| 1. |
- Kattge, Jens, et al.
(författare)
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TRY plant trait database - enhanced coverage and open access
- 2020
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Ingår i: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188
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Tidskriftsartikel (refereegranskat)abstract
- Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
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| 2. |
- Huyghe, Jeroen R, et al.
(författare)
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Genetic architectures of proximal and distal colorectal cancer are partly distinct
- 2021
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Ingår i: Gut. - : BMJ Publishing Group Ltd. - 0017-5749 .- 1468-3288. ; 70:7, s. 1325-1334
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Tidskriftsartikel (refereegranskat)abstract
- Objective: An understanding of the etiologic heterogeneity of colorectal cancer (CRC) is critical for improving precision prevention, including individualized screening recommendations and the discovery of novel drug targets and repurposable drug candidates for chemoprevention. Known differences in molecular characteristics and environmental risk factors among tumors arising in different locations of the colorectum suggest partly distinct mechanisms of carcinogenesis. The extent to which the contribution of inherited genetic risk factors for CRC differs by anatomical subsite of the primary tumor has not been examined.Design: To identify new anatomical subsite-specific risk loci, we performed genome-wide association study (GWAS) meta-analyses including data of 48 214 CRC cases and 64 159 controls of European ancestry. We characterised effect heterogeneity at CRC risk loci using multinomial modelling.Results: We identified 13 loci that reached genome-wide significance (p<5×10-8) and that were not reported by previous GWASs for overall CRC risk. Multiple lines of evidence support candidate genes at several of these loci. We detected substantial heterogeneity between anatomical subsites. Just over half (61) of 109 known and new risk variants showed no evidence for heterogeneity. In contrast, 22 variants showed association with distal CRC (including rectal cancer), but no evidence for association or an attenuated association with proximal CRC. For two loci, there was strong evidence for effects confined to proximal colon cancer.Conclusion: Genetic architectures of proximal and distal CRC are partly distinct. Studies of risk factors and mechanisms of carcinogenesis, and precision prevention strategies should take into consideration the anatomical subsite of the tumour.
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| 3. |
- Schmit, Stephanie L, et al.
(författare)
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Novel Common Genetic Susceptibility Loci for Colorectal Cancer.
- 2019
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 111:2, s. 146-157
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Tidskriftsartikel (refereegranskat)abstract
- Background: Previous genome-wide association studies (GWAS) have identified 42 loci (P < 5 × 10-8) associated with risk of colorectal cancer (CRC). Expanded consortium efforts facilitating the discovery of additional susceptibility loci may capture unexplained familial risk.Methods: We conducted a GWAS in European descent CRC cases and control subjects using a discovery-replication design, followed by examination of novel findings in a multiethnic sample (cumulative n = 163 315). In the discovery stage (36 948 case subjects/30 864 control subjects), we identified genetic variants with a minor allele frequency of 1% or greater associated with risk of CRC using logistic regression followed by a fixed-effects inverse variance weighted meta-analysis. All novel independent variants reaching genome-wide statistical significance (two-sided P < 5 × 10-8) were tested for replication in separate European ancestry samples (12 952 case subjects/48 383 control subjects). Next, we examined the generalizability of discovered variants in East Asians, African Americans, and Hispanics (12 085 case subjects/22 083 control subjects). Finally, we examined the contributions of novel risk variants to familial relative risk and examined the prediction capabilities of a polygenic risk score. All statistical tests were two-sided.Results: The discovery GWAS identified 11 variants associated with CRC at P < 5 × 10-8, of which nine (at 4q22.2/5p15.33/5p13.1/6p21.31/6p12.1/10q11.23/12q24.21/16q24.1/20q13.13) independently replicated at a P value of less than .05. Multiethnic follow-up supported the generalizability of discovery findings. These results demonstrated a 14.7% increase in familial relative risk explained by common risk alleles from 10.3% (95% confidence interval [CI] = 7.9% to 13.7%; known variants) to 11.9% (95% CI = 9.2% to 15.5%; known and novel variants). A polygenic risk score identified 4.3% of the population at an odds ratio for developing CRC of at least 2.0.Conclusions: This study provides insight into the architecture of common genetic variation contributing to CRC etiology and improves risk prediction for individualized screening.
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| 4. |
- Bateman, Eric D., et al.
