be compared in order to identify opportunities to achieve optimization and reduce water availability impact.
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30.
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31.
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32.
  • Fahlström, Markus, et al. (författare)
  • A mathematical model for temporal cerebral blood flow response to acetazolamide evaluated in patients with Moyamoya disease
  • 2024
  • Ingår i: Magnetic Resonance Imaging. - : Elsevier. - 0730-725X .- 1873-5894. ; 110, s. 35-42
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Paired cerebral blood flow (CBF) measurement is usually acquired before and after vasoactive stimulus to estimate cerebrovascular reserve (CVR). However, CVR may be confounded because of variations in time-to-maximum CBF response (tmax) following acetazolamide injection. With a mathematical model, CVR can be calculated insensitive to variations in tmax, and a model offers the possibility to calculate additional model-derived parameters. A model that describes the temporal CBF response following a vasodilating acetazolamide injection is proposed and evaluated.Methods: A bi-exponential model was adopted and fitted to four CBF measurements acquired using arterial spin labelling before and initialised at 5, 15 and 25 min after acetazolamide injection in a total of fifteen patients with Moyamoya disease. Curve fitting was performed using a non-linear least squares method with a priori constraints based on simulations.Results: Goodness of fit (mean absolute error) varied between 0.30 and 0.62 ml·100 g-1·min-1. Model-derived CVR was significantly higher compared to static CVR measures. Maximum CBF increase occurred earlier in healthy- compared to diseased vascular regions.Conclusions: The proposed mathematical model offers the possibility to calculate CVR insensitive to variations in time to maximum CBF response which gives a more detailed characterisation of CVR compared to static CVR measures. Although the mathematical model adapts generally well to this dataset of patients with MMD it should be considered as experimental; hence, further studies in healthy populations and other patient cohorts are warranted.
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33.
  • Fonseca, Joana, et al. (författare)
  • Algal Bloom Front Tracking Using an Unmanned Surface Vehicle : Numerical Experiments Based on Baltic Sea Data
  • 2021
  • Ingår i: Oceans Conference Record (IEEE). - : Institute of Electrical and Electronics Engineers (IEEE).
  • Konferensbidrag (refereegranskat)abstract
    • We consider the problem of tracking moving algal bloom fronts using an unmanned surface vehicle (USV) equipped with a sensor that measures the concentration of chlorophyll a. Chlorophyll a is a green pigment found in plants, and its concentration is an indicator of phytoplankton abundance. Our algal bloom front tracking mission consists of three stages: deployment, data collection, and front tracking. At the deployment stage, a satellite collects an image of the sea from which the location of the front, the reference value for the concentration at this front and, consequently, the appropriate initial position for the USV are determined. At the data collection stage, the USV collects data points to estimate the local algal gradient as it crosses the front. Finally, at the front tracking stage, an adaptive algorithm based on recursive least squares fitting using recent past sensor measures is executed. We evaluate the performance of the algorithm and its sensitivity to measurement noise through MATLAB simulations. We also present an implementation of the algorithm on the DUNE onboard software platform for marine robots and validate it using simulations with satellite model forecasts from Baltic sea data.
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34.
  • Pires, Ana Elisabete, et al. (författare)
  • The curious case of the Mesolithic Iberian dogs : An archaeogenetic study
  • 2019
  • Ingår i: Journal of Archaeological Science. - : Elsevier BV. - 0305-4403 .- 1095-9238. ; 105, s. 116-129
  • Tidskriftsartikel (refereegranskat)abstract
    • We investigated the genetic composition of six Canis remains from western Iberia, directly radiocarbon dated to 7,903-7,570 years (cal BP). They were identified as dogs via their archaeological and depositional context, osteometry, and a high percentage of aquatic diet shared with humans. For comparison, genetic data were obtained from an additional 37 Iberian dog remains from the Neolithic to Late Antiquity, as well as two Palaeolithic and a Chalcolithic Canis identified as wolves. Previous data indicated that dog mtDNA haplogroup A (HgA) is prevalent in extant European dogs ( > 50%), in the Near East and Asia, but rare or absent ( < 10%) in European Canis older than 3,000 years (cal BP). We found a high frequency (83%) of dog HgA in Mesolithic Iberian dog remains. This is the first report of a high frequency of dog HgA in pre-Neolithic Europe. We show that, contrary to the current view, Canis with HgA did not necessarily arrive in Europe from East-Asia. This phylogeographical difference in HgA frequency demonstrates that genetic differentiation was high prior to, or as a consequence of, domestication which may be linked with pre-Neolithic local processes for Iberian wolf domestication. Our results emphasize that knowledge of both ancient wolves' and early dogs' genetic profiles from the European periphery should improve our understanding of the evolution of the European dog.
