| 1. |
- Bousquet, Jean, et al.
(author)
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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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In: Journal of Allergy and Clinical Immunology. - : Elsevier. - 0091-6749 .- 1097-6825. ; 143:3, s. 864-879
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Journal article (peer-reviewed)abstract
- Allergic Rhinitis and its Impact on Asthma (ARIA) has evolved from a guideline by using the best approach to integrated care pathways using mobile technology in patients with allergic rhinitis (AR) and asthma multimorbidity. The proposed next phase of ARIA is change management, with the aim of providing an active and healthy life to patients with rhinitis and to those with asthma multimorbidity across the lifecycle irrespective of their sex or socioeconomic status to reduce health and social inequities incurred by the disease. ARIA has followed the 8-step model of Kotter to assess and implement the effect of rhinitis on asthma multimorbidity and to propose multimorbid guidelines. A second change management strategy is proposed by ARIA Phase 4 to increase self-medication and shared decision making in rhinitis and asthma multimorbidity. An innovation of ARIA has been the development and validation of information technology evidence-based tools (Mobile Airways Sentinel Network [MASK]) that can inform patient decisions on the basis of a self-care plan proposed by the health care professional.
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| 2. |
- Bousquet, J, et al.
(author)
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Nrf2-interacting nutrients and COVID-19: time for research to develop adaptation strategies
- 2020
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In: Clinical and translational allergy. - : Wiley. - 2045-7022. ; 10:1, s. 58-
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Journal article (peer-reviewed)abstract
- There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPARγ:Peroxisome proliferator-activated receptor, NFκB: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2α:Elongation initiation factor 2α). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT1R axis (AT1R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity.
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| 3. |
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| 4. |
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| 5. |
- Abazov, V. M., et al.
(author)
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The upgraded DO detector
- 2006
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In: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 565:2, s. 463-537
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Journal article (peer-reviewed)abstract
- The DO experiment enjoyed a very successful data-collection run at the Fermilab Tevatron collider between 1992 and 1996. Since then, the detector has been upgraded to take advantage of improvements to the Tevatron and to enhance its physics capabilities. We describe the new elements of the detector, including the silicon microstrip tracker, central fiber tracker, solenoidal magnet, preshower detectors, forward muon detector, and forward proton detector. The uranium/liquid -argon calorimeters and central muon detector, remaining from Run 1, are discussed briefly. We also present the associated electronics, triggering, and data acquisition systems, along with the design and implementation of software specific to DO.
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| 6. |
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| 7. |
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| 8. |
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| 9. |
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| 10. |
- Lukasik, J., et al.
(author)
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Discriminant analysis and secondary-beam charge recognition
- 2008
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In: Nuclear Instruments and Methods in Physics Research, Section A: Accelerators, Spectrometers, Detectors and Associated Equipment. - : Elsevier BV. - 0168-9002. ; 587:2-3, s. 413-419
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Journal article (peer-reviewed)abstract
- The discriminant-analysis method has been applied to optimize the exotic-beam charge recognition in a projectile fragmentation experiment. The experiment was carried out at the GSI using the fragment separator (FRS) to produce and select the relativistic secondary beams, and the ALADIN setup to measure their fragmentation products following collisions with Sn target nuclei. The beams of neutron poor isotopes around La-124 and Sn-107 were selected to study the isospin dependence of the limiting temperature of heavy nuclei by comparing with results for stable Sn-124 projectiles. A dedicated detector to measure the projectile charge upstream of the reaction target was not used, and alternative methods had to be developed. The presented method, based on the multivariate discriminant analysis, allowed to increase the efficacy of charge recognition up to about 90%, which was about 20% more than achieved with the simple scalar methods.
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| 11. |
- Pawlowski, P., et al.
(author)
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Neutron recognition in the LAND detector for large neutron multiplicity
- 2012
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In: Nuclear Instruments and Methods in Physics Research, Section A: Accelerators, Spectrometers, Detectors and Associated Equipment. - : Elsevier BV. - 0168-9002. ; 694, s. 47-54
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Journal article (peer-reviewed)abstract
- The performance of the LAND neutron detector is studied. Using an event-mixing technique based on one-neutron data obtained in the S107 experiment at the GSI laboratory, we test the efficiency of various analytic tools used to determine the multiplicity and kinematic properties of detected neutrons. A new algorithm developed recently for recognizing neutron showers from spectator decays in the ALADIN experiment S254 is described in detail. Its performance is assessed in comparison with other methods. The properties of the observed neutron events are used to estimate the detection efficiency of LAND in this experiment. (C) 2012 Elsevier B.V. All rights reserved.
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| 12. |
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| 13. |
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| 14. |
- Trautmann, W., et al.
