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1.
  • Carvalho, Joao, et al. (författare)
  • A drill-hole, geological and geophysical data-based 3D model for target generation in Neves-Corvo mine region, Portugal
  • 2022
  • Ingår i: International journal of earth sciences. - : Springer Nature. - 1437-3254 .- 1437-3262. ; 111, s. 403-424
  • Tidskriftsartikel (refereegranskat)abstract
    • The Neves-Corvo world class Iberian Pyrite Belt volcanogenic massive sulphide (VMS) deposit located in southern Portugal, constitutes an important Cu-Zn-Pb active mine. Seven deposits are currently known, among which the Lombador deposit alone has estimated 150 Mt of massive sulphides. The life-time of the mine is dependent on the discovery of new exploration targets and it is vital to have accurate 3D geological models, not only to guide drilling campaigns but also to drive a winning/new strategy, which in the past has led to Semblana and Monte Branco discoveries: geophysical inversion and modelling. Furthermore, 3D geological models can contribute to the understanding of the tectonic and stratigraphic evolution of the region. Therefore, the goal of this study is to produce a realistic 3D geological model of the Neves-Corvo region, as only one model is presently publicly available: the PROMINE model, which includes the study area of this work and extends from Aljustrel to the border with Spain. Lundin Mining has also produced two unpublished, confidential models in 2007 and 2017. The latest Lundin model incorporates the same geophysical data used in this work (2D and 3D seismic reflection and time-domain electromagnetic (TEM) ground loop data) and approximately 7500 surface and underground drill-holes. The model presented in this research has much more detail than the 2012 PROMINE model in the Neves-Corvo region and uses an updated and revised drill-hole database with approximately 8000 drill-holes, revised geological cross-sections built from surface geology and drill-hole logs, new geological outcrop data, petrophysical and reprocessed geophysical data, and is therefore more detailed and accurate than any of the previous models, in particular the 2007 and PROMINE models. Land gravimetric and aeromagnetic data are also available in the study area but were not directly used to build the geological model but rather to investigate and check the model produced. Modelling was performed with industry standard software and the 3D curves resulting from the geological/geophysical interpretation were interpolated using different approaches to respect the hard data (interpretation lines and drill-holes). The resulting 3D stratigraphic surfaces required strong manual editing to respect the interpretation, due to the presence of folds, thrusts and tectonic nappes in the study area. The surfaces were afterwards tied to the drill-holes, resulting in a 3D model with great accuracy and detail in the near mining area and covering a larger area than previously available 3D geological models. The model has three major stratigraphic layers: the Mertola Flysch Formation and the Volcano-Sedimentary Complex (VSC), overlying the Phyllite-Quartzite Formation basement, and also the known VMS deposits (underlying the top of the Lower VSC) geometries according to drill-hole data. In the central part of the study area, where more drill-holes are available, the top of the Lower VSC sequence surface was also built. This approach will contribute to a better exploration drill-hole planning and the generation of new targets for exploration.
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2.
  • Menditto, Enrica, et al. (författare)
  • Adherence to treatment in allergic rhinitis using mobile technology : The MASK Study
  • 2019
  • Ingår i: Clinical and Experimental Allergy. - : WILEY. - 0954-7894 .- 1365-2222. ; 49:4, s. 442-460
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Mobile technology may help to better understand the adherence to treatment. MASK-rhinitis (Mobile Airways Sentinel NetworK for allergic rhinitis) is a patient-centred ICT system. A mobile phone app (the Allergy Diary) central to MASK is available in 22 countries. Objectives: To assess the adherence to treatment in allergic rhinitis patients using the Allergy Diary App. Methods: An observational cross-sectional study was carried out on all users who filled in the Allergy Diary from 1 January 2016 to 1 August 2017. Secondary adherence was assessed by using the modified Medication Possession Ratio (MPR) and the Proportion of days covered (PDC) approach. Results: A total of 12143 users were registered. A total of 6949 users reported at least one VAS data recording. Among them, 1887 users reported >= 7 VAS data. About 1195 subjects were included in the analysis of adherence. One hundred and thirty-six (11.28%) users were adherent (MPR >= 70% and PDC <= 1.25), 51 (4.23%) were partly adherent (MPR >= 70% and PDC = 1.50) and 176 (14.60%) were switchers. On the other hand, 832 (69.05%) users were non-adherent to medications (MPR <70%). Of those, the largest group was non-adherent to medications and the time interval was increased in 442 (36.68%) users. Conclusion and clinical relevance: Adherence to treatment is low. The relative efficacy of continuous vs on-demand treatment for allergic rhinitis symptoms is still a matter of debate. This study shows an approach for measuring retrospective adherence based on a mobile app. This also represents a novel approach for analysing medication-taking behaviour in a real-world setting.
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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.
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5.
  • 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.
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6.
  • Bedard, Annabelle, et al. (författare)
  • Mobile technology offers novel insights into the control and treatment of allergic rhinitis : The MASK study
  • 2019
  • Ingår i: Journal of Allergy and Clinical Immunology. - : MOSBY-ELSEVIER. - 0091-6749 .- 1097-6825. ; 144:1, s. 135-143
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Mobile health can be used to generate innovative insights into optimizing treatment to improve allergic rhinitis (AR) control. Objectives: A cross-sectional real-world observational study was undertaken in 22 countries to complement a pilot study and provide novel information on medication use, disease control, and work productivity in the everyday life of patients with AR. Methods: A mobile phone app (Allergy Diary, which is freely available on Google Play and Apple stores) was used to collect the data of daily visual analogue scale (VAS) scores for (1) overall allergic symptoms; (2) nasal, ocular, and asthma symptoms; (3) work; and (4) medication use by using a treatment scroll list including all allergy medications (prescribed and over-the-counter) customized for 22 countries. The 4 most common intranasal medications containing intranasal corticosteroids and 8 oral H-1-antihistamines were studied. Results: Nine thousand one hundred twenty-two users filled in 112,054 days of VASs in 2016 and 2017. Assessment of days was informative. Control of days with rhinitis differed between no (best control), single (good control for intranasal corticosteroid-treated days), or multiple (worst control) treatments. Users with the worst control increased the range of treatments being used. The same trend was found for asthma, eye symptoms, and work productivity. Differences between oral H-1-antihistamines were found. Conclusions: This study confirms the usefulness of the Allergy Diary in accessing and assessing behavior in patients with AR. This observational study using a very simple assessment tool (VAS) on a mobile phone had the potential to answer questions previously thought infeasible.
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7.
  • Bousquet, Jean, et al. (författare)
  • Allergic Rhinitis and its Impact on Asthma (ARIA) Phase 4 (2018) : Change management in allergic rhinitis and asthma multimorbidity using mobile technology
  • 2019
  • Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier. - 0091-6749 .- 1097-6825. ; 143:3, s. 864-879
  • Tidskriftsartikel (refereegranskat)abstract
    • Allergic Rhinitis and its Impact on Asthma (ARIA) has evolved from a guideline by using the best approach to integrated care pathways using mobile technology in patients with allergic rhinitis (AR) and asthma multimorbidity. The proposed next phase of ARIA is change management, with the aim of providing an active and healthy life to patients with rhinitis and to those with asthma multimorbidity across the lifecycle irrespective of their sex or socioeconomic status to reduce health and social inequities incurred by the disease. ARIA has followed the 8-step model of Kotter to assess and implement the effect of rhinitis on asthma multimorbidity and to propose multimorbid guidelines. A second change management strategy is proposed by ARIA Phase 4 to increase self-medication and shared decision making in rhinitis and asthma multimorbidity. An innovation of ARIA has been the development and validation of information technology evidence-based tools (Mobile Airways Sentinel Network [MASK]) that can inform patient decisions on the basis of a self-care plan proposed by the health care professional.
