| 291. |
- Richards, David A, et al.
(författare)
-
Integrating quantitative and qualitative data and findings when undertaking randomised controlled trials.
- 2019
-
Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 9:11
-
Tidskriftsartikel (refereegranskat)abstract
- It is common to undertake qualitative research alongside randomised controlled trials (RCTs) when evaluating complex interventions. Researchers tend to analyse these datasets one by one and then consider their findings separately within the discussion section of the final report, rarely integrating quantitative and qualitative data or findings, and missing opportunities to combine data in order to add rigour, enabling thorough and more complete analysis, provide credibility to results, and generate further important insights about the intervention under evaluation. This paper reports on a 2 day expert meeting funded by the United Kingdom Medical Research Council Hubs for Trials Methodology Research with the aims to identify current strengths and weaknesses in the integration of quantitative and qualitative methods in clinical trials, establish the next steps required to provide the trials community with guidance on the integration of mixed methods in RCTs and set-up a network of individuals, groups and organisations willing to collaborate on related methodological activity. We summarise integration techniques and go beyond previous publications by highlighting the potential value of integration using three examples that are specific to RCTs. We suggest that applying mixed methods integration techniques to data or findings from studies involving both RCTs and qualitative research can yield insights that might be useful for understanding variation in outcomes, the mechanism by which interventions have an impact, and identifying ways of tailoring therapy to patient preference and type. Given a general lack of examples and knowledge of these techniques, researchers and funders will need future guidance on how to undertake and appraise them.
|
|
| 292. |
- Romanowicz, Renata J., et al.
(författare)
-
A data based mechanistic approach to nonlinear flood routing and adaptive flood level forecasting
- 2008
-
Ingår i: Advances in Water Resources. - : Elsevier BV. - 0309-1708 .- 1872-9657. ; 31:8, s. 1048-1056
-
Tidskriftsartikel (refereegranskat)abstract
- Operational flood forecasting requires accurate forecasts with a suitable lead time, in order to be able to issue appropriate warnings and take appropriate emergency actions. Recent improvements in both flood plain characterization and computational capabilities have made the use of distributed flood inundation models more common. However, problems remain with the application of such models. There are still uncertainties associated with the identifiability of parameters, with the computational burden of calculating distributed estimates of predictive uncertainty, and with the adaptive use of such models for operational, real-time flood inundation forecasting. Moreover, the application of distributed models is complex, costly and requires high degrees of skill. This paper presents an alternative to distributed inundation models for real-time flood forecasting that provides fast and accurate, medium to short-term forecasts. The Data Based Mechanistic (DBM) methodology exploits a State Dependent Parameter (SDP) modelling approach to derive a nonlinear dependence between the water levels measured at gauging stations along the river. The transformation of water levels depends on the relative geometry of the channel cross-sections, without the need to apply rating curve transformations to the discharge. The relationship obtained is used to transform water levels as an input to a linear, on-line, real-time and adaptive stochastic DBM model. The approach provides an estimate of the prediction uncertainties, including allowing for heterescadasticity of the multi-step-ahead forecasting errors. The approach is illustrated using an 80 km reach of the River Severn, in the UK.
|
|
| 293. |
- Romanowicz, Renata J., et al.
(författare)
-
Uncertainty propagation in a sequential model for flood forecasting
- 2006
-
Ingår i: Predictions in ungauged basins. - : International Association of Hydrological Sciences. - 1901502481 ; , s. 177-184
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this paper is the estimation of uncertainty in an online data assimilation model applied to a sequential, multiple-step-ahead flood forecasting system. The main aim of the forecasting system under consideration is the derivation of real-time forecasts of the water levels with the maximum possible lead-time. This is achieved through a two-level, sequential data assimilation procedure. In order to extend the maximum lead-time, we incorporate the forecasts obtained from the earlier stages of the forecasting system, both rainfall-water level and water level routing processes. The updating of the gain of each of the subsystems introduces nonlinearity into the system performance. The Generalized Likelihood Uncertainty Estimation (GLUE) technique is used to estimate the uncertainty of model predictions in the decomposed online forecasting system.
|
|
| 294. |
|
|
| 295. |
- Ross, Owen A., et al.
