| 1. |
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| 2. |
- Fresard, Laure, et al.
(författare)
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Identification of rare-disease genes using blood transcriptome sequencing and large control cohorts
- 2019
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Ingår i: Nature Medicine. - : NATURE PUBLISHING GROUP. - 1078-8956 .- 1546-170X. ; 25:6, s. 911-919
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Tidskriftsartikel (refereegranskat)abstract
- It is estimated that 350 million individuals worldwide suffer from rare diseases, which are predominantly caused by mutation in a single gene(1). The current molecular diagnostic rate is estimated at 50%, with whole-exome sequencing (WES) among the most successful approaches(2-5). For patients in whom WES is uninformative, RNA sequencing (RNA-seq) has shown diagnostic utility in specific tissues and diseases(6-8). This includes muscle biopsies from patients with undiagnosed rare muscle disorders(6,9), and cultured fibroblasts from patients with mitochondrial disorders(7). However, for many individuals, biopsies are not performed for clinical care, and tissues are difficult to access. We sought to assess the utility of RNA-seq from blood as a diagnostic tool for rare diseases of different pathophysiologies. We generated whole-blood RNA-seq from 94 individuals with undiagnosed rare diseases spanning 16 diverse disease categories. We developed a robust approach to compare data from these individuals with large sets of RNA-seq data for controls (n = 1,594 unrelated controls and n = 49 family members) and demonstrated the impacts of expression, splicing, gene and variant filtering strategies on disease gene identification. Across our cohort, we observed that RNA-seq yields a 7.5% diagnostic rate, and an additional 16.7% with improved candidate gene resolution.
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| 3. |
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| 4. |
- Schaap, M., et al.
(författare)
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Standardized evaluation methodology and reference database for evaluating coronary artery centerline extraction algorithms
- 2009
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Ingår i: Medical Image Analysis. - : Elsevier. - 1361-8415 .- 1361-8423. ; 13:5, s. 701-714
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Tidskriftsartikel (refereegranskat)abstract
- Efficiently obtaining a reliable coronary artery centerline from computed tomography angiography data is relevant in clinical practice. Whereas numerous methods have been presented for this purpose, up to now no standardized evaluation methodology has been published to reliably evaluate and compare the performance of the existing or newly developed coronary artery centerline extraction algorithms. This paper describes a standardized evaluation methodology and reference database for the quantitative evaluation of coronary artery centerline extraction algorithms. The contribution of this work is fourfold: (1) a method is described to create a consensus centerline with multiple observers, (2) well-defined measures are presented for the evaluation of coronary artery centerline extraction algorithms, (3) a database containing 32 cardiac CTA datasets with corresponding reference standard is described and made available, and (4) 13 coronary artery centerline extraction algorithms, implemented by different research groups, are quantitatively evaluated and compared. The presented evaluation framework is made available to the medical imaging community for benchmarking existing or newly developed coronary centerline extraction algorithms.
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| 5. |
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| 6. |
- Pistidda, C., et al.
(författare)
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Hydrogen storage systems from waste Mg alloys
- 2014
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Ingår i: Journal of Power Sources. - : Elsevier BV. - 1873-2755 .- 0378-7753. ; 270, s. 554-563
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Tidskriftsartikel (refereegranskat)abstract
- The production cost of materials for hydrogen storage is one of the major issues to be addressed in order to consider them suitable for large scale applications. In the last decades several authors reported on the hydrogen sorption properties of Mg and Mg-based systems. In this work magnesium industrial wastes of AZ91 alloy and Mg-10 wt.% Gd alloy are used for the production of hydrogen storage materials. The hydrogen sorption properties of the alloys were investigated by means of volumetric technique, in situ synchrotron radiation powder X-ray diffraction (SR-PXD) and calorimetric methods. The measured reversible hydrogen storage capacity for the alloys AZ91 and Mg-10 wt.% Gd are 4.2 and 5.8 wt.%, respectively. For the Mg-10 wt.% Gd alloy, the hydrogenated product was also successfully used as starting reactant for the synthesis of Mg(NH2)(2) and as MgH2 substitute in the Reactive Hydride Composite (RHC) 2LiBH(4) + MgH2. The results of this work demonstrate the concrete possibility to use Mg alloy wastes for hydrogen storage purposes. (C) 2014 Elsevier B.V. All rights reserved.
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| 7. |
- Pereira, M. P., et al.