(author)
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Isotopic dependence of the caloric curve
- 2009
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In: Progress in Particle and Nuclear Physics. - : Elsevier BV. - 0146-6410. ; 62:2, s. 407-412
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Journal article (peer-reviewed)abstract
- Isotopic effects in projectile fragmentation at relativistic energies have been studied with the ALADIN forward spectrometer at SIS. Stable and radioactive Sn and La beams with an incident energy of 600 MeV per nucleon have been used in order to explore a wide range of isotopic compositions. Chemical freeze-out temperatures are found to be nearly invariant with respect to the A/Z ratio of the produced spectator sources, consistent with predictions for expanded systems. Consequences for the proposed interpretation of chemical breakup temperatures as representing the limiting temperatures predicted by microscopic models are discussed. (C) 2009 Elsevier B.V. All rights reserved.
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| 15. |
- Aasi, J., et al.
(author)
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Parameter estimation for compact binary coalescence signals with the first generation gravitational-wave detector network
- 2013
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In: Physical Review D (Particles, Fields, Gravitation and Cosmology). - 1550-2368. ; 88:6
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Journal article (peer-reviewed)abstract
- Compact binary systems with neutron stars or black holes are one of the most promising sources for ground-based gravitational-wave detectors. Gravitational radiation encodes rich information about source physics; thus parameter estimation and model selection are crucial analysis steps for any detection candidate events. Detailed models of the anticipated waveforms enable inference on several parameters, such as component masses, spins, sky location and distance, that are essential for new astrophysical studies of these sources. However, accurate measurements of these parameters and discrimination of models describing the underlying physics are complicated by artifacts in the data, uncertainties in the waveform models and in the calibration of the detectors. Here we report such measurements on a selection of simulated signals added either in hardware or software to the data collected by the two LIGO instruments and the Virgo detector during their most recent joint science run, including a "blind injection'' where the signal was not initially revealed to the collaboration. We exemplify the ability to extract information about the source physics on signals that cover the neutron-star and black-hole binary parameter space over the component mass range 1M(circle dot)-25M(circle dot) and the full range of spin parameters. The cases reported in this study provide a snapshot of the status of parameter estimation in preparation for the operation of advanced detectors.
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| 16. |
- Aasi, J., et al.
(author)
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Search for gravitational waves from binary black hole inspiral, merger, and ringdown in LIGO-Virgo data from 2009-2010
- 2013
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In: Physical Review D (Particles, Fields, Gravitation and Cosmology). - 1550-2368. ; 87:2
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Journal article (peer-reviewed)abstract
- We report a search for gravitational waves from the inspiral, merger and ringdown of binary black holes (BBH) with total mass between 25 and 100 solar masses, in data taken at the LIGO and Virgo observatories between July 7, 2009 and October 20, 2010. The maximum sensitive distance of the detectors over this period for a (20, 20)M-circle dot coalescence was 300 Mpc. No gravitational wave signals were found. We thus report upper limits on the astrophysical coalescence rates of BBH as a function of the component masses for nonspinning components, and also evaluate the dependence of the search sensitivity on component spins aligned with the orbital angular momentum. We find an upper limit at 90% confidence on the coalescence rate of BBH with nonspinning components of mass between 19 and 28M(circle dot) of 3:3 x 10(-7) mergers Mpc(-3) yr(-1).
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| 17. |
- Aasi, J., et al.
(author)
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The characterization of Virgo data and its impact on gravitational-wave searches
- 2012
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In: Classical and Quantum Gravity. - : IOP Publishing. - 1361-6382 .- 0264-9381. ; 29:15
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Journal article (peer-reviewed)abstract
- Between 2007 and 2010 Virgo collected data in coincidence with the LIGO and GEO gravitational-wave (GW) detectors. These data have been searched for GWs emitted by cataclysmic phenomena in the universe, by non-axisymmetric rotating neutron stars or from a stochastic background in the frequency band of the detectors. The sensitivity of GW searches is limited by noise produced by the detector or its environment. It is therefore crucial to characterize the various noise sources in a GW detector. This paper reviews the Virgo detector noise sources, noise propagation, and conversion mechanisms which were identified in the three first Virgo observing runs. In many cases, these investigations allowed us to mitigate noise sources in the detector, or to selectively flag noise events and discard them from the data. We present examples from the joint LIGO-GEO-Virgo GW searches to show how well noise transients and narrow spectral lines have been identified and excluded from the Virgo data. We also discuss how detector characterization can improve the astrophysical reach of GW searches.
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| 18. |
- Adrian-Martinez, S., et al.