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  • Bousquet, Jean, et al. (författare)
  • ARIA digital anamorphosis : Digital transformation of health and care in airway diseases from research to practice
  • 2021
  • Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : John Wiley & Sons. - 0105-4538 .- 1398-9995. ; 76:1, s. 168-190
  • Forskningsöversikt (refereegranskat)abstract
    • Digital anamorphosis is used to define a distorted image of health and care that may be viewed correctly using digital tools and strategies. MASK digital anamorphosis represents the process used by MASK to develop the digital transformation of health and care in rhinitis. It strengthens the ARIA change management strategy in the prevention and management of airway disease. The MASK strategy is based on validated digital tools. Using the MASK digital tool and the CARAT online enhanced clinical framework, solutions for practical steps of digital enhancement of care are proposed.
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9.
  • Bousquet, J. Jean, et al. (författare)
  • Next-generation ARIA care pathways for rhinitis and asthma : a model for multimorbid chronic diseases
  • 2019
  • Ingår i: Clinical and Translational Allergy. - : BMC. - 2045-7022. ; 9
  • Forskningsöversikt (refereegranskat)abstract
    • Background: In all societies, the burden and cost of allergic and chronic respiratory diseases are increasing rapidly. Most economies are struggling to deliver modern health care effectively. There is a need to support the transformation of the health care system into integrated care with organizational health literacy.Main body: As an example for chronic disease care, MASK (Mobile Airways Sentinel NetworK), a new project of the ARIA (Allergic Rhinitis and its Impact on Asthma) initiative, and POLLAR (Impact of Air POLLution on Asthma and Rhinitis, EIT Health), in collaboration with professional and patient organizations in the field of allergy and airway diseases, are proposing real-life ICPs centred around the patient with rhinitis, and using mHealth to monitor environmental exposure. Three aspects of care pathways are being developed: (i) Patient participation, health literacy and self-care through technology-assisted "patient activation", (ii) Implementation of care pathways by pharmacists and (iii) Next-generation guidelines assessing the recommendations of GRADE guidelines in rhinitis and asthma using real-world evidence (RWE) obtained through mobile technology. The EU and global political agendas are of great importance in supporting the digital transformation of health and care, and MASK has been recognized by DG Sante as a Good Practice in the field of digitally-enabled, integrated, person-centred care.Conclusion: In 20 years, ARIA has considerably evolved from the first multimorbidity guideline in respiratory diseases to the digital transformation of health and care with a strong political involvement.
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10.
  • Freitas, Felipe F., et al. (författare)
  • Impact of SM parameters and of the vacua of the Higgs potential in gravitational waves detection
  • 2022
  • Ingår i: Journal of Cosmology and Astroparticle Physics. - : IOP Publishing. - 1475-7516. ; 2022:3
  • Tidskriftsartikel (refereegranskat)abstract
    • In this work we discuss two different phases of a complex singlet extension of the Standard Model (SM) together with an extension that also includes new fermion fields, in particular, a Majoron model equipped with an inverse seesaw mechanism. All considered scenarios contain a global U(1) symmetry and allow for first-order phase transitions while only two of them are strong enough to favour the detection of primordial gravitational waves (GWs) in planned experiments such as LISA. In particular, this is shown to be possible in the singlet extension with a non vanishing real VEV at zero temperature and also in the model with extra fermions. In the singlet extension with no additional fermions, the detection of GWs strongly depends on the U(1) symmetry breaking pattern of the scalar potential at zero temperature. We study for the first time the impact of the precision in the determination of the SM parameters on the strength of the GWs spectrum. It turns out that the variation of the SM parameters such as the Higgs boson mass and top quark Yukawa coupling in their allowed experimental ranges has a notable impact on GWs detectability prospects.
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11.
  • 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.
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  • Addazi, Andrea, et al. (författare)
  • Gravitational echoes of lepton number symmetry breaking with light and ultralight Majorons
  • 2023
  • Ingår i: Journal of Cosmology and Astroparticle Physics. - 1475-7516. ; 2023:9
  • Tidskriftsartikel (refereegranskat)abstract
    • We formulate a version of the low-scale Majoron model equipped with an inverse seesaw mechanism featuring lepton-number preserving dimension-6 operators in the scalar potential. Contrary to its dimension-4 counterpart, we find that the model can simultaneously provide light and ultralight Majorons, neutrino masses and their mixing, while featuring strong first-order cosmological phase transitions associated to the spontaneous breaking of the lepton number and the electroweak symmetries in the early Universe. We show by a detailed numerical analysis under which circumstances the model can be probed via the primordial gravitational wave spectrum potentially observable at LISA and other planned facilities. We discuss which implications result for collider physics observables, such as scalar trilinear couplings, the scalar mixing angle and the mass of a new CP-even Higgs boson.
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  • Bachmann, M. Consuelo, et al. (författare)
  • Electrical impedance tomography in acute respiratory distress syndrome
  • 2018
  • Ingår i: Critical Care. - : BioMed Central. - 1364-8535 .- 1466-609X. ; 22
  • Forskningsöversikt (refereegranskat)abstract
    • Acute respiratory distress syndrome (ARDS) is a clinical entity that acutely affects the lung parenchyma, and is characterized by diffuse alveolar damage and increased pulmonary vascular permeability. Currently, computed tomography (CT) is commonly used for classifying and prognosticating ARDS. However, performing this examination in critically ill patients is complex, due to the need to transfer these patients to the CT room. Fortunately, new technologies have been developed that allow the monitoring of patients at the bedside. Electrical impedance tomography (EIT) is a monitoring tool that allows one to evaluate at the bedside the distribution of pulmonary ventilation continuously, in real time, and which has proven to be useful in optimizing mechanical ventilation parameters in critically ill patients. Several clinical applications of EIT have been developed during the last years and the technique has been generating increasing interest among researchers. However, among clinicians, there is still a lack of knowledge regarding the technical principles of EIT and potential applications in ARDS patients. The aim of this review is to present the characteristics, technical concepts, and clinical applications of EIT, which may allow better monitoring of lung function during ARDS.
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18.
