| 1. |
- Azevedo, Flavio, et al.
(författare)
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Social and moral psychology of COVID-19 across 69 countries
- 2023
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Ingår i: Scientific Data. - : NATURE PORTFOLIO. - 2052-4463. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- The COVID-19 pandemic has affected all domains of human life, including the economic and social fabric of societies. One of the central strategies for managing public health throughout the pandemic has been through persuasive messaging and collective behaviour change. To help scholars better understand the social and moral psychology behind public health behaviour, we present a dataset comprising of 51,404 individuals from 69 countries. This dataset was collected for the International Collaboration on Social & Moral Psychology of COVID-19 project (ICSMP COVID-19). This social science survey invited participants around the world to complete a series of moral and psychological measures and public health attitudes about COVID-19 during an early phase of the COVID-19 pandemic (between April and June 2020). The survey included seven broad categories of questions: COVID-19 beliefs and compliance behaviours; identity and social attitudes; ideology; health and well-being; moral beliefs and motivation; personality traits; and demographic variables. We report both raw and cleaned data, along with all survey materials, data visualisations, and psychometric evaluations of key variables.
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| 2. |
- Ballester, Facundo, et al.
(författare)
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A generic high-dose rate Ir-192 brachytherapy source for evaluation of model-based dose calculations beyond the TG-43 formalism
- 2015
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Ingår i: Medical physics (Lancaster). - : American Association of Physicists in Medicine: Medical Physics. - 0094-2405. ; 42:6, s. 3048-3062
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: In order to facilitate a smooth transition for brachytherapy dose calculations from the American Association of Physicists in Medicine (AAPM) Task Group No. 43 (TG-43) formalism to model-based dose calculation algorithms (MBDCAs), treatment planning systems (TPSs) using a MBDCA require a set of well-defined test case plans characterized by Monte Carlo (MC) methods. This also permits direct dose comparison to TG-43 reference data. Such test case plans should be made available for use in the software commissioning process performed by clinical end users. To this end, a hypothetical, generic high-dose rate (HDR) Ir-192 source and a virtual water phantom were designed, which can be imported into a TPS. Methods: A hypothetical, generic HDR Ir-192 source was designed based on commercially available sources as well as a virtual, cubic water phantom that can be imported into any TPS in DICOM format. The dose distribution of the generic Ir-192 source when placed at the center of the cubic phantom, and away from the center under altered scatter conditions, was evaluated using two commercial MBDCAs [Oncentra (R) Brachy with advanced collapsed-cone engine (ACE) and BrachyVision AcuRos (TM)]. Dose comparisons were performed using state-of-the-art MC codes for radiation transport, including ALGEBRA, BrachyDose, GEANT4, MCNP5, MCNP6, and pENELopE2008. The methodologies adhered to recommendations in the AAPM TG-229 report on high-energy brachytherapy source dosimetry. TG-43 dosimetry parameters, an along-away dose-rate table, and primary and scatter separated (PSS) data were obtained. The virtual water phantom of (201)(3) voxels (1 mm sides) was used to evaluate the calculated dose distributions. Two test case plans involving a single position of the generic HDR Ir-192 source in this phantom were prepared: (i) source centered in the phantom and (ii) source displaced 7 cm laterally from the center. Datasets were independently produced by different investigators. MC results were then compared against dose calculated using TG-43 and MBDCA methods. Results: TG-43 and PSS datasets were generated for the generic source, the PSS data for use with the ACE algorithm. The dose-rate constant values obtained from seven MC simulations, performed independently using different codes, were in excellent agreement, yielding an average of 1.1109 +/- 0.0004 cGy/(h U) (k = 1, Type A uncertainty). MC calculated dose-rate distributions for the two plans were also found to be in excellent agreement, with differences within type A uncertainties. Differences between commercial MBDCA and MC results were test, position, and calculation parameter dependent. On average, however, these differences were within 1% for ACUROS and 2% for ACE at clinically relevant distances. Conclusions: A hypothetical, generic HDR Ir-192 source was designed and implemented in two commercially available TPSs employing different MBDCAs. Reference dose distributions for this source were benchmarked and used for the evaluation of MBDCA calculations employing a virtual, cubic water phantom in the form of a CT DICOM image series. The implementation of a generic source of identical design in all TPSs using MBDCAs is an important step toward supporting univocal commissioning procedures and direct comparisons between TPSs. (C) 2015 American Association of Physicists in Medicine.
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| 3. |
- Beaulieu, Luc, et al.
