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1.
  • Jacome, Cristina, et al. (author)
  • Feasibility and Acceptability of an Asthma App to Monitor Medication Adherence : Mixed Methods Study
  • 2021
  • In: JMIR mhealth and uhealth. - : JMIR Publications. - 2291-5222. ; 9:5
  • Journal article (peer-reviewed)abstract
    • Background: Poor medication adherence is a major challenge in asthma, and objective assessment of inhaler adherence is needed. The InspirerMundi app aims to monitor adherence while providing a positive experience through gamification and social support. Objective: This study aimed to evaluate the feasibility and acceptability of the InspirerMundi app to monitor medication adherence in adolescents and adults with persistent asthma (treated with daily inhaled medication). Methods: A 1-month mixed method multicenter observational study was conducted in 26 secondary care centers from Portugal and Spain. During an initial face-to-face visit, physicians reported patients' asthma therapeutic plan in a structured questionnaire. During the visits, patients were invited to use the app daily to register their asthma medication intakes. A scheduled intake was considered taken when patients registered the intake (inhaler, blister, or other drug formulation) by using the image-based medication detection tool. At 1 month, patients were interviewed by phone, and app satisfaction was assessed on a 1 (low) to 5 (high) scale. Patients were also asked to point out the most and least preferred app features and make suggestions for future app improvements. Results: A total of 107 patients (median 27 [P25-P75 14-40] years) were invited, 92.5% (99/107) installed the app, and 73.8% (79/107) completed the 1-month interview. Patients interacted with the app a median of 9 (P25-P75 1-24) days. At least one medication was registered in the app by 78% (77/99) of patients. A total of 53% (52/99) of participants registered all prescribed inhalers, and 34% (34/99) registered the complete asthma therapeutic plan. Median medication adherence was 75% (P25-P75 25%-90%) for inhalers and 82% (P25-P75 50%-94%) for other drug formulations. Patients were globally satisfied with the app, with 75% (59/79) scoring >= 4,; adherence monitoring, symptom monitoring, and gamification features being the most highly scored components; and the medication detection tool among the lowest scored. A total of 53% (42/79) of the patients stated that the app had motivated them to improve adherence to inhaled medication and 77% (61/79) would recommend the app to other patients. Patient feedback was reflected in 4 major themes: medication-related features (67/79, 85%), gamification and social network (33/79, 42%), symptom monitoring and physician communication (21/79, 27%), and other aspects (16/79, 20%). Conclusions: The InspirerMundi app was feasible and acceptable to monitor medication adherence in patients with asthma. Based on patient feedback and to increase the registering of medications, the therapeutic plan registration and medication detection tool were redesigned. Our results highlight the importance of patient participation to produce a patient-centered and engaging mHealth asthma app.
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2.
  • Jacome, Cristina, et al. (author)
  • Monitoring Adherence to Asthma Inhalers Using the InspirerMundi App : Analysis of Real-World, Medium-Term Feasibility Studies
  • 2021
  • In: Frontiers in Medical Technology. - : Frontiers Media S.A.. - 2673-3129. ; 3
  • Journal article (peer-reviewed)abstract
    • Background: Poor medication adherence is a major challenge in asthma and objective assessment of inhaler adherence is needed. InspirerMundi app aims to monitor inhaler adherence while turning it into a positive experience through gamification and social support.Objective: We assessed the medium-term feasibility of the InspirerMundi app to monitor inhaler adherence in real-world patients with persistent asthma (treated with daily inhaled medication). In addition, we attempted to identify the characteristics of the patients related to higher app use.Methods: Two real-world multicenter observational studies, with one initial face-to-face visit and a 4-month telephone interview, were conducted in 29 secondary care centers from Portugal. During an initial face-to-face visit, patients were invited to use the app daily to register their asthma medication intakes. A scheduled intake was considered taken when patients took a photo of the medication (inhaler, blister, or others) using the image-based medication detection tool. Medication adherence was calculated as the number of doses taken as a percentage of the number scheduled. Interacting with the app =30 days was used as the cut-off for higher app use.Results: A total of 114 patients {median 20 [percentile 25 to percentile 75 (P25-P75) 16-36] years, 62% adults} were invited, 107 (94%) installed the app and 83 (73%) completed the 4-month interview. Patients interacted with the app for a median of 18 [3-45] days, translated on a median use rate of 15 [3-38]%. Median inhaler adherence assessed through the app was 34 [4-73]% when considering all scheduled inhalations for the study period. Inhaler adherence assessed was not significantly correlated with self-reported estimates. Median adherence for oral and other medication was 41 [6-83]% and 43 [3-73]%, respectively. Patients with higher app use were slightly older (p = 0.012), more frequently taking medication for other health conditions (p = 0.040), and more frequently prescribed long-acting muscarinic antagonists (LAMA, p = 0.024). After 4 months, Control of Allergic Rhinitis and Asthma Test (CARAT) scores improved (p < 0.001), but no differences between patients interacting with the app for 30 days or less were seen.Conclusions: The InspirerMundi app was feasible to monitor inhaler adherence in patients with persistent asthma. The persistent use of this mHealth technology varies widely. A better understanding of characteristics related to higher app use is still needed before effectiveness studies are undertaken.
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3.
  • Menditto, Enrica, et al. (author)
  • Adherence to treatment in allergic rhinitis using mobile technology : The MASK Study
  • 2019
  • In: Clinical and Experimental Allergy. - : WILEY. - 0954-7894 .- 1365-2222. ; 49:4, s. 442-460
  • Journal article (peer-reviewed)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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4.
  • Neves, Ana Luisa, et al. (author)
  • Determinants of the Use of Health and Fitness Mobile Apps by Patients With Asthma : Secondary Analysis of Observational Studies
  • 2021
  • In: Journal of Medical Internet Research. - : JMIR Publications. - 1438-8871. ; 23:9
  • Journal article (peer-reviewed)abstract
    • Background: Health and fitness apps have potential benefits to improve self-management and disease control among patients with asthma. However, inconsistent use rates have been reported across studies, regions, and health systems. A better understanding of the characteristics of users and nonusers is critical to design solutions that are effectively integrated in patients' daily lives, and to ensure that these equitably reach out to different groups of patients, thus improving rather than entrenching health inequities. Objective: This study aimed to evaluate the use of general health and fitness apps by patients with asthma and to identify determinants of usage. Methods: A secondary analysis of the INSPIRERS observational studies was conducted using data from face-to-face visits. Patients with a diagnosis of asthma were included between November 2017 and August 2020. Individual-level data were collected, including age, gender, marital status, educational level, health status, presence of anxiety and depression, postcode, socioeconomic level, digital literacy, use of health services, and use of health and fitness apps. Multivariate logistic regression was used to model the probability of being a health and fitness app user. Statistical analysis was performed in R. Results: A total of 526 patients attended a face-to-face visit in the 49 recruiting centers and 514 had complete data. Most participants were <= 40 years old (66.4%), had at least 10 years of education (57.4%), and were in the 3 higher quintiles of the socioeconomic deprivation index (70.1%). The majority reported an overall good health status (visual analogue scale [VAS] score>70 in 93.1%) and the prevalence of anxiety and depression was 34.3% and 11.9%, respectively. The proportion of participants who reported using health and fitness mobile apps was 41.1% (n=211). Multivariate models revealed that single individuals and those with more than 10 years of education are more likely to use health and fitness mobile apps (adjusted odds ratio [aOR] 2.22, 95%CI 1.05-4.75 and aOR 1.95, 95%CI 1.12-3.45, respectively). Higher digital literacy scores were also associated with higher odds of being a user of health and fitness apps, with participants in the second, third, and fourth quartiles reporting aORs of 6.74 (95%CI 2.90-17.40), 10.30 (95%CI 4.28-27.56), and 11.52 (95%CI 4.78-30.87), respectively. Participants with depression symptoms had lower odds of using health and fitness apps (aOR 0.32, 95%CI 0.12-0.83). Conclusions: A better understanding of the barriers and enhancers of app use among patients with lower education, lower digital literacy, or depressive symptoms is key to design tailored interventions to ensure a sustained and equitable use of these technologies. Future studies should also assess users' general health-seeking behavior and their interest and concerns specifically about digital tools. These factors may impact both initial engagement and sustained use.
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6.
