| 481. |
- Berkelmans, G. F. N., et al.
(author)
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Population median imputation was noninferior to complex approaches for imputing missing values in cardiovascular prediction models in clinical practice
- 2022
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In: Journal of Clinical Epidemiology. - : Elsevier BV. - 0895-4356. ; 145, s. 70-80
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Journal article (peer-reviewed)abstract
- Objectives: To compare the validity and robustness of five methods for handling missing characteristics when using cardiovascular disease risk prediction models for individual patients in a real-world clinical setting.& nbsp;Study design and setting: The performance of the missing data methods was assessed using data from the Swedish National Diabetes Registry (n = 419,533) with external validation using the Scottish Care Information ? diabetes database (n = 226,953). Five methods for handling missing data were compared. Two methods using submodels for each combination of available data, two imputation methods: conditional imputation and median imputation, and one alternative modeling method, called the naive approach, based on hazard ratios and populations statistics of known risk factors only. The validity was compared using calibration plots and c-statistics.& nbsp;Results: C-statistics were similar across methods in both development and validation data sets, that is, 0.82 (95% CI 0.82-0.83) in the Swedish National Diabetes Registry and 0.74 (95% CI 0.74-0.75) in Scottish Care Information-diabetes database. Differences were only observed after random introduction of missing data in the most important predictor variable (i.e., age).& nbsp;Conclusion: Validity and robustness of median imputation was not dissimilar to more complex methods for handling missing values, provided that the most important predictor variables, such as age, are not missing. (C)& nbsp;2022 Elsevier Inc. All rights reserved.
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| 482. |
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| 483. |
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| 484. |
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| 485. |
- Campbell, M, et al.
(author)
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Detection of single electrons by means of a Micromegas-covered Medipix2 pixel CMOS readout circuit
- 2005
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In: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 540:2-3, s. 295-304
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Journal article (peer-reviewed)abstract
- A small drift chamber was read out by means of a MediPix2 readout chip as a direct anode. A Micromegas foil was placed above the chip, and electron multiplication occurred in the gap. With a He/isobutane 80/20 mixture, gas multiplication factors up to tens of thousands were achieved, resulting in an efficiency for detecting single electrons of better than 90%. We recorded many frames containing 2D images with tracks from cosmic muons. Along these tracks, electron clusters were observed, as well as δ-rays.
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| 486. |
- Colas, P, et al.
(author)
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The readout of a GEM or Micromegas-equipped TPC by means of the Medipix2 CMOS sensor as direct anode
- 2004
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In: Nuclear Instruments and Methods in Physics Research Section A. - 0168-9002 .- 1872-9576. ; 535:1-2, s. 506-510
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Journal article (peer-reviewed)abstract
- We have applied the Medipix2 pixel CMOS chip as direct anode readout for a TPC. For the gas amplification two options have been investigated: (i) a three-stage GEM system and (ii) a Micromegas mesh. The structure of the cloud of primary electrons, left after interactions of 55Fe quanta with the gas is visible with unprecedented precision. This proof-of-principle is an essential step in our project to realize a monolithic pixel sensor with integrated Micromegas, to be developed specially for the readout of TPCs, and applicable for drift chambers in general.
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| 487. |
- Ferrari, A., et al.
(author)
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Adolescents and young adults (AYA) with cancer : a position paper from the AYA Working Group of the European Society for Medical Oncology (ESMO) and the European Society for Paediatric Oncology (SIOPE)
- 2021
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In: ESMO Open. - : Elsevier BV. - 2059-7029. ; 6:2
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Research review (peer-reviewed)abstract
- It is well recognised that adolescents and young adults (AYA) with cancer have inequitable access to oncology services that provide expert cancer care and consider their unique needs. Subsequently, survival gains in this patient population have improved only modestly compared with older adults and children with cancer. In 2015, the European Society for Medical Oncology (ESMO) and the European Society for Paediatric Oncology (SIOPE) established the joint Cancer in AYA Working Group in order to increase awareness among adult and paediatric oncology communities, enhance knowledge on specific issues in AYA and ultimately improve the standard of care for AYA with cancer across Europe. This manuscript reflects the position of this working group regarding current AYA cancer care, the challenges to be addressed and possible solutions. Key challenges include the lack of specific biological understanding of AYA cancers, the lack of access to specialised centres with age-appropriate multidisciplinary care and the lack of available clinical trials with novel therapeutics. Key recommendations include diversifying interprofessional cooperation in AYA care and specific measures to improve trial accrual, including centralising care where that is the best means to achieve trial accrual. This defines a common vision that can lead to improved outcomes for AYA with cancer in Europe.
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| 488. |
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| 489. |
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| 490. |
- Musuamba, F. T., et al.
(author)
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Advanced Methods for Dose and Regimen Finding During Drug Development : Summary of the EMA/EFPIA Workshop on Dose Finding (London 4-5 December 2014)
- 2017
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In: CPT. - : Wiley. - 2163-8306. ; 6:7, s. 418-429
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Journal article (peer-reviewed)abstract
- Inadequate dose selection for confirmatory trials is currently still one of the most challenging issues in drug development, as illustrated by high rates of late-stage attritions in clinical development and postmarketing commitments required by regulatory institutions. In an effort to shift the current paradigm in dose and regimen selection and highlight the availability and usefulness of well-established and regulatory-acceptable methods, the European Medicines Agency (EMA) in collaboration with the European Federation of Pharmaceutical Industries Association (EFPIA) hosted a multistakeholder workshop on dose finding (London 4-5 December 2014). Some methodologies that could constitute a toolkit for drug developers and regulators were presented. These methods are described in the present report: they include five advanced methods for data analysis (empirical regression models, pharmacometrics models, quantitative systems pharmacology models, MCP-Mod, and model averaging) and three methods for study design optimization (Fisher information matrix (FIM)-based methods, clinical trial simulations, and adaptive studies). Pairwise comparisons were also discussed during the workshop; however, mostly for historical reasons. This paper discusses the added value and limitations of these methods as well as challenges for their implementation. Some applications in different therapeutic areas are also summarized, in line with the discussions at the workshop. There was agreement at the workshop on the fact that selection of dose for phase III is an estimation problem and should not be addressed via hypothesis testing. Dose selection for phase III trials should be informed by well-designed dosefinding studies; however, the specific choice of method(s) will depend on several aspects and it is not possible to recommend a generalized decision tree. There are many valuable methods available, the methods are not mutually exclusive, and they should be used in conjunction to ensure a scientifically rigorous understanding of the dosing rationale.
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