(författare)
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Overall asthma control achieved with budesonide/formoterol maintenance and reliever therapy for patients on different treatment steps
- 2011
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Ingår i: Respiratory Research. - : Springer Science and Business Media LLC. - 1465-9921 .- 1465-993X. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Adjusting medication for uncontrolled asthma involves selecting one of several options from the same or a higher treatment step outlined in asthma guidelines. We examined the relative benefit of introducing budesonide/formoterol (BUD/FORM) maintenance and reliever therapy (Symbicort SMART (R) Turbuhaler (R)) in patients previously prescribed treatments from Global Initiative for Asthma (GINA) Steps 2, 3 or 4. Methods: This is a post hoc analysis of the results of five large clinical trials (> 12000 patients) comparing BUD/FORM maintenance and reliever therapy with other treatments categorised by treatment step at study entry. Both current clinical asthma control during the last week of treatment and exacerbations during the study were examined. Results: At each GINA treatment step, the proportion of patients achieving target levels of current clinical control were similar or higher with BUD/FORM maintenance and reliever therapy compared with the same or a higher fixed maintenance dose of inhaled corticosteroid/long-acting beta(2)-agonist (ICS/LABA) (plus short-acting beta(2)-agonist [SABA] as reliever), and rates of exacerbations were lower at all treatment steps in BUD/FORM maintenance and reliever therapy versus same maintenance dose ICS/LABA (P < 0.01) and at treatment Step 4 versus higher maintenance dose ICS/LABA (P < 0.001). BUD/FORM maintenance and reliever therapy also achieved significantly higher rates of current clinical control and significantly lower exacerbation rates at most treatment steps compared with a higher maintenance dose ICS + SABA (Steps 2-4 for control and Steps 3 and 4 for exacerbations). With all treatments, the proportion of patients achieving current clinical control was lower with increasing treatment steps. Conclusions: BUD/FORM maintenance and reliever therapy may be a preferable option for patients on Steps 2 to 4 of asthma guidelines requiring a more effective treatment and, compared with other fixed dose alternatives, is most effective in the higher treatment steps.
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| 5. |
- Calverley, Peter M., et al.
(författare)
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Early efficacy of budesonide/formoterol in patients with moderate-to-very-severe COPD
- 2017
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Ingår i: International Journal of COPD. - 1176-9106. ; 12, s. 13-25
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Tidskriftsartikel (refereegranskat)abstract
- Background and objective: Large clinical trials have confirmed the long-term efficacy of inhaled corticosteroid/long-acting β2-agonist combinations in patients with chronic obstructive pulmonary disease (COPD). It was hypothesized that significant treatment effects would already be present within 3 months after the initiation of treatment across a range of clinical outcomes, irrespective of COPD severity. Methods: Post hoc analysis of 3-month post-randomization outcomes, including exacerbation rates, dropouts, symptoms, reliever use, and lung function, from three studies with similar inclusion criteria of moderate-to-very-severe COPD. Patients (n=1,571) were treated with budesonide/formoterol (B/F) 320/9 μg or placebo, twice daily; in one study, tiotropium 18 μg once daily was also given. Results: Over the first 3 months of treatment, fewer patients randomized to B/F experienced exacerbations versus the placebo group (111 and 196 patients with ≥1 exacerbation, respectively). This was true in each COPD severity group. Compared with placebo, B/F treatment led to significantly lower 3-month exacerbation rates in the moderate and severe COPD severity groups (46% and 57% reduction, respectively), with a nonsignificant reduction (29%) in very severe COPD. Fewer dropouts occurred among patients treated with B/F versus placebo, this effect being greater with increasing COPD severity. B/F was associated with improved forced expiratory volume in 1 s, morning peak expiratory flow rate, total reliever use, and total symptom score versus placebo. Conclusion: Treatment with B/F decreased exacerbations in patients with moderate-to-very-severe COPD within 3 months of commencing treatment. This effect was paralleled by improved lung function, less reliever medication use, and fewer symptoms, irrespective of disease severity.
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| 6. |
- Calverley, Peter M, et al.
(författare)
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Early response to inhaled bronchodilators and corticosteroids as a predictor of 12-month treatment responder status and COPD exacerbations.