(author)
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A first search for coincident gravitational waves and high energy neutrinos using LIGO, Virgo and ANTARES data from 2007
- 2013
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In: Journal of Cosmology and Astroparticle Physics. - : IOP Publishing. - 1475-7516. ; :6
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Journal article (peer-reviewed)abstract
- We present the results of the first search for gravitational wave bursts associated with high energy neutrinos. Together, these messengers could reveal new, hidden sources that are not observed by conventional photon astronomy, particularly at high energy. Our search uses neutrinos detected by the underwater neutrino telescope ANTARES in its 5 line configuration during the period January - September 2007, which coincided with the fifth and first science runs of LIGO and Virgo, respectively. The LIGO-Virgo data were analysed for candidate gravitational-wave signals coincident in time and direction with the neutrino events. No significant coincident events were observed. We place limits on the density of joint high energy neutrino - gravitational wave emission events in the local universe, and compare them with densities of merger and core-collapse events.
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| 19. |
- Anney, Richard, et al.
(author)
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A genome-wide scan for common alleles affecting risk for autism.
- 2010
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In: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 19:20, s. 4072-4082
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Journal article (peer-reviewed)abstract
- Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P < 5 × 10(-8). When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner's curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P < 5 × 10(-8) threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C.
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| 20. |
- Anney, Richard, et al.
(author)
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Individual common variants exert weak effects on the risk for autism spectrum disorders.
- 2012
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In: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 21:21, s. 4781-92
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Journal article (peer-reviewed)abstract
- While it is apparent that rare variation can play an important role in the genetic architecture of autism spectrum disorders (ASD), the contribution of common variation to ASD risk is less clear. To produce a more comprehensive picture, we report Stage 2 of the Autism Genome Project genome-wide association study, adding 1301 ASD families and bringing the total to 2705 families analysed (Stages 1 and 2). In addition to evaluating association of individual SNPs, we also sought evidence that common variants, en masse, might affect risk. Despite genotyping over a million SNPs covering the genome, no single SNP shows significant association with ASD or selected phenotypes at a genome-wide level. The SNP that achieves the smallest p-value from secondary analyses is rs1718101. It falls in CNTNAP2, a gene previously implicated in susceptibility for ASD. This SNP also shows modest association with age of word/phrase acquisition in ASD subjects, of interest because features of language development are also associated with other variation in CNTNAP2. By contrast, allele-scores derived from the transmission of common alleles to Stage 1 cases significantly predict case-status in the independent Stage 2 sample. Despite being significant, the variance explained by these allele scores was small (Vm< 1%). Based on results from individual SNPs and their en masse effect on risk, as inferred from the allele-score results, it is reasonable to conclude that common variants affect ASD risk but their individual effects are modest.
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| 21. |
- Bosnic-Anticevich, S, et al.
(author)
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ARIA pharmacy 2018 "Allergic rhinitis care pathways for community pharmacy"
- 2019
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In: Allergy. European Journal of Allergy and Clinical Immunology. - : Wiley. - 0105-4538 .- 1398-9995. ; 74:7, s. 1219-1236
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Research review (peer-reviewed)abstract
- Pharmacists are trusted health professionals. Many patients use over-the-counter (OTC) medications and are seen by pharmacists who are the initial point of contact of allergic rhinitis management in most countries. The role of pharmacists in integrated care pathways (ICPs) for allergic diseases is important. This paper builds on existing studies and provides tools intended to help pharmacists provide optimal advice/interventions/strategies to patients with rhinitis. The ARIA-pharmacy ICP includes a diagnostic questionnaire specifically focusing attention on key symptoms and markers of the disease, a systematic Diagnosis Guide (including differential diagnoses) and a simple flowchart with proposed treatment for rhinitis and asthma multimorbidity. Key prompts for referral within the ICP are included. The use of technology is critical to enhance the management of AR. However, the ARIA-pharmacy ICP should be adapted to local health care environments/situations as regional (national) differences exist in pharmacy care.
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| 22. |
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| 23. |
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| 24. |
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| 25. |
- Bousquet, Jean, et al.
(author)
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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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In: Allergy. European Journal of Allergy and Clinical Immunology. - : John Wiley & Sons. - 0105-4538 .- 1398-9995. ; 76:1, s. 168-190
-
Research review (peer-reviewed)abstract
- Digital anamorphosis is used to define a distorted image of health and care that may be viewed correctly using digital tools and strategies. MASK digital anamorphosis represents the process used by MASK to develop the digital transformation of health and care in rhinitis. It strengthens the ARIA change management strategy in the prevention and management of airway disease. The MASK strategy is based on validated digital tools. Using the MASK digital tool and the CARAT online enhanced clinical framework, solutions for practical steps of digital enhancement of care are proposed.
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| 26. |
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| 27. |
- Bousquet, J. Jean, et al.