(författare)
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AAPM WGDCAB Report 372: A joint AAPM, ESTRO, ABG, and ABS report on commissioning of model-based dose calculation algorithms in brachytherapy
- 2023
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Ingår i: Medical physics (Lancaster). - : WILEY. - 0094-2405. ; 50:8, s. E946-E960
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Tidskriftsartikel (refereegranskat)abstract
- The introduction of model-based dose calculation algorithms (MBDCAs) in brachytherapy provides an opportunity for a more accurate dose calculation and opens the possibility for novel, innovative treatment modalities. The joint AAPM, ESTRO, and ABG Task Group 186 (TG-186) report provided guidance to early adopters. However, the commissioning aspect of these algorithms was described only in general terms with no quantitative goals. This report, from the Working Group on Model-Based Dose Calculation Algorithms in Brachytherapy, introduced a field-tested approach to MBDCA commissioning. It is based on a set of well-characterized test cases for which reference Monte Carlo (MC) and vendor-specific MBDCA dose distributions are available in a Digital Imaging and Communications in Medicine-Radiotherapy (DICOM-RT) format to the clinical users. The key elements of the TG-186 commissioning workflow are now described in detail, and quantitative goals are provided. This approach leverages the well-known Brachytherapy Source Registry jointly managed by the AAPM and the Imaging and Radiation Oncology Core (IROC) Houston Quality Assurance Center (with associated links at ESTRO) to provide open access to test cases as well as step-by-step user guides. While the current report is limited to the two most widely commercially available MBDCAs and only for Ir-192-based afterloading brachytherapy at this time, this report establishes a general framework that can easily be extended to other brachytherapy MBDCAs and brachytherapy sources. The AAPM, ESTRO, ABG, and ABS recommend that clinical medical physicists implement the workflow presented in this report to validate both the basic and the advanced dose calculation features of their commercial MBDCAs. Recommendations are also given to vendors to integrate advanced analysis tools into their brachytherapy treatment planning system to facilitate extensive dose comparisons. The use of the test cases for research and educational purposes is further encouraged.
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| 4. |
- Campbell, PJ, et al.
(författare)
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Pan-cancer analysis of whole genomes
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Tidskriftsartikel (refereegranskat)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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| 5. |
- de Ávila, Renato Ivan, et al.
(författare)
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Evaluation of in vitro testing strategies for hazard assessment of the skin sensitization potential of “real-life” mixtures : The case of henna-based hair-colouring products containing p-phenylenediamine
- 2019
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Ingår i: Contact Dermatitis. - : Wiley. - 0105-1873 .- 1600-0536. ; 81:3, s. 194-209
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Tidskriftsartikel (refereegranskat)abstract
- Background: Allergic contact dermatitis caused by henna-based hair-colouring products has been associated with adulteration of henna with p-phenylenediamine (PPD). Objectives: To develop a testing approach based on in vitro techniques that address key events within the skin sensitization adverse outcome pathway in order to evaluate the allergenic potential of hair-colouring products. Methods: The following in vitro assays were used to test the sensitizing capacity of hair dye ingredients: the micro-direct peptide reactivity assay (mDPRA); the HaCaT keratinocyte-associated interleukin (IL)-18 assay; the U937 cell line activation test (U-SENS)/IL-8 levels; the blood monocyte-derived dendritic cell test; and genomic allergen rapid detection (GARD skin). Those techniques with better human concordance were selected to evaluate the allergenic potential of 10 hair-colouring products. Results: In contrast to the information on the label, chromatographic analyses identified PPD in all products. The main henna biomarker, lawsone, was not detected in one of the 10 products. Among the techniques evaluated by testing hair dye ingredients, the mDPRA, the IL-18 assay, GARD skin and the U-SENS correlated better with human classification (concordances of 91.7%-100%) and were superior to the animal testing (concordance of 78.5%). Thus, these assays were used to evaluate hair-colouring products, which were classified as skin sensitizers by the use of different two-of-three approaches. Conclusions: Our findings highlight the toxicological consequences of, and risks associated with, the undisclosed use of PPD in henna-based “natural” “real-life” products.
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| 6. |
- Gustafsson, Gabriel, et al.
