| 1. |
- Bousquet, Jean, et al.
(författare)
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Allergic Rhinitis and its Impact on Asthma (ARIA) Phase 4 (2018) : Change management in allergic rhinitis and asthma multimorbidity using mobile technology
- 2019
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Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier. - 0091-6749 .- 1097-6825. ; 143:3, s. 864-879
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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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| 2. |
- Menditto, Enrica, et al.
(författare)
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Adherence to treatment in allergic rhinitis using mobile technology : The MASK Study
- 2019
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Ingår i: Clinical and Experimental Allergy. - : WILEY. - 0954-7894 .- 1365-2222. ; 49:4, s. 442-460
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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. |
- Bousquet, J. Jean, et al.
(författare)
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Next-generation ARIA care pathways for rhinitis and asthma : a model for multimorbid chronic diseases
- 2019
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Ingår i: Clinical and Translational Allergy. - : BMC. - 2045-7022. ; 9
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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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| 4. |
- Bousquet, Jean, et al.
(författare)
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ARIA digital anamorphosis : Digital transformation of health and care in airway diseases from research to practice
- 2021
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Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : John Wiley & Sons. - 0105-4538 .- 1398-9995. ; 76:1, s. 168-190
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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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| 5. |
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| 6. |
- Smid, Marcel, et al.
(författare)
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Breast cancer genome and transcriptome integration implicates specific mutational signatures with immune cell infiltration
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- A recent comprehensive whole genome analysis of a large breast cancer cohort was used to link known and novel drivers and substitution signatures to the transcriptome of 266 cases. Here, we validate that subtype-specific aberrations show concordant expression changes for, for example, TP53, PIK3CA, PTEN, CCND1 and CDH1. We find that CCND3 expression levels do not correlate with amplification, while increased GATA3 expression in mutant GATA3 cancers suggests GATA3 is an oncogene. In luminal cases the total number of substitutions, irrespective of type, associates with cell cycle gene expression and adverse outcome, whereas the number of mutations of signatures 3 and 13 associates with immune-response specific gene expression, increased numbers of tumour-infiltrating lymphocytes and better outcome. Thus, while earlier reports imply that the sheer number of somatic aberrations could trigger an immune-response, our data suggests that substitutions of a particular type are more effective in doing so than others.
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| 7. |
- Smid, Marcel, et al.
(författare)
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The circular RNome of primary breast cancer
- 2019
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Ingår i: Genome Research. - : Cold Spring Harbor Laboratory. - 1088-9051 .- 1549-5469. ; 29:3, s. 356-366
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Tidskriftsartikel (refereegranskat)abstract
- Circular RNAs (circRNAs) are a class of RNAs that is under increasing scrutiny, although their functional roles are debated. We analyzed RNA-seq data of 348 primary breast cancers and developed a method to identify circRNAs that does not rely on unmapped reads or known splice junctions. We identified 95,843 circRNAs, of which 20,441 were found recurrently. Of the circRNAs that match exon boundaries of the same gene, 668 showed a poor or even negative (R <0.2) correlation with the expression level of the linear gene. In silico analysis showed only a minority (8.5%) of circRNAs could be explained by known splicing events. Both these observations suggest that specific regulatory processes for circRNAs exist. We confirmed the presence of circRNAs of CNOT2, CREBBP, and RERE in an independent pool of primary breast cancers. We identified circRNA profiles associated with subgroups of breast cancers and with biological and clinical features, such as amount of tumor lymphocytic infiltrate and proliferation index. siRNA-mediated knockdown of circCNOT2 was shown to significantly reduce viability of the breast cancer cell lines MCF-7 and BT-474, further underlining the biological relevance of circRNAs. Furthermore, we found that circular, and not linear, CNOT2 levels are predictive for progression-free survival time to aromatase inhibitor (AI) therapy in advanced breast cancer patients, and found that circCNOT2 is detectable in cell-free RNA from plasma. We showed that circRNAs are abundantly present, show characteristics of being specifically regulated, are associated with clinical and biological properties, and thus are relevant in breast cancer.
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| 8. |
- Davies, Helen R., et al.
(författare)
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HRDetect is a predictor of BRCA1 and BRCA2 deficiency based on mutational signatures
- 2017
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1546-170X .- 1078-8956. ; 23:4, s. 517-525
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Tidskriftsartikel (refereegranskat)abstract
- Approximately 1-5% of breast cancers are attributed to inherited mutations in BRCA1 or BRCA2 and are selectively sensitive to poly(ADP-ribose) polymerase (PARP) inhibitors. In other cancer types, germline and/or somatic mutations in BRCA1 and/or BRCA2 (BRCA1/BRCA2) also confer selective sensitivity to PARP inhibitors. Thus, assays to detect BRCA1/BRCA2-deficient tumors have been sought. Recently, somatic substitution, insertion/deletion and rearrangement patterns, or 'mutational signatures', were associated with BRCA1/BRCA2 dysfunction. Herein we used a lasso logistic regression model to identify six distinguishing mutational signatures predictive of BRCA1/BRCA2 deficiency. A weighted model called HRDetect was developed to accurately detect BRCA1/BRCA2-deficient samples. HRDetect identifies BRCA1/BRCA2-deficient tumors with 98.7% sensitivity (area under the curve (AUC) = 0.98). Application of this model in a cohort of 560 individuals with breast cancer, of whom 22 were known to carry a germline BRCA1 or BRCA2 mutation, allowed us to identify an additional 22 tumors with somatic loss of BRCA1 or BRCA2 and 47 tumors with functional BRCA1/BRCA2 deficiency where no mutation was detected. We validated HRDetect on independent cohorts of breast, ovarian and pancreatic cancers and demonstrated its efficacy in alternative sequencing strategies. Integrating all of the classes of mutational signatures thus reveals a larger proportion of individuals with breast cancer harboring BRCA1/BRCA2 deficiency (up to 22%) than hitherto appreciated (∼1-5%) who could have selective therapeutic sensitivity to PARP inhibition.