  • Bonilla, Cesar, et al. (författare)
  • Collider signatures of vector-like fermions from a flavor symmetric model
  • 2022
  • Ingår i: Journal of High Energy Physics. - 1029-8479. ; 2022:1
  • Tidskriftsartikel (refereegranskat)abstract
    • We propose a model with two Higgs doublets and several SU(2) scalar singlets with a global non-Abelian flavor symmetry Q6× Z2. This discrete group accounts for the observed pattern of fermion masses and mixing angles after spontaneous symmetry breaking. In this scenario only the third generation of fermions get their masses as in the Standard Model (SM). The masses of the remaining fermions are generated through a seesaw-like mechanism. To that end, the matter content of the model is enlarged by introducing electrically charged vector-like fermions (VLFs), right handed Majorana neutrinos and several SM scalar singlets. Here we study the processes involving VLFs that are within the reach of the Large Hadron Collider (LHC). We perform collider studies for vector-like leptons (VLLs) and vector-like quarks (VLQs), focusing on double production channels for both cases, while for VLLs single production topologies are also included. Utilizing genetic algorithms for neural network optimization, we determine the statistical significance for a hypothetical discovery at future LHC runs. In particular, we show that we can not safely exclude VLLs for masses greater than 200 GeV. For VLQ’s in our model, we show that we can probe their masses up to 3.8 TeV, if we take only into account the high-luminosity phase of the LHC. Considering Run-III luminosities, we can also exclude VLQs for masses up to 3.4 TeV. We also show how the model with predicted VLL masses accommodates the muon anomalous magnetic moment.
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19.
  • Bonilla, Cesar, et al. (författare)
  • Gravitational waves from a scotogenic two-loop neutrino mass model
  • 2024
  • Ingår i: Physical Review D. - 2470-0010. ; 109:9
  • Tidskriftsartikel (refereegranskat)abstract
    • We propose a framework to account for neutrino masses at the two-loop level. This mechanism introduces new scalars and Majorana fermions to the Standard Model. It assumes the existence of a global U(1)×Z2 symmetry which after partial breaking provides the stability of the dark matter candidates of the theory. The rich structure of the potential allows for the possibility of first-order phase transitions (FOPTs) in the early Universe which can lead to the generation of primordial gravitational waves. Taking into account relevant constraints from lepton flavor violation, neutrino physics, as well as the trilinear Higgs couplings at next-to-leading order accuracy, we have found a wide range of possible FOPTs which are strong enough to be probed at the proposed gravitational-wave interferometer experiments such as LISA.
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20.
  • 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.
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21.
  • Courbis, Anne-Lise, et al. (författare)
  • Electronic Clinical Decision Support System for allergic rhinitis management : MASK e-CDSS
  • 2018
  • Ingår i: Clinical and Experimental Allergy. - : WILEY. - 0954-7894 .- 1365-2222. ; 48:12, s. 1640-1653
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Allergic rhinitis (AR) management has changed in recent years following the switch from the concept of disease severity to the concept of disease control, publication of the AR clinical decision support system (CDSS) and development of mobile health (m-health) tools for patients (eg Allergy Diary). The Allergy Diary Companion app for healthcare providers is currently being developed and will be launched in 2018. It incorporates the AR CDSS to provide evidence-based treatment recommendations, linking all key stakeholders in AR management.Objective: To produce an electronic version of the AR CDSS (e-CDSS) for incorporation into the Allergy Diary Companion, to describe the app interfaces used to collect information necessary to inform the e-CDSS and to summarize some key features of the Allergy Diary Companion.Methods: The steps involved in producing the e-CDSS and incorporating it into the Allergy Diary Companion were (a) generation of treatment management scenarios; (b) expert consensus on treatment recommendations; (c) generation of electronic decisional algorithms to describe all AR CDSS scenarios; (d) digitization of these algorithms to form the e-CDSS; and (e) embedding the e-CDSS into the app to permit easy user e-CDSS interfacing.Results: Key experts in the AR field agreed on the AR CDSS approach to AR management and on specific treatment recommendations provided by Allergy Diary Companion. Based on this consensus, decision processes were developed and programmed into the Allergy Diary Companion using Titanium Appcelerator (JavaScript) for IOS tablets. To our knowledge, this is the first time the development of any m-health tool has been described in this transparent and detailed way, providing confidence, not only in the app, but also in the provided management recommendations.Conclusion: The Allergy Diary Companion for providers provides guideline and expert-endorsed AR management recommendations. [MASK paper No 32].
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  • De Caterina, Raffaele, et al. (författare)
  • New Oral Anticoagulants in Atrial Fibrillation and Acute Coronary Syndromes : ESC Working Group on Thrombosis - Task Force on Anticoagulants in Heart Disease Position Paper
  • 2012
  • Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 59:16, s. 1413-1425
  • Forskningsöversikt (refereegranskat)abstract
    • Until recently, vitamin K antagonists were the only available oral anticoagulants, but with numerous limitations that prompted the introduction of new oral anticoagulants targeting the single coagulation enzymes thrombin (dabigatran) or factor Xa (apixaban, rivaroxaban, and edoxaban) and given in fixed doses without coagulation monitoring. Here we review the pharmacology and the results of clinical trials with these new agents in stroke prevention in atrial fibrillation and secondary prevention after acute coronary syndromes, providing perspectives on their future incorporation into clinical practice. In phase III trials in atrial fibrillation, compared with warfarin, dabigatran etexilate 150 mg B.I.D. reduced the rates of stroke/systemic embolism without any difference in major bleeding; dabigatran etexilate 110 mg B.I.D. had similar efficacy with decreased bleeding; apixaban 5 mg B.I.D. reduced stroke, systemic embolism, and mortality as well as major bleeding; and rivaroxaban 20 mg Q.D. was noninferior to warfarin for stroke and systemic embolism without a difference in major bleeding. All these agents reduced intracranial hemorrhage. Edoxaban is currently being evaluated in a further large phase III trial. Apixaban and rivaroxaban were evaluated in phase III trials for prevention of recurrent ischemia in patients with acute coronary syndromes who were mostly receiving dual antiplatelet therapy, with conflicting results on efficacy but consistent results for increased major bleeding. Overall, the new oral anticoagulants are poised to replace vitamin K antagonists for many patients with atrial fibrillation and may have a role after acute coronary syndromes. Although convenient to administer and manage, they present challenges that need to be addressed.
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23.
  • De Caterina, Raffaele, et al. (författare)
  • Oral anticoagulants in coronary heart disease (Section IV) Position paper of the ESC Working Group on Thrombosis - Task Force on Anticoagulants in Heart Disease
  • 2016
  • Ingår i: Thrombosis and Haemostasis. - 0340-6245 .- 2567-689X. ; 115:4, s. 685-711
  • Tidskriftsartikel (refereegranskat)abstract
    • Until recently, vitamin K antagonists (VKAs) were the only available oral anticoagulants evaluated for long-term treatment of patients with coronary heart disease (CHD), particularly after an acute coronary syndrome (ACS). Despite efficacy in this setting, VKAs are rarely used because they are cumbersome to administer. Instead, the more readily manageable antiplatelet agents are the mainstay of prevention in ACS patients. This situation has the potential to change with the introduction of non-VKA oral anticoagulants (NOACs), which are easier to administer than VKAs because they can be given in fixed doses without routine coagulation monitoring. The NOACs include dabigatran, which inhibits thrombin, and apixaban, rivaroxaban and edoxaban, which inhibit factor Xa. Apixaban and rivaroxaban were evaluated in phase III trials for prevention of recurrent ischaemia in ACS patients, most of whom were also receiving dual antiplatelet therapy with aspirin and clopidogrel. Although at the doses tested rivaroxaban was effective and apixaban was not, both agents increased major bleeding. The role for the NOACs in ACS management, although promising, is therefore complicated, because it is uncertain how they compare with newer antiplatelet agents, such as prasugrel, ticagrelor or vorapaxar, and because their safety in combination with these other drugs is unknown. Ongoing studies are also now evaluating the use of NOACs in non-valvular atrial fibrillation patients, where their role is established, with coexistent ACS or coronary stenting. Focusing on CHD, we review the results of clinical trials with the NOACs and provide a perspective on their future incorporation into clinical practice.
