| 1. |
- Papini, Chiara, et al.
(författare)
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Evolving therapies, neurocognitive outcomes, and functional independence in adult survivors of childhood glioma
- 2024
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Ingår i: Journal of the National Cancer Institute. - 0027-8874. ; 116:2, s. 288-298
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Tidskriftsartikel (refereegranskat)abstract
- Background: Treatment of childhood glioma has evolved to reduce radiotherapy exposure with the goal of limiting late toxicity. However, the associations between treatment changes and neurocognition, and the contribution of neurocognition and chronic health conditions to attainment of adult independence, remain unknown. Methods: Adult survivors of childhood glioma diagnosed in 1970-1999 in the Childhood Cancer Survivor Study (n ¼ 1284; median [minimum-maximum] 30 [18-51] years of age at assessment; 22 [15-34] years from diagnosis) self-reported neurocognitive impairment and chronic health conditions. Multivariable models evaluated associations between changes in treatment exposures (surgery only, chemotherapy [with or without surgery], cranial radiation [with or without chemotherapy and/or surgery]), and neurocognitive impairment. Latent class analysis with 5 indicators (employment, independent living, assistance with routine and/or personal care needs, driver’s license, marital or partner status) identified classes of functional independence. Path analysis tested associations among treatment exposures, neurocognitive impairment, chronic health conditions, and functional independence. Statistical tests were 2-sided. Results: Cranial radiation exposure decreased over time (51%, 1970s; 46%, 1980s; 27%, 1990s]. However, compared with siblings, survivors with any treatment exposure were at elevated risk for neurocognitive impairment, including surgery only (eg, memory: relative risk ¼ 2.22; task efficiency: relative risk ¼ 1.88; both P < .001). Three classes of functional independence were identified: independent (58%), moderately independent (20%), and nonindependent (22%). Cranial radiation was associated with nonindependence through impaired task efficiency (b ¼ 0.06), sensorimotor (b ¼ 0.06), and endocrine (b ¼ 0.10) chronic health conditions and through the associations between these conditions and task efficiency (each b ¼ 0.04). Sensorimotor and endocrine chronic health conditions were associated with nonindependence through memory. Conclusion: Most long-term glioma survivors achieve adult independence. However, functional nonindependence is associated with treatment-related neurocognitive impairment and chronic health conditions.
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| 2. |
- Ahearn, Thomas U., et al.
(författare)
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Common variants in breast cancer risk loci predispose to distinct tumor subtypes
- 2022
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Ingår i: Breast Cancer Research. - : Springer Nature. - 1465-5411 .- 1465-542X. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundGenome-wide association studies (GWAS) have identified multiple common breast cancer susceptibility variants. Many of these variants have differential associations by estrogen receptor (ER) status, but how these variants relate with other tumor features and intrinsic molecular subtypes is unclear.MethodsAmong 106,571 invasive breast cancer cases and 95,762 controls of European ancestry with data on 173 breast cancer variants identified in previous GWAS, we used novel two-stage polytomous logistic regression models to evaluate variants in relation to multiple tumor features (ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and grade) adjusting for each other, and to intrinsic-like subtypes.ResultsEighty-five of 173 variants were associated with at least one tumor feature (false discovery rate < 5%), most commonly ER and grade, followed by PR and HER2. Models for intrinsic-like subtypes found nearly all of these variants (83 of 85) associated at p < 0.05 with risk for at least one luminal-like subtype, and approximately half (41 of 85) of the variants were associated with risk of at least one non-luminal subtype, including 32 variants associated with triple-negative (TN) disease. Ten variants were associated with risk of all subtypes in different magnitude. Five variants were associated with risk of luminal A-like and TN subtypes in opposite directions.ConclusionThis report demonstrates a high level of complexity in the etiology heterogeneity of breast cancer susceptibility variants and can inform investigations of subtype-specific risk prediction.
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| 3. |
- Alcorn, J, et al.
(författare)
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Basic instrumentation for Hall A at Jefferson Lab
- 2004
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Ingår i: Nuclear Instruments & Methods in Physics Research. Section A: Accelerators, Spectrometers, Detectors, and Associated Equipment. - : Elsevier BV. - 0167-5087 .- 0168-9002. ; 522:3, s. 294-346
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Tidskriftsartikel (refereegranskat)abstract
- The instrumentation in Hall A at the Thomas Jefferson National Accelerator Facility was designed to study electro-and photo-induced reactions at very high luminosity and good momentum and angular resolution for at least one of the reaction products. The central components of Hall A are two identical high resolution spectrometers, which allow the vertical drift chambers in the focal plane to provide a momentum resolution of better than 2 x 10(-4). A variety of Cherenkov counters, scintillators and lead-glass calorimeters provide excellent particle identification. The facility has been operated successfully at a luminosity well in excess of 10(38) CM-2 s(-1). The research program is aimed at a variety of subjects, including nucleon structure functions, nucleon form factors and properties of the nuclear medium. (C) 2003 Elsevier B.V. All rights reserved.