(author)
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Next-generation ARIA care pathways for rhinitis and asthma : a model for multimorbid chronic diseases
- 2019
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In: Clinical and Translational Allergy. - : BMC. - 2045-7022. ; 9
-
Research review (peer-reviewed)abstract
- Background: In all societies, the burden and cost of allergic and chronic respiratory diseases are increasing rapidly. Most economies are struggling to deliver modern health care effectively. There is a need to support the transformation of the health care system into integrated care with organizational health literacy.Main body: As an example for chronic disease care, MASK (Mobile Airways Sentinel NetworK), a new project of the ARIA (Allergic Rhinitis and its Impact on Asthma) initiative, and POLLAR (Impact of Air POLLution on Asthma and Rhinitis, EIT Health), in collaboration with professional and patient organizations in the field of allergy and airway diseases, are proposing real-life ICPs centred around the patient with rhinitis, and using mHealth to monitor environmental exposure. Three aspects of care pathways are being developed: (i) Patient participation, health literacy and self-care through technology-assisted "patient activation", (ii) Implementation of care pathways by pharmacists and (iii) Next-generation guidelines assessing the recommendations of GRADE guidelines in rhinitis and asthma using real-world evidence (RWE) obtained through mobile technology. The EU and global political agendas are of great importance in supporting the digital transformation of health and care, and MASK has been recognized by DG Sante as a Good Practice in the field of digitally-enabled, integrated, person-centred care.Conclusion: In 20 years, ARIA has considerably evolved from the first multimorbidity guideline in respiratory diseases to the digital transformation of health and care with a strong political involvement.
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| 28. |
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| 29. |
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| 30. |
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| 31. |
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| 32. |
- Casey, Jillian P, et al.
(author)
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A novel approach of homozygous haplotype sharing identifies candidate genes in autism spectrum disorder.
- 2012
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In: Human Genetics. - : Springer Science and Business Media LLC. - 0340-6717 .- 1432-1203. ; 131:4, s. 565-579
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Journal article (peer-reviewed)abstract
- Autism spectrum disorder (ASD) is a highly heritable disorder of complex and heterogeneous aetiology. It is primarily characterized by altered cognitive ability including impaired language and communication skills and fundamental deficits in social reciprocity. Despite some notable successes in neuropsychiatric genetics, overall, the high heritability of ASD (~90%) remains poorly explained by common genetic risk variants. However, recent studies suggest that rare genomic variation, in particular copy number variation, may account for a significant proportion of the genetic basis of ASD. We present a large scale analysis to identify candidate genes which may contain low-frequency recessive variation contributing to ASD while taking into account the potential contribution of population differences to the genetic heterogeneity of ASD. Our strategy, homozygous haplotype (HH) mapping, aims to detect homozygous segments of identical haplotype structure that are shared at a higher frequency amongst ASD patients compared to parental controls. The analysis was performed on 1,402 Autism Genome Project trios genotyped for 1 million single nucleotide polymorphisms (SNPs). We identified 25 known and 1,218 novel ASD candidate genes in the discovery analysis including CADM2, ABHD14A, CHRFAM7A, GRIK2, GRM3, EPHA3, FGF10, KCND2, PDZK1, IMMP2L and FOXP2. Furthermore, 10 of the previously reported ASD genes and 300 of the novel candidates identified in the discovery analysis were replicated in an independent sample of 1,182 trios. Our results demonstrate that regions of HH are significantly enriched for previously reported ASD candidate genes and the observed association is independent of gene size (odds ratio 2.10). Our findings highlight the applicability of HH mapping in complex disorders such as ASD and offer an alternative approach to the analysis of genome-wide association data.
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| 33. |
- Evans, P. A., et al.
(author)
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Swift Follow-up Observations of Candidate Gravitational-wave Transient Events
- 2012
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In: The Astrophysical Journal Supplement Series. - : American Astronomical Society. - 0067-0049 .- 1538-4365. ; 203:2
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Journal article (peer-reviewed)abstract
- We present the first multi-wavelength follow-up observations of two candidate gravitational-wave (GW) transient events recorded by LIGO and Virgo in their 2009-2010 science run. The events were selected with low latency by the network of GW detectors (within less than 10 minutes) and their candidate sky locations were observed by the Swift observatory (within 12 hr). Image transient detection was used to analyze the collected electromagnetic data, which were found to be consistent with background. Off-line analysis of the GW data alone has also established that the selected GW events show no evidence of an astrophysical origin; one of them is consistent with background and the other one was a test, part of a "blind injection challenge." With this work we demonstrate the feasibility of rapid follow-ups of GW transients and establish the sensitivity improvement joint electromagnetic and GW observations could bring. This is a first step toward an electromagnetic follow-up program in the regime of routine detections with the advanced GW instruments expected within this decade. In that regime, multi-wavelength observations will play a significant role in completing the astrophysical identification of GW sources. We present the methods and results from this first combined analysis and discuss its implications in terms of sensitivity for the present and future instruments.