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| 9. |
- Hoshino, Ayuko, et al.
(författare)
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Tumour exosome integrins determine organotropic metastasis
- 2015
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Ingår i: Nature. - : NATURE PUBLISHING GROUP. - 0028-0836 .- 1476-4687. ; 527:7578, s. 329-
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Tidskriftsartikel (refereegranskat)abstract
- Ever since Stephen Pagets 1889 hypothesis, metastatic organotropism has remained one of cancers greatest mysteries. Here we demonstrate that exosomes from mouse and human lung-, liver-and brain-tropic tumour cells fuse preferentially with resident cells at their predicted destination, namely lung fibroblasts and epithelial cells, liver Kupffer cells and brain endothelial cells. We show that tumour-derived exosomes uptaken by organ-specific cells prepare the pre-metastatic niche. Treatment with exosomes from lung-tropic models redirected the metastasis of bone-tropic tumour cells. Exosome proteomics revealed distinct integrin expression patterns, in which the exosomal integrins alpha(6)beta(4) and alpha(6)beta(1) were associated with lung metastasis, while exosomal integrin alpha(v)beta(5) was linked to liver metastasis. Targeting the integrins alpha(6)beta(4) and alpha(v)beta(5) decreased exosome uptake, as well as lung and liver metastasis, respectively. We demonstrate that exosome integrin uptake by resident cells activates Src phosphorylation and pro-inflammatory S100 gene expression. Finally, our clinical data indicate that exosomal integrins could be used to predict organ-specific metastasis.
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| 10. |
- Nik-Zainal, Serena, et al.
(författare)
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Landscape of somatic mutations in 560 breast cancer whole-genome sequences
- 2016
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 534:7605, s. 47-54
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Tidskriftsartikel (refereegranskat)abstract
- We analysed whole-genome sequences of 560 breast cancers to advance understanding of the driver mutations conferring clonal advantage and the mutational processes generating somatic mutations. We found that 93 protein-coding cancer genes carried probable driver mutations. Some non-coding regions exhibited high mutation frequencies, but most have distinctive structural features probably causing elevated mutation rates and do not contain driver mutations. Mutational signature analysis was extended to genome rearrangements and revealed twelve base substitution and six rearrangement signatures. Three rearrangement signatures, characterized by tandem duplications or deletions, appear associated with defective homologous-recombination-based DNA repair: one with deficient BRCA1 function, another with deficient BRCA1 or BRCA2 function, the cause of the third is unknown. This analysis of all classes of somatic mutation across exons, introns and intergenic regions highlights the repertoire of cancer genes and mutational processes operating, and progresses towards a comprehensive account of the somatic genetic basis of breast cancer.
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| 11. |
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| 12. |
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| 13. |
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| 14. |
- Bedard, Annabelle, et al.
(författare)
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Mobile technology offers novel insights into the control and treatment of allergic rhinitis : The MASK study
- 2019
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Ingår i: Journal of Allergy and Clinical Immunology. - : MOSBY-ELSEVIER. - 0091-6749 .- 1097-6825. ; 144:1, s. 135-143
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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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| 15. |
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| 16. |
- Halonen, Jaana I., et al.
(författare)
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A call for urgent action to safeguard our planet and our health in line with the helsinki declaration
- 2021
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Ingår i: Environmental Research. - : Elsevier. - 0013-9351 .- 1096-0953. ; 193
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Tidskriftsartikel (refereegranskat)abstract
- In 2015, the Rockefeller Foundation-Lancet Commission launched a report introducing a novel approach called Planetary Health and proposed a concept, a strategy and a course of action. To discuss the concept of Planetary Health in the context of Europe, a conference entitled: "Europe That Protects: Safeguarding Our Planet, Safeguarding Our Health" was held in Helsinki in December 2019. The conference participants concluded with a need for action to support Planetary Health during the 2020s. The Helsinki Declaration emphasizes the urgency to act as scientific evidence shows that human activities are causing climate change, biodiversity loss, land degradation, overuse of natural resources and pollution. They threaten the health and safety of human kind.Global, regional, national, local and individual initiatives are called for and multidisciplinary and multisectorial actions and measures are needed. A framework for an action plan is suggested that can be modified for local needs. Accordingly, a shift from fragmented approaches to policy and practice towards systematic actions will promote human health and health of the planet. Systems thinking will feed into conserving nature and biodiversity, and into halting climate change.The Planetary Health paradigm ‒ the health of human civilization and the state of natural systems on which it depends ‒ must become the driver for all policies.
