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1.	Jacome, Cristina, et al. (författare) Feasibility and Acceptability of an Asthma App to Monitor Medication Adherence : Mixed Methods Study 2021 Ingår i: JMIR mhealth and uhealth. - : JMIR Publications. - 2291-5222. ; 9:5 Tidskriftsartikel (refereegranskat)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.
2.	Jacome, Cristina, et al. (författare) Monitoring Adherence to Asthma Inhalers Using the InspirerMundi App : Analysis of Real-World, Medium-Term Feasibility Studies 2021 Ingår i: Frontiers in Medical Technology. - : Frontiers Media S.A.. - 2673-3129. ; 3 Tidskriftsartikel (refereegranskat)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.
3.	Neves, Ana Luisa, et al. (författare) Determinants of the Use of Health and Fitness Mobile Apps by Patients With Asthma : Secondary Analysis of Observational Studies 2021 Ingår i: Journal of Medical Internet Research. - : JMIR Publications. - 1438-8871. ; 23:9 Tidskriftsartikel (refereegranskat)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.
4.	Klionsky, Daniel J, et al. (författare) Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). 2016 Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 12:1, s. 1-222 Tidskriftsartikel (refereegranskat)
5.	Lozano, Rafael, et al. (författare) Measuring progress from 1990 to 2017 and projecting attainment to 2030 of the health-related Sustainable Development Goals for 195 countries and territories: a systematic analysis for the Global Burden of Disease Study 2017 2018 Ingår i: The Lancet. - : Elsevier. - 1474-547X .- 0140-6736. ; 392:10159, s. 2091-2138 Tidskriftsartikel (refereegranskat)abstract Background: Efforts to establish the 2015 baseline and monitor early implementation of the UN Sustainable Development Goals (SDGs) highlight both great potential for and threats to improving health by 2030. To fully deliver on the SDG aim of “leaving no one behind”, it is increasingly important to examine the health-related SDGs beyond national-level estimates. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017), we measured progress on 41 of 52 health-related SDG indicators and estimated the health-related SDG index for 195 countries and territories for the period 1990–2017, projected indicators to 2030, and analysed global attainment. Methods: We measured progress on 41 health-related SDG indicators from 1990 to 2017, an increase of four indicators since GBD 2016 (new indicators were health worker density, sexual violence by non-intimate partners, population census status, and prevalence of physical and sexual violence [reported separately]). We also improved the measurement of several previously reported indicators. We constructed national-level estimates and, for a subset of health-related SDGs, examined indicator-level differences by sex and Socio-demographic Index (SDI) quintile. We also did subnational assessments of performance for selected countries. To construct the health-related SDG index, we transformed the value for each indicator on a scale of 0–100, with 0 as the 2·5th percentile and 100 as the 97·5th percentile of 1000 draws calculated from 1990 to 2030, and took the geometric mean of the scaled indicators by target. To generate projections through 2030, we used a forecasting framework that drew estimates from the broader GBD study and used weighted averages of indicator-specific and country-specific annualised rates of change from 1990 to 2017 to inform future estimates. We assessed attainment of indicators with defined targets in two ways: first, using mean values projected for 2030, and then using the probability of attainment in 2030 calculated from 1000 draws. We also did a global attainment analysis of the feasibility of attaining SDG targets on the basis of past trends. Using 2015 global averages of indicators with defined SDG targets, we calculated the global annualised rates of change required from 2015 to 2030 to meet these targets, and then identified in what percentiles the required global annualised rates of change fell in the distribution of country-level rates of change from 1990 to 2015. We took the mean of these global percentile values across indicators and applied the past rate of change at this mean global percentile to all health-related SDG indicators, irrespective of target definition, to estimate the equivalent 2030 global average value and percentage change from 2015 to 2030 for each indicator. Findings: The global median health-related SDG index in 2017 was 59·4 (IQR 35·4–67·3), ranging from a low of 11·6 (95% uncertainty interval 9·6–14·0) to a high of 84·9 (83·1–86·7). SDG index values in countries assessed at the subnational level varied substantially, particularly in China and India, although scores in Japan and the UK were more homogeneous. Indicators also varied by SDI quintile and sex, with males having worse outcomes than females for non-communicable disease (NCD) mortality, alcohol use, and smoking, among others. Most countries were projected to have a higher health-related SDG index in 2030 than in 2017, while country-level probabilities of attainment by 2030 varied widely by indicator. Under-5 mortality, neonatal mortality, maternal mortality ratio, and malaria indicators had the most countries with at least 95% probability of target attainment. Other indicators, including NCD mortality and suicide mortality, had no countries projected to meet corresponding SDG targets on the basis of projected mean values for 2030 but showed some probability of attainment by 2030. For some indicators, including child malnutrition, several infectious diseases, and most violence measures, the annualised rates of change required to meet SDG targets far exceeded the pace of progress achieved by any country in the recent past. We found that applying the mean global annualised rate of change to indicators without defined targets would equate to about 19% and 22% reductions in global smoking and alcohol consumption, respectively; a 47% decline in adolescent birth rates; and a more than 85% increase in health worker density per 1000 population by 2030. Interpretation: The GBD study offers a unique, robust platform for monitoring the health-related SDGs across demographic and geographic dimensions. Our findings underscore the importance of increased collection and analysis of disaggregated data and highlight where more deliberate design or targeting of interventions could accelerate progress in attaining the SDGs. Current projections show that many health-related SDG indicators, NCDs, NCD-related risks, and violence-related indicators will require a concerted shift away from what might have driven past gains—curative interventions in the case of NCDs—towards multisectoral, prevention-oriented policy action and investments to achieve SDG aims. Notably, several targets, if they are to be met by 2030, demand a pace of progress that no country has achieved in the recent past. The future is fundamentally uncertain, and no model can fully predict what breakthroughs or events might alter the course of the SDGs. What is clear is that our actions—or inaction—today will ultimately dictate how close the world, collectively, can get to leaving no one behind by 2030.
6.	Marto, João Pedro, et al. (författare) Safety and Outcome of Revascularization Treatment in Patients With Acute Ischemic Stroke and COVID-19: The Global COVID-19 Stroke Registry. 2023 Ingår i: Neurology. - 1526-632X. ; 100:7 Tidskriftsartikel (refereegranskat)abstract COVID-19-related inflammation, endothelial dysfunction, and coagulopathy may increase the bleeding risk and lower the efficacy of revascularization treatments in patients with acute ischemic stroke (AIS). We aimed to evaluate the safety and outcomes of revascularization treatments in patients with AIS and COVID-19.This was a retrospective multicenter cohort study of consecutive patients with AIS receiving intravenous thrombolysis (IVT) and/or endovascular treatment (EVT) between March 2020 and June 2021 tested for severe acute respiratory syndrome coronavirus 2 infection. With a doubly robust model combining propensity score weighting and multivariate regression, we studied the association of COVID-19 with intracranial bleeding complications and clinical outcomes. Subgroup analyses were performed according to treatment groups (IVT-only and EVT).Of a total of 15,128 included patients from 105 centers, 853 (5.6%) were diagnosed with COVID-19; of those, 5,848 (38.7%) patients received IVT-only and 9,280 (61.3%) EVT (with or without IVT). Patients with COVID-19 had a higher rate of symptomatic intracerebral hemorrhage (SICH) (adjusted OR 1.53; 95% CI 1.16-2.01), symptomatic subarachnoid hemorrhage (SSAH) (OR 1.80; 95% CI 1.20-2.69), SICH and/or SSAH combined (OR 1.56; 95% CI 1.23-1.99), 24-hour mortality (OR 2.47; 95% CI 1.58-3.86), and 3-month mortality (OR 1.88; 95% CI 1.52-2.33). Patients with COVID-19 also had an unfavorable shift in the distribution of the modified Rankin score at 3 months (OR 1.42; 95% CI 1.26-1.60).Patients with AIS and COVID-19 showed higher rates of intracranial bleeding complications and worse clinical outcomes after revascularization treatments than contemporaneous non-COVID-19 patients receiving treatment. Current available data do not allow direct conclusions to be drawn on the effectiveness of revascularization treatments in patients with COVID-19 or to establish different treatment recommendations in this subgroup of patients with ischemic stroke. Our findings can be taken into consideration for treatment decisions, patient monitoring, and establishing prognosis.The study was registered under ClinicalTrials.gov identifier NCT04895462.