  • Bedard, Annabelle, et al. (author)
  • Mobile technology offers novel insights into the control and treatment of allergic rhinitis : The MASK study
  • 2019
  • In: Journal of Allergy and Clinical Immunology. - : MOSBY-ELSEVIER. - 0091-6749 .- 1097-6825. ; 144:1, s. 135-143
  • Journal article (peer-reviewed)abstract
    • Background: Mobile health can be used to generate innovative insights into optimizing treatment to improve allergic rhinitis (AR) control. Objectives: A cross-sectional real-world observational study was undertaken in 22 countries to complement a pilot study and provide novel information on medication use, disease control, and work productivity in the everyday life of patients with AR. Methods: A mobile phone app (Allergy Diary, which is freely available on Google Play and Apple stores) was used to collect the data of daily visual analogue scale (VAS) scores for (1) overall allergic symptoms; (2) nasal, ocular, and asthma symptoms; (3) work; and (4) medication use by using a treatment scroll list including all allergy medications (prescribed and over-the-counter) customized for 22 countries. The 4 most common intranasal medications containing intranasal corticosteroids and 8 oral H-1-antihistamines were studied. Results: Nine thousand one hundred twenty-two users filled in 112,054 days of VASs in 2016 and 2017. Assessment of days was informative. Control of days with rhinitis differed between no (best control), single (good control for intranasal corticosteroid-treated days), or multiple (worst control) treatments. Users with the worst control increased the range of treatments being used. The same trend was found for asthma, eye symptoms, and work productivity. Differences between oral H-1-antihistamines were found. Conclusions: This study confirms the usefulness of the Allergy Diary in accessing and assessing behavior in patients with AR. This observational study using a very simple assessment tool (VAS) on a mobile phone had the potential to answer questions previously thought infeasible.
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7.
  • Bousquet, Jean, et al. (author)
  • Allergic Rhinitis and its Impact on Asthma (ARIA) Phase 4 (2018) : Change management in allergic rhinitis and asthma multimorbidity using mobile technology
  • 2019
  • In: Journal of Allergy and Clinical Immunology. - : Elsevier. - 0091-6749 .- 1097-6825. ; 143:3, s. 864-879
  • Journal article (peer-reviewed)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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8.
  • Bousquet, Jean, et al. (author)
  • ARIA digital anamorphosis : Digital transformation of health and care in airway diseases from research to practice
  • 2021
  • In: Allergy. European Journal of Allergy and Clinical Immunology. - : John Wiley & Sons. - 0105-4538 .- 1398-9995. ; 76:1, s. 168-190
  • Research review (peer-reviewed)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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9.
  • Sator, Lea, et al. (author)
  • Overdiagnosis of COPD in Subjects With Unobstructed Spirometry A BOLD Analysis
  • 2019
  • In: Chest. - : Elsevier BV. - 0012-3692 .- 1931-3543. ; 156:2, s. 277-288
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: There are several reports on underdiagnosis of COPD, while little is known about COPD overdiagnosis and overtreatment. We describe the overdiagnosis and the prevalence of spirometrically defined false positive COPD, as well as their relationship with overtreatment across 23 population samples in 20 countries participating in the BOLD Study between 2003 and 2012.METHODS: A false positive diagnosis of COPD was considered when participants reported a doctor's diagnosis of COPD, but postbronchodilator spirometry was unobstructed (FEV1/FVC > LLN). Additional analyses were performed using the fixed ratio criterion (FEV1/FVC < 0.7).RESULTS: Among 16,177 participants, 919 (5.7%) reported a previous medical diagnosis of COPD. Postbronchodilator spirometry was unobstructed in 569 subjects (61.9%): false positive COPD. A similar rate of overdiagnosis was seen when using the fixed ratio criterion (55.3%). In a subgroup analysis excluding participants who reported a diagnosis of "chronic bronchitis" or "emphysema" (n = 220), 37.7% had no airflow limitation. The site-specific prevalence of false positive COPD varied greatly, from 1.9% in low- to middle-income countries to 4.9% in high-income countries. In multivariate analysis, overdiagnosis was more common among women, and was associated with higher education; former and current smoking; the presence of wheeze, cough, and phlegm; and concomitant medical diagnosis of asthma or heart disease. Among the subjects with false positive COPD, 45.7% reported current use of respiratory medication. Excluding patients with reported asthma, 34.4% of those with normal spirometry still used a respiratory medication.CONCLUSIONS: False positive COPD is frequent. This might expose nonobstructed subjects to possible adverse effects of respiratory medication.
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10.
  • Sousa-Pinto, Bernardo, et al. (author)
  • Development and validation of combined symptom-medication scores for allergic rhinitis*
  • 2022
  • In: Allergy. European Journal of Allergy and Clinical Immunology. - : John Wiley & Sons. - 0105-4538 .- 1398-9995. ; 77:7, s. 2147-2162
  • Journal article (peer-reviewed)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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12.
  • Alexandre, Luana, et al. (author)
  • Patients' Satisfaction with Remote Asthma Medical Follow-Up Before and During the COVID-19 Pandemic
  • 2023
  • In: Telemedicine journal and e-health. - : Mary Ann Liebert. - 1530-5627 .- 1556-3669. ; 29:9, s. 1383-1389
  • Journal article (peer-reviewed)abstract
    • Background: The COVID-19 pandemic forced the change of health care services, favoring the use of remote consultations.Objective: To assess the differences in asthma medical follow-up before and during the COVID-19 pandemic and to evaluate patients' satisfaction regarding remote consultations.Methods: A cross-sectional, observational, web-based study, including 335 Portuguese patients with self-reported physician-diagnosed asthma, was conducted. The survey was available between February and May 2021 and included questions about patients' sociodemographic and clinical characteristics and follow-up (consultations' type and satisfaction in 2019 and 2020). Satisfaction was assessed using 10 statements on different aspects of patient experience (Likert scale 1-5), with a total score between 10 and 50.Results: The 335 patients included had a median [P25-P75] age of 27 [21-43] years and 75% had uncontrolled asthma. Overall, fewer participants had consultations during the pandemic compared to 2019 (161 vs. 185; p < 0.001). Most patients had >= 1 face-to-face consultation both in 2020 and 2019 (131 vs. 184; p < 0.001). In 2020, there was an increase in the proportion of participants reporting >= 1 remote (telephonic plus video) consultation (40% vs. 3%; p < 0.001). This increase was mainly attributed to the use of telephonic consultation (38% vs. video 3%, p < 0.001). Patients' satisfaction was similar in 2020 and 2019 for face-to-face consultations (44 [38-47] and 44 [39-48], p = 0.136). In 2020, satisfaction with remote consultations was slightly lower than with face-to-face (43 [37-46] vs. 44 [38-47], p < 0.001).Conclusions: Even though patients were slightly more satisfied with face-to-face consultations, remote consultations can be an alternative in follow-up services for patients with asthma in the near future.
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13.
  • Amaral, Rita, et al. (author)
  • Profiling Persistent Asthma Phenotypes in Adolescents : A Longitudinal Diagnostic Evaluation from the INSPIRERS Studies
  • 2021
  • In: International Journal of Environmental Research and Public Health. - : MDPI. - 1661-7827 .- 1660-4601. ; 18:3
  • Journal article (peer-reviewed)abstract
    • We aimed to identify persistent asthma phenotypes among adolescents and to evaluate longitudinally asthma-related outcomes across phenotypes. Adolescents (13-17 years) from the prospective, observational, and multicenter INSPIRERS studies, conducted in Portugal and Spain, were included (n = 162). Latent class analysis was applied to demographic, environmental, and clinical variables, collected at a baseline medical visit. Longitudinal differences in clinical variables were assessed at a 4-month follow-up telephone contact (n = 128). Three classes/phenotypes of persistent asthma were identified. Adolescents in class 1 (n = 87) were highly symptomatic at baseline and presented the highest number of unscheduled healthcare visits per month and exacerbations per month, both at baseline and follow-up. Class 2 (n = 32) was characterized by female predominance, more frequent obesity, and uncontrolled upper/lower airways symptoms at baseline. At follow-up, there was a significant increase in the proportion of controlled lower airway symptoms (p < 0.001). Class 3 (n = 43) included mostly males with controlled lower airways symptoms; at follow-up, while keeping symptom control, there was a significant increase in exacerbations/month (p = 0.015). We have identified distinct phenotypes of persistent asthma in adolescents with different patterns in longitudinal asthma-related outcomes, supporting the importance of profiling asthma phenotypes in predicting disease outcomes that might inform targeted interventions and reduce future risk.
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14.