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| 34. |
- Le Contel, O., et al.
(author)
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The Search-Coil Magnetometer for MMS
- 2016
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In: Space Science Reviews. - : Springer Netherlands. - 0038-6308 .- 1572-9672. ; 199:1-4, s. 257-282
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Research review (peer-reviewed)abstract
- The tri-axial search-coil magnetometer (SCM) belongs to the FIELDS instrumentation suite on the Magnetospheric Multiscale (MMS) mission (Torbert et al. in Space Sci. Rev. (2014), this issue). It provides the three magnetic components of the waves from 1 Hz to 6 kHz in particular in the key regions of the Earth's magnetosphere namely the subsolar region and the magnetotail. Magnetospheric plasmas being collisionless, such a measurement is crucial as the electromagnetic waves are thought to provide a way to ensure the conversion from magnetic to thermal and kinetic energies allowing local or global reconfigurations of the Earth's magnetic field. The analog waveforms provided by the SCM are digitized and processed inside the digital signal processor (DSP), within the Central Electronics Box (CEB), together with the electric field data provided by the spin-plane double probe (SDP) and the axial double probe (ADP). On-board calibration signal provided by DSP allows the verification of the SCM transfer function once per orbit. Magnetic waveforms and on-board spectra computed by DSP are available at different time resolution depending on the selected mode. The SCM design is described in details as well as the different steps of the ground and in-flight calibrations.
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| 35. |
- Martin, W. P., et al.
(author)
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Urinary Metabolomic Changes Accompanying Albuminuria Remission following Gastric Bypass Surgery for Type 2 Diabetic Kidney Disease
- 2022
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In: Metabolites. - : MDPI AG. - 2218-1989. ; 12:2
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Journal article (peer-reviewed)abstract
- In the Microvascular Outcomes after Metabolic Surgery randomised clinical trial (MOMS RCT, NCT01821508), combined metabolic surgery (gastric bypass) plus medical therapy (CSM) was superior to medical therapy alone (MTA) as a means of achieving albuminuria remission at 2‐year follow‐up in patients with obesity and early diabetic kidney disease (DKD). In the present study, we assessed the urinary1H‐NMR metabolome in a subgroup of patients from both arms of the MOMS RCT at baseline and 6‐month follow‐up. Whilst CSM and MTA both reduced the urinary excretion of sugars, CSM generated a distinctive urinary metabolomic profile characterised by increases in host–microbial co‐metabolites (N‐phenylacetylglycine, trimethylamine N‐oxide, and 4‐ aminobutyrate (GABA)) and amino acids (arginine and glutamine). Furthermore, reductions in aromatic amino acids (phenylalanine and tyrosine), as well as branched‐chain amino acids (BCAAs) and related catabolites (valine, leucine, 3‐hydroxyisobutyrate, 3‐hydroxyisovalerate, and 3‐methyl‐ 2‐oxovalerate), were observed following CSM but not MTA. Improvements in BMI did not correlate with improvements in metabolic and renal indices following CSM. Conversely, urinary metabolites changed by CSM at 6 months were moderately to strongly correlated with improvements in blood pressure, glycaemia, triglycerides, and albuminuria up to 24 months following treatment initiation, highlighting the potential involvement of these shifts in the urinary metabolomic profile in the metabolic and renoprotective effects of CSM. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.
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| 36. |
- Menditto, Enrica, et al.
(author)
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Adherence to treatment in allergic rhinitis using mobile technology : The MASK Study
- 2019
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In: Clinical and Experimental Allergy. - : WILEY. - 0954-7894 .- 1365-2222. ; 49:4, s. 442-460
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Journal article (peer-reviewed)abstract
- Background: Mobile technology may help to better understand the adherence to treatment. MASK-rhinitis (Mobile Airways Sentinel NetworK for allergic rhinitis) is a patient-centred ICT system. A mobile phone app (the Allergy Diary) central to MASK is available in 22 countries. Objectives: To assess the adherence to treatment in allergic rhinitis patients using the Allergy Diary App. Methods: An observational cross-sectional study was carried out on all users who filled in the Allergy Diary from 1 January 2016 to 1 August 2017. Secondary adherence was assessed by using the modified Medication Possession Ratio (MPR) and the Proportion of days covered (PDC) approach. Results: A total of 12143 users were registered. A total of 6949 users reported at least one VAS data recording. Among them, 1887 users reported >= 7 VAS data. About 1195 subjects were included in the analysis of adherence. One hundred and thirty-six (11.28%) users were adherent (MPR >= 70% and PDC <= 1.25), 51 (4.23%) were partly adherent (MPR >= 70% and PDC = 1.50) and 176 (14.60%) were switchers. On the other hand, 832 (69.05%) users were non-adherent to medications (MPR <70%). Of those, the largest group was non-adherent to medications and the time interval was increased in 442 (36.68%) users. Conclusion and clinical relevance: Adherence to treatment is low. The relative efficacy of continuous vs on-demand treatment for allergic rhinitis symptoms is still a matter of debate. This study shows an approach for measuring retrospective adherence based on a mobile app. This also represents a novel approach for analysing medication-taking behaviour in a real-world setting.