(författare)
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European academy of dermatology and venereology European prurigo project : Expert consensus on the definition, classification and terminology of chronic prurigo
- 2018
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Ingår i: Journal of the European Academy of Dermatology and Venereology. - : Wiley. - 0926-9959. ; 32:7, s. 1059-1065
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Tidskriftsartikel (refereegranskat)abstract
- Background: The term prurigo has been used for many decades in dermatology without clear definition, and currently used terminology of prurigo is inconsistent and confusing. Especially, itch-related prurigo remains unexplored regarding the epidemiology, clinical profile, natural course, underlying causes, available treatments and economic burden, although burdensome and difficult to treat. Objective: To address these issues, the multicentre European Prurigo Project (EPP) was designed to increase knowledge on chronic prurigo (CPG). In the first step, European experts of the EADV Task Force Pruritus (TFP) aimed to achieve a consensus on the definition, classification and terminology of CPG. Additionally, procedures of the cross-sectional EPP were discussed and agreed upon. Methods: Discussions and surveys between members of the TFP served as basis for a consensus conference. Using the Delphi method, consensus was defined as an agreement ≥75% among the present members. Results: Twenty-four members of the TFP participated in the consensus conference. Experts consented that CPG should be used as an umbrella term for the range of clinical manifestations (e.g. papular, nodular, plaque or umbilicated types). CPG is considered a distinct disease defined by the presence of chronic pruritus for ≥6 weeks, history and/or signs of repeated scratching and multiple localized/generalized pruriginous skin lesions (whitish or pink papules, nodules and/or plaques). CPG occurs due to a neuronal sensitization to itch and the development of an itch-scratch cycle. Conclusion: This new definition and terminology of CPG should be implemented in dermatology to harmonize communication in the clinical routine, clinical trials and scientific literature. Acute/subacute forms of prurigo are separated entities, which need to be differentiated from CPG and will be discussed in a next step. In the near future, the cross-sectional EPP will provide relevant clinical data on various aspects of CPG leading to new directions in the scientific investigation of CGP.
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| 8. |
- Kirişli, Hortense, et al.
(författare)
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Standardized evaluation framework for evaluating coronary artery stenosis detection, stenosis quantification and lumen segmentation algorithms in computed tomography angiography
- 2013
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Ingår i: Medical Image Analysis. - : Elsevier. - 1361-8415 .- 1361-8423. ; 17:8, s. 859-876
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Tidskriftsartikel (refereegranskat)abstract
- Though conventional coronary angiography (CCA) has been the standard of reference for diagnosing coronary artery disease in the past decades, computed tomography angiography (CIA) has rapidly emerged, and is nowadays widely used in clinical practice. Here, we introduce a standardized evaluation framework to reliably evaluate and compare the performance of the algorithms devised to detect and quantify the coronary artery stenoses, and to segment the coronary artery lumen in CIA data. The objective of this evaluation framework is to demonstrate the feasibility of dedicated algorithms to: (I) (semi-)automatically detect and quantify stenosis on CIA, in comparison with quantitative coronary angiography (QCA) and CIA consensus reading, and (2) (semi-)automatically segment the coronary lumen on CIA, in comparison with expert's manual annotation. A database consisting of 48 multicenter multivendor cardiac CIA datasets with corresponding reference standards are described and made available. The algorithms from 11 research groups were quantitatively evaluated and compared. The results show that (1) some of the current stenosis detection/quantification algorithms may be used for triage or as a second-reader in clinical practice, and that (2) automatic lumen segmentation is possible with a precision similar to that obtained by experts. The framework is open for new submissions through the website, at http://coronary.bigr.nl/stenoses/.
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| 9. |
- Pereira, M. P., et al.