7.	Simoes Cunha, Mafalda, et al. (författare) Symptoms of anxiety and depression in patients with persistent asthma : a cross-sectional analysis of the INSPIRERS studies 2023 Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 13:5 Tidskriftsartikel (refereegranskat)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.
8.	Stanaway, Jeffrey D., et al. (författare) Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990-2017: A systematic analysis for the Global Burden of Disease Study 2017 2018 Ingår i: The Lancet. - 1474-547X .- 0140-6736. ; 392:10159, s. 1923-1994 Tidskriftsartikel (refereegranskat)abstract Background The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 comparative risk assessment (CRA) is a comprehensive approach to risk factor quantification that offers a useful tool for synthesising evidence on risks and risk-outcome associations. With each annual GBD study, we update the GBD CRA to incorporate improved methods, new risks and risk-outcome pairs, and new data on risk exposure levels and risk- outcome associations. Methods We used the CRA framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017. This study included 476 risk-outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk and exposure estimates from 46 749 randomised controlled trials, cohort studies, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. We explored the relationship between development and risk exposure by modelling the relationship between the Socio-demographic Index (SDI) and risk-weighted exposure prevalence and estimated expected levels of exposure and risk-attributable burden by SDI. Finally, we explored temporal changes in risk-attributable DALYs by decomposing those changes into six main component drivers of change as follows: (1) population growth; (2) changes in population age structures; (3) changes in exposure to environmental and occupational risks; (4) changes in exposure to behavioural risks; (5) changes in exposure to metabolic risks; and (6) changes due to all other factors, approximated as the risk-deleted death and DALY rates, where the risk-deleted rate is the rate that would be observed had we reduced the exposure levels to the TMREL for all risk factors included in GBD 2017.
9.	Amaral, Rita, et al. (författare) Profiling Persistent Asthma Phenotypes in Adolescents : A Longitudinal Diagnostic Evaluation from the INSPIRERS Studies 2021 Ingår i: International Journal of Environmental Research and Public Health. - : MDPI. - 1661-7827 .- 1660-4601. ; 18:3 Tidskriftsartikel (refereegranskat)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.
10.	Crona, Joakim, et al. (författare) ENSAT registry-based randomized clinical trials for adrenocortical carcinoma 2021 Ingår i: European Journal of Endocrinology. - : Bioscientifica. - 0804-4643 .- 1479-683X. ; 184:2, s. R51-R59 Forskningsöversikt (refereegranskat)abstract Adrenocortical carcinoma (ACC) is an orphan disease lacking effective systemic treatment options. The low incidence of the disease and high cost of clinical trials are major obstacles in the search for improved treatment strategies. As a novel approach, registry-based clinical trials have been introduced in clinical research, so allowing for significant cost reduction, but without compromising scientific benefit. Herein, we describe how the European Network for the Study of Adrenal Tumours (ENSAT) could transform its current registry into one fit for a clinical trial infrastructure. The rationale to perform randomized registry-based trials in ACC is outlined including an analysis of relevant limitations and challenges. We summarize a survey on this concept among ENSAT members who expressed a strong interest in the concept and rated its scientific potential as high. Legal aspects, including ethical approval of registry-based randomization were identified as potential obstacles. Finally, we describe three potential randomized registry-based clinical trials in an adjuvant setting and for advanced disease with a high potential to be executed within the framework of an advanced ENSAT registry. Thus we, therefore, provide the basis for future registry-based trials for ACC patients. This could ultimately provide proof-of-principle of how to perform more effective randomized trials for an orphan disease.
11.	Sator, Lea, et al. (författare) Overdiagnosis of COPD in Subjects With Unobstructed Spirometry A BOLD Analysis 2019 Ingår i: Chest. - : Elsevier BV. - 0012-3692 .- 1931-3543. ; 156:2, s. 277-288 Tidskriftsartikel (refereegranskat)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.
12.	Studnicka, Michael, et al. (författare) COPD : Should Diagnosis Match Physiology? 2020 Ingår i: Chest. - : Elsevier BV. - 0012-3692 .- 1931-3543. ; 157:2, s. 473-475 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
13.	Abbafati, Cristiana, et al. (författare) 2020 Tidskriftsartikel (refereegranskat)
14.	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.
15.	Erjefält, Jonas S., et al. (författare) Diffuse alveolar damage patterns reflect the immunological and molecular heterogeneity in fatal COVID-19 2022 Ingår i: EBioMedicine. - : Elsevier BV. - 2352-3964. ; 83 Tidskriftsartikel (refereegranskat)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.
16.	Fullman, Nancy, et al. (författare) Measuring performance on the Healthcare Access and Quality Index for 195 countries and territories and selected subnational locations: A systematic analysis from the Global Burden of Disease Study 2016 2018 Ingår i: The Lancet. - : Lancet Publishing Group. - 1474-547X .- 0140-6736. ; 391:10136, s. 2236-2271 Tidskriftsartikel (refereegranskat)
17.	Hess, Georg, et al. (författare) Health-related quality of life data from a phase 3, international, randomized, open-label, multicenter study in patients with previously treated mantle cell lymphoma treated with ibrutinib versus temsirolimus 2017 Ingår i: Leukemia and Lymphoma. - : Informa UK Limited. - 1042-8194 .- 1029-2403. ; 58:12, s. 2824-2832 Tidskriftsartikel (refereegranskat)abstract Mantle cell lymphoma (MCL) is a rare, aggressive, incurable B-cell malignancy. Ibrutinib has been shown to be highly active for patients with relapsed/refractory (R/R) MCL. The RAY trial (MCL3001) was a phase 3, randomized, open-label, multicenter study that compared ibrutinib with temsirolimus in patients with R/R MCL. Active disease is frequently associated with impaired functional status and reduced well-being. Therefore, the current study employed two patient-reported outcome instruments, the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) and the EQ-5D-5L, to assess symptoms, well-being, health status, and health-related quality of life of patients on treatment within the RAY trial. We found that patients on ibrutinib had substantial improvement in FACT-Lym subscale and total scores, and had improvement in EQ-5D-5L utility and VAS scores compared with temsirolimus patients, indicating a superior well-being. These improvements in well-being correlated with clinical response, indicating that better health-related quality of life was associated with decreased disease burden.
18.	Santangelo, James S., et al. (författare) Global urban environmental change drives adaptation in white clover 2022 Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 375 Tidskriftsartikel (refereegranskat)abstract Urbanization transforms environments in ways that alter biological evolution. We examined whether urban environmental change drives parallel evolution by sampling 110,019 white clover plants from 6169 populations in 160 cities globally. Plants were assayed for a Mendelian antiherbivore defense that also affects tolerance to abiotic stressors. Urban-rural gradients were associated with the evolution of clines in defense in 47% of cities throughout the world. Variation in the strength of clines was explained by environmental changes in drought stress and vegetation cover that varied among cities. Sequencing 2074 genomes from 26 cities revealed that the evolution of urban-rural dines was best explained by adaptive evolution, but the degree of parallel adaptation varied among cities. Our results demonstrate that urbanization leads to adaptation at a global scale.