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| 4. |
- Alqasim, A., et al.
(författare)
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TOI−757 b: an eccentric transiting mini−Neptune on a 17.5−d orbit
- 2024
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Ingår i: Monthly Notices of the Royal Astronomical Society. - 0035-8711 .- 1365-2966. ; 533:1, s. 1-26
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Tidskriftsartikel (refereegranskat)abstract
- We report the spectroscopic confirmation and fundamental properties of TOI−757 b, a mini−Neptune on a 17.5−d orbit transiting a bright star (V = 9.7 mag) discovered by the TESS mission. We acquired high−precision radial velocity measurements with the HARPS, ESPRESSO, and PFS spectrographs to confirm the planet detection and determine its mass. We also acquired space−borne transit photometry with the CHEOPS space telescope to place stronger constraints on the planet radius, supported with ground−based LCOGT photometry. WASP and KELT photometry were used to help constrain the stellar rotation period. We also determined the fundamental parameters of the host star. We find that TOI−757 b has a radius of Rp = 2.5 ± 0.1R. and a mass of Mp = 10.5+−2212M, implying a bulk density of ρp = 3.6 ± 0.8 g cm−3. Our internal composition modelling was unable to constrain the composition of TOI−757 b, highlighting the importance of atmospheric observations for the system. We also find the planet to be highly eccentric with e = 0.39+−000708, making it one of the very few highly eccentric planets among precisely characterized mini−Neptunes. Based on comparisons to other similar eccentric systems, we find a likely scenario for TOI−757 b’s formation to be high eccentricity migration due to a distant outer companion. We additionally propose the possibility of a more intrinsic explanation for the high eccentricity due to star−star interactions during the earlier epoch of the Galactic disc formation, given the low metallicity and older age of TOI−757.
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| 5. |
- Bourrier, V., et al.
(författare)
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A CHEOPS-enhanced view of the HD 3167 system
- 2022
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 668
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Tidskriftsartikel (refereegranskat)abstract
- Much remains to be understood about the nature of exoplanets smaller than Neptune, most of which have been discovered in compact multi-planet systems. With its inner ultra-short period planet b aligned with the star and two larger outer planets d-c on polar orbits, the multi-planet system HD 3167 features a peculiar architecture and offers the possibility to investigate both dynamical and atmospheric evolution processes. To this purpose we combined multiple datasets of transit photometry and radial velocimetry (RV) to revise the properties of the system and inform models of its planets. This effort was spearheaded by CHEOPS observations of HD 3167b, which appear inconsistent with a purely rocky composition despite its extreme irradiation. Overall the precision on the planetary orbital periods are improved by an order of magnitude, and the uncertainties on the densities of the transiting planets b and c are decreased by a factor of 3. Internal structure and atmospheric simulations draw a contrasting picture between HD 3167d, likely a rocky super-Earth that lost its atmosphere through photo-evaporation, and HD 3167c, a mini-Neptune that kept a substantial primordial gaseous envelope. We detect a fourth, more massive planet on a larger orbit, likely coplanar with HD 3167d-c. Dynamical simulations indeed show that the outer planetary system d-c-e was tilted, as a whole, early in the system history, when HD 3167b was still dominated by the star influence and maintained its aligned orbit. RV data and direct imaging rule out that the companion that could be responsible for the present-day architecture is still bound to the HD 3167 system. Similar global studies of multi-planet systems will tell how many share the peculiar properties of the HD 3167 system, which remains a target of choice for follow-up observations and simulations.
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| 6. |
- Dinsdale, Graham, et al.
(författare)
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Intra-and inter-observer reliability of nailfold videocapillaroscopy - A possible outcome measure for systemic sclerosis-related microangiopathy
- 2017
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Ingår i: Microvascular Research. - : Elsevier BV. - 1095-9319 .- 0026-2862. ; 112, s. 1-6
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Our aim was to assess the reliability of nailfold capillary assessment in terms of image evaluability, image severity grade ('normal', 'early', 'active', 'late'), capillary density, capillary (apex) width, and presence of giant capillaries, and also to gain further insight into differences in these parameters between patients with systemic sclerosis (SSc), patients with primary Raynaud's phenomenon (PRP) and healthy control subjects.METHODS: Videocapillaroscopy images (magnification 300×) were acquired from all 10 digits from 173 participants: 101 patients with SSc, 22 with PRP and 50 healthy controls. Ten capillaroscopy experts from 7 European centres evaluated the images. Custom image mark-up software allowed extraction of the following outcome measures: overall grade ('normal', 'early', 'active', 'late', 'non-specific', or 'ungradeable'), capillary density (vessels/mm), mean vessel apical width, and presence of giant capillaries.RESULTS: Observers analysed a median of 129 images each. Evaluability (i.e. the availability of measures) varied across outcome measures (e.g. 73.0% for density and 46.2% for overall grade in patients with SSc). Intra-observer reliability for evaluability was consistently higher than inter- (e.g. for density, intra-class correlation coefficient [ICC] was 0.71 within and 0.14 between observers). Conditional on evaluability, both intra- and inter-observer reliability were high for grade (ICC 0.93 and 0.78 respectively), density (0.91 and 0.64) and width (0.91 and 0.85).CONCLUSIONS: Evaluability is one of the major challenges in assessing nailfold capillaries. However, when images are evaluable, the high intra- and inter-reliabilities suggest that overall image grade, capillary density and apex width have potential as outcome measures in longitudinal studies.