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35.
  • Rocha De Sousa, Amandio, et al. (författare)
  • Hospital prevalence of visual of visual impairment caused by diabetic retinopathy
  • 2015
  • Ingår i: Acta Ophthalmologica. - : Wiley. - 1755-375X .- 1755-3768. ; 93:S255
  • Tidskriftsartikel (refereegranskat)abstract
    • PurposeTo investigate cases of visual impairment caused by diabetic retinopathy (DR) in a hospital population.MethodsAs part of an observational study to estimate the prevalence and costs of visual impairment in Portugal (PCVIP study), clinical records of all patients attending the ophthalmology department of a tertiary hospital were analysed looking for patients meeting the inclusion criteria. Inclusion criteria were: (i) presenting visual acuity in the better eye <5/10 (20/40) and/or (ii) visual field <20°. Diagnosis of cases with VI were classified according with ICD9. Results reported here were selected from the total number of patients with VI by filtering ICD9 codes staring by 362.ResultsIn 12 weeks, 1920 cases of VI were detected, 586 (31%) caused by any type of DR. From those: 54% were caused by non-proliferative-DR, 40% by proliferative-DR and 6% by diabetic macular oedema. The mean age of the patients with VI caused by DR was 69.4 (sd = 9.5) years and 57% were female. The estimated hospital prevalence (for 52 weeks) of VI caused by DR is 39% (95%CI = 38–41).ConclusionsOur results show that DR remains the leading cause of VI in the population attending our hospital. Information about the number of patients reaching VI will be fundamental to assess the cost-benefits of treatments and public health campaigns to reduce the burden of diabetic retinopathy in Portugal.
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36.
  • Sousa, João M., et al. (författare)
  • Accuracy and precision of zero-echo-time, single- and multi-atlas attenuation correction for dynamic [11C]PE2I PET-MR brain imaging
  • 2020
  • Ingår i: EJNMMI Physics. - : Springer Science and Business Media LLC. - 2197-7364. ; 7:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: A valid photon attenuation correction (AC) method is instrumental for obtaining quantitatively correct PET images. Integrated PET/MR systems provide no direct information on attenuation, and novel methods for MR-based AC (MRAC) are still under investigation. Evaluations of various AC methods have mainly focused on static brain PET acquisitions. In this study, we determined the validity of three MRAC methods in a dynamic PET/MR study of the brain.METHODS: Nine participants underwent dynamic brain PET/MR scanning using the dopamine transporter radioligand [11C]PE2I. Three MRAC methods were evaluated: single-atlas (Atlas), multi-atlas (MaxProb) and zero-echo-time (ZTE). The 68Ge-transmission data from a previous stand-alone PET scan was used as reference method. Parametric relative delivery (R1) images and binding potential (BPND) maps were generated using cerebellar grey matter as reference region. Evaluation was based on bias in MRAC maps, accuracy and precision of [11C]PE2I BPND and R1 estimates, and [11C]PE2I time-activity curves. BPND was examined for striatal regions and R1 in clusters of regions across the brain.RESULTS: For BPND, ZTE-MRAC showed the highest accuracy (bias < 2%) in striatal regions. Atlas-MRAC exhibited a significant bias in caudate nucleus (- 12%) while MaxProb-MRAC revealed a substantial, non-significant bias in the putamen (9%). R1 estimates had a marginal bias for all MRAC methods (- 1.0-3.2%). MaxProb-MRAC showed the largest intersubject variability for both R1 and BPND. Standardized uptake values (SUV) of striatal regions displayed the strongest average bias for ZTE-MRAC (~ 10%), although constant over time and with the smallest intersubject variability. Atlas-MRAC had highest variation in bias over time (+10 to - 10%), followed by MaxProb-MRAC (+5 to - 5%), but MaxProb showed the lowest mean bias. For the cerebellum, MaxProb-MRAC showed the highest variability while bias was constant over time for Atlas- and ZTE-MRAC.CONCLUSIONS: Both Maxprob- and ZTE-MRAC performed better than Atlas-MRAC when using a 68Ge transmission scan as reference method. Overall, ZTE-MRAC showed the highest precision and accuracy in outcome parameters of dynamic [11C]PE2I PET analysis with use of kinetic modelling.