(författare)
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Position Statement : Linear prurigo is a subtype of chronic prurigo
- 2019
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Ingår i: Journal of the European Academy of Dermatology and Venereology. - : Wiley. - 0926-9959 .- 1468-3083. ; 33:2, s. 263-266
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Tidskriftsartikel (refereegranskat)abstract
- Background: Chronic prurigo (CPG) is a distinct disease characterized by chronic pruritus, history and/or signs of prolonged scratching and multiple pruriginous lesions. It may present with various clinical manifestations, including papules, nodules, plaques or umbilicated lesions. Some patients with chronic pruritus show pruriginous linear and scaring scratch lesions (LSSL) and it is unclear whether these lesions belong to the spectrum of CPG. Objective: To achieve a consensus on the classification of pruriginous LSSL and establish criteria to differentiate them from similar appearing conditions of different nature. Methods: Members of the Task Force Pruritus (TFP) of the European Academy of Dermatology and Venereology participated in the consensus conference, discussing representative clinical cases. Using the Delphi method, consensus was reached when ≥75% of members agreed on a statement. Results: Twenty-one members of the TFP with voting rights participated in the meeting. It was consented that LSSL occurs due to chronic pruritus and prolonged scratching, and share common pathophysiological mechanisms with CPG. LSSL were thus considered as belonging to the spectrum of CPG and the term ‘linear prurigo’ was chosen to describe this manifestation. Conclusion: Considering linear prurigo as belonging to the spectrum of CPG has important clinical implications, since both the diagnostic and therapeutic approach of these patients should be performed as recommended for CPG. Importantly, linear prurigo should be differentiated from self-inflicted skin lesions as factitious disorders or skin picking syndromes. In the latter, artificial manipulation rather than pruritus itself leads to the development of cutaneous lesions, which can show clinical similarities to linear prurigo.
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| 10. |
- Ständer, Sonja, et al.
(författare)
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IFSI-Guideline on Chronic Prurigo including Prurigo nodularis.
- 2020
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Ingår i: ITCH. - : Ovid Technologies (Wolters Kluwer Health). - 2380-5048. ; 5:4, s. 1-13
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Forskningsöversikt (refereegranskat)abstract
- Chronic prurigo (CPG) is a highly burdensome pruritic disease characterized by chronic itch, a prolonged scratching behavior and the development of localized or generalized hyperkeratotic pruriginous lesions. Neuronal sensitization and the development of an itch-scratch cycle contribute to the augmentation of pruritus and the chronicity of the disease. We provide here the first international guideline for a rational diagnostic and therapeutic approach for CPG. Recommendations are based on available evidence and expert opinion. The diagnosis of CPG is made clinically. A detailed medical history together with laboratory and radiological examinations are advised in order to determine the severity of CPG, identify the underlying origin of the itch and assist in the elaboration of a treatment plan. Therapeutically, it is advised to adopt a multimodal approach, including general strategies to control itch, treatment of the underlying pruritic conditions, and of the pruriginous lesions. Topical (corticosteroids, calcineurin inhibitors, capsaicin) and systemic antipruritic agents (eg, gabapentinoids, immunosuppressants, and opioid modulators) as well as physical treatment modalities (phototherapy, cryotherapy) should be employed in a step-wise approach. Psychosomatic or psychological interventions may be recommended in CPG patients with signs of psychiatric/psychological comorbidities.
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| 11. |
- Kerkhoven, Eduard, 1985, et al.
(författare)
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Leucine Biosynthesis Is Involved in Regulating High Lipid Accumulation in Yarrowia lipolytica
- 2017
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Ingår i: mBio. - 2150-7511 .- 2161-2129. ; 8:3, s. Article no. e00857-17
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Tidskriftsartikel (refereegranskat)abstract
- The yeast Yarrowia lipolytica is a potent accumulator of lipids, and lipogenesis in this organism can be influenced by a variety of factors, such as genetics and environmental conditions. Using a multifactorial study, we elucidated the effects of both genetic and environmental factors on regulation of lipogenesis in Y. lipolytica and identified how two opposite regulatory states both result in lipid accumulation. This study involved comparison of a strain overexpressing diacylglycerol acyltransferase (DGA1) with a control strain grown under either nitrogen or carbon limitation conditions. A strong correlation was observed between the responses on the transcript and protein levels. Combination of DGA1 overexpression with nitrogen limitation resulted in a high level of lipid accumulation accompanied by downregulation of several amino acid biosynthetic pathways, including that of leucine in particular, and these changes were further correlated with a decrease in metabolic fluxes. This downregulation was supported by the measured decrease in the level of 2-isopropylmalate, an intermediate of leucine biosynthesis. Combining the multi-omics data with putative transcription factor binding motifs uncovered a contradictory role for TORC1 in controlling lipid accumulation, likely mediated through 2-isopropylmalate and a Leu3-like transcription factor. IMPORTANCE The ubiquitous metabolism of lipids involves refined regulation, and an enriched understanding of this regulation would have wide implications. Various factors can influence lipid metabolism, including the environment and genetics. We demonstrated, using a multi-omics and multifactorial experimental setup, that multiple factors affect lipid accumulation in the yeast Yarrowia lipolytica. Using integrative analysis, we identified novel interactions between nutrient restriction and genetic factors involving regulators that are highly conserved among eukaryotes. Given that lipid metabolism is involved in many diseases but is also vital to the development of microbial cell factories that can provide us with sustainable fuels and oleochemicals, we envision that our report introduces foundational work to further unravel the regulation of lipid accumulation in eukaryal cells.
