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- 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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| 2. |
- Casey, Caitlin M., et al.
(författare)
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Physical Characterization of an Unlensed, Dusty Star-forming Galaxy at z = 5.85
- 2019
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 887:1
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Tidskriftsartikel (refereegranskat)abstract
- We present a physical characterization of MM J100026.36+021527.9 (a.k.a. "Mambo-9"), a dusty star-forming galaxy (DSFG) at z = 5.850 ± 0.001. This is the highest-redshift unlensed DSFG (and fourth most distant overall) found to date and is the first source identified in a new 2 mm blank-field map in the COSMOS field. Though identified in prior samples of DSFGs at 850 μm to 1.2 mm with unknown redshift, the detection at 2 mm prompted further follow-up as it indicated a much higher probability that the source was likely to sit at z > 4. Deep observations from the Atacama Large Millimeter and submillimeter Array (ALMA) presented here confirm the redshift through the secure detection of 12CO(J = 6→5) and p-H2O (21,1 → 20,2). Mambo-9 is composed of a pair of galaxies separated by 6 kpc with corresponding star formation rates of 590 M o˙ yr-1 and 220 M o˙ yr-1, total molecular hydrogen gas mass of (1.7 ± 0.4) × 1011 M o˙, dust mass of (1.3 ± 0.3) × 109 M o˙, and stellar mass of (3.2-1.5+1.0) × 109 M o˙. The total halo mass, (3.3 ± 0.8) × 1012 M o˙, is predicted to exceed 1015 M o˙ by z = 0. The system is undergoing a merger-driven starburst that will increase the stellar mass of the system tenfold in τ depl = 40-80 Myr, converting its large molecular gas reservoir (gas fraction of 96-2+1) into stars. Mambo-9 evaded firm spectroscopic identification for a decade, following a pattern that has emerged for some of the highest-redshift DSFGs found. And yet, the systematic identification of unlensed DSFGs like Mambo-9 is key to measuring the global contribution of obscured star formation to the star formation rate density at z ⪆ 4, the formation of the first massive galaxies, and the formation of interstellar dust at early times (≲1 Gyr).
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| 4. |
- Marouli, Eirini, et al.
(författare)
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Rare and low-frequency coding variants alter human adult height
- 2017
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 542:7640, s. 186-190
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Tidskriftsartikel (refereegranskat)abstract
- Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.
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| 6. |
- Turcot, Valerie, et al.
(författare)
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Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity
- 2018
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:1, s. 26-41
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are similar to 10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed similar to 7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.
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