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24.
  • De Caterina, Raffaele, et al. (författare)
  • Parenteral anticoagulants in heart disease : Current status and perspectives (Section II) Position Paper of the ESC Working Group on Thrombosis - Task Force on Anticoagulants in Heart Disease
  • 2013
  • Ingår i: Thrombosis and Haemostasis. - 0340-6245 .- 2567-689X. ; 109:5, s. 769-786
  • Tidskriftsartikel (refereegranskat)abstract
    • Anticoagulants are a mainstay of cardiovascular therapy, and parenteral anticoagulants have widespread use in cardiology, especially in acute situations. Parenteral anticoagulants include unfractionated heparin, low-molecular-weight heparins, the synthetic pentasaccharides fondaparinux, idraparinux and idrabiotaparinux, and parenteral direct thrombin inhibitors. The several shortcomings of unfractionated heparin and of low-molecular-weight heparins have prompted the development of the other newer agents. Here we review the mechanisms of action, pharmacological properties and side effects of parenteral anticoagulants used in the management of coronary heart disease treated with or without percutaneous coronary interventions, cardioversion for atrial fibrillation, and prosthetic heart valves and valve repair. Using an evidence-based approach, we describe the results of completed clinical trials, highlight ongoing research with currently available agents, and recommend therapeutic options for specific heart diseases.
  •  
25.
  • De Caterina, Raffaele, et al. (författare)
  • Vitamin K antagonists in heart disease : Current status and perspectives (Section III)
  • 2013
  • Ingår i: Thrombosis and Haemostasis. - 0340-6245 .- 2567-689X. ; 110:6, s. 1087-1107
  • Tidskriftsartikel (refereegranskat)abstract
    • Oral anticoagulants are a mainstay of cardiovascular therapy, and for over 60 years vitamin K antagonists (VKAs) were the only available agents for long-term use. VKAs interfere with the cyclic inter-conversion of vitamin K and its 2,3 epoxide, thus inhibiting gamma-carboxylation of glutamate residues at the amino-termini of vitamin K-dependent proteins, including the coagulation factors (F) II (prothrombin), VII, IX and X, as well as of the anticoagulant proteins C, S and Z. The overall effect of such interference is a dose-dependent anticoagulant effect, which has been therapeutically exploited in heart disease since the early 1950s. In this position paper, we review the mechanisms of action, pharmacological properties and side effects of VKAs, which are used in the management of cardiovascular diseases, including coronary heart disease (where their use is limited), stroke prevention in atrial fibrillation, heart valves and/or chronic heart failure. Using an evidence-based approach, we describe the results of completed clinical trials, highlight areas of uncertainty, and recommend therapeutic options for specific disorders. Although VKAs are being increasingly replaced in most patients with non-valvular atrial fibrillation by the new oral anticoagulants, which target either thrombin or FXa, the VKAs remain the agents of choice for patients with atrial fibrillation in the setting of rheumatic valvular disease and for those with mechanical heart valves.
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26.
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27.
  • Dias, Pedro, et al. (författare)
  • Geophysical investigation of the down-dip extension of the Lombador massive sulphide deposit, Neves-Corvo, Portugal
  • 2021
  • Ingår i: International journal of earth sciences. - : Springer Nature. - 1437-3254 .- 1437-3262. ; 110:3, s. 911-922
  • Tidskriftsartikel (refereegranskat)abstract
    • The 150 Mt Lombador massive sulphide deposit is one of the seven known deposits of the Neves-Corvo mine. The deposit dips approximately 30o-35o to the NE and is open down dip, with current exploitation reaching down at 1 km depth. To investigate the possible downwards continuation of the deposit, a 1D constrained inversion of time-domain electromagnetic (TEM) ground loop data was conducted, followed by 3D electromagnetic (EM) forward modeling and a constrained 3D gravimetric inversion over the same area. To perform the EM and gravity modeling/inversion, a 3D geologic model was built using a density database comprising of approximately 300 drill-holes, and an electrical conductivity database with measurements from resistivity surveys and 1D inversion of the TEM data. The EM modeling shows that the Neves Formation shales are a regional conductive layer extending down to approximately 1.6 km depth in the Lombador area. This layer, often topped by massive sulphides, has an average density of 2.83 g/cm(3), whereas stockwork and massive sulphide reach on average 3.1 g/cm(3) and 4.5 g/cm(3), respectively. The 3D constrained gravity inversion results do not support the hypothesis of the presence of massive sulphides located in the down-dip direction of the Lombador deposit in the immediate vicinity of the known deposit. The lack of spatial resolution of the gravity grid, the study area limited size and the lack of information from within the basement suggest further studies are required to confirm the presence and amount of stockwork mineralization down-dip the Lombador deposit inside the Neves-Formation or the Phyllite-Quartzite basement.
  •  
28.
  • Donis, Daphne, et al. (författare)
  • Stratification strength and light climate explain variation in chlorophyll a at the continental scale in a European multilake survey in a heatwave summer
  • 2021
  • Ingår i: Limnology and Oceanography. - : John Wiley & Sons. - 0024-3590 .- 1939-5590. ; 66:12, s. 4314-4333
  • Tidskriftsartikel (refereegranskat)abstract
    • To determine the drivers of phytoplankton biomass, we collected standardized morphometric, physical, and biological data in 230 lakes across the Mediterranean, Continental, and Boreal climatic zones of the European continent. Multilinear regression models tested on this snapshot of mostly eutrophic lakes (median total phosphorus [TP] = 0.06 and total nitrogen [TN] = 0.7 mg L-1), and its subsets (2 depth types and 3 climatic zones), show that light climate and stratification strength were the most significant explanatory variables for chlorophyll a (Chl a) variance. TN was a significant predictor for phytoplankton biomass for shallow and continental lakes, while TP never appeared as an explanatory variable, suggesting that under high TP, light, which partially controls stratification strength, becomes limiting for phytoplankton development. Mediterranean lakes were the warmest yet most weakly stratified and had significantly less Chl a than Boreal lakes, where the temperature anomaly from the long-term average, during a summer heatwave was the highest (+4 degrees C) and showed a significant, exponential relationship with stratification strength. This European survey represents a summer snapshot of phytoplankton biomass and its drivers, and lends support that light and stratification metrics, which are both affected by climate change, are better predictors for phytoplankton biomass in nutrient-rich lakes than nutrient concentrations and surface temperature.
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29.