19.	Abozid, Hazim, et al. (författare) Prevalence of chronic cough, its risk factors and population attributable risk in the Burden of Obstructive Lung Disease (BOLD) study : a multinational cross-sectional study 2024 Ingår i: eClinicalMedicine. - : Elsevier. - 2589-5370. ; 68 Tidskriftsartikel (refereegranskat)abstract Background Chronic cough is a common respiratory symptom with an impact on daily activities and quality of life. Global prevalence data are scarce and derive mainly from European and Asian countries and studies with outcomes other than chronic cough. In this study, we aimed to estimate the prevalence of chronic cough across a large number of study sites as well as to identify its main risk factors using a standardised protocol and definition. Methods We analysed cross-sectional data from 33,983 adults (>= 40 years), recruited between Jan 2, 2003 and Dec 26, 2016, in 41 sites (34 countries) from the Burden of Obstructive Lung Disease (BOLD) study. We estimated the prevalence of chronic cough for each site accounting for sampling design. To identify risk factors, we conducted multivariable logistic regression analysis within each site and then pooled estimates using random -effects metaanalysis. We also calculated the population attributable risk (PAR) associated with each of the identifed risk factors. Findings The prevalence of chronic cough varied from 3% in India (rural Pune) to 24% in the United States of America (Lexington,KY). Chronic cough was more common among females, both current and passive smokers, those working in a dusty job, those with a history of tuberculosis, those who were obese, those with a low level of education and those with hypertension or airflow limitation. The most influential risk factors were current smoking and working in a dusty job. Interpretation Our findings suggested that the prevalence of chronic cough varies widely across sites in different world regions. Cigarette smoking and exposure to dust in the workplace are its major risk factors.
20.	Alexandre, Luana, et al. (författare) Patients' Satisfaction with Remote Asthma Medical Follow-Up Before and During the COVID-19 Pandemic 2023 Ingår i: Telemedicine journal and e-health. - : Mary Ann Liebert. - 1530-5627 .- 1556-3669. ; 29:9, s. 1383-1389 Tidskriftsartikel (refereegranskat)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.
21.	Alix, James J. P., et al. (författare) Assessment of the reliability of the motor unit size index (MUSIX) in single subject "round-robin" and multi-centre settings 2019 Ingår i: Clinical Neurophysiology. - : ELSEVIER IRELAND LTD. - 1388-2457 .- 1872-8952. ; 130:5, s. 666-674 Tidskriftsartikel (refereegranskat)abstract Objective: The motor unit size index (MUSIX) is incorporated into the motor unit number index (MUNIX). Our objective was to assess the intra-/inter-rater reliability of MUSIX in healthy volunteers across single subject "round robin" and multi-centre settings.Methods: Data were obtained from (i) a round-robin assessment in which 12 raters (6 with prior experience and 6 without) assessed six muscles (abductor pollicis brevis, abductor digiti minimi, biceps brachii, tibialis anterior, extensor digitorum brevis and abductor hallucis) and (ii) a multi-centre study with 6 centres studying the same muscles in 66 healthy volunteers. Intrafinter-rater data were provided by 5 centres, 1 centre provided only intra-rater data. Intrafinter-rater variability was assessed using the coefficient of variation (COV), Bland-Altman plots, bias and 95% limits of agreement.Results: In the round-robin assessment intra-rater COVs for MUSIX ranged from 7.8% to 28.4%. Inter-rater variability was between 7.8% and 16.2%. Prior experience did not impact on MUSIX values. In the multi-centre study MUSIX was more consistent than the MUNIX. Abductor hallucis was the least reliable muscle.Conclusions: The MUSIX is a reliable neurophysiological biomarker of reinnervation.Significance: MUSIX could provide insights into the pathophysiology of a range of neuromuscular disorders, providing a quantitative biomarker of reinnervation.
22.	Allentoft, Morten E., et al. (författare) Population genomics of post-glacial western Eurasia 2024 Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 625:7994, s. 301-311 Tidskriftsartikel (refereegranskat)abstract Western Eurasia witnessed several large-scale human migrations during the Holocene1–5. Here, to investigate the cross-continental effects of these migrations, we shotgun-sequenced 317 genomes—mainly from the Mesolithic and Neolithic periods—from across northern and western Eurasia. These were imputed alongside published data to obtain diploid genotypes from more than 1,600 ancient humans. Our analyses revealed a ‘great divide’ genomic boundary extending from the Black Sea to the Baltic. Mesolithic hunter-gatherers were highly genetically differentiated east and west of this zone, and the effect of the neolithization was equally disparate. Large-scale ancestry shifts occurred in the west as farming was introduced, including near-total replacement of hunter-gatherers in many areas, whereas no substantial ancestry shifts happened east of the zone during the same period. Similarly, relatedness decreased in the west from the Neolithic transition onwards, whereas, east of the Urals, relatedness remained high until around 4,000 bp, consistent with the persistence of localized groups of hunter-gatherers. The boundary dissolved when Yamnaya-related ancestry spread across western Eurasia around 5,000 bp, resulting in a second major turnover that reached most parts of Europe within a 1,000-year span. The genetic origin and fate of the Yamnaya have remained elusive, but we show that hunter-gatherers from the Middle Don region contributed ancestry to them. Yamnaya groups later admixed with individuals associated with the Globular Amphora culture before expanding into Europe. Similar turnovers occurred in western Siberia, where we report new genomic data from a ‘Neolithic steppe’ cline spanning the Siberian forest steppe to Lake Baikal. These prehistoric migrations had profound and lasting effects on the genetic diversity of Eurasian populations.
23.	Blösch, Günter, et al. (författare) Twenty-three unsolved problems in hydrology (UPH) - a community perspective 2019 Ingår i: Hydrological Sciences Journal. - : Informa UK Limited. - 0262-6667 .- 2150-3435. ; 64:10, s. 1141-1158 Tidskriftsartikel (refereegranskat)abstract This paper is the outcome of a community initiative to identify major unsolved scientific problems in hydrology motivated by a need for stronger harmonisation of research efforts. The procedure involved a public consultation through online media, followed by two workshops through which a large number of potential science questions were collated, prioritised, and synthesised. In spite of the diversity of the participants (230 scientists in total), the process revealed much about community priorities and the state of our science: a preference for continuity in research questions rather than radical departures or redirections from past and current work. Questions remain focused on the process-based understanding of hydrological variability and causality at all space and time scales. Increased attention to environmental change drives a new emphasis on understanding how change propagates across interfaces within the hydrological system and across disciplinary boundaries. In particular, the expansion of the human footprint raises a new set of questions related to human interactions with nature and water cycle feedbacks in the context of complex water management problems. We hope that this reflection and synthesis of the 23 unsolved problems in hydrology will help guide research efforts for some years to come.
24.	Cachim, Afonso, et al. (författare) Measuring adherence to inhaled control medication in patients with asthma : Comparison among an asthma app, patient self-report and physician assessment 2023 Ingår i: Clinical and Translational Allergy. - : John Wiley & Sons. - 2045-7022. ; 13:2 Tidskriftsartikel (refereegranskat)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.