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37.
  • Sousa, Joao M., 1989- (författare)
  • Assessment of attenuation correction methods for quantitative neuro-PET/MR
  • 2021
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Hybrid PET/magnetic resonance (MR) can provide physiological, functional, and structural information simultaneously, facilitating research in neurological disorders. For quantitative PET, correction for photon attenuation (AC) is necessary. However, in contrast to dedicated PET and PET/computed tomography (CT) systems, PET/MR has no direct possibility to measure photon attenuation. As such, MR-based methods are required for AC (MRAC), and these need to be thoroughly validated before clinical implementation.The primary aim of this thesis was to evaluate two vendor-provided MRAC methods (single-atlas and zero echo time, ZTE), a previously published maximum probability (MaxProb) method, and a composite transmission scan atlas (CTR) method for a SIGNA PET/MR. This evaluation was done both in terms of absolute quantification in static scans and of outcome measures of tracer kinetic modelling based on dynamic scans. The secondary aim was to compare quantitative brain PET measurements acquired on the SIGNA PET/MR with those acquired on a dedicated PET scanner. Ten patients with parkinsonism who underwent dynamic dopamine transporter scans using 11C-PE2I in a PET/MR and dedicated PET were included. Standardized uptake values (SUV), binding potential (BPND), and relative delivery (R1) were assessed at volume of interest (VOI) and voxel level to compare the various MRAC methods with the gold-standard, a 68Ge transmission scan, and to compare quantitative outcomes between scanners.In general, ZTE provided the highest precision in SUV, R1 and BPND, showing the least inter-subject variability in bias compared to 68Ge-transmission AC, whereas MaxProb and CTR showed the lowest precision. Contrary to this, accuracy of absolute SUV values was best for CTR followed by MaxProb, with ZTE showing a homogeneous positive bias of about 10%. ZTE provided the highest accuracy in outcome measures of tracer kinetic analysis. Differences in quantitative results between stand-alone PET and PET/MR exceeded what can be explained by difference in AC alone, although they were still comparable to previously published test-retest variability of 11C-PE2I. Additionally, an activation in the auditory cortex was seen in PET data from the PET/MR because of the noise produced by the MR gradients.ZTE-MRAC appears to be the best method for dynamic scanning and tracer kinetic analysis using reference methods, while CTR- and MaxProb-MRAC appear the most appropriate for absolute quantification. Also, attention should be taken to the auditory cortex activation in R1 images when comparing data from PET/MR and other PET- systems.
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38.