(författare)
-
Association of LRRK2 exonic variants with susceptibility to Parkinson's disease: a case-control study
- 2011
-
Ingår i: Lancet Neurology. - 1474-4465. ; 10:10, s. 898-908
-
Tidskriftsartikel (refereegranskat)abstract
- Background The leucine-rich repeat kinase 2 gene (LRRK2) harbours highly penetrant mutations that are linked to familial parkinsonism. However, the extent of its polymorphic variability in relation to risk of Parkinson's disease (PD) has not been assessed systematically. We therefore assessed the frequency of LRRK2 exonic variants in individuals with and without PD, to investigate the role of the variants in PD susceptibility. Methods LRRK2 was genotyped in patients with PD and controls from three series (white, Asian, and Arab-Berber) from sites participating in the Genetic Epidemiology of Parkinson's Disease Consortium. Genotyping was done for exonic variants of LRRK2 that were identified through searches of literature and the personal communications of consortium members. Associations with PD were assessed by use of logistic regression models. For variants that had a minor allele frequency of 0.5% or greater, single variant associations were assessed, whereas for rarer variants information was collapsed across variants. Findings 121 exonic LRRK2 variants were assessed in 15 540 individuals: 6995 white patients with PD and 5595 controls, 1376 Asian patients and 962 controls, and 240 Arab-Berber patients and 372 controls. After exclusion of carriers of known pathogenic mutations, new independent risk associations were identified for polymorphic variants in white individuals (M1646T, odds ratio 1.43, 95% CI 1.15-1.78; p=0.0012) and Asian individuals (A419V, 2.27, 1.35-3.83; p=0.0011). A protective haplotype (N551K-R1398H-K1423K) was noted at a frequency greater than 5% in the white and Asian series, with a similar finding in the Arab-Berber series (combined odds ratio 0.82, 0.72-0.94; p=0.0043). Of the two previously reported Asian risk variants, G2385R was associated with disease (1.73, 1.20-2.49; p=0.0026), but no association was noted for R1628P (0.62, 0.36-1.07; p=0.087). In the Arab-Berber series, Y2189C showed potential evidence of risk association with PD (4.48, 133-15.09; p=0.012). Interpretation The results for LRRK2 show that several rare and common genetic variants in the same gene can have independent effects on disease risk. LRRK2, and the pathway in which it functions, is important in the cause and pathogenesis of PD in a greater proportion of patients with this disease than previously believed. These results will help discriminate those patients who will benefit most from therapies targeted at LRRK2 pathogenic activity. Funding Michael J Fox Foundation and National Institutes of Health.
|
|
| 296. |
- Rusz, Jan, et al.
(författare)
-
Probing the electronic structure of pure and doped CeMIn5 (M=Co,Rh,Ir) crystals with nuclear quadrupolar resonance
- 2008
-
Ingår i: Physical Review B. Condensed Matter and Materials Physics. - 1098-0121 .- 1550-235X. ; 77:24, s. 245124-
-
Tidskriftsartikel (refereegranskat)abstract
- We report calculations of the electric-field gradients (EFGs) in pure and doped CeMIn5 (M=Co, Rh, and Ir) compounds and compare with experiment. The degree to which the Ce 4f electron is localized is treated within various models: the local-density approximation, generalized gradient approximation (GGA), GGA+U, and 4f-core approaches. We find that there is a correlation between the observed EFG and whether the 4f electron participates in the band formation or not. We also find that the EFG evolves linearly with Sn doping in CeRhIn5, suggesting the electronic structure is modified by doping. In contrast, the observed EFG in CeCoIn5 doped with Cd changes little with doping. These results indicate that nuclear quadrupolar resonance is a sensitive probe of electronic structure.
|
|
| 297. |
- Saboya, Eric, et al.
(författare)
-
Combining Top-Down and Bottom-Up Approaches to Evaluate Recent Trends and Seasonal Patterns in UK N2O Emissions
- 2024
-
Ingår i: Journal of Geophysical Research: Atmospheres. - 2169-897X. ; 129:14
-
Tidskriftsartikel (refereegranskat)abstract
- Atmospheric trace gas measurements can be used to independently assess national greenhouse gas inventories through inverse modeling. Atmospheric nitrous oxide (N2O) measurements made in the United Kingdom (UK) and Republic of Ireland are used to derive monthly N2O emissions for 2013–2022 using two different inverse methods. We find mean UK emissions of 90.5 ± 23.0 (1σ) and 111.7 ± 32.1 (1σ) Gg N2O yr−1 for 2013–2022, and corresponding trends of −0.68 ± 0.48 (1σ) Gg N2O yr−2 and −2.10 ± 0.72 (1σ) Gg N2O yr−2, respectively, for the two inverse methods. The UK National Atmospheric Emissions Inventory (NAEI) reported mean N2O emissions of 73.9 ± 1.7 (1σ) Gg N2O yr−1 across this period, which is 22%–51% smaller than the emissions derived from atmospheric data. We infer a pronounced seasonal cycle in N2O emissions, with a peak occurring in the spring and a second smaller peak in the late summer for certain years. The springtime peak has a long seasonal decline that contrasts with the sharp rise and fall of N2O emissions estimated from the bottom-up UK Emissions Model (UKEM). Bayesian inference is used to minimize the seasonal cycle mismatch between the average top-down (atmospheric data-based) and bottom-up (process model and inventory-based) seasonal emissions at a sub-sector level. Increasing agricultural manure management and decreasing synthetic fertilizer N2O emissions reduces some of the discrepancy between the average top-down and bottom-up seasonal cycles. Other possibilities could also explain these discrepancies, such as missing emissions from NH3 deposition, but these require further investigation.