  • Ekblom, Anneli, 1969- (författare)
  • Changing Landscapes : An Environmental History of Chibuene, Southern Mozambique
  • 2004
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • This thesis analyses the dynamics of environmental change and its embeddedness in the long term interactions of social history and rainfall variability through the building of an environmental history of the Chibuene locality, the coastal plain of southern Mozambique, 5 km south of the town Vilanculos, from 400 AD to present day. Land-use practices over time are discussed on the basis of vegetation and land-use history based pollen analysis, charcoal influx and diatom analysis. It is shown that the savanna vegetation is a long term feature of the Chibuene landscapes and that there have been several expansions of savannas and subsequent retractions of forests through time, linked primarily with rainfall variation. Written sources and archaeological material are drawn upon for a discussion on changing practices of environmental management and it is argued that as the Chibuene landscape is marked by a high degree of environmental insecurity, it is the competent management of resources that has enabled the continuous occupation of Chibuene from c. the 7th century AD, through management of natural resources, flexible farming practices and wide reaching social networks. The last two decades have seen a marked change in land-use patterns, reflected in a decrease in forests of the Chibuene area, the reasons for which are complex and needs to be further studied. Interviews with individual elders in the village community provide alternative ways of understanding environmental degradation as merely the loss of disappearance of forests, or the failure of crops due to droughts, but also as the erosion of local power, wars and social unrest. In a similar way, through a long-term perspective this study stresses that socio-political life, climatic variability and environmental dynamics are interlinked, highlighting the importance of the complimentarity of different forms of knowledge and ways of knowing the Chibuene landscape.
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30.
  • Ferreira, P. M., et al. (författare)
  • Collider phenomenology of new neutral scalars in a flavored multi-Higgs model
  • 2023
  • Ingår i: Physical Review D. - 2470-0010. ; 107:9
  • Tidskriftsartikel (refereegranskat)abstract
    • In this work, we propose and explore for the first time a new collider signature of heavy neutral scalars typically found in many distinct classes of multi-Higgs models. This signature, particularly relevant in the context of the Large Hadron Collider (LHC) measurements, is based on a topology with two charged leptons and four jets arising from first and second generation quarks. As an important benchmark scenario of the multi-Higgs models, we focus on a recently proposed Branco-Grimus-Lavoura (BGL) type model enhanced with an Abelian U(1) flavor symmetry and featuring an additional sector of right-handed neutrinos. We discuss how kinematics of the scalar fields in this model can be used to efficiently separate the signal from the dominant backgrounds and explore the discovery potential of the new heavy scalars in the forthcoming LHC runs. The proposed method can be applied for analysis of the statistical significance of heavy scalars' production at the LHC and future colliders in any multi-Higgs model.
  •  
31.
  • Ferreira, P. M., et al. (författare)
  • Phenomenology of a flavored multiscalar Branco-Grimus-Lavoura-like model with three generations of massive neutrinos
  • 2022
  • Ingår i: Physical Review D. - 2470-0010. ; 106:7
  • Tidskriftsartikel (refereegranskat)abstract
    • In this paper, we present several possible anomaly free implementations of the Branco-Grimus-Lavoura (BGL) model with two Higgs doublets and one singlet scalar. The model also includes three generations of massive neutrinos that get their mass via a type-I seesaw mechanism. A particular anomaly free realization, which we dub νBGL-1 scenario, is subjected to an extensive phenomenological analysis, from the perspective of flavor physics and collider phenomenology.
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32.
  • Franchi, Francesco, et al. (författare)
  • Impact of Diabetes Mellitus and Chronic Kidney Disease on Cardiovascular Outcomes and Platelet P2Y12 Receptor Antagonist Effects in Patients With Acute Coronary Syndromes : Insights From the PLATO Trial
  • 2019
  • Ingår i: Journal of the American Heart Association. - 2047-9980. ; 8:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Background-There are limited data on how the combination of diabetes mellitus (DM) and chronic kidney disease (CKD) affects cardiovascular outcomes as well as response to different P2Y(12) receptor antagonists, which represented the aim of the present investigation. Methods and Results-In this post hoc analysis of the PLATO (Platelet Inhibition and Patient Outcomes) trial, which randomized acute coronary syndrome patients to ticagrelor versus clopidogrel, patients (n=15 108) with available DM and CKD status were classified into 4 groups: DM+/CKD+ (n=1058), DM+/CKD- (n=2748), DM-/CKD+ (n=2160), and DM-/CKD- (n=9142). The primary efficacy end point was a composite of cardiovascular death, myocardial infarction, or stroke at 12 months. The primary safety end point was PLATO major bleeding. DM+/CKD+ patients had a higher incidence of the primary end point compared with DM-/CKD- patients (23.3% versus 7.1%; adjusted hazard ratio 2.22; 95% CI 1.88-2.63; P<0.001). Patients with DM+/CKD- and DM-/CKD+ had an intermediate risk profile. The same trend was shown for the individual components of the primary end point and for major bleeding. Compared with clopidogrel, ticagrelor reduced the incidence of the primary end point consistently across subgroups (P-interaction=0.264), but with an increased absolute risk reduction in DM+/CKD+. The effects on major bleeding were also consistent across subgroups (P-interaction=0.288). Conclusions-In acute coronary syndrome patients, a gradient of risk was observed according to the presence or absence of DM and CKD, with patients having both risk factors at the highest risk. Although the ischemic benefit of ticagrelor over clopidogrel was consistent in all subgroups, the absolute risk reduction was greatest in patients with both DM and CKD.
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33.
  • Freitas, Felipe F., et al. (författare)
  • Interplay between flavor anomalies and neutrino properties
  • 2023
  • Ingår i: Physical Review D. - 2470-0010. ; 108:11
  • Tidskriftsartikel (refereegranskat)abstract
    • A minimal extension of the Standard Model (SM) featuring two scalar leptoquarks, an SU(2) doublet with hypercharge 1/6 and a singlet with hypercharge 1/3, is proposed as an economical benchmark model for studies of an interplay between flavor physics and properties of the neutrino sector. The presence of such type of leptoquarks radiatively generates neutrino masses and offers a simultaneous explanation for the current B-physics anomalies involving b→cℓνℓ decays. The model can also accommodate both the muon magnetic moment and the recently reported W-mass anomalies, while complying with the most stringent lepton flavor-violating observables.
  •  
34.
  • Freitas, Felipe F., et al. (författare)
  • Phenomenology at the large hadron collider with deep learning : the case of vector-like quarks decaying to light jets
  • 2022
  • Ingår i: European Physical Journal C. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 82:9
  • Tidskriftsartikel (refereegranskat)abstract
    • In this work, we continue our exploration of TeV-scale vector-like fermion signatures inspired by a Grand Unification scenario based on the trinification gauge group. A particular focus is given to pair-production topologies of vector-like quarks (VLQs) at the LHC, in a multi-jet plus a charged lepton and a missing energy signature. We employ Deep Learning methods and techniques based in evolutive algorithms that optimize hyper-parameters in the neural network construction, whose objective is to maximise the Asimov estimate for distinct VLQ masses. In this article, we consider the implications of an innovative approach by simultaneously combining detector images (also known as jet images) and tabular data containing kinematic information from the final states. With this technique we are able to exclude VLQs, that are specific for the considered model, up to a mass of 800 GeV in both the high-luminosity the Run-III phases of the LHC programme.
  •  
35.