  • Sousa, Joao M., 1989-, et al. (författare)
  • Comparison of quantitative [11C]PE2I brain PET studies between an integrated PET/MR and a stand-alone PET system
  • 2024
  • Ingår i: Physica medica (Testo stampato). - : Elsevier. - 1120-1797 .- 1724-191X. ; 117
  • Tidskriftsartikel (refereegranskat)abstract
    • PET/MR systems demanded great efforts for accurate attenuation correction (AC) but differences in technology, geometry and hardware attenuation may also affect quantitative results. Dedicated PET systems using transmission-based AC are regarded as the gold standard for quantitative brain PET. The study aim was to investigate the agreement between quantitative PET outcomes from a PET/MR scanner against a stand-alone PET system.Nine patients with Parkinsonism underwent two 80-min dynamic PET scans with the dopamine transporter ligand [11C]PE2I. Images were reconstructed with resolution-matched settings using 68Ge-transmission (standalone PET), and zero-echo-time MR (PET/MR) scans for AC. Non-displaceable binding potential (BPND) and relative delivery (R1) were evaluated using volumes of interest and voxel-wise analysis.Correlations between systems were high (r >= 0.85) for both quantitative outcome parameters in all brain regions. Striatal BPND was significantly lower on PET/MR than on stand-alone PET (-7%). R1 was significantly overestimated in posterior cortical regions (9%) and underestimated in striatal (-9%) and limbic areas (-6%). The voxel-wise evaluation revealed that the MR-safe headphones caused a negative bias in both parametric BPND and R1 images. Additionally, a significant positive bias of R1 was found in the auditory cortex, most likely due to the acoustic background noise during MR imaging. The relative bias of the quantitative [11C]PE2I PET data acquired from a SIGNA PET/MR system was in the same order as the expected test-retest reproducibility of [11C]PE2I BPND and R1, compared to a stand-alone ECAT PET scanner. MR headphones and background noise are potential sources of error in functional PET/MR studies.
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39.
  • Sousa, Joao M., 1989-, et al. (författare)
  • Comparison of quantitative [11C]PE2I PET scans acquired on PET/MR and stand-alone PET
  • Ingår i: Journal of Cerebral Blood Flow and Metabolism. - 0271-678X .- 1559-7016.
  • Tidskriftsartikel (populärvet., debatt m.m.)abstract
    • Dedicated PET systems using transmission-based attenuation correction (AC) are regarded as the gold standard for quantitative brain PET. PET/MR systems demanded great efforts for accurate AC but differences in technology, geometry and hardware attenuation may also affect quantitative results. This study compares PET quantitative outcomes between a stand-alone PET and PET/MR scanner. Ten patients with parkinsonism underwent two 80-min dynamic PET scans with the dopamine transporter ligand [11C]PE2I. Images were reconstructed using resolution-matched settings and transmission scans (stand-alone PET) and zero-echo-time (PET/MR) for AC. SUV, relative delivery (R1), and dopamine transporter availability (BPND) were compared on a VOI- and voxel-basis.  Correlations between systems were high (≥ 0.85) for all quantitative parameters. On VOI-basis, striatal BPND was significantly lower on PET/MR than on stand-alone PET (-7%). R1 was significantly overestimated in posterior cortical regions (9%) and underestimated in striatal (-9%) and limbic areas (-6%). SUV showed a similar pattern as R1. Voxel-by-voxel analysis showed significant positive bias of R1 in the auditory cortex. PET/MR significantly underestimated striatal BPND, similar to previously reported [11C]PE2I BPND  test-retest variability. The acoustic noise in the PET/MR environment may attribute to an overestimation of R1 in the auditory cortex, which needs consideration when using PET/MR data.
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40.