25.	Carraminana, Albert, et al. (författare) Rationale and Study Design for an Individualized Perioperative Open Lung Ventilatory Strategy in Patients on One-Lung Ventilation (iPROVE-OLV) 2019 Ingår i: Journal of Cardiothoracic and Vascular Anesthesia. - : W B SAUNDERS CO-ELSEVIER INC. - 1053-0770 .- 1532-8422. ; 33:9, s. 2492-2502 Tidskriftsartikel (refereegranskat)abstract Objective: The aim of this clinical trial is to examine whether it is possible to reduce postoperative complications using an individualized perioperative ventilatory strategy versus using a standard lung-protective ventilation strategy in patients scheduled for thoracic surgery requiring one-lung ventilation. Design: International, multicenter, prospective, randomized controlled clinical trial. Setting: A network of university hospitals. Participants: The study comprises 1,380 patients scheduled for thoracic surgery. Interventions: The individualized group will receive intraoperative recruitment maneuvers followed by individualized positive end-expiratory pressure (open lung approach) during the intraoperative period plus postoperative ventilatory support with high-flow nasal cannula, whereas the control group will be managed with conventional lung-protective ventilation. Measurements and Main Results: Individual and total number of postoperative complications, including atelectasis, pneumothorax, pleural effusion, pneumonia, acute lung injury; unplanned readmission and reintubation; length of stay and death in the critical care unit and in the hospital will be analyzed for both groups. The authors hypothesize that the intraoperative application of an open lung approach followed by an individual indication of high-flow nasal cannula in the postoperative period will reduce pulmonary complications and length of hospital stay in high-risk surgical patients. (C) 2019 Published by Elsevier Inc.
26.	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.
27.	Da Silva Santos Sundström, Admeire, et al. (författare) Filme de ficção para a Ciência da Informação : um estudo sobre as abordagens de organização e representação temática 2019 Ingår i: Encontros Bibli. - : Universidade Federal de Santa Catarina. - 1518-2924. ; 24:54, s. 124-134 Tidskriftsartikel (refereegranskat)abstract O documento audiovisual é um material que integra a imagem em movimento e o som em sua essência. Constata-se que esse tipo documental está cada vez mais presente nas relações interpessoais e, concomitantemente, nas unidades de informação. O documento audiovisual em foco nesta pesquisa é o filme de ficção. Desse modo, questiona-se: como a Ciência da Informação está tratando a temática desses materiais? Assim, foi feito um levantamento bibliométrico em base de dados com o objetivo de analisar a literatura a respeito dos modos de tratamento temático de filmes de ficção no âmbito da Ciência da Informação e, também, entender como vem ocorrendo o tratamento temático desses materiais. O método é documental e bibliométrico. Como resultados destacam-se a baixa incidência de estudos que abordam a temática; a influência do Cinema enquanto disciplina nos processos de indexação de audiovisual e a presença de um campo vasto para o desenvolvimento de pesquisas.
28.	de Castro Araujo Moreira, Andrea Cristina, et al. (författare) The first Brazilian Field Lab fully dedicated to CO2 MMV experiments : from the start-up to the initial results 2014 Ingår i: 12th International Conference on Greenhouse Gas Control Technologies, GHGT-12. - : Elsevier. ; , s. 6227-6238 Konferensbidrag (refereegranskat)abstract Currently one of the main challenges in CO2 storage research is the development, testing and validation of accurate and efficient Measuring, Monitoring and Verification (MMV) techniques to be deployed at geological sequestration sites that are cost effective yet help minimize risk. This perspective motivated PETROBRAS, the National Oil Major in Brazil, through its R&D investments portfolio to prioritize research projects that would contribute to decreasing the technological gap in the area. The Company's periodic surveys indicated the lack of infrastructure, as well as expertise in CO2 MMV, as two of the most critical issues at the national level. In order to bridge that gap, initial steps were taken in 2010 for the start-up and development of the first CO2 MMV Field Lab in Brazil, fully sponsored by PETROBRAS, with a long term goal of enabling the ranking of the best, most cost-effective MMV technology alternatives to be deployed at commercial large scale CCGS sites scheduled to be installed in the country. In addition to providing basic infrastructure to carry out the CO2 injection and controlled release experiments, the facility was designed for the simultaneous testing of multiple measuring methodologies. Additional benefits of the initiative are the creation of expertise and the acceleration of the know-how in MMV in Brazil, as well as the development of a deeper and more practical knowledge of CO2 dynamics and impacts in a real world, open air scenario. Under the full support of the PETROBRAS R&D Center (CENPES), through its Climate Change Mitigation Technological Program (PROCLIMA), the Brazilian Pilot CO2 MMV Lab was made possible through a joint 4-year research Project, conceived and carried out by PETROBRAS and local academia in Brazil, in close cooperation with international experts. An overview of the Project and the multiple research areas encompassed will be presented, together with the preliminary results of the first CO2 injection campaign, which took place in 2013. (c) 2014 The Authors. Published by Elsevier
29.	Dreyling, Martin, et al. (författare) Ibrutinib versus temsirolimus in patients with relapsed or refractory mantle-cell lymphoma: an international, randomised, open-label, phase 3 study. 2016 Ingår i: The Lancet. - 1474-547X. ; 387:10020, s. 770-778 Tidskriftsartikel (refereegranskat)abstract Mantle-cell lymphoma is an aggressive B-cell lymphoma with a poor prognosis. Both ibrutinib and temsirolimus have shown single-agent activity in patients with relapsed or refractory mantle-cell lymphoma. We undertook a phase 3 study to assess the efficacy and safety of ibrutinib versus temsirolimus in relapsed or refractory mantle-cell lymphoma.
30.	Engelmann, Pâmela de Medeiros, et al. (författare) Environmental monitoring of a landfill area through the application of carbon stable isotopes, chemical parameters and multivariate analysis 2018 Ingår i: Waste Management. - : Elsevier BV. - 0956-053X .- 1879-2456. ; 76, s. 591-605 Tidskriftsartikel (refereegranskat)abstract Leachate produced during an organic matter decomposition process has a complex composition and can cause contamination of surface and groundwaters adjacent to a landfill area. The monitoring of these areas is extremely important for the characterization of the leachate produced and to avoid or mitigate environmental damages. Thus, the present study has the objective of monitoring the area of a Brazilian landfill using conventional parameters (dissolved metals and anions in water) and alternative, stable carbon isotopes parameters (δ13C of dissolved organic and inorganic carbons in water) in addition to multivariate analysis techniques. The use of conventional and alternative parameters together with multivariate analysis showed that cells of the residues are at different phases of stabilization of the organic matter and probably already at C3 of the methanogenic phase of decomposition. In addition, the data showed that organic matter stabilization ponds present in the landfill are efficient and improve the quality of the leachate. Enrichment of the heavy 13C isotope in both surface and groundwater suggested contamination in two sampling sites.
31.	Engelmann, Pamela de Medeiros, et al. (författare) Environmental monitoring of water resources around a municipal landfill of the Rio Grande do Sul state, Brazil 2017 Ingår i: Environmental Science and Pollution Research. - : Springer Science and Business Media LLC. - 0944-1344 .- 1614-7499. ; 24:26, s. 21398-21411 Tidskriftsartikel (refereegranskat)abstract In Brazil, landfills are commonly used as a method for the final disposal of waste that is compliant with the legislation. This technique, however, presents a risk to surface water and groundwater resources, owing to the leakage of metals, anions, and organic compounds. The geochemical monitoring of water resources is therefore extremely important, since the leachate can compromise the quality and use of surface water and groundwater close to landfills. In this paper, the results of analyses of metals, anions, ammonia, and physicochemical parameters were used to identify possible contamination of surface water and groundwater in a landfill area. A statistical multivariate approach was used. The values found for alkali metals, nitrate, and chloride indicate contamination in the regional groundwater and, moreover, surface waters also show variation when compared to the other background points, mainly for ammonia. Thus, the results of this study evidence the landfill leachate influence on the quality of groundwater and surface water in the study area.