  • Freitas, Felipe F., et al. (författare)
  • Phenomenology of vector-like leptons with Deep Learning at the Large Hadron Collider
  • 2021
  • Ingår i: Journal of High Energy Physics. - 1029-8479. ; 2021:1
  • Tidskriftsartikel (refereegranskat)abstract
    • In this paper, a model inspired by Grand Unification principles featuring three generations of vector-like fermions, new Higgs doublets and a rich neutrino sector at the low scale is presented. Using the state-of-the-art Deep Learning techniques we perform the first phenomenological analysis of this model focusing on the study of new charged vector-like leptons (VLLs) and their possible signatures at CERN’s Large Hadron Collider (LHC). In our numerical analysis we consider signal events for vector-boson fusion and VLL pair production topologies, both involving a final state containing a pair of charged leptons of different flavor and two sterile neutrinos that provide a missing energy. We also consider the case of VLL single production where, in addition to a pair of sterile neutrinos, the final state contains only one charged lepton. We propose a novel method to identify missing transverse energy vectors by comparing the detector response with Monte-Carlo simulated data. All calculated observables are provided as data sets for Deep Learning analysis, where a neural network is constructed, based on results obtained via an evolutive algorithm, whose objective is to maximise either the accuracy metric or the Asimov significance for different masses of the VLL. Taking into account the effect of the three analysed topologies, we have found that the combined significance for the observation of new VLLs at the high-luminosity LHC can range from 5.7σ, for a mass of 1.25 TeV, all the way up to 28σ if the VLL mass is 200 GeV. We have also shown that by the end of the LHC Run-III a 200 GeV VLL can be excluded with a confidence of 8.8 standard deviations. The results obtained show that our model can be probed well before the end of the LHC operations and, in particular, providing important phenomenological information to constrain the energy scale at which new gauge symmetries emergent from the considered Grand Unification picture can be manifest.
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36.
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37.
  • Giannitsis, Evangelos, et al. (författare)
  • Contra
  • 2021
  • Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 42:31, s. 2979-2985
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
  •  
38.
  • Gonçalves, João, et al. (författare)
  • Exploring mixed lepton-quark interactions in non-resonant leptoquark production at the LHC
  • 2023
  • Ingår i: Journal of High Energy Physics. - 1029-8479. ; 2023:11
  • Tidskriftsartikel (refereegranskat)abstract
    • Searches for new physics (NP) at particle colliders typically involve multivariate analysis of kinematic distributions of final state particles produced in a decay of a hypothetical NP resonance. Since the pair-production cross-sections mediated by such resonances are strongly suppressed by the NP scale, this analysis becomes less relevant for NP searches for masses of the BSM resonance above 1 TeV. On the other hand, t-channel processes are less sensitive to the mass of the virtual mediator and therefore larger phase-space can be potentially probed as well as the couplings between the NP particles and the Standard Model fields. The fact that transitions between different generations of quarks and leptons may exist, the potential of the search presented in this article can be used, as a reference guide, to enlarge significantly the scope of searches performed at the LHC to flavour off-diagonal channels, in a theoretically consistent approach. In this work, we study non-resonant production of scalar leptoquarks which have been proposed in the literature to provide a potential avenue for radiative generation of neutrino masses, accommodating as well the existing flavour physics data. Final states involving just two muons at the LHC (μ + μ −), are used as a well-motivated case study.
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39.
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40.
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41.
  • Husted, Steen, et al. (författare)
  • The efficacy of ticagrelor is maintained in women with acute coronary syndromes participating in the prospective, randomized, PLATelet inhibition and patient Outcomes (PLATO) trial
  • 2014
  • Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 35:23, s. 1541-1550
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims The aim of this study was to assess the relationship between sex and clinical outcomes and treatment-related complications in patients with ST-elevation or non-ST-elevation acute coronary syndromes (ACS) randomized to treatment with ticagrelor or clopidogrel in the PLATelet inhibition and patient Outcomes (PLATO) trial. Methods The associations between sex subgroup and the primary composite outcomes, secondary outcomes, and major bleeding endpoints as well as interaction of sex subgroup with treatment effects were analysed using Cox proportional-hazards models. Results Sex was not significantly associated with the probability of the primary composite endpoint [adjusted hazard ratio (HR): 1.02 (0.91-1.16)], or other adverse cardiovascular endpoints. Ticagrelor was similarly more effective than clopidogrel in reducing rates of the primary endpoint in women 11.2 vs. 13.2% [adjusted HR: 0.88 (0.74-1.06)] and men 9.4 vs. 11.1% [adjusted HR: 0.86 (0.76-0.97)] (interaction P-value 0.78), all-cause death in women 5.8 vs. 6.8% [adjusted HR: 0.90 (0.69-1.16)] and men 4.0 vs. 5.7% [adjusted HR: 0.80 (0.67-0.96)] (interaction P-value 0.49), and definite stent thrombosis in women 1.2 vs. 1.4% [adjusted HR: 0.71 (0.36-1.38)] and men 1.4 vs. 2.1% [adjusted HR: 0.63 (0.45-0.89)] (interaction P-value 0.78). The treatments did not differ for PLATO-defined overall major bleeding complications in women [adjusted HR: 1.01 (0.83-1.23)] or men [adjusted HR: 1.10 (0.98-1.24)]. Sex had no significant association with these outcomes (interactions P = 0.43-0.88). Conclusion Female sex is not an independent risk factor for adverse clinical outcomes in moderate-to-high risk ACS patients. Ticagrelor has a similar efficacy and safety profile in men and women.
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42.
  • Husted, Steen, et al. (författare)
  • Ticagrelor Versus Clopidogrel in Elderly Patients With Acute Coronary Syndromes A Substudy From the Prospective Randomized PLATelet Inhibition and Patient Outcomes (PLATO) Trial
  • 2012
  • Ingår i: Circulation. Cardiovascular Quality and Outcomes. - 1941-7713 .- 1941-7705. ; 5:5, s. 680-688
  • Tidskriftsartikel (refereegranskat)abstract
    • Background-Elderly patients with acute coronary syndrome are at high risk of recurrent ischemic events and death, and for both antithrombotic therapy and catheter-based complications. This prespecified analysis investigates the effect and treatment-related complications of ticagrelor versus clopidogrel in elderly patients (>= 75 years of age) with acute coronary syndrome compared with those < 75 years of age. Methods and Results-The association between age and the primary composite outcome, as well as major bleeding were evaluated in the PLATelet inhibition and patient Outcomes (PLATO) trial using Cox proportional hazards. Similar models were used to evaluate the interaction of age with treatment effects. Hazard ratios were adjusted for baseline characteristics. The clinical benefit of ticagrelor over clopidogrel was not significantly different between patients aged >= 75 years of age (n=2878) and those < 75 years of age (n=15744) with respect to the composite of cardiovascular death, myocardial infarction, or stroke (interaction P=0.56), myocardial infarction (P=0.33), cardiovascular death (P=0.47), definite stent thrombosis (P=0.81), or all-cause mortality (P=0.76). No increase in PLATO-defined overall major bleeding with ticagrelor versus clopidogrel was observed in patients aged >= 75 years (hazard ratio, 1.02; 95% confidence interval, 0.82-1.27) or patients aged < 75 years (hazard ratio, 1.04; 95% confidence interval, 0.94-1.15). Dyspnea and ventricular pauses were more common during ticagrelor than clopidogrel treatment, with no evidence of an age-by-treatment interaction. Conclusions-The significant clinical benefit and overall safety of ticagrelor compared with clopidogrel in acute coronary syndrome patients in the PLATO cohort were not found to depend on age. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00391872. (Circ Cardiovasc Qual Outcomes. 2012;5:680-688.)
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43.