  • Sousa, Joao M., 1989-, et al. (författare)
  • Composite 68Ge attenuation correction for quantitative brain PET/MR
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • Accurate attenuation correction (AC) in positron emission tomography (PET) imaging is a prerequisite for obtaining quantitatively correct images and 68Ge-AC is considered the gold standard for PET AC. In this study we developed an alternative AC method for PET/MR, based on the registration of a database of 68Ge-AC maps and T1-weighted MR image pairs. The present work aimed to evaluate this composite 68Ge transmission AC (CTR-AC) method’s reliability compared to 68Ge-AC. The CTR database comprised 125 pairs of previously acquired 68Ge-AC maps and T1-MRI scans. Ten patients underwent 80-min dynamic PET scans with the dopamine transporter ligand [11C]PE2I on a SIGNA PET/MR. Images were reconstructed using a CTR-AC map and a previously acquired patient-specific 68Ge-AC map on a stand-alone PET scanner. SUV as well as outcome parameters of [11C]PE2I kinetic analysis, i.e., relative delivery (R1) and dopamine transporter availability (BPND), were compared on a VOI and voxel-by-voxel basis.CTR-AC showed high accuracy, with a mean bias of 0 ± 3% for whole-brain SUV, -0.1 ± 3.2% for whole-brain R1, and 3.7 ± 8.1% for striatal BPND. The precision of SUV and R1 was modest and lowest in the anterior cortex, with an R1 bias of -1.1 ± 6.4%.CTR-AC is straightforward and provides MRAC maps with continuous linear attenuation coefficient values. The method’s accuracy is comparable to the best MRAC methods published so far, with a near-zero bias in SUV and a bias similar to that previously found for ZTE-AC in outcome parameters of kinetic modelling.
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41.
  • Sousa, Joao M., 1989-, et al. (författare)
  • Composite attenuation correction method using a 68Ge-transmission multi-atlas for quantitative brain PET/MR.
  • 2022
  • Ingår i: Physica medica (Testo stampato). - : Elsevier. - 1120-1797 .- 1724-191X. ; 97, s. 36-43
  • Tidskriftsartikel (refereegranskat)abstract
    • In positron emission tomography (PET), 68Ge-transmission scanning is considered the gold standard in attenuation correction (AC) though not available in current dual imaging systems. In this experimental study we evaluated a novel AC method for PET/magnetic resonance (MR) imaging which is essentially based on a composite database of multiple 68Ge-transmission maps and T1-weighted (T1w) MR image-pairs (composite transmission, CTR-AC). This proof-of-concept study used retrospectively a database with 125 pairs of co-registered 68Ge-AC maps and T1w MR images from anatomical normal subjects and a validation dataset comprising dynamic [11C]PE2I PET data from nine patients with Parkinsonism. CTR-AC maps were generated by non-rigid image registration of all database T1w MRI to each subject's T1w, applying the same transformation to every 68Ge-AC map, and averaging the resulting 68Ge-AC maps. [11C]PE2I PET images were reconstructed using CTR-AC and a patient-specific 68Ge-AC map as the reference standard. Standardized uptake values (SUV) and quantitative parameters of kinetic analysis were compared, i.e., relative delivery (R1) and non-displaceable binding potential (BPND). CTR-AC showed high accuracy for whole-brain SUV (mean %bias ± SD: 0.5 ± 3.5%), whole-brain R1 (-0.1 ± 3.2%), and putamen BPND (3.7 ± 8.1%). SUV and R1 precision (SD of %bias) were modest and lowest in the anterior cortex, with an R1 %bias of -1.1 ± 6.4%). The prototype CTR-AC is capable of providing accurate MRAC-maps with continuous linear attenuation coefficients though still experimental. The method's accuracy is comparable to the best MRAC methods published so far, both in SUV and as found for ZTE-AC in quantitative parameters of kinetic modelling.
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42.
