Large-scale genome-wide association studies and meta-analyses of longitudinal change in adult lung function.

BACKGROUND: Genome-wide association studies (GWAS) have identified numerous loci influencing cross-sectional lung function, but less is known about genes influencing longitudinal change in lung function. METHODS: We performed GWAS of the rate of change in forced expiratory volume in the first second (FEV1) in 14 longitudinal, population-based cohort studies comprising 27,249 adults of European ancestry using linear mixed effects model and combined cohort-specific results using fixed effect meta-analysis to identify novel genetic loci associated with longitudinal change in lung function. Gene expression analyses were subsequently performed for identified genetic loci. As a secondary aim, we estimated the mean rate of decline in FEV1 by smoking pattern, irrespective of genotypes, across these 14 studies using meta-analysis. RESULTS: The overall meta-analysis produced suggestive evidence for association at the novel IL16/STARD5/TMC3 locus on chromosome 15 (P  =  5.71 × 10(-7)). In addition, meta-analysis using the five cohorts with ≥3 FEV1 measurements per participant identified the novel ME3 locus on chromosome 11 (P  =  2.18 × 10(-8)) at genome-wide significance. Neither locus was associated with FEV1 decline in two additional cohort studies. We confirmed gene expression of IL16, STARD5, and ME3 in multiple lung tissues. Publicly available microarray data confirmed differential expression of all three genes in lung samples from COPD patients compared with controls. Irrespective of genotypes, the combined estimate for FEV1 decline was 26.9, 29.2 and 35.7 mL/year in never, former, and persistent smokers, respectively. CONCLUSIONS: In this large-scale GWAS, we identified two novel genetic loci in association with the rate of change in FEV1 that harbor candidate genes with biologically plausible functional links to lung function

TOI-5126: A hot super-Neptune and warm Neptune pair discovered by TESS\textit{TESS} and CHEOPS\textit{CHEOPS}

We present the confirmation of a hot super-Neptune with an exterior Neptune companion orbiting a bright (V = 10.1 mag) F-dwarf identified by the $\textit{Transiting Exoplanet Survey Satellite}$ ($\textit{TESS}$). The two planets, observed in sectors 45, 46 and 48 of the $\textit{TESS}$ extended mission, are $4.74^{+0.16}_{-0.14}$ $R_{\oplus}$ and $3.86^{+0.17}_{-0.16}$ $R_{\oplus}$ with $5.4588385^{+0.0000070}_{-0.0000072}$ d and $17.8999^{+0.0018}_{-0.0013}$ d orbital periods, respectively. We also obtained precise space based photometric follow-up of the system with ESAs $\textit{CHaracterising ExOplanets Satellite}$ ($\textit{CHEOPS}$) to constrain the radius and ephemeris of TOI-5126 b. TOI 5126 b is located in the "hot Neptune Desert" and is an ideal candidate for follow-up transmission spectroscopy due to its high predicted equilibrium temperature ($T_{eq} = 1442^{+46}_{-40}$ K) implying a cloud-free atmosphere. TOI-5126 c is a warm Neptune ($T_{eq}= 971^{+31}_{-27}$ K) also suitable for follow-up. Tentative transit timing variations (TTVs) have also been identified in analysis, suggesting the presence of at least one additional planet, however this signal may be caused by spot-crossing events, necessitating further precise photometric follow-up to confirm these signals.Comment: Accepted in MNRAS, 18 pages, 14 figure

TOI-1338 : TESS' first transiting circumbinary planet

Funding: Funding for the DPAC has been provided by national institutions, in particular, the institutions participating in the Gaia Multilateral Agreement. W.F.W. and J.A.O.thank John Hood Jr. for his generous support of exoplanet research at SDSU. Support was also provided and acknowledged through NASA Habitable Worlds grant 80NSSC17K0741 and NASA XRP grant 80NSSC18K0519. This work is partly supported by NASA Habitable Worlds grant 80NSSC17K0741. This material is based upon work supported by the National Science Foundation Graduate Research Fellowship Program under grant No.(DGE-1746045). A.H.M.J.T. has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No. 803193/BEBOP) and from a Leverhulme Trust Research Project grant No. RPG-2018-418. A.C. acknowledges support by CFisUC strategic project (UID/FIS/04564/2019).We report the detection of the first circumbinary planet (CBP) found by Transiting Exoplanet Survey Satellite (TESS). The target, a known eclipsing binary, was observed in sectors 1 through 12 at 30 minute cadence and in sectors 4 through 12 at 2 minute cadence. It consists of two stars with masses of 1.1 M⊙ and 0.3 M⊙ on a slightly eccentric (0.16), 14.6 day orbit, producing prominent primary eclipses and shallow secondary eclipses. The planet has a radius of ∼6.9 R⊕ and was observed to make three transits across the primary star of roughly equal depths (∼0.2%) but different durations—a common signature of transiting CBPs. Its orbit is nearly circular (e ≍ 0.09) with an orbital period of 95.2 days. The orbital planes of the binary and the planet are aligned to within ∼1°. To obtain a complete solution for the system, we combined the TESS photometry with existing ground-based radial-velocity observations in a numerical photometric-dynamical model. The system demonstrates the discovery potential of TESS for CBPs and provides further understanding of the formation and evolution of planets orbiting close binary stars.Publisher PDFPeer reviewe

A practical guide to the analysis of non-response and attrition in longitudinal research using a real data example

Selective non-participation and attrition pose a ubiquitous threat to the validity of inferences drawn from observational longitudinal studies. We investigate various potential predictors for non-response and attrition of parents as well as young persons at different stages of a multi-informant study. Various phases of renewed consent from parents and young persons allowed for a unique comparison of factors that drive participation. The target sample consisted of 1675 children entering primary school at age seven in 2004. Seven waves of interviews, over the course of 10 years, measured levels of problem behavior as rated by children, parents, and teachers. In the initial study recruitment, where participation was driven by parental consent, non-response was highest amongst certain socially disadvantaged immigrant minority groups. There were fewer significant group differences at wave 5, when young people could be directly recruited into the study. Similarly, attrition was higher for some immigrant background groups. Methodological implications for future analyses are discussed

The Uniform grading tooL for flexIble ureterorenoscoPes (TULIP-tool): a Delphi consensus project on standardised evaluation of flexible ureterorenoscopes

Objective: To develop a standardised tool to evaluate flexible ureterorenoscopes (fURS). Materials and Methods: A three-stage consensus building approach based on the modified Delphi technique was performed under guidance of a steering group. First, scope- and user-related parameters used to evaluate fURS were identified through a systematic scoping review. Then, the main categories and subcategories were defined, and the expert panel was selected. Finally, a two-step modified Delphi consensus project was conducted to firstly obtain consensus on the relevance and exact definition of each (sub)category necessary to evaluate fURS, and secondly on the evaluation method (setting, used tools and unit of outcome) of those (sub)categories. Consensus was reached at a predefined threshold of 80% high agreement. Results: The panel consisted of 30 experts in the field of endourology. The first step of the modified Delphi consensus project consisted of two questionnaires with a response rate of 97% (n = 29) for both. Consensus was reached for the relevance and definition of six main categories and 12 subcategories. The second step consisted of three questionnaires (response rate of 90%, 97% and 100%, respectively). Consensus was reached on the method of measurement for all (sub)categories. Conclusion: This modified Delphi consensus project reached consensus on a standardised grading tool for the evaluation of fURS – The Uniform grading tooL for flexIble ureterorenoscoPes (TULIP) tool. This is a first step in creating uniformity in this field of research to facilitate future comparison of outcomes of the functionality and handling of fURS