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| 17. |
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| 18. |
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| 19. |
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| 20. |
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| 21. |
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| 22. |
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| 23. |
- Sousa-Pinto, Bernardo, et al.
(författare)
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Comparison of rhinitis treatments using MASK-air® data and considering the minimal important difference
- 2022
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Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : John Wiley & Sons. - 0105-4538 .- 1398-9995. ; 77:10, s. 3002-3014
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Tidskriftsartikel (refereegranskat)abstract
- Background: Different treatments exist for allergic rhinitis (AR), including pharmacotherapy and allergen immunotherapy (AIT), but they have not been compared using direct patient data (i.e., “real-world data”). We aimed to compare AR pharmacological treatments on (i) daily symptoms, (ii) frequency of use in co-medication, (iii) visual analogue scales (VASs) on allergy symptom control considering the minimal important difference (MID) and (iv) the effect of AIT.Methods: We assessed the MASK-air® app data (May 2015–December 2020) by users self-reporting AR (16–90 years). We compared eight AR medication schemes on reported VAS of allergy symptoms, clustering data by the patient and controlling for confounding factors. We compared (i) allergy symptoms between patients with and without AIT and (ii) different drug classes used in co-medication.Results: We analysed 269,837 days from 10,860 users. Most days (52.7%) involved medication use. Median VAS levels were significantly higher in co-medication than in monotherapy (including the fixed combination azelastine-fluticasone) schemes. In adjusted models, azelastine-fluticasone was associated with lower average VAS global allergy symptoms than all other medication schemes, while the contrary was observed for oral corticosteroids. AIT was associated with a decrease in allergy symptoms in some medication schemes. A difference larger than the MID compared to no treatment was observed for oral steroids. Azelastine-fluticasone was the drug class with the lowest chance of being used in co-medication (adjusted OR = 0.75; 95% CI = 0.71–0.80).Conclusion: Median VAS levels were higher in co-medication than in monotherapy. Patients with more severe symptoms report a higher treatment, which is currently not reflected in guidelines.
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| 24. |
- Sousa-Pinto, Bernardo, et al.
(författare)
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Consistent trajectories of rhinitis control and treatment in 16,177 weeks : the MASK-air® longitudinal study
- 2023
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Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : John Wiley & Sons. - 0105-4538 .- 1398-9995. ; 78:4, s. 968-983
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Data from mHealth apps can provide valuable information on rhinitis control and treatment patterns. However, in MASK-air®, these data have only been analyzed cross-sectionally, without considering the changes of symptoms over time. We analyzed data from MASK-air® longitudinally, clustering weeks according to reported rhinitis symptoms. Methods: We analyzed MASK-air® data, assessing the weeks for which patients had answered a rhinitis daily questionnaire on all 7 days. We firstly used k-means clustering algorithms for longitudinal data to define clusters of weeks according to the trajectories of reported daily rhinitis symptoms. Clustering was applied separately for weeks when medication was reported or not. We compared obtained clusters on symptoms and rhinitis medication patterns. We then used the latent class mixture model to assess the robustness of results. Results: We analyzed 113,239 days (16,177 complete weeks) from 2590 patients (mean age ± SD = 39.1 ± 13.7 years). The first clustering algorithm identified ten clusters among weeks with medication use: seven with low variability in rhinitis control during the week and three with highly-variable control. Clusters with poorly-controlled rhinitis displayed a higher frequency of rhinitis co-medication, a more frequent change of medication schemes and more pronounced seasonal patterns. Six clusters were identified in weeks when no rhinitis medication was used, displaying similar control patterns. The second clustering method provided similar results. Moreover, patients displayed consistent levels of rhinitis control, reporting several weeks with similar levels of control. Conclusions: We identified 16 patterns of weekly rhinitis control. Co-medication and medication change schemes were common in uncontrolled weeks, reinforcing the hypothesis that patients treat themselves according to their symptoms.
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| 25. |
- Sousa-Pinto, Bernardo, et al.