  • Blaschikoff, Ludmilla, et al. (author)
  • A multidisciplinary study of Iberian Chalcolithic dogs
  • 2022
  • In: Journal of Archaeological Science. - : Elsevier BV. - 2352-409X .- 2352-4103. ; 42
  • Journal article (peer-reviewed)abstract
    • Domesticated dogs have been present in the Iberian Peninsula long before other domesticated species, back to the late Palaeolithic period. Their origin is still uncertain, but dogs were already well established during the Chalcolithic period (ca. 5000-4000 BP). This study employed a multidisciplinary approach comprising osteometric, radiographic and palaeogenomic analyses to characterize Chalcolithic Iberian Canis remains. Two Chalcolithic archaeological sites - Leceia, Oeiras, in Portugal, and El Caset ' on de la Era, Villalba de los Alcores, Valladolid, in Spain - were the main focus of this study. Osteometric and odontometric data from eleven other sites in Iberia were also included. Osteometric results show signs of phenotypic variability, likely the result of human-driven selective pressure. Dental radiographic and dental wear analyses allowed age at death estimation for four individuals (two juvenile and two adults). Three Chalcolithic Iberian dogs had their mitogenomes resequenced and the mitochondrial DNA analysis allowed to assign each individual to two of the major known haplogroups - A and C. Molecular sex infered by the chromosomeX/chromosome1 coverage ratio allowed to identify one female and two males. This study unveils some aspects of the Iberian Chalcolithic dogs: these dogs already exhibited various morphotypes whose profiles might be associated to the performance of certain tasks, as well as mitogenomes of two distinct lineages that help tracking the evolutionary paths of Iberian dogs.
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15.
  • Bousquet, J. Jean, et al. (author)
  • Next-generation ARIA care pathways for rhinitis and asthma : a model for multimorbid chronic diseases
  • 2019
  • In: Clinical and Translational Allergy. - : BMC. - 2045-7022. ; 9
  • Research review (peer-reviewed)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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16.
  • Cachim, Afonso, et al. (author)
  • Measuring adherence to inhaled control medication in patients with asthma : Comparison among an asthma app, patient self-report and physician assessment
  • 2023
  • In: Clinical and Translational Allergy. - : John Wiley & Sons. - 2045-7022. ; 13:2
  • Journal article (peer-reviewed)abstract
    • BackgroundPrevious studies have demonstrated the feasibility of using an asthma app to support medication management and adherence but failed to compare with other measures currently used in clinical practice. However, in a clinical setting, any additional adherence measurement must be evaluated in the context of both the patient and physician perspectives so that it can also help improve the process of shared decision making. Thus, we aimed to compare different measures of adherence to asthma control inhalers in clinical practice, namely through an app, patient self-report and physician assessment.MethodsThis study is a secondary analysis of three prospective multicentre observational studies with patients (≥13 years old) with persistent asthma recruited from 61 primary and secondary care centres in Portugal. Patients were invited to use the InspirerMundi app and register their inhaled medication. Adherence was measured by the app as the number of doses taken divided by the number of doses scheduled each day and two time points were considered for analysis: 1-week and 1-month. At baseline, patients and physicians independently assessed adherence to asthma control inhalers during the previous week using a Visual Analogue Scale (VAS 0–100).ResultsA total of 193 patients (72% female; median [P25–P75] age 28 [19–41] years old) were included in the analysis. Adherence measured by the app was lower (1 week: 31 [0–71]%; 1 month: 18 [0–48]%) than patient self-report (80 [60–95]) and physician assessment (82 [51–94]) (p < 0.001). A negligible non-significant correlation was found between the app and subjective measurements (ρ 0.118–0.156, p > 0.05). There was a moderate correlation between patient self-report and physician assessment (ρ = 0.596, p < 0.001).ConclusionsAdherence measured by the app was lower than that reported by the patient or the physician. This was expected as objective measurements are commonly lower than subjective evaluations, which tend to overestimate adherence. Nevertheless, the low adherence measured by the app may also be influenced by the use of the app itself and this needs to be considered in future studies.
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17.
  • Costa, João T., et al. (author)
  • Gephyrin Cleavage in In Vitro Brain Ischemia Decreases GABAA Receptor Clustering and Contributes to Neuronal Death
  • 2016
  • In: Molecular Neurobiology. - : Springer Science and Business Media LLC. - 0893-7648 .- 1559-1182. ; 53:6, s. 3513-3527
  • Journal article (peer-reviewed)abstract
    • GABA (γ-aminobutyric acid) is the major inhibitory neurotransmitter in the central nervous system, and changes in GABAergic neurotransmission modulate the activity of neuronal networks. Gephyrin is a scaffold protein responsible for the traffic and synaptic anchoring of GABAA receptors (GABAAR); therefore, changes in gephyrin expression and oligomerization may affect the activity of GABAergic synapses. In this work, we investigated the changes in gephyrin protein levels during brain ischemia and in excitotoxic conditions, which may affect synaptic clustering of GABAAR. We found that gephyrin is cleaved by calpains following excitotoxic stimulation of hippocampal neurons with glutamate, as well as after intrahippocampal injection of kainate, giving rise to a stable cleavage product. Gephyrin cleavage was also observed in cultured hippocampal neurons subjected to transient oxygen-glucose deprivation (OGD), an in vitro model of brain ischemia, and after transient middle cerebral artery occlusion (MCAO) in mice, a model of focal brain ischemia. Furthermore, a truncated form of gephyrin decreased the synaptic clustering of the protein, reduced the synaptic pool of GABAAR containing γ2 subunits and upregulated OGD-induced cell death in hippocampal cultures. Our results show that excitotoxicity and brain ischemia downregulate full-length gephyrin with a concomitant generation of truncated products, which affect synaptic clustering of GABAAR and cell death.
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18.
  • Erjefält, Jonas S., et al. (author)
  • Diffuse alveolar damage patterns reflect the immunological and molecular heterogeneity in fatal COVID-19
  • 2022
  • In: EBioMedicine. - : Elsevier BV. - 2352-3964. ; 83
  • Journal article (peer-reviewed)abstract
    • Background: Severe COVID-19 lung disease exhibits a high degree of spatial and temporal heterogeneity, with different histological features coexisting within a single individual. It is important to capture the disease complexity to support patient management and treatment strategies. We provide spatially decoded analyses on the immunopathology of diffuse alveolar damage (DAD) patterns and factors that modulate immune and structural changes in fatal COVID-19. Methods: We spatially quantified the immune and structural cells in exudative, intermediate, and advanced DAD through multiplex immunohistochemistry in autopsy lung tissue of 18 COVID-19 patients. Cytokine profiling, viral, bacteria, and fungi detection, and transcriptome analyses were performed. Findings: Spatial DAD progression was associated with expansion of immune cells, macrophages, CD8+ T cells, fibroblasts, and (lymph)angiogenesis. Viral load correlated positively with exudative DAD and negatively with disease/hospital length. In all cases, enteric bacteria were isolated, and Candida parapsilosis in eight cases. Cytokines correlated mainly with macrophages and CD8+T cells. Pro-coagulation and acute repair were enriched pathways in exudative DAD whereas intermediate/advanced DAD had a molecular profile of elevated humoral and innate immune responses and extracellular matrix production. Interpretation: Unraveling the spatial and molecular immunopathology of COVID-19 cases exposes the responses to SARS-CoV-2-induced exudative DAD and subsequent immune-modulatory and remodeling changes in proliferative/advanced DAD that occur side-by-side together with secondary infections in the lungs. These complex features have important implications for disease management and the development of novel treatments. Funding: CNPq, Bill and Melinda Gates Foundation, HC-Convida, FAPESP, Regeneron Pharmaceuticals, and the Swedish Heart & Lung Foundation.
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19.
  • Holtkötter, Jannis, et al. (author)
  • Development and Validation of a Digital Image Processing-Based Pill Detection Tool for an Oral Medication Self-Monitoring System
  • 2022
  • In: Sensors. - : MDPI AG. - 1424-8220. ; 22:8
  • Journal article (peer-reviewed)abstract
    • Long-term adherence to medication is of critical importance for the successful management of chronic diseases. Objective tools to track oral medication adherence are either lacking, expensive, difficult to access, or require additional equipment. To improve medication adherence, cheap and easily accessible objective tools able to track compliance levels are necessary. A tool to monitor pill intake that can be implemented in mobile health solutions without the need for additional devices was developed. We propose a pill intake detection tool that uses digital image processing to analyze images of a blister to detect the presence of pills. The tool uses the Circular Hough Transform as a feature extraction technique and is therefore primarily useful for the detection of pills with a round shape. This pill detection tool is composed of two steps. First, the registration of a full blister and storing of reference values in a local database. Second, the detection and classification of taken and remaining pills in similar blisters, to determine the actual number of untaken pills. In the registration of round pills in full blisters, 100% of pills in gray blisters or blisters with a transparent cover were successfully detected. In the counting of untaken pills in partially opened blisters, 95.2% of remaining and 95.1% of taken pills were detected in gray blisters, while 88.2% of remaining and 80.8% of taken pills were detected in blisters with a transparent cover. The proposed tool provides promising results for the detection of round pills. However, the classification of taken and remaining pills needs to be further improved, in particular for the detection of pills with non-oval shapes.
  •  
20.