  • James, Stefan K., 1964-, et al. (författare)
  • Ticagrelor Versus Clopidogrel in Patients With Acute Coronary Syndromes and a History of Stroke or Transient Ischemic Attack
  • 2012
  • Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 125:23, s. 2914-2921
  • Tidskriftsartikel (refereegranskat)abstract
    • Background-Patients with acute coronary syndromes and history of stroke or transient ischemic attack (TIA) have an increased rate of recurrent cardiac events and intracranial hemorrhages.Methods and Results-We evaluated treatment effects of ticagrelor versus clopidogrel in patients with acute coronary syndrome with and without a history of prior stroke or TIA in the PLATelet inhibition and patient Outcomes (PLATO) trial. Of the 18 624 randomized patients, 1152 (6.2%) had a history of stroke or TIA. Such patients had higher rates of myocardial infarction (11.5% versus 6.0%), death (10.5% versus 4.9%), stroke (3.4% versus 1.2%), and intracranial bleeding (0.8% versus 0.2%) than patients without prior stroke or TIA. Among patients with a history of stroke or TIA, the reduction of the primary composite outcome and total mortality at 1 year with ticagrelor versus clopidogrel was consistent with the overall trial results: 19.0% versus 20.8% (hazard ratio, 0.87; 95% confidence interval, 0.66-1.13; interaction P=0.84) and 7.9% versus 13.0% (hazard ratio, 0.62; 95% confidence interval, 0.42-0.91). The overall PLATO-defined bleeding rates were similar: 14.6% versus 14.9% (hazard ratio, 0.99; 95% confidence interval, 0.71-1.37), and intracranial bleeding occurred infrequently (4 versus 4 cases, respectively).Conclusions-Patients with acute coronary syndrome with a prior history of ischemic stroke or TIA had higher rates of clinical outcomes than patients without prior stroke or TIA. However, the efficacy and bleeding results of ticagrelor in these high-risk patients were consistent with the overall trial population, with a favorable clinical net benefit and associated impact on mortality.
  •  
44.
  • James, Stefan K., et al. (författare)
  • Ticagrelor versus clopidogrel in patients with acute coronary syndromes intended for non-invasive management : substudy from prospective randomised PLATelet inhibition and patient Outcomes (PLATO) trial
  • 2011
  • Ingår i: The BMJ. - : BMJ. - 1756-1833. ; 342, s. d3527-
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective To evaluate efficacy and safety outcomes in patients in the PLATelet inhibition and patient Outcomes (PLATO) trial who at randomisation were planned for a non-invasive treatment strategy. Design Pre-specified analysis of pre-randomisation defined subgroup of prospective randomised clinical trial. Setting 862 centres in 43 countries. Participants 5216 (28%) of 18 624 patients admitted to hospital for acute coronary syndrome who were specified as planned for non-invasive management. Interventions Randomised treatment with ticagrelor (n=2601) versus clopidogrel (2615). Main outcome measurements Primary composite end point of cardiovascular death, myocardial infarction, and stroke; their individual components; and PLATO defined major bleeding during one year. Results 2183 (41.9%) patients had coronary angiography during their initial hospital admission, 1065 (20.4%) had percutaneous coronary intervention, and 208 (4.0%) had coronary artery bypass surgery. Cumulatively, 3143 (60.3%) patients had been managed non-invasively by the end of follow-up. The incidence of the primary end point was lower with ticagrelor than with clopidogrel (12.0% (n=295) v 14.3% (346); hazard ratio 0.85, 95% confidence interval 0.73 to 1.00; P=0.04). Overall mortality was also lower (6.1% (147) v 8.2% (195); 0.75, 0.61 to 0.93; P=0.01). The incidence of total major bleeding (11.9% (272) v 10.3% (238); 1.17, 0.98 to 1.39; P=0.08) and non-coronary artery bypass grafting related major bleeding (4.0% (90) v 3.1% (71); 1.30, 0.95 to 1.77; P=0.10) was numerically higher with ticagrelor than with clopidogrel. Conclusions In patients with acute coronary syndrome initially intended for non-invasive management, the benefits of ticagrelor over clopidogrel were consistent with those from the overall PLATO results, indicating the broad benefits of P2Y12 inhibition with ticagrelor regardless of intended management strategy.
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45.
  •  
46.
  • Kohli, Payal, et al. (författare)
  • Reduction in First and Recurrent Cardiovascular Events with Ticagrelor Compared with Clopidogrel in the PLATO Study
  • 2013
  • Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 127:6, s. 673-
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND:We sought to evaluate the effect of potent platelet inhibition following acute coronary syndrome on total (i.e. first and recurrent) occurrences of any of the primary outcome events (e.g. cardiovascular death, myocardial infarction, and stroke) as well as on other ischemic events, such as urgent revascularization, (severe) recurrent ischemia (SRI/RI), transient ischemic attacks (TIA) and arterial thrombotic events (ATE).METHODS AND RESULTS:In the PLATelet inhibition and patient Outcomes (PLATO) study, 18,624 patients presenting with acute coronary syndromes randomly received ticagrelor (N=9333) or clopidogrel (N=9291). Cox proportional hazard models were used to calculate time to first event and hazard ratios. Total events were compared using a Poisson regression model and time to second event or death was calculated with the Wei Lin Weissfeld method. Patients randomized to ticagrelor had 1057 total primary endpoint events vs. 1225 for patients on clopidogrel (rate ratio=0.86, 95% CI 0.79-0.93, p=0.003). The number of additional events was numerically lower for ticagrelor (189 vs. 205, p=0.40), resulting in a hazard for time to second event/death of 0.80 (95% CI 0.70-0.90, p<0.001) and a number needed to treat of 54. For CVD/MI/Stroke/SRI/RI/TIA/ATE, total events were fewer with ticagrelor (2030 vs. 2290, rate ratio 0.88, 95% CI 0.82-0.95, p<0.001), with fewer recurrent events with ticagrelor (740 vs. 834, p=0.01) and a highly significant concurrent reduction in hazard for time to second event or death of 0.83 (95% CI 0.75-0.91, p<0.001). Recurrent PLATO major or TIMI major non-CABG bleeding events were infrequent and not different between the two therapies (p=0.96 and 0.38, respectively).CONCLUSIONS: In PLATO, treatment with ticagrelor compared with clopidogrel resulted in a reduction in total events, including first and subsequent recurrent cardiovascular events, when compared to clopidogrel. These types of analyses demonstrate an even greater absolute benefit of ticagrelor over clopidogrel than previously reported.CLINICAL TRIAL REGISTRATION INFORMATION:http://www.clinicaltrials.gov. Identifier: NCT00391872.
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47.