(författare)
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Development and validation of combined symptom-medication scores for allergic rhinitis*
- 2022
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Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : John Wiley & Sons. - 0105-4538 .- 1398-9995. ; 77:7, s. 2147-2162
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Tidskriftsartikel (refereegranskat)abstract
- Background: Validated combined symptom-medication scores (CSMSs) are needed to investigate the effects of allergic rhinitis treatments. This study aimed to use real-life data from the MASK-air® app to generate and validate hypothesis- and data-driven CSMSs.Methods: We used MASK-air® data to assess the concurrent validity, test-retest reliability and responsiveness of one hypothesis-driven CSMS (modified CSMS: mCSMS), one mixed hypothesis- and data-driven score (mixed score), and several data-driven CSMSs. The latter were generated with MASK-air® data following cluster analysis and regression models or factor analysis. These CSMSs were compared with scales measuring (i) the impact of rhinitis on work productivity (visual analogue scale [VAS] of work of MASK-air®, and Work Productivity and Activity Impairment: Allergy Specific [WPAI-AS]), (ii) quality-of-life (EQ-5D VAS) and (iii) control of allergic diseases (Control of Allergic Rhinitis and Asthma Test [CARAT]).Results: We assessed 317,176 days of MASK-air® use from 17,780 users aged 16-90 years, in 25 countries. The mCSMS and the factor analyses-based CSMSs displayed poorer validity and responsiveness compared to the remaining CSMSs. The latter displayed moderate-to-strong correlations with the tested comparators, high test-retest reliability and moderate-to-large responsiveness. Among data-driven CSMSs, a better performance was observed for cluster analyses-based CSMSs. High accuracy (capacity of discriminating different levels of rhinitis control) was observed for the latter (AUC-ROC = 0.904) and for the mixed CSMS (AUC-ROC = 0.820).Conclusion: The mixed CSMS and the cluster-based CSMSs presented medium-high validity, reliability and accuracy, rendering them as candidates for primary endpoints in future rhinitis trials.
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| 26. |
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| 27. |
- Amin, Kawa, et al.
(författare)
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Inflammatory cell and epithelial characteristics of perennial allergic and nonallergic rhinitis with a symptom history of 1 to 3 years' duration
- 2001
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Ingår i: Clinical and Experimental Allergy. - : Elsevier BV. - 0954-7894 .- 1365-2222. ; 107:2, s. 249-257
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Perennial rhinitis is an inflammatory condition of the mucosal lining of the nose that may be caused by allergic and nonallergic mechanisms. OBJECTIVE: We sought to characterize the cellular pattern and structural changes in the nasal mucous membrane of patients with perennial rhinitis and compare them with those of control subjects. METHODS: Biopsy specimens were obtained from 27 patients with perennial allergic rhinitis (PAR), from 12 patients with perennial nonallergic rhinitis (PNAR) with eosinophils present in the nasal smear, and from 6 control subjects without rhinitis. In 10 of 27 patients with PAR who were also allergic to pollen, biopsy specimens were taken within the respective season (PARseason). In the other 17 patients, the biopsy was taken outside the pollen season (PARoutside season). Inflammatory cells were identified by using mAbs to their unique granular proteins. RESULTS: The characteristic feature of perennial rhinitis was the accumulation of activated (degranulated) mast cells and eosinophils in the nasal mucosa. The tissue eosinophil/neutrophil ratio was higher, and the loss of epithelial integrity was greater in all patient groups compared with the control subjects. The extent of epithelial damage was significantly larger in patients in the PARseason group compared with that in the PARoutside season and PNAR groups, which did not significantly differ from each other in this respect. The number of eosinophils and mast cells was higher in the PNAR group compared with the PAR groups. In all patient groups, the number of eosinophils correlated with the loss of epithelial integrity. The number of mast cells did not correlate with the extent of epithelial damage nor did the number of neutrophils, except in patients in the PARseason group. CONCLUSION: The accumulation of eosinophils and mast cells, as well as loss of epithelial integrity, was characteristic for perennial rhinitis. Loss of epithelial integrity in the nasal mucosa may be a consequence of the activity of accumulated eosinophils.
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| 28. |
- Garcia-Larsen, Vanessa, et al.
(författare)
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Is fruit and vegetable intake associated with asthma or chronic rhino-sinusitis in European adults? : Results from the Global Allergy and Asthma Network of Excellence (GA(2)LEN) Survey
- 2017
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Ingår i: Clinical and Translational Allergy. - : BIOMED CENTRAL LTD. - 2045-7022. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Background: Fruits and vegetables are rich in compounds with proposed antioxidant, anti-allergic and anti-inflammatory properties, which could contribute to reduce the prevalence of asthma and allergic diseases. Objective: We investigated the association between asthma, and chronic rhino-sinusitis (CRS) with intake of fruits and vegetables in European adults. Methods: A stratified random sample was drawn from the Global Allergy and Asthma Network of Excellence (GA(2)LEN) screening survey, in which 55,000 adults aged 15-75 answered a questionnaire on respiratory symptoms. Asthma score (derived from self-reported asthma symptoms) and CRS were the outcomes of interest. Dietary intake of 22 subgroups of fruits and vegetables was ascertained using the internationally validated GA(2)LEN Food Frequency Questionnaire. Adjusted associations were examined with negative binomial and multiple regressions. Simes procedure was used to control for multiple testing. Results: A total of 3206 individuals had valid data on asthma and dietary exposures of interest. 22.8% reported having at least 1 asthma symptom (asthma score >= 1), whilst 19.5% had CRS. After adjustment for potential confounders, asthma score was negatively associated with intake of dried fruits (beta-coefficient -2.34;95% confidence interval [CI] -4.09,-0.59), whilst CRS was statistically negatively associated with total intake of fruits (OR 0.73; 95% CI 0.55, 0.97). Conversely, a positive association was observed between asthma score and alliums vegetables (adjusted beta-coefficient 0.23; 95% CI 0.06, 0.40). None of these associations remained statistically significant after controlling for multiple testing. Conclusion and clinical relevance: There was no consistent evidence for an association of asthma or CRS with fruit and vegetable intake in this representative sample of European adults.