32.	Engert, Andreas, et al. (författare) The European Hematology Association Roadmap for European Hematology Research : a consensus document 2016 Ingår i: Haematologica. - Pavia, Italy : Ferrata Storti Foundation (Haematologica). - 0390-6078 .- 1592-8721. ; 101:2, s. 115-208 Tidskriftsartikel (refereegranskat)abstract The European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology research. Initiated by the EHA, around 300 experts contributed to the consensus document, which will help European policy makers, research funders, research organizations, researchers, and patient groups make better informed decisions on hematology research. It also aims to raise public awareness of the burden of blood disorders on European society, which purely in economic terms is estimated at (sic)23 billion per year, a level of cost that is not matched in current European hematology research funding. In recent decades, hematology research has improved our fundamental understanding of the biology of blood disorders, and has improved diagnostics and treatments, sometimes in revolutionary ways. This progress highlights the potential of focused basic research programs such as this EHA Roadmap. The EHA Roadmap identifies nine 'sections' in hematology: normal hematopoiesis, malignant lymphoid and myeloid diseases, anemias and related diseases, platelet disorders, blood coagulation and hemostatic disorders, transfusion medicine, infections in hematology, and hematopoietic stem cell transplantation. These sections span 60 smaller groups of diseases or disorders. The EHA Roadmap identifies priorities and needs across the field of hematology, including those to develop targeted therapies based on genomic profiling and chemical biology, to eradicate minimal residual malignant disease, and to develop cellular immunotherapies, combination treatments, gene therapies, hematopoietic stem cell treatments, and treatments that are better tolerated by elderly patients.
33.	Gehrmann, Sebastian, et al. (författare) GEMv2: Multilingual NLG Benchmarking in a Single Line of Code 2022 Ingår i: Proceedings of the 2022 Conference on Empirical Methods in Natural Language Processing: System Demonstrations. - : Association for Computational Linguistics (ACL). ; , s. 266-281 Konferensbidrag (refereegranskat)abstract Evaluations in machine learning rarely use the latest metrics, datasets, or human evaluation in favor of remaining compatible with prior work. The compatibility, often facilitated through leaderboards, thus leads to outdated but standardized evaluation practices. We pose that the standardization is taking place in the wrong spot. Evaluation infrastructure should enable researchers to use the latest methods and what should be standardized instead is how to incorporate these new evaluation advances.We introduce GEMv2, the new version of the Generation, Evaluation, and Metrics Benchmark which uses a modular infrastructure for dataset, model, and metric developers to benefit from each other’s work. GEMv2 supports 40 documented datasets in 51 languages, ongoing online evaluation for all datasets, and our interactive tools make it easier to add new datasets to the living benchmark.
34.	Gehrmann, Sebastian, et al. (författare) The GEM Benchmark : Natural Language Generation, its Evaluation and Metrics 2021 Ingår i: The 1st Workshop on Natural Language Generation, Evaluation, and Metrics. - Stroudsburg, PA, USA : Association for Computational Linguistics. ; , s. 96-120 Konferensbidrag (refereegranskat)abstract We introduce GEM, a living benchmark for natural language Generation (NLG), its Evaluation, and Metrics. Measuring progress in NLG relies on a constantly evolving ecosystem of automated metrics, datasets, and human evaluation standards. Due to this moving target, new models often still evaluate on divergent anglo-centric corpora with well-established, but flawed, metrics. This disconnect makes it challenging to identify the limitations of current models and opportunities for progress. Addressing this limitation, GEM provides an environment in which models can easily be applied to a wide set of tasks and in which evaluation strategies can be tested. Regular updates to the benchmark will help NLG research become more multilingual and evolve the challenge alongside models. This paper serves as the description of the data for the 2021 shared task at the associated GEM Workshop.
35.	Gertz, Morie, et al. (författare) Avoiding misdiagnosis : expert consensus recommendations for the suspicion and diagnosis of transthyretin amyloidosis for the general practitioner 2020 Ingår i: BMC Family Practice. - : BMC. - 1471-2296. ; 21:1 Tidskriftsartikel (refereegranskat)abstract Background Transthyretin amyloidosis (also known as ATTR amyloidosis) is a systemic, life-threatening disease characterized by transthyretin (TTR) fibril deposition in organs and tissue. A definitive diagnosis of ATTR amyloidosis is often a challenge, in large part because of its heterogeneous presentation. Although ATTR amyloidosis was previously considered untreatable, disease-modifying therapies for the treatment of this disease have recently become available. This article aims to raise awareness of the initial symptoms of ATTR amyloidosis among general practitioners to facilitate identification of a patient with suspicious signs and symptoms. Methods These consensus recommendations for the suspicion and diagnosis of ATTR amyloidosis were developed through a series of development and review cycles by an international working group comprising key amyloidosis specialists. This working group met to discuss the barriers to early and accurate diagnosis of ATTR amyloidosis and develop a consensus recommendation through a thorough search of the literature performed using PubMed Central. Results The cardiac and peripheral nervous systems are most frequently involved in ATTR amyloidosis; however, many patients often also experience gastrointestinal and other systemic manifestations. Given the multisystemic nature of symptoms, ATTR amyloidosis is often misdiagnosed as a more common disorder, leading to significant delays in the initiation of treatment. Although histologic evaluation has been the gold standard to confirm ATTR amyloidosis, a range of tools are available that can facilitate early and accurate diagnosis. Of importance, genetic testing should be considered early in the evaluation of a patient with unexplained peripheral neuropathy. Conclusions A diagnostic algorithm based on initial red flag symptoms and manifestations of cardiac or neurologic involvement will facilitate identification by the general practitioner of a patient with clinically suspicious symptoms, enabling subsequent referral of the patient to a multidisciplinary specialized medical center.
36.	Hedenius, Martina, et al. (författare) Grammar predicts procedural learning and consolidation deficits in children with Specific Language Impairment 2011 Ingår i: Research in Developmental Disabilities. - : Elsevier. - 0891-4222 .- 1873-3379. ; 32:6, s. 2362-2375 Tidskriftsartikel (refereegranskat)abstract The Procedural Deficit Hypothesis (PDH) posits that Specific Language Impairment (SLI) can be largely explained by abnormalities of brain structures that subserve procedural memory. The PDH predicts impairments of procedural memory itself, and that such impairments underlie the grammatical deficits observed in the disorder. Previous studies have indeed reported procedural learning impairments in SLI, and have found that these are associated with grammatical difficulties. The present study extends this research by examining consolidation and longer-term procedural sequence learning in children with SLI. The Alternating Serial Reaction Time (ASRT) task was given to children with SLI and typically developing (TD) children in an initial learning session and an average of three days later to test for consolidation and longer-term learning. Although both groups showed evidence of initial sequence learning, only the TD children showed clear signs of consolidation, even though the two groups did not differ in longer-term learning. When the children were re-categorized on the basis of grammar deficits rather than broader language deficits, a clearer pattern emerged. Whereas both the grammar impaired and normal grammar groups showed evidence of initial sequence learning, only those with normal grammar showed consolidation and longer-term learning. Indeed, the grammar-impaired group appeared to lose any sequence knowledge gained during the initial testing session. These findings held even when controlling for vocabulary or a broad non-grammatical language measure, neither of which were associated with procedural memory. When grammar was examined as a continuous variable over all children, the same relationships between procedural memory and grammar, but not vocabulary or the broader language measure, were observed. Overall, the findings support and further specify the PDH. They suggest that consolidation and longer-term procedural learning are impaired in SLI, but that these impairments are specifically tied to the grammatical deficits in the disorder. The possibility that consolidation and longer-term learning are problematic in the disorder suggests a locus of potential study for therapeutic approaches. In sum, this study clarifies our understanding of the underlying deficits in SLI, and suggests avenues for further research.