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| 37. |
- Micah, Angela E., et al.
(author)
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Tracking development assistance for health and for COVID-19 : a review of development assistance, government, out-of-pocket, and other private spending on health for 204 countries and territories, 1990-2050
- 2021
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In: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 398:10308, s. 1317-1343
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Research review (peer-reviewed)abstract
- Background The rapid spread of COVID-19 renewed the focus on how health systems across the globe are financed, especially during public health emergencies. Development assistance is an important source of health financing in many low-income countries, yet little is known about how much of this funding was disbursed for COVID-19. We aimed to put development assistance for health for COVID-19 in the context of broader trends in global health financing, and to estimate total health spending from 1995 to 2050 and development assistance for COVID-19 in 2020. Methods We estimated domestic health spending and development assistance for health to generate total health-sector spending estimates for 204 countries and territories. We leveraged data from the WHO Global Health Expenditure Database to produce estimates of domestic health spending. To generate estimates for development assistance for health, we relied on project-level disbursement data from the major international development agencies' online databases and annual financial statements and reports for information on income sources. To adjust our estimates for 2020 to include disbursements related to COVID-19, we extracted project data on commitments and disbursements from a broader set of databases (because not all of the data sources used to estimate the historical series extend to 2020), including the UN Office of Humanitarian Assistance Financial Tracking Service and the International Aid Transparency Initiative. We reported all the historic and future spending estimates in inflation-adjusted 2020 US$, 2020 US$ per capita, purchasing-power parity-adjusted US$ per capita, and as a proportion of gross domestic product. We used various models to generate future health spending to 2050. Findings In 2019, health spending globally reached $8. 8 trillion (95% uncertainty interval [UI] 8.7-8.8) or $1132 (1119-1143) per person. Spending on health varied within and across income groups and geographical regions. Of this total, $40.4 billion (0.5%, 95% UI 0.5-0.5) was development assistance for health provided to low-income and middle-income countries, which made up 24.6% (UI 24.0-25.1) of total spending in low-income countries. We estimate that $54.8 billion in development assistance for health was disbursed in 2020. Of this, $13.7 billion was targeted toward the COVID-19 health response. $12.3 billion was newly committed and $1.4 billion was repurposed from existing health projects. $3.1 billion (22.4%) of the funds focused on country-level coordination and $2.4 billion (17.9%) was for supply chain and logistics. Only $714.4 million (7.7%) of COVID-19 development assistance for health went to Latin America, despite this region reporting 34.3% of total recorded COVID-19 deaths in low-income or middle-income countries in 2020. Spending on health is expected to rise to $1519 (1448-1591) per person in 2050, although spending across countries is expected to remain varied. Interpretation Global health spending is expected to continue to grow, but remain unequally distributed between countries. We estimate that development organisations substantially increased the amount of development assistance for health provided in 2020. Continued efforts are needed to raise sufficient resources to mitigate the pandemic for the most vulnerable, and to help curtail the pandemic for all. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.
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| 38. |
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| 39. |
- Nguyen, Yann, et al.
(author)
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Association Between Severe Nonadherence to Hydroxychloroquine and Systemic Lupus Erythematosus Flares, Damage, and Mortality in 660 Patients From the SLICC Inception Cohort
- 2023
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In: Arthritis and Rheumatology. - 2326-5191. ; 75:12, s. 2195-2206
-
Journal article (peer-reviewed)abstract
- Objective: The goals of this study were to assess the associations of severe nonadherence to hydroxychloroquine (HCQ), objectively assessed by HCQ serum levels, and risks of systemic lupus erythematosus (SLE) flares, damage, and mortality rates over five years of follow-up. Methods: The Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort is an international multicenter initiative (33 centers throughout 11 countries). The serum of patients prescribed HCQ for at least three months at enrollment were analyzed. Severe nonadherence was defined by a serum HCQ level <106 ng/mL or <53 ng/mL for HCQ doses of 400 or 200 mg/day, respectively. Associations with the risk of a flare (defined as a Systemic Lupus Erythematosus Disease Activity Index 2000 increase ≥4 points, initiation of prednisone or immunosuppressive drugs, or new renal involvement) were studied with logistic regression, and associations with damage (first SLICC/American College of Rheumatology Damage Index [SDI] increase ≥1 point) and mortality with separate Cox proportional hazard models. Results: Of the 1,849 cohort participants, 660 patients (88% women) were included. Median (interquartile range) serum HCQ was 388 ng/mL (244–566); 48 patients (7.3%) had severe HCQ nonadherence. No covariates were clearly associated with severe nonadherence, which was, however, independently associated with both flare (odds ratio 3.38; 95% confidence interval [CI] 1.80–6.42) and an increase in the SDI within each of the first three years (hazard ratio [HR] 1.92 at three years; 95% CI 1.05–3.50). Eleven patients died within five years, including 3 with severe nonadherence (crude HR 5.41; 95% CI 1.43–20.39). Conclusion: Severe nonadherence was independently associated with the risks of an SLE flare in the following year, early damage, and five-year mortality. (Figure presented.).