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| 29. |
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| 30. |
- Hoseiny Farahabady, M. Reza, et al.
(författare)
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Data-Intensive Workload Consolidation in Serverless (Lambda/FaaS) Platforms
- 2021
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Ingår i: 2021 IEEE 20TH INTERNATIONAL SYMPOSIUM ON NETWORK COMPUTING AND APPLICATIONS (NCA). - : Institute of Electrical and Electronics Engineers (IEEE). - 9781665495509 ; , s. 1-8
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Konferensbidrag (refereegranskat)abstract
- A significant amount of research studies in the past years has been devoted on developing efficient mechanisms to control the level of degradation among consolidate workloads in a shared platform. Workload consolidation is a promising feature that is employed by most service providers to reduce the total operating costs in traditional computing systems [1]-[3]. Serverless paradigm - also known as Function as a Service, FaaS, and Lambda - recently emerged as a new virtualization run-time model that disentangles the traditional state of applications' users from the burden of provisioning physical computing resources, leaving the difficulty of providing the adequate resource capacity on the service provider's side. This paper focuses on a number of challenges associated with workload consolidation when a serverless platform is expected to execute several data-intensive functional units. Each functional unit is considered to be the atomic component that reacts to a stream of input data. A serverless application in the proposed model is composed of a series of functional units. Through a systematic approach, we highlight the main challenges for devising an efficient workload consolidation process in a data-intensive serverless platform. To this end, we first study the performance interference among multiple workloads to obtain the capacity of last level cache (LLC). We show how such contention among workloads can lead to a significant throughput degradation on a single physical server. We expand our investigation into a general case with the aim to prevent the total throughput never falling below a predefined utilization level. Based on the empirical results, we develop a consolidation model and then design a computationally efficient controller to optimize the throughput degradation among a platform consists fs multiple machines. The performance evaluation is conducted using modern workloads inspired by data management services, and data analytic benchmark tools in our in-house four node platform showing the efficiency of the proposed solution to mitigate the QoS violation rate for high priority applications by 90% while can enhance the normalized throughput usage of disk devices by 39%.
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| 31. |
- Hoseinyfarahabady, M. R., et al.
(författare)
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A Dynamic Resource Controller for Resolving Quality of Service Issues in Modern Streaming Processing Engines
- 2020
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Ingår i: 2020 IEEE 19th International Symposium on Network Computing and Applications, NCA 2020. - : Institute of Electrical and Electronics Engineers (IEEE). - 9781728183268
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Konferensbidrag (refereegranskat)abstract
- Devising an elastic resource allocation controller of data analytical applications in virtualized data-center has received a great attention recently, mainly due to the fact that even a slight performance improvement can translate to huge monetary savings in practical large-scale execution. Apache Flink is among modern streamed data processing run-times that can provide both low latency and high throughput computation in to execute processing pipelines over high-volume and high-velocity data-items under tight latency constraints. However, a yet to be answered challenge in a large-scale platform with tens of worker nodes is how to resolve the run-time violation in the quality of service (QoS) level in a multi-tenant data streaming platforms, particularly when the amount of workload generated by different users fluctuates. Studies showed that a static resource allocation algorithm (round-robin), which is used by default in Apache Flink, suffer from lack of responsiveness to sudden traffic surges happening unpredictably during the run-time. In this paper, we address the problem of resource management in a Flink platform for ensuring different QoS enforcement levels in a platform with shared computing resources. The proposed solution applies theoretical principals borrowed from close-loop control theory to design a CPU and memory adjustment mechanism with the primary goal to fulfill the different QoS levels requested by submitted applications while the resource interference is considered as the critical performance-limiting factor. The performance evaluation is carried out by comparing the proposed resource allocation mechanism with two static heuristics (round robin and class-based weighted fair queuing) in a 80-core cluster under multiple traffic patterns resembling sudden changes in the incoming workloads of low-priory streaming applications. The experimental results confirm the stability of the proposed controller to regulate the underlying platform resources to smoothly follow the target values (QoS violation rates). Particularly, the proposed solution can achieve higher efficiency compared to the other heuristics by reducing the response-time of high priority applications by 53% while maintaining the enforced QoS levels during the burst traffic periods.
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| 32. |
- Hoseinyfarahabady, M. R., et al.
(författare)
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Auto-tuning of large-scale iterative operations on modern streaming platforms
- 2020
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Ingår i: CoNEXT 2020 - Proceedings of the 16th International Conference on Emerging Networking EXperiments and Technologies. - New York, NY, USA : Association for Computing Machinery (ACM). - 9781450379489 ; , s. 554-555
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Konferensbidrag (refereegranskat)abstract
- As more analytical applications today require real-time processing over high volume data streams, finding an optimal implementation of traditional algorithms which possess iterative computations are gaining popularity and become crucial in most commercial contexts, particularly in edge processing and cloud applications. In this work, we propose an auto-tuning mechanism for enhancing the run-time performance of real-world iterative and cyclic stream processing applications (Multi-Join Operation as the study case) to correctly adjust the right performance bounds for workloads with different characteristics and data-sizes running on modern streaming data processing platform.