  • Sousa, João M., et al. (författare)
  • Evaluation of zero-echo-time attenuation correction for integrated PET/MR brain imaging-comparison to head atlas and 68Ge-transmission-based attenuation correction
  • 2018
  • Ingår i: EJNMMI Physics. - : Springer Science and Business Media LLC. - 2197-7364. ; 5:20
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: MRI does not offer a direct method to obtain attenuation correction maps as its predecessors (stand-alone PET and PET/CT), and bone visualisation is particularly challenging. Recently, zero-echo-time (ZTE) was suggested for MR-based attenuation correction (AC). The aim of this work was to evaluate ZTE- and atlas-AC by comparison to 68Ge-transmission scan-based AC.Nine patients underwent brain PET/MR and stand-alone PET scanning using the dopamine transporter ligand 11C-PE2I. For each of them, two AC maps were obtained from the MR images: an atlas-based, obtained from T1-weighted LAVA-FLEX imaging with cortical bone inserted using a CT-based atlas, and an AC map generated from proton-density-weighted ZTE images. Stand-alone PET 68Ge-transmission AC map was used as gold standard. PET images were reconstructed using the three AC methods and standardised uptake value (SUV) values for the striatal, limbic and cortical regions, as well as the cerebellum (VOIs) were compared. SUV ratio (SUVR) values normalised for the cerebellum were also assessed. Bias, precision and agreement were calculated; statistical significance was evaluated using Wilcoxon matched-pairs signed-rank test.Results: Both ZTE- and atlas-AC showed a similar bias of 6–8% in SUV values across the regions. Correlation coefficients with 68Ge-AC were consistently high for ZTE-AC (r 0.99 for all regions), whereas they were lower for atlas-AC, varying from 0.99 in the striatum to 0.88 in the posterior cortical regions. SUVR showed an overall bias of 2.9 and 0.5% for atlas-AC and ZTE-AC, respectively. Correlations with 68Ge-AC were higher for ZTE-AC, varying from 0.99 in the striatum to 0.96 in the limbic regions, compared to atlas-AC (0.99 striatum to 0.77 posterior cortex).Conclusions: Absolute SUV values showed less variability for ZTE-AC than for atlas-AC when compared to 68Ge-AC, but bias was similar for both methods. This bias is largely caused by higher linear attenuation coefficients in atlas- and ZTE-AC image compared to 68Ge-images. For SUVR, bias was lower when using ZTE-AC than for atlas-AC. ZTE-AC shows to be a more robust technique than atlas-AC in terms of both intra- and inter-patient variability.
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43.
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44.
  • Sousa-Pinto, Bernardo, et al. (författare)
  • Validity, reliability, and responsiveness of daily monitoring visual analog scales in MASK-air®
  • 2021
  • Ingår i: Clinical and Translational Allergy. - : John Wiley & Sons. - 2045-7022. ; 11:7
  • Forskningsöversikt (refereegranskat)abstract
    • Background: MASK-air® is an app that supports allergic rhinitis patients in disease control. Users register daily allergy symptoms and their impact on activities using visual analog scales (VASs). We aimed to assess the concurrent validity, reliability, and responsiveness of these daily VASs.Methods: Daily monitoring VAS data were assessed in MASK-air® users with allergic rhinitis. Concurrent validity was assessed by correlating daily VAS values with those of the EuroQol-5 Dimensions (EQ-5D) VAS, the Control of Allergic Rhinitis and Asthma Test (CARAT) score, and the Work Productivity and Activity Impairment Allergic Specific (WPAI-AS) Questionnaire (work and activity impairment scores). Intra-rater reliability was assessed in users providing multiple daily VASs within the same day. Test–retest reliability was tested in clinically stable users, as defined by the EQ-5D VAS, CARAT, or “VAS Work” (i.e., VAS assessing the impact of allergy on work). Responsiveness was determined in users with two consecutive measurements of EQ-5D-VAS or “VAS Work” indicating clinical change.Results: A total of 17,780 MASK-air® users, with 317,176 VAS days, were assessed. Concurrent validity was moderate–high (Spearman correlation coefficient range: 0.437–0.716). Intra-rater reliability intraclass correlation coefficients (ICCs) ranged between 0.870 (VAS assessing global allergy symptoms) and 0.937 (VAS assessing allergy symptoms on sleep). Test–retest reliability ICCs ranged between 0.604 and 0.878—“VAS Work” and “VAS asthma” presented the highest ICCs. Moderate/large responsiveness effect sizes were observed—the sleep VAS was associated with lower responsiveness, while the global allergy symptoms VAS demonstrated higher responsiveness.Conclusion: In MASK-air®, daily monitoring VASs have high intra-rater reliability and moderate–high validity, reliability, and responsiveness, pointing to a reliable measure of symptom loads.
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