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| 40. |
- Papadopoulos, N G, et al.
(author)
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International consensus on (ICON) pediatric asthma.
- 2012
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In: Allergy. - : Wiley. - 1398-9995 .- 0105-4538. ; 67:8, s. 976-97
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Journal article (peer-reviewed)abstract
- Asthma is the most common chronic lower respiratory disease in childhood throughout the world. Several guidelines and/or consensus documents are available to support medical decisions on pediatric asthma. Although there is no doubt that the use of common systematic approaches for management can considerably improve outcomes, dissemination and implementation of these are still major challenges. Consequently, the International Collaboration in Asthma, Allergy and Immunology (iCAALL), recently formed by the EAACI, AAAAI, ACAAI, and WAO, has decided to propose an International Consensus on (ICON) Pediatric Asthma. The purpose of this document is to highlight the key messages that are common to many of the existing guidelines, while critically reviewing and commenting on any differences, thus providing a concise reference. The principles of pediatric asthma management are generally accepted. Overall, the treatment goal is disease control. To achieve this, patients and their parents should be educated to optimally manage the disease, in collaboration with healthcare professionals. Identification and avoidance of triggers is also of significant importance. Assessment and monitoring should be performed regularly to re-evaluate and fine-tune treatment. Pharmacotherapy is the cornerstone of treatment. The optimal use of medication can, in most cases, help patients control symptoms and reduce the risk for future morbidity. The management of exacerbations is a major consideration, independent of chronic treatment. There is a trend toward considering phenotype-specific treatment choices; however, this goal has not yet been achieved.
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| 41. |
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| 42. |
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| 43. |
- Pinto, Dalila, et al.
(author)
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Convergence of Genes and Cellular Pathways Dysregulated in Autism Spectrum Disorders.
- 2014
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In: American journal of human genetics. - : Elsevier BV. - 1537-6605 .- 0002-9297. ; 94:5, s. 677-694
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Journal article (peer-reviewed)abstract
- Rare copy-number variation (CNV) is an important source of risk for autism spectrum disorders (ASDs). We analyzed 2,446 ASD-affected families and confirmed an excess of genic deletions and duplications in affected versus control groups (1.41-fold, p = 1.0× 10(-5)) and an increase in affected subjects carrying exonic pathogenic CNVs overlapping known loci associated with dominant or X-linked ASD and intellectual disability (odds ratio = 12.62, p = 2.7× 10(-15), ∼3% of ASD subjects). Pathogenic CNVs, often showing variable expressivity, included rare de novo and inherited events at 36 loci, implicating ASD-associated genes (CHD2, HDAC4, and GDI1) previously linked to other neurodevelopmental disorders, as well as other genes such as SETD5, MIR137, and HDAC9. Consistent with hypothesized gender-specific modulators, females with ASD were more likely to have highly penetrant CNVs (p = 0.017) and were also overrepresented among subjects with fragile X syndrome protein targets (p = 0.02). Genes affected by de novo CNVs and/or loss-of-function single-nucleotide variants converged on networks related to neuronal signaling and development, synapse function, and chromatin regulation.
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| 44. |
- Pinto, Dalila, et al.
(author)
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Functional impact of global rare copy number variation in autism spectrum disorders.