(författare)
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Cellular Uptake of alpha-Synuclein Oligomer-Selective Antibodies is Enhanced by the Extracellular Presence of alpha-Synuclein and Mediated via Fc gamma Receptors
- 2017
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Ingår i: Cellular and molecular neurobiology. - : Springer Science and Business Media LLC. - 0272-4340 .- 1573-6830. ; 37:1, s. 121-131
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Tidskriftsartikel (refereegranskat)abstract
- Immunotherapy targeting aggregated alpha-synuclein has emerged as a potential treatment strategy against Parkinson's disease and other alpha-synucleinopathies. We have developed alpha-synuclein oligomer/protofibril selective antibodies that reduce toxic alpha-synuclein in a human cell line and, upon intraperitoneal administration, in spinal cord of transgenic mice. Here, we investigated under which conditions and by which mechanisms such antibodies can be internalized by cells. For this purpose, human neuroglioma H4 cells were treated with either monoclonal oligomer/protofibril selective alpha-synuclein antibodies, linear epitope monoclonal alpha-synuclein antibodies, or with a control antibody. The oligomer/protofibril selective antibody mAb47 displayed the highest cellular uptake and was therefore chosen for additional analyses. Next, alpha-synuclein overexpressing cells were incubated with mAb47, which resulted in increased antibody internalization as compared to non-transfected cells. Similarly, regular cells exposed to mAb47 together with media containing alpha-synuclein displayed a higher uptake as compared to cells incubated with regular media. Finally, different Fc gamma receptors were targeted and we then found that blockage of Fc gamma RI and Fc gamma RIIB/C resulted in reduced antibody internalization. Our data thus indicate that the robust uptake of the oligomer/protofibril selective antibody mAb47 by human CNS-derived cells is enhanced by extracellular alpha-synuclein and mediated via Fc gamma receptors. Altogether, our finding lend further support to the belief that alpha-synuclein pathology can be modified by monoclonal antibodies and that these can target toxic alpha-synuclein species in the extracellular milieu. In the context of immunotherapy, antibody binding of alpha-synuclein would then not only block further aggregation but also mediate internalization and subsequent degradation of antigen-antibody complexes.
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| 7. |
- Kjekshus, John, et al.
(författare)
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Rosuvastatin in older patients with systolic heart failure.
- 2007
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Ingår i: The New England journal of medicine. - 1533-4406. ; 357:22, s. 2248-61
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Patients with systolic heart failure have generally been excluded from statin trials. Acute coronary events are uncommon in this population, and statins have theoretical risks in these patients. METHODS: A total of 5011 patients at least 60 years of age with New York Heart Association class II, III, or IV ischemic, systolic heart failure were randomly assigned to receive 10 mg of rosuvastatin or placebo per day. The primary composite outcome was death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. Secondary outcomes included death from any cause, any coronary event, death from cardiovascular causes, and the number of hospitalizations. RESULTS: As compared with the placebo group, patients in the rosuvastatin group had decreased levels of low-density lipoprotein cholesterol (difference between groups, 45.0%; P<0.001) and of high-sensitivity C-reactive protein (difference between groups, 37.1%; P<0.001). During a median follow-up of 32.8 months, the primary outcome occurred in 692 patients in the rosuvastatin group and 732 in the placebo group (hazard ratio, 0.92; 95% confidence interval [CI], 0.83 to 1.02; P=0.12), and 728 patients and 759 patients, respectively, died (hazard ratio, 0.95; 95% CI, 0.86 to 1.05; P=0.31). There were no significant differences between the two groups in the coronary outcome or death from cardiovascular causes. In a prespecified secondary analysis, there were fewer hospitalizations for cardiovascular causes in the rosuvastatin group (2193) than in the placebo group (2564) (P<0.001). No excessive episodes of muscle-related or other adverse events occurred in the rosuvastatin group. CONCLUSIONS: Rosuvastatin did not reduce the primary outcome or the number of deaths from any cause in older patients with systolic heart failure, although the drug did reduce the number of cardiovascular hospitalizations. The drug did not cause safety problems. (ClinicalTrials.gov number, NCT00206310.)
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| 8. |
- Ma, Yunzhi, et al.