  • Metcalfe, Daniel B., et al. (author)
  • Impacts of experimentally imposed drought on leaf respiration and morphology in an Amazon rain forest
  • 2010
  • In: Functional Ecology. - : Wiley. - 0269-8463 .- 1365-2435. ; 24:3, s. 524-533
  • Journal article (peer-reviewed)abstract
    • P>1. The Amazon region may experience increasing moisture limitation over this century. Leaf dark respiration (R) is a key component of the Amazon rain forest carbon (C) cycle, but relatively little is known about its sensitivity to drought. 2. Here, we present measurements of R standardized to 25 degrees C and leaf morphology from different canopy heights over 5 years at a rain forest subject to a large-scale through-fall reduction (TFR) experiment, and nearby, unmodified Control forest, at the Caxiuana reserve in the eastern Amazon. 3. In all five post-treatment measurement campaigns, mean R at 25 degrees C was elevated in the TFR forest compared to the Control forest experiencing normal rainfall. After 5 years of the TFR treatment, R per unit leaf area and mass had increased by 65% and 42%, respectively, relative to pre-treatment means. In contrast, leaf area index (L) in the TFR forest was consistently lower than the Control, falling by 23% compared to the pre-treatment mean, largely because of a decline in specific leaf area (S). 4. The consistent and significant effects of the TFR treatment on R, L and S suggest that severe drought events in the Amazon, of the kind that may occur more frequently in future, could cause a substantial increase in canopy carbon dioxide emissions from this ecosystem to the atmosphere.
  •  
21.
  • Monteiro, Bernardo, et al. (author)
  • Lanthanide-based complexes as efficient physiological temperature sensors
  • 2022
  • In: Materials Chemistry and Physics. - : Elsevier BV. - 0254-0584 .- 1879-3312. ; 277
  • Journal article (peer-reviewed)abstract
    • A new molecular thermometric sensor based on the terbium(III) complex [C(2)mim][Tb(fod)4] (C(2)mim - 1-methyl-3-ethylimidazolium, fod(-) - tetrakis-6,6,7,7,8,8,8-heptafluoro-2,2-dimethyl-3,5-octanedionate),doped with 0.015% of its europium(III) analogue (1, [C(2)mim][Tb(fod)(4)]0.99985:[C(2)mim][Eu(fod)(4)]0.00015), was prepared and its thermochromic behaviour evaluated from ambient temperature up to 75 degrees C, including in the physiological range (35-45 degrees C). It was found that the intensity ratio of the D-5(4)-> F-7(5) (TbIII) and D-5(0)-> F-7(2) (EuIII) transitions is correlated with temperature having three different linear regimes. Visual colorimetry allowed the evaluation of the temperature in different ranges from green at ambient temperature, to yellow and finally red at higher temperatures. The TbIII complex emission intensity is extremely sensitive to small temperature variations, particularly between 25 and 35 degrees C, were it reaches only 40% of the initial intensity. Confinement of the dopped TbIII tetrakis-complex in the organic polymeric matrix poly(methylmethacrylate) (PMMA) induced higher thermal stability in 1, together with a strong temperature dependence of the most intense emissive transition of the TbIII complexes. The photoluminescence quantum yield of polymer-lanthanide hybrid materials increased significantly compared with that of 1. Under 366 nm irradiation, the hybrid material presents a green colour at 25 degrees C that evolves to yellow at 30 degrees C and to a white tone at 35 degrees C.
  •  
22.
  • Pereira, Ana Margarida, et al. (author)
  • Multidisciplinary Development and Initial Validation of a Clinical Knowledge Base on Chronic Respiratory Diseases for mHealth Decision Support Systems
  • 2023
  • In: Journal of Medical Internet Research. - : JMIR PUBLICATIONS, INC. - 1438-8871. ; 25
  • Journal article (peer-reviewed)abstract
    • Most mobile health (mHealth) decision support systems currently available for chronic obstructive respiratory diseases (CORDs) are not supported by clinical evidence or lack clinical validation. The development of the knowledge base that will feed the clinical decision support system is a crucial step that involves the collection and systematization of clinical knowledge from relevant scientific sources and its representation in a human-understandable and computer-interpretable way. This work describes the development and initial validation of a clinical knowledge base that can be integrated into mHealth decision support systems developed for patients with CORDs. A multidisciplinary team of health care professionals with clinical experience in respiratory diseases, together with data science and IT professionals, defined a new framework that can be used in other evidence-based systems. The knowledge base development began with a thorough review of the relevant scientific sources (eg, disease guidelines) to identify the recommendations to be implemented in the decision support system based on a consensus process. Recommendations were selected according to predefined inclusion criteria: (1) applicable to individuals with CORDs or to prevent CORDs, (2) directed toward patient self-management, (3) targeting adults, and (4) within the scope of the knowledge domains and subdomains defined. Then, the selected recommendations were prioritized according to (1) a harmonized level of evidence (reconciled from different sources); (2) the scope of the source document (international was preferred); (3) the entity that issued the source document; (4) the operability of the recommendation; and (5) health care professionals' perceptions of the relevance, potential impact, and reach of the recommendation. A total of 358 recommendations were selected. Next, the variables required to trigger those recommendations were defined (n=116) and operationalized into logical rules using Boolean logical operators (n=405). Finally, the knowledge base was implemented in an intelligent individualized coaching component , pretested with an asthma use case. Initial validation of the knowledge base was conducted internally using data from a population-based observational study of individuals with or without asthma or rhinitis. External validation of the appropriateness of the recommendations with the highest priority level was conducted independently by 4 physicians. In addition, a strategy for knowledge base updates, including an easy-to-use rules editor, was defined. Using this process, based on consensus and iterative improvement, we developed and conducted preliminary validation of a clinical knowledge base for CORDs that translates disease guidelines into personalized patient recommendations. The knowledge base can be used as part of mHealth decision support systems. This process could be replicated in other clinical areas.
  •  
23.
  • Pereira, Ana Margarida, et al. (author)
  • What Do Physicians Think About the Use of Telemedicine to Recruit and Assess Participants in mHealth-Related Clinical Studies as a Consequence of the COVID-19 Pandemic?
  • 2022
  • In: Telemedicine journal and e-health. - : Mary Ann Liebert. - 1530-5627 .- 1556-3669. ; 28:9, s. 1386-1392
  • Journal article (peer-reviewed)abstract
    • Objectives: To evaluate physician's opinion and availability to participate in mHealth-related clinical studies with patient recruitment and assessment via telemedicine and to identify characteristics associated with the willingness to participate.Methods: Cross-sectional, observational study, based on an anonymous web survey conducted in May-Jun of 2020 to 237 physicians, from Portugal and Spain that collaborated with an asthma mHealth project (INSPIRERS).Results: Response rate was 51% (n = 120). Most (74%, n = 89) physicians were available to participate in such studies, but 62% anticipated lower recruiting capacity and 40% increased difficulty in obtaining quality data. Physicians aged <= 40 years, from secondary care (vs. general practitioners) and that used apps in personal life or clinical practice were more likely to be available.Conclusions: Three-quarters of the physicians were available to participate in mHealth-related clinical studies with patient recruitment and assessment through telemedicine. Age group, medical specialty, and app use were associated with the willingness to participate.
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24.
  • Rodrigues Gomes, Joao Carlos, et al. (author)
  • Excitotoxicity Downregulates TrkB.FL Signaling and Upregulates the Neuroprotective Truncated TrkB Receptors in Cultured Hippocampal and Striatal Neurons.
  • 2012
  • In: The Journal of Neuroscience : the official journal of the Society for Neuroscience. - 1529-2401. ; 32:13, s. 4610-4622
  • Journal article (peer-reviewed)abstract
    • Brain-derived neurotrophic factor (BDNF) plays an important role in neuronal survival through activation of TrkB receptors. The trkB gene encodes a full-length receptor tyrosine kinase (TrkB.FL) and its truncated (T1/T2) isoforms. We investigated the changes in TrkB protein levels and signaling activity under excitotoxic conditions, which are characteristic of brain ischemia, traumatic brain injury, and neurodegenerative disorders. Excitotoxic stimulation of cultured rat hippocampal or striatal neurons downregulated TrkB.FL and upregulated a truncated form of the receptor (TrkB.T). Downregulation of TrkB.FL was mediated by calpains, whereas the increase in TrkB.T protein levels required transcription and translation activities. Downregulation of TrkB.FL receptors in hippocampal neurons correlated with a decrease in BDNF-induced activation of the Ras/ERK and PLCγ pathways. However, calpain inhibition, which prevents TrkB.FL degradation, did not preclude the decrease in signaling activity of these receptors. On the other hand, incubation with anisomycin, to prevent the upregulation of TrkB.T, protected to a large extent the TrkB.FL signaling activity, suggesting that truncated receptors may act as dominant-negatives. The upregulation of TrkB.T under excitotoxic conditions was correlated with an increase in BDNF-induced inhibition of RhoA, a mediator of excitotoxic neuronal death. BDNF fully protected hippocampal neurons transduced with TrkB.T when present during excitotoxic stimulation with glutamate, in contrast with the partial protection observed in cells overexpressing TrkB.FL or expressing GFP. These results indicate that BDNF protects hippocampal neurons by two distinct mechanisms: through the neurotrophic effects of TrkB.FL receptors and by activation of TrkB.T receptors coupled to inhibition of the excitotoxic signaling.