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| 12. |
- Nogly, P., et al.
(författare)
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Lipidic cubic phase serial millisecond crystallography using synchrotron radiation
- 2015
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Ingår i: Iucrj. - : International Union of Crystallography (IUCr). - 2052-2525. ; 2
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Tidskriftsartikel (refereegranskat)abstract
- Lipidic cubic phases (LCPs) have emerged as successful matrixes for the crystallization of membrane proteins. Moreover, the viscous LCP also provides a highly effective delivery medium for serial femtosecond crystallography (SFX) at X-ray free-electron lasers (XFELs). Here, the adaptation of this technology to perform serial millisecond crystallography (SMX) at more widely available synchrotron microfocus beamlines is described. Compared with conventional microcrystallography, LCP-SMX eliminates the need for difficult handling of individual crystals and allows for data collection at room temperature. The technology is demonstrated by solving a structure of the light-driven proton-pump bacteriorhodopsin (bR) at a resolution of 2.4 angstrom. The room-temperature structure of bR is very similar to previous cryogenic structures but shows small yet distinct differences in the retinal ligand and proton-transfer pathway.
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| 13. |
- Pereira, M. P., et al.
(författare)
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Chronic nodular prurigo : clinical profile and burden. A European cross-sectional study
- 2020
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Ingår i: Journal of the European Academy of Dermatology and Venereology. - : Wiley. - 0926-9959 .- 1468-3083. ; 34:10, s. 2373-2383
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Tidskriftsartikel (refereegranskat)abstract
- Background: Chronic nodular prurigo (CNPG) is a condition characterized by chronic itch, a prolonged scratching behaviour and the presence of pruriginous nodules. A comprehensive understanding of this condition, especially regarding its clinical characteristics and impact on quality of life is still lacking. Objectives: Aim of this pan-European multicentre cross-sectional study was to establish the clinical profile of CNPG, including its associated burden. Methods: Fifteen centres from 12 European countries recruited CNPG patients presenting at the centre or using the centres' own databases. Patients were asked to complete a questionnaire in paper or electronic format. Demography, current co-morbidities, underlying disease, itch intensity, additional sensory symptoms, quality of life, highest burden and emotional experience of itch were assessed. Results: A total of 509 patients (210 male, median age: 64 years [52; 72]) were enrolled. Of these, 406 reported itch and CNPG lesions in the previous 7 days and qualified to complete the whole questionnaire. We recorded moderate to severe worst itch intensity scores in the previous 24 h. Scores were higher in patients with lower educational levels and those coming from Eastern or Southern Europe. Most patients experience itch often or always (71%) and report that their everyday life is negatively affected (53%). Itch intensity was considered to be the most burdensome aspect of the disease by 49% of the patients, followed by the visibility of skin lesions (21%) and bleeding of lesions (21%). The majority of patients was unaware of an underlying condition contributing to CNPG (64%), while psychiatric diseases were the conditions most often mentioned in association with CNPG (19%). Conclusions: This multicentre cross-sectional study shows that itch is the dominant symptom in CNPG and reveals that the profile of the disease is similar throughout Europe.
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| 14. |
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| 15. |
- Allentoft, Morten E., et al.