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| 33. |
- HoseinyFarahabady, M. R., et al.
(författare)
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Graceful Performance Degradation in Apache Storm
- 2021
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Ingår i: Parallel and Distributed Computing, Applications and Technologies. - Cham : Springer Science+Business Media B.V.. - 9783030692438 ; , s. 389-400
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Konferensbidrag (refereegranskat)abstract
- The concept of stream data processing is becoming challenging in most business sectors where try to improve their operational efficiency by deriving valuable information from unstructured, yet, contentiously generated high volume raw data in an expected time spans. A modern streamlined data processing platform is required to execute analytical pipelines over a continues flow of data-items that might arrive in a high rate. In most cases, the platform is also expected to dynamically adapt to dynamic characteristics of the incoming traffic rates and the ever-changing condition of underlying computational resources while fulfill the tight latency constraints imposed by the end-users. Apache Storm has emerged as an important open source technology for performing stream processing with very tight latency constraints over a cluster of computing nodes. To increase the overall resource utilization, however, the service provider might be tempted to use a consolidation strategy to pack as many applications as possible in a (cloud-centric) cluster with limited number of working nodes. However, collocated applications can negatively compete with each other, for obtaining the resource capacity in a shared platform that, in turn, the result may lead to a severe performance degradation among all running applications. The main objective of this work is to develop an elastic solution in a modern stream processing ecosystem, for addressing the shared resource contention problem among collocated applications. We propose a mechanism, based on design principles of Model Predictive Control theory, for coping with the extreme conditions in which the collocated analytical applications have different quality of service (QoS) levels while the shared-resource interference is considered as a key performance limiting parameter. Experimental results confirm that the proposed controller can successfully enhance the p -99 latency of high priority applications by 67%, compared to the default round robin resource allocation strategy in Storm, during the high traffic load, while maintaining the requested quality of service levels.
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| 34. |
- HoseinyFarahabady, M. Reza, et al.
(författare)
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Low Latency Execution Guarantee Under Uncertainty in Serverless Platforms
- 2022
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Ingår i: Parallel and Distributed Computing, Applications and Technologies. PDCAT 2021. - Cham : Springer. - 9783030967727 - 9783030967710 ; , s. 324-335
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Konferensbidrag (refereegranskat)abstract
- Serverless computing recently emerged as a new run-time paradigm to disentangle the client from the burden of provisioning physical computing resources, leaving such difficulty on the service provider's side. However, an unsolved problem in such an environment is how to cope with the challenges of executing several co-running applications while fulfilling the requested Quality of Service (QoS) level requested by all application owners. In practice, developing an efficient mechanism to reach the requested performance level (such as p-99 latency and throughput) is limited to the awareness (resource availability, performance interference among consolidation workloads, etc.) of the controller about the dynamics of the underlying platforms. In this paper, we develop an adaptive feedback controller for coping with the buffer instability of serverless platforms when several collocated applications are run in a shared environment. The goal is to support a low-latency execution by managing the arrival event rate of each application when shared resource contention causes a significant throughput degradation among workloads with different priorities. The key component of the proposed architecture is a continues management of server-side internal buffers for each application to provide a low-latency feedback control mechanism based on the requested QoS level of each application (e.g., buffer information) and the worker nodes throughput. The empirical results confirm the response stability for high priority workloads when a dynamic condition is caused by low priority applications. We evaluate the performance of the proposed solution with respect to the response time and the QoS violation rate for high priority applications in a serverless platform with four worker nodes set up in our in-house virtualized cluster. We compare the proposed architecture against the default resource management policy in Apache OpenWhisk which is extensively used in commercial serverless platforms. The results show that our approach achieves a very low overhead (less than 0.7%) while it can improve the p-99 latency of high priority applications by 64%, on average, in the presence of dynamic high traffic conditions.
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| 35. |
- HoseinyFarahabady, M. Reza, et al.