  •  
25.
  • Simoes Cunha, Mafalda, et al. (author)
  • Symptoms of anxiety and depression in patients with persistent asthma : a cross-sectional analysis of the INSPIRERS studies
  • 2023
  • In: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 13:5
  • Journal article (peer-reviewed)abstract
    • ObjectivesAnxiety and depression are relevant comorbidities in asthma, but, in Portugal and Spain, data on this topic are scarce. We assessed, in patients with asthma, the frequency of anxiety and depression using the Hospital Anxiety and Depression Scale (HADS) and the European Quality of Life Five Dimension Questionnaire (EQ-5D); the level of agreement between these questionnaires, and the factors associated with these symptoms.MethodsThis is a secondary analysis of the INSPIRERS studies. A total of 614 adolescents and adults with persistent asthma (32.6 +/- 16.9 years, 64.7% female) were recruited from 30 primary care centres and 32 allergy, pulmonology and paediatric clinics. Demographic and clinical characteristics, HADS and EQ-5D were collected. A score >= 8 on Hospital Anxiety and Depression Scale-Anxiety/Hospital Anxiety and Depression Scale-Depression or a positive answer to EQ-5D item 5 indicated the presence of these symptoms. Agreement was determined by Cohen's kappa. Two multivariable logistic regressions were built.ResultsAccording to HADS, 36% of the participants had symptoms of anxiety and 12% of depression. According to EQ-5D, 36% of the participants had anxiety/depression. The agreement between questionnaires in identifying anxiety/depression was moderate (k=0.55, 95% CI 0.48 to 0.62). Late asthma diagnosis, comorbidities and female gender were predictors of anxiety/depression, while better asthma control, health-related quality of life and perception of health were associated with lower odds for anxiety/depression.ConclusionAt least 1/3 of the patients with persistent asthma experience symptoms of anxiety/depression, showing the relevance of screening these disorders in patients with asthma. EQ-5D and HADS questionnaires showed a moderate agreement in the identification of anxiety/depression symptoms. The identified associated factors need to be further investigated in long-term studies.
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26.
  • Sousa-Pinto, Bernardo, et al. (author)
  • Validity, reliability, and responsiveness of daily monitoring visual analog scales in MASK-air®
  • 2021
  • In: Clinical and Translational Allergy. - : John Wiley & Sons. - 2045-7022. ; 11:7
  • Research review (peer-reviewed)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.
  •  
27.
  • Swift, Imogen J, et al. (author)
  • A systematic review of progranulin concentrations in biofluids in over 7,000 people-assessing the pathogenicity of GRN mutations and other influencing factors.
  • 2024
  • In: Alzheimer's Research & Therapy. - 1758-9193. ; 16:1
  • Journal article (peer-reviewed)abstract
    • Pathogenic heterozygous mutations in the progranulin gene (GRN) are a key cause of frontotemporal dementia (FTD), leading to significantly reduced biofluid concentrations of the progranulin protein (PGRN). This has led to a number of ongoing therapeutic trials aiming to treat this form of FTD by increasing PGRN levels in mutation carriers. However, we currently lack a complete understanding of factors that affect PGRN levels and potential variation in measurement methods. Here, we aimed to address this gap in knowledge by systematically reviewing published literature on biofluid PGRN concentrations.Published data including biofluid PGRN concentration, age, sex, diagnosis and GRN mutation were collected for 7071 individuals from 75 publications. The majority of analyses (72%) had focused on plasma PGRN concentrations, with many of these (56%) measured with a single assay type (Adipogen) and so the influence of mutation type, age at onset, sex, and diagnosis were investigated in this subset of the data.We established a plasma PGRN concentration cut-off between pathogenic mutation carriers and non-carriers of 74.8ng/mL using the Adipogen assay based on 3301 individuals, with a CSF concentration cut-off of 3.43ng/mL. Plasma PGRN concentration varied by GRN mutation type as well as by clinical diagnosis in those without a GRN mutation. Plasma PGRN concentration was significantly higher in women than men in GRN mutation carriers (p=0.007) with a trend in non-carriers (p=0.062), and there was a significant but weak positive correlation with age in both GRN mutation carriers and non-carriers. No significant association was seen with weight or with TMEM106B rs1990622 genotype. However, higher plasma PGRN levels were seen in those with the GRN rs5848 CC genotype in both GRN mutation carriers and non-carriers.These results further support the usefulness of PGRN concentration for the identification of the large majority of pathogenic mutations in the GRN gene. Furthermore, these results highlight the importance of considering additional factors, such as mutation type, sex and age when interpreting PGRN concentrations. This will be particularly important as we enter the era of trials for progranulin-associated FTD.
  •  
28.
  • Almeida, Diogo, 1991-, et al. (author)
  • Team KTH’s Picking Solution for the Amazon Picking Challenge 2016
  • 2017
  • In: Warehouse Picking Automation Workshop 2017.
  • Conference paper (pop. science, debate, etc.)abstract
    • In this work we summarize the solution developed by Team KTH for the Amazon Picking Challenge 2016 in Leipzig, Germany. The competition simulated a warehouse automation scenario and it was divided in two tasks: a picking task where a robot picks items from a shelf and places them in a tote and a stowing task which is the inverse task where the robot picks items from a tote and places them in a shelf. We describe our approach to the problem starting from a high level overview of our system and later delving into details of our perception pipeline and our strategy for manipulation and grasping. The solution was implemented using a Baxter robot equipped with additional sensors.
  •  
29.
  • Almeida, Diogo, 1991-, et al. (author)
  • Team KTH’s Picking Solution for the Amazon Picking Challenge 2016
  • 2020
  • In: Advances on Robotic Item Picking: Applications in Warehousing and E-Commerce Fulfillment. - Cham : Springer Nature. ; , s. 53-62
  • Book chapter (other academic/artistic)abstract
    • In this chapter we summarize the solution developed by team KTH for the Amazon Picking Challenge 2016 in Leipzig, Germany. The competition, which simulated a warehouse automation scenario, was divided into two parts: a picking task, where the robot picks items from a shelf and places them into a tote, and a stowing task, where the robot picks items from a tote and places them in a shelf. We describe our approach to the problem starting with a high-level overview of the system, delving later into the details of our perception pipeline and strategy for manipulation and grasping. The hardware platform used in our solution consists of a Baxter robot equipped with multiple vision sensors.
  •  
30.
  • Almeida, Joao, et al. (author)
  • Carbon fluxes of xylose-consuming Saccharomyces cerevisiae strains are affected differently by NADH and NADPH usage in HMF reduction.
  • 2009
  • In: Applied Microbiology and Biotechnology. - : Springer Science and Business Media LLC. - 1432-0614 .- 0175-7598. ; 84, s. 751-761
  • Journal article (peer-reviewed)abstract
    • Industrial Saccharomyces cerevisiae strains able to utilize xylose have been constructed by overexpression of XYL1 and XYL2 genes encoding the NADPH-preferring xylose reductase (XR) and the NAD(+)-dependent xylitol dehydrogenase (XDH), respectively, from Pichia stipitis. However, the use of different co-factors by XR and XDH leads to NAD(+) deficiency followed by xylitol excretion and reduced product yield. The furaldehydes 5-hydroxymethyl-furfural (HMF) and furfural inhibit yeast metabolism, prolong the lag phase, and reduce the ethanol productivity. Recently, genes encoding furaldehyde reductases were identified and their overexpression was shown to improve S. cerevisiae growth and fermentation rate in HMF containing media and in lignocellulosic hydrolysate. In the current study, we constructed a xylose-consuming S. cerevisiae strain using the XR/XDH pathway from P. stipitis. Then, the genes encoding the NADH- and the NADPH-dependent HMF reductases, ADH1-S110P-Y295C and ADH6, respectively, were individually overexpressed in this background. The performance of these strains, which differed in their co-factor usage for HMF reduction, was evaluated under anaerobic conditions in batch fermentation in absence or in presence of HMF. In anaerobic continuous culture, carbon fluxes were obtained for simultaneous xylose consumption and HMF reduction. Our results show that the co-factor used for HMF reduction primarily influenced formation of products other than ethanol, and that NADH-dependent HMF reduction influenced product formation more than NADPH-dependent HMF reduction. In particular, NADH-dependent HMF reduction contributed to carbon conservation so that biomass was produced at the expense of xylitol and glycerol formation.
  •  
31.