(författare)
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A generic TG-186 shielded applicator for commissioning model-based dose calculation algorithms for high-dose-rate Ir-192 brachytherapy
- 2017
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Ingår i: Medical physics (Lancaster). - : WILEY. - 0094-2405 .- 2473-4209. ; 44:11, s. 5961-5976
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Tidskriftsartikel (refereegranskat)abstract
- PurposeA joint working group was created by the American Association of Physicists in Medicine (AAPM), the European Society for Radiotherapy and Oncology (ESTRO), and the Australasian Brachytherapy Group (ABG) with the charge, among others, to develop a set of well-defined test case plans and perform calculations and comparisons with model-based dose calculation algorithms (MBDCAs). Its main goal is to facilitate a smooth transition from the AAPM Task Group No. 43 (TG-43) dose calculation formalism, widely being used in clinical practice for brachytherapy, to the one proposed by Task Group No. 186 (TG-186) for MBDCAs. To do so, in this work a hypothetical, generic high-dose rate (HDR) Ir-192 shielded applicator has been designed and benchmarked. MethodsA generic HDR Ir-192 shielded applicator was designed based on three commercially available gynecological applicators as well as a virtual cubic water phantom that can be imported into any DICOM-RT compatible treatment planning system (TPS). The absorbed dose distribution around the applicator with the TG-186 Ir-192 source located at one dwell position at its center was computed using two commercial TPSs incorporating MBDCAs (Oncentra((R)) Brachy with Advanced Collapsed-cone Engine, ACE, and BrachyVision ACUROS) and state-of-the-art Monte Carlo (MC) codes, including ALGEBRA, BrachyDose, egs_brachy, Geant4, MCNP6, and Penelope2008. TPS-based volumetric dose distributions for the previously reported source centered in water and source displaced test cases, and the new source centered in applicator test case, were analyzed here using the MCNP6 dose distribution as a reference. Volumetric dose comparisons of TPS results against results for the other MC codes were also performed. Distributions of local and global dose difference ratios are reported. ResultsThe local dose differences among MC codes are comparable to the statistical uncertainties of the reference datasets for the source centered in water and source displaced test cases and for the clinically relevant part of the unshielded volume in the source centered in applicator case. Larger local differences appear in the shielded volume or at large distances. Considering clinically relevant regions, global dose differences are smaller than the local ones. The most disadvantageous case for the MBDCAs is the one including the shielded applicator. In this case, ACUROS agrees with MC within [-4.2%, +4.2%] for the majority of voxels (95%) while presenting dose differences within [-0.12%, +0.12%] of the dose at a clinically relevant reference point. For ACE, 95% of the total volume presents differences with respect to MC in the range [-1.7%, +0.4%] of the dose at the reference point. ConclusionsThe combination of the generic source and generic shielded applicator, together with the previously developed test cases and reference datasets (available in the Brachytherapy Source Registry), lay a solid foundation in supporting uniform commissioning procedures and direct comparisons among treatment planning systems for HDR Ir-192 brachytherapy.
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| 9. |
- Marto, João Pedro, et al.
(författare)
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Safety and Outcome of Revascularization Treatment in Patients With Acute Ischemic Stroke and COVID-19: The Global COVID-19 Stroke Registry.
- 2023
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Ingår i: Neurology. - 1526-632X. ; 100:7
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Tidskriftsartikel (refereegranskat)abstract
- COVID-19-related inflammation, endothelial dysfunction, and coagulopathy may increase the bleeding risk and lower the efficacy of revascularization treatments in patients with acute ischemic stroke (AIS). We aimed to evaluate the safety and outcomes of revascularization treatments in patients with AIS and COVID-19.This was a retrospective multicenter cohort study of consecutive patients with AIS receiving intravenous thrombolysis (IVT) and/or endovascular treatment (EVT) between March 2020 and June 2021 tested for severe acute respiratory syndrome coronavirus 2 infection. With a doubly robust model combining propensity score weighting and multivariate regression, we studied the association of COVID-19 with intracranial bleeding complications and clinical outcomes. Subgroup analyses were performed according to treatment groups (IVT-only and EVT).Of a total of 15,128 included patients from 105 centers, 853 (5.6%) were diagnosed with COVID-19; of those, 5,848 (38.7%) patients received IVT-only and 9,280 (61.3%) EVT (with or without IVT). Patients with COVID-19 had a higher rate of symptomatic intracerebral hemorrhage (SICH) (adjusted OR 1.53; 95% CI 1.16-2.01), symptomatic subarachnoid hemorrhage (SSAH) (OR 1.80; 95% CI 1.20-2.69), SICH and/or SSAH combined (OR 1.56; 95% CI 1.23-1.99), 24-hour mortality (OR 2.47; 95% CI 1.58-3.86), and 3-month mortality (OR 1.88; 95% CI 1.52-2.33). Patients with COVID-19 also had an unfavorable shift in the distribution of the modified Rankin score at 3 months (OR 1.42; 95% CI 1.26-1.60).Patients with AIS and COVID-19 showed higher rates of intracranial bleeding complications and worse clinical outcomes after revascularization treatments than contemporaneous non-COVID-19 patients receiving treatment. Current available data do not allow direct conclusions to be drawn on the effectiveness of revascularization treatments in patients with COVID-19 or to establish different treatment recommendations in this subgroup of patients with ischemic stroke. Our findings can be taken into consideration for treatment decisions, patient monitoring, and establishing prognosis.The study was registered under ClinicalTrials.gov identifier NCT04895462.
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| 10. |
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