(författare)
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QSpark : Distributed Execution of Batch & Streaming Analytics in Spark Platform
- 2021
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Ingår i: 2021 IEEE 20TH INTERNATIONAL SYMPOSIUM ON NETWORK COMPUTING AND APPLICATIONS (NCA). - : IEEE. - 9781665495509
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Konferensbidrag (refereegranskat)abstract
- A significant portion of research work in the past decade has been devoted on developing resource allocation and task scheduling solutions for large-scale data processing platforms. Such algorithms are designed to facilitate deployment of data analytic applications across either conventional cluster computing systems or modern virtualized data-centers. The main reason for such a huge research effort stems from the fact that even a slight improvement in the performance of such platforms can bring a considerable monetary savings for vendors, especially for modern data processing engines that are designed solely to perform high throughput or/and low-latency computations over massive-scale batch or streaming data. A challenging question to be yet answered in such a context is to design an effective resource allocation solution that can prevent low resource utilization while meeting the enforced performance level (such as 99-th latency percentile) in circumstances where contention among applications to obtain the capacity of shared resources is a non negligible performance-limiting parameter. This paper proposes a resource controller system, called QSpark, to cope with the problem of (i) low performance (i.e., resource utilization in the batch mode and p-99 response time in the streaming mode), and (ii) the shared resource interference among collocated applications in a multi-tenancy modern Spark platform. The proposed solution leverages a set of controlling mechanisms for dynamic partitioning of the allocation of computing resources, in a way that it can fulfill the QoS requirements of latency-critical data processing applications, while enhancing the throughput for all working nodes without reaching their saturation points. Through extensive experiments in our in-house Spark cluster, we compared the achieved performance of proposed solution against the default Spark resource allocation policy for a variety of Machine Learning (ML), Artificial Intelligence (AI), and Deep Learning (DL) applications. Experimental results show the effectiveness of the proposed solution by reducing the p-99 latency of high priority applications by 32% during the burst traffic periods (for both batch and stream modes), while it can enhance the QoS satisfaction level by 65% for applications with the highest priority (compared with the results of default Spark resource allocation strategy).
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| 36. |
- Hoseinyfarahabady, M. R., et al.
(författare)
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Spark-Tuner : An elastic auto-tuner for apache spark streaming
- 2020
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Ingår i: IEEE International Conference on Cloud Computing, CLOUD. - : IEEE Computer Society. - 9781728187808 ; , s. 544-548
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Konferensbidrag (refereegranskat)abstract
- Spark has emerged as one of the most widely and successfully used data analytical engine for large-scale enterprise, mainly due to its unique characteristics that facilitate computations to be scaled out in a distributed environment. This paper deals with the performance degradation due to resource contention among collocated analytical applications with different priority and dissimilar intrinsic characteristics in a shared Spark platform. We propose an auto-tuning strategy of computing resources in a distributed Spark platform for handling scenarios in which submitted analytical applications have different quality of service (QoS) requirements (e.g., latency constraints), while the interference among computing resources is considered as a key performance-limiting parameter. We compared Spark-Tuner to two widely used resource allocation heuristics in a large scale Spark cluster through extensive experimental settings across several traffic patterns with uncertain rate and application types. Experimental results show that with Spark-Tuner, the Spark engine can decrease the $p$-99 latency of high priority applications by 43% during the high-rate traffic periods, while maintaining the same level of CPU throughput across a cluster.
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| 37. |
- Hoseinyfarahabady, M. Reza, et al.
(författare)
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Toward designing a dynamic CPU cap manager for timely dataflow platforms
- 2018
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Ingår i: HPC '18 Proceedings of the High Performance Computing Symposium. - : Association for Computing Machinery (ACM). - 9781510860162 ; , s. 60-70
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Konferensbidrag (refereegranskat)abstract
- In this work, we propose a control-based solution for the problem of CPU resource allocation in data-flow platform that considers the degradation of performance caused by running concurrent data-flow processes. Our aim is to cut the QoS violation incidents for applications belonging to the highest QoS class. The performance of the proposed solution is bench-marked with the famous round robin algorithm. The experimental results confirms that the proposed algorithm can decrease the latency of processing data records for applications by 48% compared to the round robin policy.
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| 38. |
- Reza Hoseinyfarahabady, M., et al.
(författare)
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Q-Flink : A QoS-Aware Controller for Apache Flink
- 2020
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Ingår i: Proceedings - 20th IEEE/ACM International Symposium on Cluster, Cloud and Internet Computing, CCGRID 2020. - : Institute of Electrical and Electronics Engineers (IEEE). - 9781728160955 ; , s. 629-638
-
Konferensbidrag (refereegranskat)abstract
- Modern stream-data processing platforms are required to execute processing pipelines over high-volume, yet high-velocity, datasets under tight latency constraints. Apache Flink has emerged as an important new technology of large-scale platform that can distribute processing over a large number of computing nodes in a cluster (i.e., scale-out processing). Flink allows application developers to design and execute queries over continuous raw-inputs to analyze a large amount of streaming data in a parallel and distributed fashion. To increase the throughput of computing resources in stream processing platforms, a service provider might be tempted to use a consolidation strategy to pack as many processing applications as possible on the working nodes, with the hope of increasing the total revenue by improving the overall resource utilization. However, there is a hidden trap for achieving such a higher throughput solely by relying on an interference-oblivious consolidation strategy. In practice, collocated applications in a shared platform can fiercely compete with each others for obtaining the capacity of shared resources (e.g., cache and memory bandwidth) which in turn can lead to a severe performance degradation for all consolidated workloads.This paper addresses the shared resource contention problem associated with the auto-resource controlling mechanism of Apache Flink engine running across a distributed cluster. A controlling strategy is proposed to handle scenarios in which stream processing applications may have different quality of service (QoS) requirements while the resource interference is considered as the key performance-limiting parameter. The performance evaluation is carried out by comparing the proposed controller with the default Flink resource allocation strategy in a testbed cluster with total 32 Intel Xeon cores under different workload traffic with up to 4000 streaming applications chosen from various benchmarking tools. Experimental results demonstrate that the proposed controller can successfully decrease the average latency of high priority applications by 223% during the burst traffic while maintaining the requested QoS enforcement levels.