  • Krychtiuk, Konstantin A., et al. (författare)
  • Biomarkers of coagulation and fibrinolysis in acute myocardial infarction : a joint position paper of the Association for Acute Cardio Vascular Care and the European Society of Cardiology Working Group on Thrombosis
  • 2021
  • Ingår i: European Heart Journal. - : Oxford University Press. - 2048-8726 .- 2048-8734. ; 10:3, s. 343-355
  • Forskningsöversikt (refereegranskat)abstract
    • The formation of a thrombus in an epicardial artery may result in an acute myocardial infarction (AMI). Despite major advances in acute treatment using network approaches to allocate patients to timely reperfusion and optimal antithrombotic treatment, patients remain at high risk for thrombotic complications. Ongoing activation of the coagulation system as well as thrombin-mediated platelet activation may both play a crucial role in this context. Whether measurement of circulating biomarkers of coagulation and fibrinolysis could be useful for risk stratification in secondary prevention is currently not fully understood. In addition, measurement of such biomarkers could be helpful to identify thrombus formation as the leading mechanism for AMI. The introduction of biomarkers of myocardial injury such as high-sensitivity cardiac troponins made rule-out of AMI even more precise. However, elevated markers of myocardial injury cannot provide proof of a type 1 AMI, let alone thrombus formation. The combined measurement of markers of myocardial injury with biomarkers reflecting ongoing thrombus formation might be helpful for the fast and correct diagnosis of an atherothrombotic type 1 AMI. This position paper gives an overview of the current knowledge and possible role of biomarkers of coagulation and fibrinolysis for the diagnosis of AMI, risk stratification, and individualized treatment strategies in patients with AMI.
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48.
  • Lowenstern, Angela, et al. (författare)
  • Platelet-related biomarkers and their response to inhibition with aspirin and p2y12-receptor antagonists in patients with acute coronary syndrome
  • 2017
  • Ingår i: Journal of Thrombosis and Thrombolysis. - : Springer Science and Business Media LLC. - 0929-5305 .- 1573-742X. ; 44:2, s. 145-153
  • Tidskriftsartikel (refereegranskat)abstract
    • The PLATelet inhibition and patient Outcomes (PLATO) trial showed that treatment with ticagrelor reduced the rate of death due to vascular causes, myocardial infarction and stroke when compared to clopidogrel in patients with ST-elevation or non-ST-elevation acute coronary syndrome (ACS). While the comparative benefit of ticagrelor over clopidogrel increased over time, event rates accrued in both groups during the study period. The purpose of our biomarker-based exploratory analysis was to determine whether long-term platelet inhibition may be associated with platelet adaptation. A sample of 4000 participants from the PLATO trial also consented to participate in a prospectively designed biomarker substudy. Blood samples were procured at baseline, immediately prior to hospital discharge and at 1 and 6 months. Markers of platelet activity, including platelet count, serum CD40-ligand and soluble P-selectin were analyzed. Mean levels were compared at discharge, 1 and 6 months following study drug initiation-first for all patients and subsequently stratified by treatment group. A linear mixed model was used to estimate the short-term change rate (baseline to 1 month) and long-term change rate (1-6 months) for each biomarker. A Cox proportional hazards model was used to calculate hazard ratios for each change in biomarker over the two time periods examined: baseline to 1 month and 1 to 6 months. Prior to randomized treatment (baseline), sCD40 ligand and sP-selectin levels were elevated above the normal range of the assay (0.39 and 33.5 A μg/L, respectively). The mean level of each biomarker was significantly different at 1 month compared to baseline (p < 0.0001). When stratified by treatment group, at 1 month patients treated with ticagrelor had a larger increase in platelet count compared to those treated with clopidogrel (p < 0.0001). Similarly, when comparing biomarker levels for all patients at 6 months with those at 1 month, each differed significantly (p < 0.05). There was no significant difference between treatment groups during this time period. The rate of change for both platelet count and sP-selectin were significantly different between baseline and 1 month when compared to the 1 to 6-month time period (p < 0.0001). When comparing treatment groups, the rate of increase in platelets from baseline to 1 month was greater for patients treated with ticagrelor (p < 0.0001). This was no longer observed in the 1 to 6-month interval. Using a Cox proportional hazard model, the increase in platelet count from 1 to 6 months was associated with ischemic-thrombotic events, while sCD40 ligand decrease from 1 to 6 months was associated with hemorrhagic events. There were no differences between treatment groups for the associations with clinical endpoints. Dynamic changes in platelet count, sCD-40 ligand and sP-selectin occur over time among patients with ACS. Platelet-directed therapy with a P2Y12 receptor inhibitor in combination with aspirin modestly impacts the expression of these biomarkers. Platelet count and sCD40 ligand may offer modest overall predictive value for future ischemic-thrombotic or hemorrhagic clinical events, respectively. The existence of a platelet adaptome and its overall clinical significance among patients at risk for thrombotic events will require a more in-depth and platelet-biology specific investigation.
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49.
  • Lundström, Jens, 1981-, et al. (författare)
  • Halmstad intelligent home - Capabilities and opportunities
  • 2016
  • Ingår i: Internet of Things Technologies for HealthCare. - Berlin : Springer Berlin/Heidelberg. - 9783319512334 ; , s. 9-15
  • Konferensbidrag (refereegranskat)abstract
    • Research on intelligent environments, such as smart homes, concerns the mechanisms that intelligently orchestrate the pervasive technical infrastructure in the environment. However, significant challenges are to build, configure, use and maintain these systems. Providing personalized services while preserving the privacy of the occupants is also difficult. As an approach to facilitate research in this area, this paper presents the Halmstad Intelligent Home and a novel approach for multioccupancy detection utilizing the presented environment. This paper also presents initial results and ongoing work. © ICST Institute for Computer Sciences, Social Informatics and Telecommunications Engineering 2016.
  •  
50.
  • Mahaffey, Kenneth W., et al. (författare)
  • Ticagrelor Effects on Myocardial Infarction and the Impact of Event Adjudication in the PLATO (Platelet Inhibition and Patient Outcomes) Trial
  • 2014
  • Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 63:15, s. 1493-1499
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives This study sought to report the treatment effect of ticagrelor on myocardial infarction (MI) and the strategy for and impact of event adjudication in the PLATO (Platelet Inhibition and Patient Outcomes) trial. Background In PLATO, ticagrelor reduced cardiovascular death, MI, or stroke in patients with acute coronary syndromes (ACS). Methods A CIinical events committee (CEC) prospectively defined and adjudicated all suspected MI events, on the basis of events reported by investigators and by triggers on biomarkers. Treatment comparisons used CEC-adjudicated data, and per protocol, exCIuded silent MI. Results Overall, 1,299 (610 ticagrelor, 689 CIopidogrel) MIs reported by the CEC occurred during the trial. Of these, 1,097 (504 ticagrelor, 593 CIopidogrel) contributed to the primary composite endpoint. Site investigators reported 1,198 (580 ticagrelor, 618 CIopidogrel) MIs. Ticagrelor significantly reduced overall MI rates (12-month CEC-adjudicated Kaplan-Meier rates: 5.8% ticagrelor, 6.9% CIopidogrel; hazard ratio [HR]: 0.84; 95% confidence interval [CI]: 0.75 to 0.95). Nonprocedural MI (HR: 0.86; 95% CI: 0.74 to 1.01) and MI related to percutaneous coronary intervention or stent thrombosis tended to be lower with ticagrelor. MIs related to coronary artery bypass graft surgery were few, but numerical excess was observed in patients assigned ticagrelor. Analyses of overall MIs using investigator-reported data showed similar results but did not reach statistical significance (HR: 0.88; 95% CI: 0.78 to 1.00). ConCIusions In patients with ACS, ticagrelor significantly reduced the incidence of MI compared with CIopidogrel, with consistent results across most MI subtypes. CEC procedures identified more MI endpoints compared with site investigators. (A Comparison of Ticagrelor [AZD6140] and CIopidogrel in Patients With Acute Coronary Syndrome [PLATO]; NCT00391872)
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