(författare)
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Population genomics of post-glacial western Eurasia
- 2024
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Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 625:7994, s. 301-311
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Tidskriftsartikel (refereegranskat)abstract
- Western Eurasia witnessed several large-scale human migrations during the Holocene1–5. Here, to investigate the cross-continental effects of these migrations, we shotgun-sequenced 317 genomes—mainly from the Mesolithic and Neolithic periods—from across northern and western Eurasia. These were imputed alongside published data to obtain diploid genotypes from more than 1,600 ancient humans. Our analyses revealed a ‘great divide’ genomic boundary extending from the Black Sea to the Baltic. Mesolithic hunter-gatherers were highly genetically differentiated east and west of this zone, and the effect of the neolithization was equally disparate. Large-scale ancestry shifts occurred in the west as farming was introduced, including near-total replacement of hunter-gatherers in many areas, whereas no substantial ancestry shifts happened east of the zone during the same period. Similarly, relatedness decreased in the west from the Neolithic transition onwards, whereas, east of the Urals, relatedness remained high until around 4,000 bp, consistent with the persistence of localized groups of hunter-gatherers. The boundary dissolved when Yamnaya-related ancestry spread across western Eurasia around 5,000 bp, resulting in a second major turnover that reached most parts of Europe within a 1,000-year span. The genetic origin and fate of the Yamnaya have remained elusive, but we show that hunter-gatherers from the Middle Don region contributed ancestry to them. Yamnaya groups later admixed with individuals associated with the Globular Amphora culture before expanding into Europe. Similar turnovers occurred in western Siberia, where we report new genomic data from a ‘Neolithic steppe’ cline spanning the Siberian forest steppe to Lake Baikal. These prehistoric migrations had profound and lasting effects on the genetic diversity of Eurasian populations.
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| 16. |
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| 17. |
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| 18. |
- Bein, T, et al.
(författare)
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Ventilation-perfusion relationships in acute respiratory failure
- 1996
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Ingår i: ANAESTHESIST. - : SPRINGER VERLAG. ; 45:4
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Acute respiratory failure is characterised by mismatch of ventilation with perfusion (V-A/Q). The multiple inert gas elimination technique (MIGET) is a complex method which allows the description of a virtually continuous distribution of V-A/Q ratios. We
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| 19. |
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| 20. |
- Lynga, C, et al.
(författare)
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A laser system providing tunable, narrow-band radiation from 35 nm to 2 mu m
- 2001
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Ingår i: Applied Physics B. - : Springer Science and Business Media LLC. - 0946-2171 .- 1432-0649. ; 72:8, s. 913-920
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Tidskriftsartikel (refereegranskat)abstract
- We describe a laser system that readily provides radiation tunable from 2 mum in the infra-red to 35 nm in the extreme ultraviolet spectral range. The broad spectral range is covered through a range of non-linear processes such as Raman shifting and high-order harmonic generation. Pulses with duration of tens of picoseconds are obtained. The relative bandwidth of the radiation is delta lambda/lambda = 10(-4), comparable with what can be achieved by using high-resolution monochromators at state-of-the-art synchrotron beamlines. We discuss different methods for characterising the radiation in this wide wavelength regime. We also discuss the capabilities of the system from the measured parameters.
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| 21. |
- Rothe, J., et al.
(författare)
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The INE-Beamline for actinide science at ANKA
- 2012
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Ingår i: Review of Scientific Instruments. - : AIP Publishing. - 0034-6748 .- 1089-7623. ; 83:4, s. 043105-
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Tidskriftsartikel (refereegranskat)abstract
- Since its inauguration in 2005, the INE-Beamline for actinide research at the synchrotron source ANKA (KIT North Campus) provides dedicated instrumentation for x-ray spectroscopic characterization of actinide samples and other radioactive materials. R&D work at the beamline focuses on various aspects of nuclear waste disposal within INE's mission to provide the scientific basis for assessing long-term safety of a final nuclear waste repository. The INE-Beamline is accessible for the actinide and radiochemistry community through the ANKA proposal system and the European Union Integrated Infrastructure Initiative ACTINET-I3. Experiments with activities up to 1 x 10(+6) times the European exemption limit are feasible within a safe but flexible containment concept. Measurements with monochromatic radiation are performed at photon energies varying between similar to 2.1 keV (P K-edge) and similar to 25 keV (Pd K-edge), including the lanthanide L-edges and the actinide M-and L3-edges up to Cf. The close proximity of the INE-Beamline to INE controlled area labs offers infrastructure unique in Europe for the spectroscopic and microscopic characterization of actinide samples. The modular beamline design enables sufficient flexibility to adapt sample environments and detection systems to many scientific questions. The well-established bulk techniques x-ray absorption fine structure (XAFS) spectroscopy in transmission and fluorescence mode have been augmented by advanced methods using a microfocused beam, including (confocal) XAFS/x-ray fluorescence detection and a combination of (micro-)XAFS and (micro-)x-ray diffraction. Additional instrumentation for high energy-resolution x-ray emission spectroscopy has been successfully developed and tested.
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| 22. |
- Sabel, Magnus, 1966, et al.