  • Almeida, Joao, et al. (author)
  • Characterization of major enzymes and genes involved in flavonoid and proanthocyanidin biosynthesis during fruit development in strawberry (Fragaria x ananassa)
  • 2007
  • In: Archives of Biochemistry and Biophysics. - : Elsevier BV. - 0003-9861. ; 465:1, s. 61-71
  • Journal article (peer-reviewed)abstract
    • The biosynthesis of flavonoids and proanthocyanidins was studied in cultivated strawberry (Fragaria x ananassa) by combining biochemical and molecular approaches. Chemical analyses showed that ripe strawberries accumulate high amounts of pelargonidin-derived anthocyanins, and a larger pool of 3',4'-hydroxylated proanthocyanidins. Activities and properties of major recombinant enzymes were demonstrated by means of in vitro assays, with special emphasis on specificity for the biologically relevant 4'- and 3',4'-hydroxylated compounds. Only leucoanthocyanidin reductase showed a strict specificity for the 3',4'-hydroxylated leucocyanidin, while other enzymes accepted either hydroxylated substrate with different relative activity rates. The structure of late flavonoid pathway genes, leading to the synthesis of major compounds in ripe fruits, was elucidated. Complex developmental and spatial expression patterns were shown for phenylpropanoid and flavonoid genes in fruits throughout ripening as well as in leaves, petals and roots. Presented results elucidate key steps in the biosynthesis of strawberry flavonoid end products. (c) 2007 Elsevier Inc. All rights reserved.
  •  
32.
  • Almeida, Joao, et al. (author)
  • Developing Saccharomyces cerevisiae strains for second generation bioethanol: Improving xylose fermentation and inhibitor tolerance
  • 2009
  • In: International Sugar Journal. - 0020-8841. ; 111:1323, s. 172-180
  • Journal article (peer-reviewed)abstract
    • The 2nd generation bioethanol will be produced from lignocellulose biomass including agricultural residues such as bagasse, straw, and stover, forest products residues and dedicated energy crops. The bioconversion of lignocellulose raw materials to ethanol requires microorganisms that are able (i) to ferment both hexose and pentose sugars present in lignocellulose and (ii) to tolerate and to remain active in presence of inhibiting compounds generated during lignocellulose pretreatment and hydrolysis. In this review we focus on the development of strains of baker's yeast Saccharomyces cerevisiae. We discuss genetic and metabolic engineering strategies that have been used to improve, independently, xylose fermentation and strain tolerance. Then, we deliberate strategies for simultaneous improvement of xylose utilization and inhibitor tolerance, with the view that a new generation of xylose-utilizing S. cerevisiae strains harboring beneficial traits for xylose consumption and inhibitor tolerance is expected to be available in the foreseeable future.
  •  
33.
  • Almeida, Jose, et al. (author)
  • Evolutionary Algorithms for Energy Scheduling under uncertainty considering Multiple Aggregators
  • 2021
  • In: 2021 IEEE CONGRESS ON EVOLUTIONARY COMPUTATION (CEC 2021). - 9781728183923 ; , s. 225-232
  • Conference paper (peer-reviewed)abstract
    • The ever-increasing number of electric vehicles (EVs) circulating on the roads and renewable energy production to achieve carbon footprint reduction targets has brought many challenges to the electrical grid. The increasing integration of distributed energy resources (DER) in the grid is causing severe operational challenges, such as congestion and overloading for the grid. Active management of distribution network using the smart grid (SG) technologies and artificial intelligence (AI) techniques can support the grid's operation under such situations. Implementing evolutionary computational algorithms has become possible using SG technologies. This paper proposes an optimal day-ahead resource scheduling to minimize multiple aggregators' operational costs in a SG, considering a high DER penetration. The optimization is achieved considering three metaheuristics (DE, HyDE-DF, CUMDANCauchy++). Results show that CUMDANCauchy++ and HyDE-DF present the best overall results in comparison to the standard DE.
  •  
34.
  • Almeida, Joao G., et al. (author)
  • Impact of the 2016 ASE/EACVI recommendations on the prevalence of diastolic dysfunction in the general population
  • 2018
  • In: European Heart Journal Cardiovascular Imaging. - : Oxford University Press (OUP). - 2047-2404 .- 2047-2412. ; 19:4, s. 380-386
  • Journal article (peer-reviewed)abstract
    • Aims: Diastolic dysfunction (DD) is frequent in the general population; however, the assessment of diastolic function remains challenging. We aimed to evaluate the impact of the recent 2016 American Society of Echocardiography (ASE)/European Association of Cardiovascular Imaging (EACVI) recommendations in the prevalence and grades of DD compared with the 2009 guidelines and the Canberra Study Criteria (CSC).Methods and results: Within a population-based cohort, a total of 1000 individuals, aged ≥45 years, were evaluated retrospectively. Patients with previously known cardiac disease or ejection fraction <50% were excluded. Diastolic function was assessed by transthoracic echocardiography. DD prevalence and grades were determined according to the three classifications. The mean age was 62.0 ± 10.5 years and 37% were men. The prevalence of DD was 1.4% (n = 14) with the 2016 recommendations, 38.1% (n = 381) with the 2009 recommendations, and 30.4% (n = 304) using the CSC. The concordance between the updated recommendations and the other two was poor (from k = 0.13 to k = 0.18, P < 0.001). Regarding the categorization in DD grades, none of the 14 individuals with DD by the 2016 guidelines were assigned to Grade 1 DD, 64% were classified as Grade 2, 7% had Grade 3, and 29% had indeterminate grade.Conclusion: The application of the new 2016 ASE/EACVI recommendations resulted in a much lower prevalence of DD. The concordance between the classifications was poor. The updated algorithm seems to be able to diagnose only the most advanced cases.
  •  
35.
  • Almeida, Joao (author)
  • Improving the Response of Saccharomyces cerevisiae to Lignocellulosic Hydrolysate Inhibitors in Ethanolic Fermentation
  • 2009
  • Doctoral thesis (other academic/artistic)abstract
    • The production of ethanol based on lignocellulosic biomass requires the fermentation of a hydrolysate containing hexose and pentose sugars in an inhibitory environment. In fact, the lignocellulosic hydrolysate obtained from pretreatment and hydrolysis of the raw material contains a variety of inhibitory compounds, including (i) the furaldehydes 5-hydroxymethyl-2-furaldehyde (HMF) and 2-furaldehyde (furfural), (ii) weak acids (e.g. acetic acid) and (iii) phenolic compounds. These compounds reduce ethanol yield and the specific ethanol productivity, extend the lag phase, and reduce the growth rate and viability of microorganisms. In this work, the enzymes ADH6, mut-ADH1 and XR were identified as being responsible for NADPH-, NADH-, and NAD(P)H-dependent HMF and furfural reduction, respectively, in yeast. The tolerance and fermentation rates of Saccharomyces cerevisiae laboratory strains on defined medium and/or on lignocellulosic hydrolysate were improved by overexpression of the genes encoding for these enzymes. It was also shown that overexpression of furaldehyde reductases benefits product distribution in recombinant xylose-utilizing S. cerevisiae strains carrying the xylose reductase/xylitol dehydrogenase pathway during xylose fermentation. Finally, strains with higher furaldehyde conversion rates were shown to grow faster and ferment lignocellulosic hydrolysates faster. Evaluation of industrial strains of S. cerevisiae showed that the selection of a robust strain and its evaluation under representative conditions are essential for lignocellulosic hydrolysate fermentation, since strains perform differentially depending on the hydrolysate and the conditions employed. The use of fed-batch mode is advantageous not only because the inhibitors are kept at low concentrations and the capacity of the yeast to convert them is not surpassed, but also because it allows cells to adapt to the inhibitors in the lignocellulosic hydrolysate. Indeed, using microarray analysis, and in vitro and in vivo activity measurements it was demonstrated that short-term adaptation of the yeast to lignocellulosic hydrolysate increased detoxifying activities and induced the expression of genes related to the repair of cellular damage. The results presented in this work show that integration of process design and strain improvement strategies could be used to improve the yeast performance in ethanolic fermentation of lignocellulosic hydrolysates.
  •  
36.
  • Almeida, Joao, et al. (author)
  • Increased tolerance and conversion of inhibitors in lignocellulosic hydrolysates by Saccharomyces cerevisiae
  • 2007
  • In: Journal of Chemical Technology and Biotechnology. - : Wiley. - 0268-2575 .- 1097-4660. ; 82:4, s. 340-349
  • Research review (peer-reviewed)abstract
    • During hydrolysis of lignocellulosic biomass, monomeric sugars and a broad range of inhibitory compounds are formed and released. These inhibitors, which can be organized around three main groups, furans, weak acids and phenolics, reduce ethanol yield and productivity by affecting the microorganism performance during the fermentation step. Among the microorganisms that have been evaluated for lignocellulosic hydrolysate ethanol fermentation, the yeast Saccharomyces cerevisiae appears to be the least sensitive. In order to overcome the effect of inhibitors, strategies that include improvement of natural tolerance of microorganism and use of fermentation control strategies have been developed. An overview of the origin, effects and mechanisms of action of known inhibitors on S. cerevisiae is given. Fermentation control strategies as well as metabolic, genetic and evolutionary engineering strategies to obtain S. cerevisiae strains with improved tolerance are discussed.