37.	Holtkötter, Jannis, et al. (författare) Development and Validation of a Digital Image Processing-Based Pill Detection Tool for an Oral Medication Self-Monitoring System 2022 Ingår i: Sensors. - : MDPI AG. - 1424-8220. ; 22:8 Tidskriftsartikel (refereegranskat)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.
38.	Hudson, Lawrence N, et al. (författare) The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project 2017 Ingår i: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 7:1, s. 145-188 Tidskriftsartikel (refereegranskat)abstract The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.
39.	Ingegnoli, Francesca, et al. (författare) A comparison between nailfold capillaroscopy patterns in adulthood in juvenile and adult-onset systemic sclerosis: A EUSTAR exploratory study 2015 Ingår i: Microvascular Research. - : Elsevier BV. - 1095-9319 .- 0026-2862. ; 102, s. 19-24 Tidskriftsartikel (refereegranskat)abstract Objective: Qualitative capillaroscopy patterns in juvenile- and adult-onset systemic sclerosis (SSc) were studied in adulthood using data from the EULAR Scleroderma Trials and Research (EUSTAR) database. Methods: Data collected between June 2004 and April 2013 were examined with focus on capillaroscopy. In this retrospective exploratory study, series of patients with juvenile-onset SSc were matched with series of adult-onset SSc having the same gender and autoantibody profile. Results: 30 of 123 patients with juvenile-onset and 2108 of 7133 with adult-onset SSc had data on capillaroscopy. Juvenile-onset SSc showed scleroderma pattern more frequently than adult-onset SSc (93.3% and 88%). The OR was 2.44 and 95% Cl 0.57-10.41. An active scleroderma pattern was present in 58% of juvenile- and 61% of adult-onset SSc. The OR was 0.91 and 95% Cl 0.28-2.93. The late scleroderma pattern was present in 61% of juvenile- and 55.5% of adult-onset SSc. The OR was 1.06 and 95% Cl 0.34-3.56. Conclusion: This is the first exploratory study on the comparison of capillaroscopy between juvenile- and adult-onset SSc in adulthood. Juvenile-onset SSc had an increase prevalence of sderoderma pattern, but a similar distribution of the three patterns was suggested. Further studies are needed to define this issue. (C) 2015 Elsevier Inc. All rights reserved.
40.	Kouyoumdjian, Joao Aris, et al. (författare) Concentric needle jitter on stimulated frontalis and extensor digitorum in 20 myasthenia gravis patients 2011 Ingår i: Muscle and Nerve. - : Wiley. - 0148-639X .- 1097-4598. ; 44:6, s. 912-918 Tidskriftsartikel (refereegranskat)abstract Introduction: Our objective was to study jitter parameters using a concentric needle electrode (CNE) in the extensor digitorum (ED) and frontalis (FR) muscles. Methods: Twenty myasthenia gravis (MG) patients, mean age 44.5 years, were studied. Percutaneous (FR) and intramuscular needle (ED) stimulation approaches were used. Jitter was expressed as the mean consecutive difference (MCD). The filter settings were from 1000 HZ to 10 kHZ. Results: Abnormal MCD was found in 85% for both ED and FR and in 90% when combining the two muscles. An abnormal percentage of outliers was found in 90% for ED and 85% for FR. The mean MCD did not show a difference for ED and FR, but the percentage of outliers and blocking were higher in FR. Abnormality was found in 93.7% (generalized) and in 75% (ocular) of MG cases. For ED outliers abnormality was greater than the MCD. Conclusion: CNE jitter is reliable for investigation of MG, although borderline findings should be judged with caution.
41.	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.
42.	Melo, Clarissa L., et al. (författare) CO2MOVE Project : The New Brazilian Field Lab Fully Dedicated to CO2 MMV Experiments 2017 Ingår i: 13th International Conference on Greenhouse Gas Control Technologies, GHGT-13. - : Elsevier. ; , s. 3699-3715 Konferensbidrag (refereegranskat)abstract After the Ressacada Project experience acquired from 2011 to 2015 when PUCRS, UNESP and other institutions conducted three controlled CO2 release experiments, PETROBRAS, the national oil company that is sponsoring the project, has launched a new challenge to its partners. The company stimulated the implementation of a new Brazilian experimental site where there will be a deepening of studies in geologically more complex conditions and more challenging from a technological point of view. The choice of an area inside PUCRS campus, in Viamao - Rio Grande do Sul state, was motivated by a predominantly clay subsoil and the privileged location of the site in terms of ease logistics and security, which is required for a project of this size that houses high-tech equipment with significant cost. The CO2MOVE project started at 2015 with the subsurface characterization of the site and the assembly and manufacture of an automated system for CO2 and gas tracers with injection capacity for 5 to 50 kg/ day. Based on physical characterization studies and on numerical modeling that is being developed, the site infrastructure will be completed in the next months with the positioning of vertical injection wells, monitoring wells, and other equipment and monitoring mesh. Monitoring tools should be arranged in an area of approximately 100m(2), occupying the entire region surrounding the injection wells. Fieldwork involving CO2 injection and monitoring should have a 60 days duration of which 15 days are for preliminary surveys (pre-injection), 30 days for injection and CO2 monitoring and the last 15 days for post-injection measurements. Following this work, the collected data will be analyzed in the university labs. Similarly to Ressacada Project, this experiment will run measurements of soil CO2 flux with accumulation chambers, CO2 turbulent fluxes with Eddy Covariance, subsurface gases and groundwater monitoring, and resistivity measurements. Other monitoring methods still not tested by the research team will be held as gas tracers monitoring and laser measurements. (C) 2017 The Authors. Published by Elsevier Ltd.
43.	Melo, Clarissa L., et al. (författare) Integration results of soil CO2 flux and subsurface gases in the Ressacada Pilot site, Southern Brazil 2017 Ingår i: 13th International Conference on Greenhouse Gas Control Technologies, GHGT-13. - : Elsevier. ; , s. 3793-3804 Konferensbidrag (refereegranskat)abstract The first CO2 monitoring field lab at the Ressacada Farm, in the Southern region of Brazil, started in 2011 and until 2015 offered an excellent opportunity to run controlled CO2 releases experiments in soil and shallow subsurface through vertical injection wells. This paper focus on the presentation and comparison of the results obtained at the last campaign realized at this site in August 2015. The results integrate a time-lapse monitoring experiment of CO2 migration in both saturated and unsaturated sand-rich sediments and soil, using soil CO2 flux measurements and subsurface gas analyses through CO2 concentrations (ppm) and carbon isotope ratios (delta C-13 of CO2). The CO2 flux results in the studied area showed an increase in the flux values according to the increasing of injection rate and along the campaign are directed to the southwest portion of the area. However, even by injecting large amounts of CO2, fluxes are greatly reduced when it rains. The gas analysis also showed an increase in CO2 concentrations according to the increasing of the injection rate mainly in the superficial levels of the monitoring wells (0.5m and 2m depth). The delta C-13 of CO2 found on the 3rd injection day showed the presence of CO2 injected and demonstrate that the sampling methodology with vacutainer vial was effective, since there is no atmospheric contamination. The correlation of isotopic analysis were consistent with the results of concentrations and CO2 fluxes and thus, it is clear that the CO2 breakthrough occurred from the 3rd day of injection, while were obtained the largest CO2 fluxes, the higher gas concentrations in the subsurface, as well as the industrial origin of delta C-13 of CO2.