(författare)
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Relapse patterns and outcome after relapse in standard risk medulloblastoma: a report from the HIT-SIOP-PNET4 study
- 2016
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Ingår i: Journal of Neuro-Oncology. - : Springer Science and Business Media LLC. - 0167-594X .- 1573-7373. ; 129:3, s. 515-524
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Tidskriftsartikel (refereegranskat)abstract
- © 2016 The Author(s)The HIT-SIOP-PNET4 randomised trial for standard risk medulloblastoma (MB) (2001–2006) included 338 patients and compared hyperfractionated and conventional radiotherapy. We here report the long-term outcome after a median follow up of 7.8 years, including detailed information on relapse and the treatment of relapse. Data were extracted from the HIT Group Relapsed MB database and by way of a specific case report form. The event-free and overall (OS) survival at 10 years were 76 ± 2 % and 78 ± 2 % respectively with no significant difference between the treatment arms. Seventy-two relapses and three second malignant neoplasms were reported. Thirteen relapses (18 %) were isolated local relapses in the posterior fossa (PF) and 59 (82 %) were craniospinal, metastatic relapses (isolated or multiple) with or without concurrent PF disease. Isolated PF relapse vs all other relapses occurred at mean/median of 38/35 and 28/26 months respectively (p = 0.24). Late relapse, i.e. >5 years from diagnosis, occurred in six patients (8 %). Relapse treatment consisted of combinations of surgery (25 %), focal radiotherapy (RT 22 %), high dose chemotherapy with stem cell rescue (HDSCR 21 %) and conventional chemotherapy (90 %). OS at 5 years after relapse was 6.0 ± 4 %. In multivariate analysis; isolated relapse in PF, and surgery were significantly associated with prolonged survival whereas RT and HDSCR were not. Survival after relapse was not related to biological factors and was very poor despite several patients receiving intensive treatments. Exploration of new drugs is warranted, preferably based on tumour biology from biopsy of the relapsed tumour.
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| 23. |
- Torchia, Jonathon, et al.
(författare)
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Molecular subgroups of atypical teratoid rhabdoid tumours in children : an integrated genomic and clinicopathological analysis
- 2015
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Ingår i: The Lancet Oncology. - 1470-2045 .- 1474-5488. ; 16:5, s. 569-582
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Tidskriftsartikel (refereegranskat)abstract
- Background Rhabdoid brain tumours, also called atypical teratoid rhabdoid tumours, are lethal childhood cancers with characteristic genetic alterations of SMARCB1/hSNF5. Lack of biological understanding of the substantial clinical heterogeneity of these tumours restricts therapeutic advances. We integrated genomic and clinicopathological analyses of a cohort of patients with atypical teratoid rhabdoid tumours to find out the molecular basis for clinical heterogeneity in these tumours. Methods We obtained 259 rhabdoid tumours from 37 international institutions and assessed transcriptional profiles in 43 primary tumours and copy number profiles in 38 primary tumours to discover molecular subgroups of atypical teratoid rhabdoid tumours. We used gene and pathway enrichment analyses to discover group-specific molecular markers and did immunohistochemical analyses on 125 primary tumours to evaluate clinicopathological significance of molecular subgroup and ASCL1-NOTCH signalling. Findings Transcriptional analyses identified two atypical teratoid rhabdoid tumour subgroups with differential enrichment of genetic pathways, and distinct clinicopathological and survival features. Expression of ASCL1, a regulator of NOTCH signalling, correlated with supratentorial location (p=0.004) and superior 5-year overall survival (35%, 95% CI 13-57, and 20%, 6-34, for ASCL1-positive and ASCL1-negative tumours, respectively; p=0.033) in 70 patients who received multimodal treatment. ASCL1 expression also correlated with superior 5-year overall survival (34%, 7-61, and 9%, 0-21, for ASCL1-positive and ASCL1-negative tumours, respectively; p=0.001) in 39 patients who received only chemotherapy without radiation. Cox hazard ratios for overall survival in patients with differential ASCL1 enrichment treated with chemotherapy with or without radiation were 2.02 (95% CI 1.04-3.85; p=0.038) and 3.98 (1.71-9.26; p=0.001). Integrated analyses of molecular subgroupings with clinical prognostic factors showed three distinct clinical risk groups of tumours with different therapeutic outcomes. Interpretation An integration of clinical risk factors and tumour molecular groups can be used to identify patients who are likely to have improved long-term radiation-free survival and might help therapeutic stratification of patients with atypical teratoid rhabdoid tumours.
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