  •  
37.
  • Almeida, Joao, et al. (author)
  • Metabolic effects of furaldehydes and impacts on biotechnological processes.
  • 2009
  • In: Applied Microbiology and Biotechnology. - : Springer Science and Business Media LLC. - 1432-0614 .- 0175-7598. ; 82:4, s. 625-638
  • Research review (peer-reviewed)abstract
    • There is a growing awareness that lignocellulose will be a major raw material for production of both fuel and chemicals in the coming decades-most likely through various fermentation routes. Considerable attention has been given to the problem of finding efficient means of separating the major constituents in lignocellulose (i.e., lignin, hemicellulose, and cellulose) and to efficiently hydrolyze the carbohydrate parts into sugars. In these processes, by-products will inevitably form to some extent, and these will have to be dealt with in the ensuing microbial processes. One group of compounds in this category is the furaldehydes. 2-Furaldehyde (furfural) and substituted 2-furaldehydes-most importantly 5-hydroxymethyl-2-furaldehyde-are the dominant inhibitory compounds found in lignocellulosic hydrolyzates. The furaldehydes are known to have biological effects and act as inhibitors in fermentation processes. The effects of these compounds will therefore have to be considered in the design of biotechnological processes using lignocellulose. In this short review, we take a look at known metabolic effects, as well as strategies to overcome problems in biotechnological applications caused by furaldehydes.
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38.
  • Almeida, Joao, et al. (author)
  • Molecular understanding of sulphuric acid-amine particle nucleation in the atmosphere
  • 2013
  • In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 502:7471, s. 359-
  • Journal article (peer-reviewed)abstract
    • Nucleation of aerosol particles from trace atmospheric vapours is thought to provide up to half of global cloud condensation nuclei(1). Aerosols can cause a net cooling of climate by scattering sunlight and by leading to smaller but more numerous cloud droplets, which makes clouds brighter and extends their lifetimes(2). Atmospheric aerosols derived from human activities are thought to have compensated for a large fraction of the warming caused by greenhouse gases(2). However, despite its importance for climate, atmospheric nucleation is poorly understood. Recently, it has been shown that sulphuric acid and ammonia cannot explain particle formation rates observed in the lower atmosphere(3). It is thought that amines may enhance nucleation(4-16), but until now there has been no direct evidence for amine ternary nucleation under atmospheric conditions. Here we use the CLOUD (Cosmics Leaving OUtdoor Droplets) chamber at CERN and find that dimethylamine above three parts per trillion by volume can enhance particle formation rates more than 1,000-fold compared with ammonia, sufficient to account for the particle formation rates observed in the atmosphere. Molecular analysis of the clusters reveals that the faster nucleation is explained by a base-stabilization mechanism involving acid-amine pairs, which strongly decrease evaporation. The ion-induced contribution is generally small, reflecting the high stability of sulphuric acid-dimethylamine clusters and indicating that galactic cosmic rays exert only a small influence on their formation, except at low overall formation rates. Our experimental measurements are well reproduced by a dynamical model based on quantum chemical calculations of binding energies of molecular clusters, without any fitted parameters. These results show that, in regions of the atmosphere near amine sources, both amines and sulphur dioxide should be considered when assessing the impact of anthropogenic activities on particle formation.
  •  
39.
  • Almeida, Joao, et al. (author)
  • NADH- vs NADPH-coupled reduction of 5-hydroxymethyl furfural (HMF) and its implications on product distribution in Saccharomyces cerevisiae.
  • 2008
  • In: Applied Microbiology and Biotechnology. - : Springer Science and Business Media LLC. - 1432-0614 .- 0175-7598. ; 78:6, s. 939-945
  • Journal article (peer-reviewed)abstract
    • Saccharomyces cerevisiae alcohol dehydrogenases responsible for NADH-, and NADPH-specific reduction of the furaldehydes 5-hydroxymethyl-furfural (HMF) and furfural have previously been identified. In the present study, strains overexpressing the corresponding genes (mut-ADH1 and ADH6), together with a control strain, were compared in defined medium for anaerobic fermentation of glucose in the presence and absence of HMF. All strains showed a similar fermentation pattern in the absence of HMF. In the presence of HMF, the strain overexpressing ADH6 showed the highest HMF reduction rate and the highest specific ethanol productivity, followed by the strain overexpressing mut-ADH1. This correlated with in vitro HMF reduction capacity observed in the ADH6 overexpressing strain. Acetate and glycerol yields per biomass increased considerably in the ADH6 strain. In the other two strains, only the overall acetate yield per biomass was affected. When compared in batch fermentation of spruce hydrolysate, strains overexpressing ADH6 and mut-ADH1 had five times higher HMF uptake rate than the control strain and improved specific ethanol productivity. Overall, our results demonstrate that (1) the cofactor usage in the HMF reduction affects the product distribution, and (2) increased HMF reduction activity results in increased specific ethanol productivity in defined mineral medium and in spruce hydrolysate.
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40.
  • Almeida, Joao, et al. (author)
  • Pichia stipitis xylose reductase helps detoxifying lignocellulosic hydrolysate by reducing 5-hydroxymethyl-furfural (HMF)
  • 2008
  • In: Biotechnology for Biofuels. - : Springer Science and Business Media LLC. - 1754-6834. ; 1
  • Journal article (peer-reviewed)abstract
    • Background: Pichia stipitis xylose reductase (Ps-XR) has been used to design Saccharomyces cerevisiae strains that are able to ferment xylose. One example is the industrial S. cerevisiae xyloseconsuming strain TMB3400, which was constructed by expression of P. stipitis xylose reductase and xylitol dehydrogenase and overexpression of endogenous xylulose kinase in the industrial S. cerevisiae strain USM21. Results: In this study, we demonstrate that strain TMB3400 not only converts xylose, but also displays higher tolerance to lignocellulosic hydrolysate during anaerobic batch fermentation as well as 3 times higher in vitro HMF and furfural reduction activity than the control strain USM21. Using laboratory strains producing various levels of Ps-XR, we confirm that Ps-XR is able to reduce HMF both in vitro and in vivo. Ps-XR overexpression increases the in vivo HMF conversion rate by approximately 20%, thereby improving yeast tolerance towards HMF. Further purification of Ps-XR shows that HMF is a substrate inhibitor of the enzyme. Conclusion: We demonstrate for the first time that xylose reductase is also able to reduce the furaldehyde compounds that are present in undetoxified lignocellulosic hydrolysates. Possible implications of this newly characterized activity of Ps-XR on lignocellulosic hydrolysate fermentation are discussed.
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41.
  • Almeida, João R.M., et al. (author)
  • Physiological and Molecular Characterization of Yeast Cultures Pre-Adapted for Fermentation of Lignocellulosic Hydrolysate
  • 2023
  • In: Fermentation. - : MDPI AG. - 2311-5637. ; 9:1
  • Journal article (peer-reviewed)abstract
    • Economically feasible bioethanol process from lignocellulose requires efficient fermentation by yeast of all sugars present in the hydrolysate. However, when exposed to lignocellulosic hydrolysate, Saccharomyces cerevisiae is challenged with a variety of inhibitors that reduce yeast viability, growth, and fermentation rate, and in addition damage cellular structures. In order to evaluate the capability of S. cerevisiae to adapt and respond to lignocellulosic hydrolysates, the physiological effect of cultivating yeast in the spruce hydrolysate was comprehensively studied by assessment of yeast performance in simultaneous saccharification and fermentation (SSF), measurement of furaldehyde reduction activity, assessment of conversion of phenolic compounds and genome-wide transcription analysis. The yeast cultivated in spruce hydrolysate developed a rapid adaptive response to lignocellulosic hydrolysate, which significantly improved its fermentation performance in subsequent SSF experiments. The adaptation was shown to involve the induction of NADPH-dependent aldehyde reductases and conversion of phenolic compounds during the fed-batch cultivation. These properties were correlated to the expression of several genes encoding oxidoreductases, notably AAD4, ADH6, OYE2/3, and YML131w. The other most significant transcriptional changes involved genes involved in transport mechanisms, such as YHK8, FLR1, or ATR1. A large set of genes were found to be associated with transcription factors (TFs) involved in stress response (Msn2p, Msn4p, Yap1p) but also cell growth and division (Gcr4p, Ste12p, Sok2p), and these TFs were most likely controlling the response at the post-transcriptional level.
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42.