44.	Melo, Clarissa Lovato, et al. (författare) Study of gas tracers for CO2 monitoring 2014 Ingår i: 12th International Conference on Greenhouse Gas Control Technologies, GHGT-12. - : Elsevier. ; , s. 3864-3868 Konferensbidrag (refereegranskat)abstract Gas tracers have been tested libr monitoring and detecting CO, displacement in the underground and eventually leakages to the upper layers in geological storage sites. Commonly used tracers are perfluorocarbons (PFCs) and sulfur hexafluoride (SF6). In Brazil, we are canying out gas tracers studies in laboratory for further application in field test 'facilities. These experiments consist of injecting CO, with perfluorocarbon (perfluoropropane PP and pealuormethylcyclopentane PMCP) at low pressure (ca. 290 psi) in pressurized vessels with different types of sediments and soil samples. After flowing through the sample pores, the tracer is adsorbed into a capillary adsorption tube (CAT) with a specific fiber for perfluorcabon. Then, the tracer is extracted from the CAT through a Thermal Desorption System and subsequently analyzed in a Gas Chromatograph with an Electron Capture Detector (GC ECD). The objective of these experiments is to evaluate the PFCs as a monitoring tool; analyzing the tracer retention times in different sediments, as well as understanding the CATs adsorption capacity and performance. After laboratory tests, field experiments will be conducted in the course of this project. Several experiments of CO2 injection and controlled leaks will be developed in shallow vertical wells at the project site as a continuity of the experiments started at Ressacada Fann Site (Florianopolis, Brazil). The project aim is to understand the flow and dispersion of CO2 in soil and atmosphere simulating an eventual leakage from a geological reservoir using an automated system with a dedicated module for tracers injection into CO2 stream. (C) 2015 Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creavativecommons.org/licesses/by-nc-nd/3.0/). Peer-review under responsibility of the Organizing Committee of GLIGT-12
45.	Moreau, Philippe, et al. (författare) Adverse event management in patients with relapsed and refractory multiple myeloma taking pomalidomide plus low-dose dexamethasone : A pooled analysis 2017 Ingår i: European Journal of Haematology. - : Wiley. - 0902-4441. ; 99:3, s. 199-206 Tidskriftsartikel (refereegranskat)abstract Objectives: Heavily pretreated patients with relapsed and refractory multiple myeloma are susceptible to treatment-related adverse events (AEs). Managing AEs are important to ensure patients continue therapy long enough to receive the best clinical benefit. Data from the MM-002, MM-003, and MM-010 trials were pooled to further characterize the safety profile of pomalidomide plus low-dose dexamethasone and AE management. Methods: This analysis included 1088 patients who received ≥ 2 prior therapies, including lenalidomide and bortezomib, and progressed ≤ 60 days of last therapy. Patients received 28-day cycles of pomalidomide 4 mg/day on days 1-21 and low-dose dexamethasone 40 mg (20 mg if aged > 75 years) weekly until disease progression or unacceptable toxicity. Thromboprophylaxis was required. Results: The most common grade 3/4 AEs were neutropenia (56.2%), anemia (32.3%), and thrombocytopenia (25.8%), which occurred within the first few cycles of treatment. Grade 3/4 infections occurred in 33.7% patients, of whom 13.9% had pneumonia, and 40.3% had neutropenia. Pomalidomide dose reductions or interruptions were reported in 24.2% and 66.0% of patients, respectively. AEs were managed by dose modifications and/or supportive care. Conclusions: Pomalidomide plus low-dose dexamethasone showed an acceptable safety profile, and AEs were well managed according to study protocols and established guidelines.
46.	Murray, Christopher J. L., et al. (författare) Population and fertility by age and sex for 195 countries and territories, 1950–2017: a systematic analysis for the Global Burden of Disease Study 2017 2018 Ingår i: The Lancet. - 1474-547X .- 0140-6736. ; 392:10159, s. 1995-2051 Tidskriftsartikel (refereegranskat)abstract Background: Population estimates underpin demographic and epidemiological research and are used to track progress on numerous international indicators of health and development. To date, internationally available estimates of population and fertility, although useful, have not been produced with transparent and replicable methods and do not use standardised estimates of mortality. We present single-calendar year and single-year of age estimates of fertility and population by sex with standardised and replicable methods. Methods: We estimated population in 195 locations by single year of age and single calendar year from 1950 to 2017 with standardised and replicable methods. We based the estimates on the demographic balancing equation, with inputs of fertility, mortality, population, and migration data. Fertility data came from 7817 location-years of vital registration data, 429 surveys reporting complete birth histories, and 977 surveys and censuses reporting summary birth histories. We estimated age-specific fertility rates (ASFRs; the annual number of livebirths to women of a specified age group per 1000 women in that age group) by use of spatiotemporal Gaussian process regression and used the ASFRs to estimate total fertility rates (TFRs; the average number of children a woman would bear if she survived through the end of the reproductive age span [age 10–54 years] and experienced at each age a particular set of ASFRs observed in the year of interest). Because of sparse data, fertility at ages 10–14 years and 50–54 years was estimated from data on fertility in women aged 15–19 years and 45–49 years, through use of linear regression. Age-specific mortality data came from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 estimates. Data on population came from 1257 censuses and 761 population registry location-years and were adjusted for underenumeration and age misreporting with standard demographic methods. Migration was estimated with the GBD Bayesian demographic balancing model, after incorporating information about refugee migration into the model prior. Final population estimates used the cohort-component method of population projection, with inputs of fertility, mortality, and migration data. Population uncertainty was estimated by use of out-of-sample predictive validity testing. With these data, we estimated the trends in population by age and sex and in fertility by age between 1950 and 2017 in 195 countries and territories. Findings: From 1950 to 2017, TFRs decreased by 49·4% (95% uncertainty interval [UI] 46·4–52·0). The TFR decreased from 4·7 livebirths (4·5–4·9) to 2·4 livebirths (2·2–2·5), and the ASFR of mothers aged 10–19 years decreased from 37 livebirths (34–40) to 22 livebirths (19–24) per 1000 women. Despite reductions in the TFR, the global population has been increasing by an average of 83·8 million people per year since 1985. The global population increased by 197·2% (193·3–200·8) since 1950, from 2·6 billion (2·5–2·6) to 7·6 billion (7·4–7·9) people in 2017; much of this increase was in the proportion of the global population in south Asia and sub-Saharan Africa. The global annual rate of population growth increased between 1950 and 1964, when it peaked at 2·0%; this rate then remained nearly constant until 1970 and then decreased to 1·1% in 2017. Population growth rates in the southeast Asia, east Asia, and Oceania GBD super-region decreased from 2·5% in 1963 to 0·7% in 2017, whereas in sub-Saharan Africa, population growth rates were almost at the highest reported levels ever in 2017, when they were at 2·7%. The global average age increased from 26·6 years in 1950 to 32·1 years in 2017, and the proportion of the population that is of working age (age 15–64 years) increased from 59·9% to 65·3%. At the national level, the TFR decreased in all countries and territories between 1950 and 2017; in 2017, TFRs ranged from a low of 1·0 livebirths (95% UI 0·9–1·2) in Cyprus to a high of 7·1 livebirths (6·8–7·4) in Niger. The TFR under age 25 years (TFU25; number of livebirths expected by age 25 years for a hypothetical woman who survived the age group and was exposed to current ASFRs) in 2017 ranged from 0·08 livebirths (0·07–0·09) in South Korea to 2·4 livebirths (2·2–2·6) in Niger, and the TFR over age 30 years (TFO30; number of livebirths expected for a hypothetical woman ageing from 30 to 54 years who survived the age group and was exposed to current ASFRs) ranged from a low of 0·3 livebirths (0·3–0·4) in Puerto Rico to a high of 3·1 livebirths (3·0–3·2) in Niger. TFO30 was higher than TFU25 in 145 countries and territories in 2017. 33 countries had a negative population growth rate from 2010 to 2017, most of which were located in central, eastern, and western Europe, whereas population growth rates of more than 2·0% were seen in 33 of 46 countries in sub-Saharan Africa. In 2017, less than 65% of the national population was of working age in 12 of 34 high-income countries, and less than 50% of the national population was of working age in Mali, Chad, and Niger. Interpretation: Population trends create demographic dividends and headwinds (ie, economic benefits and detriments) that affect national economies and determine national planning needs. Although TFRs are decreasing, the global population continues to grow as mortality declines, with diverse patterns at the national level and across age groups. To our knowledge, this is the first study to provide transparent and replicable estimates of population and fertility, which can be used to inform decision making and to monitor progress. Funding: Bill & Melinda Gates Foundation.