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| 7. |
- Dinsdale, Graham, et al.
(författare)
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Nailfold capillaroscopy-how many fingers should be examined to detect abnormality?
- 2019
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Ingår i: Rheumatology (Oxford, England). - : Oxford University Press (OUP). - 1462-0332 .- 1462-0324. ; 58:2, s. 284-288
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Nailfold capillaroscopy is being increasingly used by rheumatologists in the diagnosis of SSc. However, assessment of all nailfolds can be time-consuming in a busy outpatient clinic. Our aim was to answer the question as to how many (and which) fingers a clinician should routinely assess to capture accurately the true state. Methods: A total of 2994 assessments (by an international panel of expert observers) of 1600 images from 173 participants (101 with SSc, 22 with primary RP and 50 healthy controls) were included in this analysis. Seven single-finger or finger combinations (derived from the middle and ring fingers) were then tested for sensitivity for the presence of two markers of capillary abnormality [presence of giant capillaries and an SSc grade (early, active or late)] compared with assessment of all eight fingers. Results: For the eight-finger gold standard, sensitivity against the diagnostic criteria was 74.6% (53.0% for the presence of giants alone and 73.1% for image grade alone). Examining only one finger gave low sensitivity (ranging from right middle 31.7% to left ring 46.6%). Examining both ring fingers gave a sensitivity of 59.8%, whereas examining the four-finger combination of both ring and both middle fingers gave a sensitivity of 66.7%. Conclusion: During routine capillaroscopic examination, ideally all eight nailbeds (excluding thumbs) should be examined, otherwise some abnormalities will be missed. Examining only four fingers reduces capillaroscopy sensitivity.
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| 8. |
- Dinsdale, Graham, et al.
(författare)
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Quantitative outcome measures for systemic sclerosis-related Microangiopathy – Reliability of image acquisition in Nailfold Capillaroscopy
- 2017
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Ingår i: Microvascular Research. - : Elsevier BV. - 0026-2862. ; 113, s. 56-59
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Tidskriftsartikel (refereegranskat)abstract
- Background Nailfold capillaroscopic parameters hold increasing promise as outcome measures for clinical trials in systemic sclerosis (SSc). Their inclusion as outcomes would often naturally require capillaroscopy images to be captured at several time points during any one study. Our objective was to assess repeatability of image acquisition (which has been little studied), as well as of measurement. Method 41 patients (26 with SSc, 15 with primary Raynaud's phenomenon) and 10 healthy controls returned for repeat high-magnification (300 ×) videocapillaroscopy mosaic imaging of 10 digits one week after initial imaging (as part of a larger study of reliability). Images were assessed in a random order by an expert blinded observer and 4 outcome measures extracted: (1) overall image grade and then (where possible) distal vessel locations were marked, allowing (2) vessel density (across the whole nailfold) to be calculated (3) apex width measurement and (4) giant vessel count. Intra-rater, intra-visit and intra-rater inter-visit (baseline vs. 1 week) reliability were examined in 475 and 392 images respectively. A linear, mixed-effects model was used to estimate variance components, from which intra-class correlation coefficients (ICCs) were determined. Results Intra-visit and inter-visit reliability estimates (ICCs) were (respectively): overall image grade, 0.97 and 0.90; vessel density, 0.92 and 0.65; mean vessel width, 0.91 and 0.79; presence of giant capillary, 0.68 and 0.56. These estimates were conditional on each parameter being measurable. Conclusion Within-operator image analysis and acquisition are reproducible. Quantitative nailfold capillaroscopy, at least with a single observer, provides reliable outcome measures for clinical studies including randomised controlled trials.
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| 9. |
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| 10. |
- Escala-Garcia, Maria, et al.
(författare)
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A network analysis to identify mediators of germline-driven differences in breast cancer prognosis
- 2020
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Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Identifying the underlying genetic drivers of the heritability of breast cancer prognosis remains elusive. We adapt a network-based approach to handle underpowered complex datasets to provide new insights into the potential function of germline variants in breast cancer prognosis. This network-based analysis studies similar to 7.3 million variants in 84,457 breast cancer patients in relation to breast cancer survival and confirms the results on 12,381 independent patients. Aggregating the prognostic effects of genetic variants across multiple genes, we identify four gene modules associated with survival in estrogen receptor (ER)-negative and one in ER-positive disease. The modules show biological enrichment for cancer-related processes such as G-alpha signaling, circadian clock, angiogenesis, and Rho-GTPases in apoptosis.
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