  • Almeida, Joao, et al. (author)
  • Screening of Saccharomyces cerevisiae strains with respect to anaerobic growth in non-detoxified lignocellulose hydrolysate.
  • 2009
  • In: Bioresource Technology. - : Elsevier BV. - 1873-2976 .- 0960-8524. ; 100, s. 3674-3677
  • Journal article (peer-reviewed)abstract
    • A microplate screening method was used to assess anaerobic growth of 12 Saccharomyces cerevisiae strains in barley straw, spruce and wheat straw hydrolysate. The assay demonstrated significant differences in inhibitor tolerance among the strains. In addition, growth inhibition by the three hydrolysates differed so that wheat hydrolysate supported growth up to 70%, while barley hydrolysate only supported growth up to 50%, with dilute-acid spruce hydrolysate taking an intermediate position.
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43.
  • Almeida, Joao, et al. (author)
  • Stress-related challenges in pentose fermentation to ethanol by the yeast Saccharomyces cerevisiae.
  • 2011
  • In: Biotechnology Journal. - : Wiley. - 1860-6768. ; 6, s. 286-299
  • Research review (peer-reviewed)abstract
    • Conversion of agricultural residues, energy crops and forest residues into bioethanol requires hydrolysis of the biomass and fermentation of the released sugars. During the hydrolysis of the hemicellulose fraction, substantial amounts of pentose sugars, in particular xylose, are released. Fermentation of these pentose sugars to ethanol by engineered Saccharomyces cerevisiae under industrial process conditions is the subject of this review. First, fermentation challenges originating from the main steps of ethanol production from lignocellulosic feedstocks are discussed, followed by genetic modifications that have been implemented in S. cerevisiae to obtain xylose and arabinose fermenting capacity per se. Finally, the fermentation of a real lignocellulosic medium is discussed in terms of inhibitory effects of furaldehydes, phenolics and weak acids and the presence of contaminating microbiota.
  •  
44.
  • Almeida, João Tiago, et al. (author)
  • Would you help me? : Linking robot's perspective-taking to human prosocial behavior
  • 2023
  • In: HRI 2023. - New York, NY, USA : Association for Computing Machinery (ACM). ; , s. 388-397
  • Conference paper (peer-reviewed)abstract
    • Despite the growing literature on human attitudes toward robots, particularly prosocial behavior, little is known about how robots' perspective-taking, the capacity to perceive and understand the world from other viewpoints, could infuence such attitudes and perceptions of the robot. To make robots and AI more autonomous and self-aware, more researchers have focused on developing cognitive skills such as perspective-taking and theory of mind in robots and AI. The present study investigated whether a robot's perspectivetaking choices could infuence the occurrence and extent of exhibiting prosocial behavior toward the robot.We designed an interaction consisting of a perspective-taking task, where we manipulated how the robot instructs the human to fnd objects by changing its frame of reference and measured the human's exhibition of prosocial behavior toward the robot. In a between-subject study (N=70), we compared the robot's egocentric and addressee-centric instructions against a control condition, where the robot's instructions were object-centric. Participants' prosocial behavior toward the robot was measured using a voluntary data collection session. Our results imply that the occurrence and extent of prosocial behavior toward the robot were signifcantly infuenced by the robot's visuospatial perspective-taking behavior. Furthermore, we observed, through questionnaire responses, that the robot's choice of perspectivetaking could potentially infuence the humans' perspective choices, were they to reciprocate the instructions to the robot.
  •  
45.
  • Almeida, Rafael M., et al. (author)
  • Phosphorus transport by the largest Amazon tributary (Madeira River, Brazil) and its sensitivity to precipitation and damming
  • 2015
  • In: Inland Waters. - 2044-2041 .- 2044-205X. ; 5:3, s. 275-282
  • Journal article (peer-reviewed)abstract
    • Originating in the Bolivian and Peruvian Andes, the Madeira River is the largest tributary of the Amazon River in terms of discharge. Andean rivers transport large quantities of nutrient-rich suspended sediments and are the main source of phosphorus (P) to the Amazon basin. Here, we show the seasonal variability in concentrations and loads of different P forms (total, particulate, dissolved, and soluble reactive P) in the Madeira River through 8 field campaigns between 2009 and 2011. At our sampling reach in Porto Velho, Brazil, the Madeira River transports similar to 177-247 Gg yr(-1) of P, mostly linked to particles (similar to 85%). Concentrations and loads of all P forms have a maximum at rising waters and a minimum at low waters. Total P concentrations were substantially higher at a given discharge at rising water than at a similar discharge at falling water. The peak of P concentrations matched the peak of rainfall in the upper basin, suggesting an influence of precipitation-driven erosion. Projected precipitation increase in the eastern slopes of the Andes could enhance sediment yield and hence the P transport in the Madeira River. Because most of the P is particulate, however, we hypothesize that the planned proliferation of hydropower dams in the Madeira basin has the potential to reduce P loads substantially, possibly counteracting any precipitation-related increases. In the long term, this could be detrimental to highly productive downstream floodplain forests that are seasonally fertilized with P-rich deposits.
  •  
46.
  • Alves, Gustavo R., et al. (author)
  • International Cooperation for Remote Laboratory Use
  • 2018
  • In: Contributions to Higher Engineering Education. - Singapore : Springer. - 9789811089176 ; , s. 1-31
  • Book chapter (peer-reviewed)abstract
    • Experimenting is fundamental to the training process of all scientists and engineers. While experiments have been traditionally done inside laboratories, the emergence of Information and Communication Technologies added two alternatives accessible anytime, anywhere. These two alternatives are known as virtual and remote laboratories and are sometimes indistinguishably referred as online laboratories. Similarly to other instructional technologies, virtual and remote laboratories require some effort from teachers in integrating them into curricula, taking into consideration several factors that affect their adoption (i.e., cost) and their educational effectiveness (i.e., benefit). This chapter analyzes these two dimensions and sustains the case where only through international cooperation it is possible to serve the large number of teachers and students involved in engineering education. It presents an example in the area of electrical and electronics engineering, based on a remote laboratory named Virtual Instruments System in Reality, and it then describes how a number of European and Latin American institutions have been cooperating under the scope of an Erasmus+ project, for spreading its use in Brazil and Argentina.
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47.
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48.
  • Bouckaert, Igor, et al. (author)
  • A Hybrid Discrete-Finite Element method for continuous and discontinuous beam-like members including nonlinear geometric and material effects
  • 2024
  • In: International Journal of Solids and Structures. - 0020-7683 .- 1879-2146. ; 294
  • Journal article (other academic/artistic)abstract
    • This paper introduces a novel formulation, called Hybrid Discrete-Finite Element (HybriDFEM) method, for modeling one-directional continuous and discontinuous planar beam-like members, including nonlinear geometric and material effects. In this method, the structure is modeled as a series of distinct rigid blocks, connected to each other through contact pairs distributed along the interfaces. Each of those contact pairs are composed of two nonlinear multidirectional springs in series, which can represent either the deformation of the blocks themselves, or the deformation of their interface. Unlike the Applied Element Method, in which contact pairs are composed of one single spring, the current approach allows capturing phenomena such as sectional deformations or relative deformations between two blocks composed of different materials. This method shares similarities with the Discrete Element Methods in its ability to model contact interfaces between rigid or deformable units, but does not require a numerical time-domain integration scheme. More importantly, its formulation resembles that of the classical Finite Elements Method, allowing one to easily couple the latter with HybriDFEM. Following the presentation of its formulation, the method is benchmarked against analytical solutions selected from the literature, ranging from the linear-elastic response of a cantilever beam to the buckling and rocking response of continuous flexible columns, and rigid block stackings. One final example showcases the coupling of a HybriDFEM element with a linear beam finite element.
  •  
49.
  • Bouckaert, Igor, et al. (author)
  • A strategy for generating pushover curves of block assemblies including post-peak branch using the discrete element method
  • 2022
  • In: Proceedings of 3rd EUROPEAN CONFERENCE ON EARTHQUAKE ENGINEERING &amp; SEISMOLOGY.. ; , s. 839-
  • Conference paper (peer-reviewed)abstract
    • Pushover analyses are often used to evaluate the seismic performance of a structure. They give an estimate of the ultimate displacement a structure can undergo, as well as of the residual resisting forces in the post-peak response. When modelling masonry structures composed of multiple blocks, obtaining the post-peak branch of the pushover curve can be difficult with a classic displacement-control strategy. This paper describes a strategy designed to compute this branch for multi-block systems subjected to a given pattern of forces, without the need to apply a displacement-control algorithm. The strategy is general, therefore straightforwardly implementable in different software tools and applicable to complex block assemblies. In the present work, it is implemented in two different DEM software, namely LMCG90 and UDEC, and tested on a benchmark problem for evaluating the in-plane response of masonry walls.
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50.
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