47.	Oliva, Andresa, et al. (författare) A comparison of three methods for monitoring CO2 migration in soil and shallow subsurface in the Ressacada Pilot site, Southern Brazil 2014 Ingår i: 12th International Conference on Greenhouse Gas Control Technologies, GHGT-12. - : Elsevier. ; , s. 3992-4002 Konferensbidrag (refereegranskat)abstract In a joint R&D project under the full sponsorship of PETROBRAS, the Brazilian National Oil Company, the first CO2 monitoring field lab was started-up in Brazil in 2011. The site chosen, the Ressacada Farm, in the Southern region of the country, offered an excellent opportunity to run controlled CO2 release experiments in soil and shallow subsurface (< 3 m depth). This paper focuses on the presentation and comparison of the results obtained using electrical imaging, CO2 flux measurements and geochemical analysis of the groundwater to monitor CO2 migration in both saturated and unsaturated sand-rich sediments and soil. In 2013 a controlled release campaign was run, covering an area of approximately 6,300 m(2). Commercial food-grade gaseous carbon dioxide was continuously injected at 3 m depth for 12 days. The average injection rate was 90 g/day, totaling ca. 32kg of gas being released. The low injection rate avoided fracturing of the unconsolidated sediments composing the bulk of the local soil matrix. Monitoring techniques deployed during 30 consecutive days, including background characterization, injection and post-injection periods, were: (1) 3D electrical imaging using a Wenner array, (2) soil CO2 flux measurements using accumulation chambers, (3) water sampling and analysis, (4) 3D (tridimensional) and 4D (time-lapsed) electrical imaging covering depth levels to approximately 10 m below the surface. Water geochemical monitoring consisted of the analyses of several chemical parameters, as well as acidity and electrical conductivity in five multi-level wells (2m; 4m and 6 m depth) installed in the vicinity of the CO2 injection well. Comparison of pre- and post-injection electrical imaging shows changes in resistivity values consistent with CO(2)migration pathways. A pronounced increase in resistivity values occurred, from 1,500 ohm. m to 2,000 ohm. m, in the vicinity of the injection well. The accumulation chamber assessment show significant changes in the CO2 flux during the release experiment: maximum values detected were ca. 270 mmol/m(2)/s(during injection) as compared to background values of c.a. 34mmol/m(2)/s. The pH showed variations after CO2 injection in two monitoring wells at 2m, 4m and 6m depth. After the CO2 injection ceased, the lowest pH measured was 4.1, which represents a decrease of 0.5 relative to the background values. Slight variations in the oxidation-reduction potential (Eh) were observed near the CO2 injection well. There was a decreasing trend of this potential, especially in a monitoring well at 6m depth, ranging from 308mV to 229mV, between the background and the injection scenarios. Ppb level increments were detected in the measurements carried out for the major cations (Ca, Mg, Na, and P) and trace elements (Ag, Al, As, B, Ba, Cd, Pb, Cu, Cr, Ni, Mn, S, V, and Zn). Electrical conductivity and alkalinity, however, remained constant throughout the experiment, with values around 40 mu S.cm(-1) and 2.5 mgCaCO(3).L-1, respectively. The response to CO2 injection was not uniformly observed by the different methods deployed on site. The highest percentage change in resistivity values near the injection well occurred 5 days after the injection had started. However the highest percentage changes in the CO2 flux values occurred 9 days after the injection, 4 days after the observed changes in resistivity values. This delay is probably due to the migration time of the gas from 0.5m depth to the surface. (C) 2014 Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/). Peer-review under responsibility of the Organizing Committee of GHGT-12
48.	Pedro, Joana Reis, et al. (författare) Transient gain of function of cannabinoid CB1 receptors in the control of frontocortical glucose consumption in a rat model of Type-1 diabetes 2020 Ingår i: Brain Research Bulletin. - : Elsevier BV. - 0361-9230. ; 161, s. 106-115 Tidskriftsartikel (refereegranskat)abstract Here we aimed to unify some previous controversial reports on changes in both cannabinoid CB1 receptor (CB1R) expression and glucose metabolism in the forebrain of rodent models of diabetes. We determined how glucose metabolism and its modulation by CB1R ligands evolve in the frontal cortex of young adult male Wistar rats, in the first 8 weeks of streptozotocin-induced type-1 diabetes (T1D). We report that frontocortical CB1R protein density was biphasically altered in the first month of T1D, which was accompanied with a reduction of resting glucose uptake ex vivo in acute frontocortical slices that was normalized after eight weeks in T1D. This early reduction of glucose uptake in slices was also restored by ex vivo treatment with both the non-selective CB1R agonists, WIN55212−2 (500 nM) and the CB1R-selective agonist, ACEA (3 μM) while it was exacerbated by the CB1R-selective antagonist, O-2050 (500 nM). These results suggest a gain-of-function for the cerebrocortical CB1Rs in the control of glucose uptake in diabetes. Although insulin and IGF-1 receptor protein densities remained unaffected, phosphorylated GSKα and GSKβ levels showed different profiles 2 and 8 weeks after T1D induction in the frontal cortex. Altogether, the biphasic response in frontocortical CB1R density within a month after T1D induction resolves previous controversial reports on forebrain CB1R levels in T1D rodent models. Furthermore, this study also hints that cannabinoids may be useful to alleviate impaired glucoregulation in the diabetic cortex.
49.	Pereira, Ana Margarida, et al. (författare) Multidisciplinary Development and Initial Validation of a Clinical Knowledge Base on Chronic Respiratory Diseases for mHealth Decision Support Systems 2023 Ingår i: Journal of Medical Internet Research. - : JMIR PUBLICATIONS, INC. - 1438-8871. ; 25 Tidskriftsartikel (refereegranskat)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.
50.	Pereira, Ana Margarida, et al. (författare) 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 Ingår i: Telemedicine journal and e-health. - : Mary Ann Liebert. - 1530-5627 .- 1556-3669. ; 28:9, s. 1386-1392 Tidskriftsartikel (refereegranskat)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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