- 2016
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Ingår i: The International Journal of Chronic Obstructive Pulmonary Disease. - 1178-2005. ; 11, s. 381-390
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Tidskriftsartikel (refereegranskat)abstract
- Early treatment response markers, for example, improvement in forced expiratory volume in 1 second (FEV1) and St George's Respiratory Questionnaire (SGRQ) total score, may help clinicians to better manage patients with chronic obstructive pulmonary disease (COPD). We investigated the prevalence of clinically important improvements in FEV1 and SGRQ scores after 2-month budesonide/formoterol or formoterol treatment and whether such improvements predict subsequent improvements and exacerbation rates.
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| 7. |
- Eriksson, Göran, et al.
(författare)
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The effect of COPD severity and study duration on exacerbation outcome in randomized controlled trials
- 2017
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Ingår i: International Journal of COPD. - 1176-9106. ; 12, s. 1457-1468
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Tidskriftsartikel (refereegranskat)abstract
- Background: When discontinuation in COPD randomized controlled trials (RCTs) is unevenly distributed between treatments (differential dropout), the capacity to demonstrate treatment effects may be reduced. We investigated the impact of the time of differential dropout on exacerbation outcomes in RCTs, in relation to study duration and COPD severity. Methods: A post hoc analysis of 2,345 patients from three RCTs of 6- and 12-month duration was performed to compare budesonide/formoterol and formoterol in moderate, severe, and very severe COPD. Outcomes were exacerbation rate, time-to-first exacerbation, or discontinuation; patients were stratified by disease severity. Outcomes were studied by censoring data monthly from 1 to 12 months. Results: In patients treated with budesonide/formoterol, annualized exacerbation rates (AERs) were comparable for each study duration (rate ratio [RR] =0.6). With formoterol, the AER decreased with study duration (RR =1.20 at 1 month to RR =0.86 at 12 months). There was a treatment-related difference in exacerbation rates of 45%–48% for shorter study durations (≤4 months) and 27% for 12-month duration. This treatment-related difference in exacerbation rates was comparable for the three disease severities in studies ≤4 months (range: 39%–51%), but this difference decreased with longer study durations, especially in more severe groups (22% and 29% at 12 months). There were fewer discontinuations with budesonide/formoterol; the treatmentrelated difference in time-to-first discontinuation decreased by study duration (35%, 30%, 26%, and 22% at 3, 6, 9, and 12 months, respectively). Numbers of differential dropouts increased with increasing disease severity, being greatest during second, third, and fourth months. Conclusions: COPD severity and study duration impact exacerbation as an outcome in double-blind RCTs. This effect is most obvious in patients with severe/very severe COPD and in studies that are longer than 4 months. Early differential dropout particularly impacts study outcome, producing a “healthy survivor effect,” which reduces estimations of treatment impact on exacerbations.
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| 8. |
- Jenkins, Christine R, et al.
(författare)
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Reliever salbutamol use as a measure of exacerbation risk in chronic obstructive pulmonary disease.
- 2015
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Ingår i: BMC Pulmonary Medicine. - : Springer Science and Business Media LLC. - 1471-2466. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- Debate exists regarding which endpoints most sensitively reflect day-to-day variation in chronic obstructive pulmonary disease (COPD) symptoms and are most useful in clinical practice to predict COPD exacerbations. We hypothesized that short-acting β2-agonist (SABA) reliever use would predict short- and long-term exacerbation risk in COPD patients.
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| 9. |
- Arun, K. G., et al.
(författare)
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New horizons for fundamental physics with LISA
- 2022
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Ingår i: Living Reviews in Relativity. - : Springer Science and Business Media LLC. - 1433-8351 .- 2367-3613. ; 25:1
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Forskningsöversikt (refereegranskat)abstract
- The Laser Interferometer Space Antenna (LISA) has the potential to reveal wonders about the fundamental theory of nature at play in the extreme gravity regime, where the gravitational interaction is both strong and dynamical. In this white paper, the Fundamental Physics Working Group of the LISA Consortium summarizes the current topics in fundamental physics where LISA observations of gravitational waves can be expected to provide key input. We provide the briefest of reviews to then delineate avenues for future research directions and to discuss connections between this working group, other working groups and the consortium work package teams. These connections must be developed for LISA to live up to its science potential in these areas.
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| 10. |
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