|
|
| 298. |
- Saner, Flurina A. M., et al.
(författare)
-
Concurrent RB1 Loss and BRCA Deficiency Predicts Enhanced Immunologic Response and Long-term Survival in Tubo-ovarian High-grade Serous Carcinoma
- 2024
-
Ingår i: CLINICAL CANCER RESEARCH. - 1078-0432 .- 1557-3265. ; 30:16, s. 3481-3498
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: The purpose of this study was to evaluate RB1 expression and survival across ovarian carcinoma histotypes and how co-occurrence of BRCA1 or BRCA2 (BRCA) alterations and RB1 loss influences survival in tubo-ovarian high-grade serous carcinoma (HGSC). Experimental Design: RB1 protein expression was classified by immunohistochemistry in ovarian carcinomas of 7,436 patients from the Ovarian Tumor Tissue Analysis consortium. We examined RB1 expression and germline BRCA status in a subset of 1,134 HGSC, and related genotype to overall survival (OS), tumor-infiltrating CD8+ lymphocytes, and transcriptomic subtypes. Using CRISPR-Cas9, we deleted RB1 in HGSC cells with and without BRCA1 alterations to model co-loss with treatment response. We performed whole-genome and transcriptome data analyses on 126 patients with primary HGSC to characterize tumors with concurrent BRCA deficiency and RB1 loss. Results: RB1 loss was associated with longer OS in HGSC but with poorer prognosis in endometrioid ovarian carcinoma. Patients with HGSC harboring both RB1 loss and pathogenic germline BRCA variants had superior OS compared with patients with either alteration alone, and their median OS was three times longer than those without pathogenic BRCA variants and retained RB1 expression (9.3 vs. 3.1 years). Enhanced sensitivity to cisplatin and paclitaxel was seen in BRCA1-altered cells with RB1 knockout. Combined RB1 loss and BRCA deficiency correlated with transcriptional markers of enhanced IFN response, cell-cycle deregulation, and reduced epithelial-mesenchymal transition. CD8(+) lymphocytes were most prevalent in BRCA-deficient HGSC with co-loss of RB1. Conclusions: Co-occurrence of RB1 loss and BRCA deficiency was associated with exceptionally long survival in patients with HGSC, potentially due to better treatment response and immune stimulation.
|
|
| 299. |
- Saurer, Matthias, et al.
(författare)
-
Spatial variability and temporal trends in water-use efficiency of European forests
- 2014
-
Ingår i: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 20:12, s. 3700-3712
-
Tidskriftsartikel (refereegranskat)abstract
- The increasing carbon dioxide (CO2) concentration in the atmosphere in combination with climatic changes throughout the last century are likely to have had a profound effect on the physiology of trees: altering the carbon and water fluxes passing through the stomatal pores. However, the magnitude and spatial patterns of such changes in natural forests remain highly uncertain. Here, stable carbon isotope ratios from a network of 35 tree-ring sites located across Europe are investigated to determine the intrinsic water-use efficiency (iWUE), the ratio of photosynthesis to stomatal conductance from 1901 to 2000. The results were compared with simulations of a dynamic vegetation model (LPX-Bern 1.0) that integrates numerous ecosystem and land-atmosphere exchange processes in a theoretical framework. The spatial pattern of tree-ring derived iWUE of the investigated coniferous and deciduous species and the model results agreed significantly with a clear south-to-north gradient, as well as a general increase in iWUE over the 20th century. The magnitude of the iWUE increase was not spatially uniform, with the strongest increase observed and modelled for temperate forests in Central Europe, a region where summer soil-water availability decreased over the last century. We were able to demonstrate that the combined effects of increasing CO2 and climate change leading to soil drying have resulted in an accelerated increase in iWUE. These findings will help to reduce uncertainties in the land surface schemes of global climate models, where vegetation-climate feedbacks are currently still poorly constrained by observational data.
|
|
| 300. |
|
|