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| 39. |
- Sousa-Pinto, Bernardo, et al.
(författare)
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Validity, reliability, and responsiveness of daily monitoring visual analog scales in MASK-air®
- 2021
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Ingår i: Clinical and Translational Allergy. - : John Wiley & Sons. - 2045-7022. ; 11:7
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Forskningsöversikt (refereegranskat)abstract
- Background: MASK-air® is an app that supports allergic rhinitis patients in disease control. Users register daily allergy symptoms and their impact on activities using visual analog scales (VASs). We aimed to assess the concurrent validity, reliability, and responsiveness of these daily VASs.Methods: Daily monitoring VAS data were assessed in MASK-air® users with allergic rhinitis. Concurrent validity was assessed by correlating daily VAS values with those of the EuroQol-5 Dimensions (EQ-5D) VAS, the Control of Allergic Rhinitis and Asthma Test (CARAT) score, and the Work Productivity and Activity Impairment Allergic Specific (WPAI-AS) Questionnaire (work and activity impairment scores). Intra-rater reliability was assessed in users providing multiple daily VASs within the same day. Test–retest reliability was tested in clinically stable users, as defined by the EQ-5D VAS, CARAT, or “VAS Work” (i.e., VAS assessing the impact of allergy on work). Responsiveness was determined in users with two consecutive measurements of EQ-5D-VAS or “VAS Work” indicating clinical change.Results: A total of 17,780 MASK-air® users, with 317,176 VAS days, were assessed. Concurrent validity was moderate–high (Spearman correlation coefficient range: 0.437–0.716). Intra-rater reliability intraclass correlation coefficients (ICCs) ranged between 0.870 (VAS assessing global allergy symptoms) and 0.937 (VAS assessing allergy symptoms on sleep). Test–retest reliability ICCs ranged between 0.604 and 0.878—“VAS Work” and “VAS asthma” presented the highest ICCs. Moderate/large responsiveness effect sizes were observed—the sleep VAS was associated with lower responsiveness, while the global allergy symptoms VAS demonstrated higher responsiveness.Conclusion: In MASK-air®, daily monitoring VASs have high intra-rater reliability and moderate–high validity, reliability, and responsiveness, pointing to a reliable measure of symptom loads.
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| 40. |
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| 41. |
- Tari, M.H., et al.
(författare)
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Optimisation modelling of industrial energy systems using MIND introducing the effect of material storage
- 2002
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Ingår i: European Journal of Operational Research. - 0377-2217 .- 1872-6860. ; 142:2, s. 419-433
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Strategic decisions regarding industrial energy systems should ideally involve the entire plant. Systems analysis using optimisation methods identifies the minimum cost solution among numerous alternatives. In the deregulated Swedish (and European) energy market, there are large variations in electricity contracts. These contracts affect the possibilities of industrial energy systems to react not only through the price level but also through the price structure. Material storage can affect an industrial system in many ways. One of them is that material storage can prevent a situation in which different parts of an industrial system with different production rates counteract each other. In this paper, the influence on energy costs of the use of material storage is discussed. The importance of modelling material storage has been shown, especially in situations where there are time-of-use-prices of electricity. A case study from the pulp and paper industry has been used to confirm this. © 2002 Elsevier Science B.V. All rights reserved.
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| 42. |
- von Hertzen, Leena, et al.
(författare)
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Helsinki alert of biodiversity and health
- 2015
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Ingår i: Annals of Medicine. - : Informa UK Limited. - 1365-2060 .- 0785-3890. ; 47:3, s. 218-225
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Forskningsöversikt (refereegranskat)abstract
- Urban living in built environments, combined with the use of processed water and food, may not provide the microbial stimulation necessary for a balanced development of immune function. Many chronic inflammatory disorders, including allergic, autoimmune, metabolic, and even some behavioural disorders, are linked to alteration in the human commensal microbiota. Sedentary lifestyle is associated with reduced exposure to a broad spectrum of environmental micro-organisms and surplus energy balance, both risk factors of chronic inflammatory disorders. According to the Biodiversity Hypothesis, an environment with diverse macrobiota and microbiota modifies and enriches the human microbiota, which in turn is crucial in the development and maintenance of appropriate immune function. These issues were discussed in the symposium 'Chronic Inflammation, Lifestyle and Environment ', held in Helsinki, 20 - 22 August 2014, under the sponsorship of the Yrjo Jahnsson Foundation. This paper briefly outlines the recent findings in the context of the environment, lifestyle, and health; discusses the forces that undermine immune tolerance in urban environments; and highlights the possibilities to restore broken immune tolerance among urban dwellers, summarizing the main messages in four statements and calling for actions to combat major public health threats.
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