- 2010
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 466:7304, s. 368-372
-
Journal article (peer-reviewed)abstract
- The autism spectrum disorders (ASDs) are a group of conditions characterized by impairments in reciprocal social interaction and communication, and the presence of restricted and repetitive behaviours. Individuals with an ASD vary greatly in cognitive development, which can range from above average to intellectual disability. Although ASDs are known to be highly heritable ( approximately 90%), the underlying genetic determinants are still largely unknown. Here we analysed the genome-wide characteristics of rare (<1% frequency) copy number variation in ASD using dense genotyping arrays. When comparing 996 ASD individuals of European ancestry to 1,287 matched controls, cases were found to carry a higher global burden of rare, genic copy number variants (CNVs) (1.19 fold, P = 0.012), especially so for loci previously implicated in either ASD and/or intellectual disability (1.69 fold, P = 3.4 x 10(-4)). Among the CNVs there were numerous de novo and inherited events, sometimes in combination in a given family, implicating many novel ASD genes such as SHANK2, SYNGAP1, DLGAP2 and the X-linked DDX53-PTCHD1 locus. We also discovered an enrichment of CNVs disrupting functional gene sets involved in cellular proliferation, projection and motility, and GTPase/Ras signalling. Our results reveal many new genetic and functional targets in ASD that may lead to final connected pathways.
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| 45. |
- Szatmari, Peter, et al.
(author)
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Mapping autism risk loci using genetic linkage and chromosomal rearrangements.
- 2007
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 39:3, s. 319-328
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Journal article (peer-reviewed)abstract
- Autism spectrum disorders (ASDs) are common, heritable neurodevelopmental conditions. The genetic architecture of ASDs is complex, requiring large samples to overcome heterogeneity. Here we broaden coverage and sample size relative to other studies of ASDs by using Affymetrix 10K SNP arrays and 1,168 families with at least two affected individuals, performing the largest linkage scan to date while also analyzing copy number variation in these families. Linkage and copy number variation analyses implicate chromosome 11p12-p13 and neurexins, respectively, among other candidate loci. Neurexins team with previously implicated neuroligins for glutamatergic synaptogenesis, highlighting glutamate-related genes as promising candidates for contributing to ASDs.
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| 46. |
- Wallace, SJ, et al.
(author)
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A core outcome set for aphasia treatment research: The ROMA consensus statement
- 2019
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In: International journal of stroke : official journal of the International Stroke Society. - : SAGE Publications. - 1747-4949. ; 14:2, s. 180-185
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Journal article (peer-reviewed)abstract
- A core outcome set (COS; an agreed, minimum set of outcomes) was needed to address the heterogeneous measurement of outcomes in aphasia treatment research and to facilitate the production of transparent, meaningful, and efficient outcome data. Objective The Research Outcome Measurement in Aphasia (ROMA) consensus statement provides evidence-based recommendations for the measurement of outcomes for adults with post-stroke aphasia within phases I–IV aphasia treatment studies. Methods This statement was informed by a four-year program of research, which comprised investigation of stakeholder-important outcomes using consensus processes, a scoping review of aphasia outcome measurement instruments, and an international consensus meeting. This paper provides an overview of this process and presents the results and recommendations arising from the international consensus meeting. Results Five essential outcome constructs were identified: Language, communication, patient-reported satisfaction with treatment and impact of treatment, emotional wellbeing, and quality of life. Consensus was reached for the following measurement instruments: Language: The Western Aphasia Battery Revised (WAB-R) (74% consensus); emotional wellbeing: General Health Questionnaire (GHQ)-12 (83% consensus); quality of life: Stroke and Aphasia Quality of Life Scale (SAQOL-39) (96% consensus). Consensus was unable to be reached for measures of communication (where multiple measures exist) or patient-reported satisfaction with treatment or impact of treatment (where no measures exist). Discussion Harmonization of the ROMA COS with other core outcome initiatives in stroke rehabilitation is discussed. Ongoing research and consensus processes are outlined. Conclusion The WAB-R, GHQ-12, and SAQOL-39 are recommended to be routinely included within phases I–IV aphasia treatment studies. This consensus statement has been endorsed by the Collaboration of Aphasia Trialists, the British Aphasiology Society, the German Society for Aphasia Research and Therapy, and the Royal College of Speech Language Therapists.
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| 47. |
- Weiner, D. J., et al.
(author)
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Polygenic transmission disequilibrium confirms that common and rare variation act additively to create risk for autism spectrum disorders
- 2017
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 49:7
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Journal article (peer-reviewed)abstract
- Autism spectrum disorder (ASD) risk is influenced by common polygenic and de novo variation. We aimed to clarify the influence of polygenic risk for ASD and to identify subgroups of ASD cases, including those with strongly acting de novo variants, in which polygenic risk is relevant. Using a novel approach called the polygenic transmission disequilibrium test and data from 6,454 families with a child with ASD, we show that polygenic risk for ASD, schizophrenia, and greater educational attainment is over-transmitted to children with ASD. These findings hold independent of proband IQ. We find that polygenic variation contributes additively to risk in ASD cases who carry a strongly acting de novo variant. Lastly, we show that elements of polygenic risk are independent and differ in their relationship with phenotype. These results confirm that the genetic influences on ASD are additive and suggest that they create risk through at least partially distinct etiologic pathways.
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