| 11. |
- Högberg, Jonas, 1976, et al.
(författare)
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Simulation Model of Microsphere Distribution for Selective Internal Radiation Therapy Agrees With Observations
- 2016
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Ingår i: International Journal of Radiation Oncology Biology Physics. - : Elsevier BV. - 0360-3016. ; 96:2, s. 414-421
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To perform a detailed analysis of microsphere distribution in biopsy material from a patient treated with 90 Y-labeled resin spheres and characterize microsphere distribution in the hepatic artery tree, and to construct a novel dichotomous bifurcation model for microsphere deposits and evaluate its accuracy in simulating the observed microsphere deposits. Methods and Materials: Our virtual model consisted of arteries that successively branched into 2 new generations of arteries at 20 nodes. The artery diameter exponentially decreased from the lowest generation to the highest generation. Three variable parameters were optimized to obtain concordance between simulations and measure microsphere distributions: an artery coefficient of variation (ACV) for the diameter of all artery generations and the microsphere flow distribution at the nodes; a hepatic tree distribution volume (HDV) for the artery tree; and an artery diameter reduction (ADR) parameter. The model was tested against previously measured activity concentrations in 84 biopsies from the liver of 1 patient. In 16 of 84 biopsies, the microsphere distribution regarding cluster size and localization in the artery tree was determined via light microscopy of 30-mm sections (mean concentration, 14 microspheres/mg; distributions divided into 3 groups with mean microsphere concentrations of 4.6, 14, and 28 microspheres/mg). Results: Single spheres and small clusters were observed in terminal arterioles, whereas large clusters, up to 450 microspheres, were observed in larger arterioles. For 14 microspheres/mg, the optimized parameter values were ACV = 0.35, HDV = 50 cm(3), and ADR = 6 mu m. For 4.6 microspheres/mg, ACV and ADR decreased to 0.26 and 0 mu m, respectively, whereas HDV increased to 130 cm(3). The opposite trend was observed for 28 microspheres/mg: ACV = 0.49, HDV = 20 cm(3), and ADR = 8 mu m. Conclusion: Simulations and measurements reveal that microsphere clusters are larger and more common in volumes with high microsphere concentrations and indicate that the spatial distribution of the artery tree must be considered in estimates of microsphere distributions.
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| 12. |
- Kruse, Jacqueline J.C.M., et al.
(författare)
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A portrait of cisplatin-induced transcriptional changes in mouse embryonic stem cells reveals a dominant p53-like response
- 2007
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Ingår i: Mutation research. - : Elsevier BV. - 0027-5107 .- 1873-135X. ; 617:1-2, s. 58-70
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Tidskriftsartikel (refereegranskat)abstract
- Accumulation of damage in undifferentiated cells may threaten homeostasis and regenerative capacity. Remarkably, p53 has been suggested to be transcriptionally inactive in these cells. To gain insight in the kinetics and interplay of the predominant transcriptional responses of DNA damage signalling pathways in undifferentiated cells, mouse embryonic stem cells were exposed to cisplatin at four different time points (2, 4, 8 and 24 h) and concentrations (1, 2, 5 and 10 μM). RNA was isolated and subjected to genome-wide expression profiling. Up to one fourth of the tested genes could be identified as being differentially expressed (false discovery rate = 10%) after the cisplatin treatment. Clustering of the expression changes showed a strong time dependency. To investigate the relationship between affected genes, a gene set analysis method was used. Functionally related gene sets were defined using gene ontologies or transcription factor binding sites and were tested for overrepresentation within the differentially expressed genes. A variety of gene sets were clearly enriched among which 'apoptosis' and 'cell cycle' were the most pronounced. Furthermore, there was a strong enrichment of genes with a p53-binding motif. The involvement of the 'cell cycle' and 'apoptosis' gene sets in the cisplatin response was detected at concentrations and time points where the respective biological assays were still negative. The results reveal novel insights into the mechanisms which maintain the genomic integrity in undifferentiated cells. Additionally the results illustrate that gene set analysis of genome-wide expression changes provides a sensitive instrument to detect cellular stress responses to DNA damage.
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| 13. |
- Manfredini, Daniele, et al.
(författare)
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Standardised Tool for the Assessment of Bruxism
- 2024
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Ingår i: Journal of Oral Rehabilitation. - : John Wiley & Sons. - 1365-2842 .- 0305-182X. ; 51:1, s. 29-58
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Forskningsöversikt (refereegranskat)abstract
- Objective: This paper aims to present and describe the Standardised Tool for the Assessment of Bruxism (STAB), an instrument that was developed to provide a multidimensional evaluation of bruxism status, comorbid conditions, aetiology and consequences.Methods: The rationale for creating the tool and the road map that led to the selection of items included in the STAB has been discussed in previous publications.Results: The tool consists of two axes, specifically dedicated to the evaluation of bruxism status and consequences (Axis A) and of bruxism risk and etiological factors and comorbid conditions (Axis B). The tool includes 14 domains, accounting for a total of 66 items. Axis A includes the self-reported information on bruxism status and possible consequences (subject-based report) together with the clinical (examiner report) and instrumental (technology report) assessment. The Subject-Based Assessment (SBA) includes domains on Sleep Bruxism (A1), Awake Bruxism (A2) and Patient's Complaints (A3), with information based on patients' self-report. The Clinically Based Assessment (CBA) includes domains on Joints and Muscles (A4), Intra- and Extra-Oral Tissues (A5) and Teeth and Restorations (A6), based on information collected by an examiner. The Instrumentally Based Assessment (IBA) includes domains on Sleep Bruxism (A7), Awake Bruxism (A8) and the use of Additional Instruments (A9), based on the information gathered with the use of technological devices. Axis B includes the self-reported information (subject-based report) on factors and conditions that may have an etiological or comorbid association with bruxism. It includes domains on Psychosocial Assessment (B1), Concurrent Sleep-related Conditions Assessment (B2), Concurrent Non-Sleep Conditions Assessment (B3), Prescribed Medications and Use of Substances Assessment (B4) and Additional Factors Assessment (B5). As a rule, whenever possible, existing instruments, either in full or partial form (i.e. specific subscales), are included. A user's guide for scoring the different items is also provided to ease administration.Conclusions: The instrument is now ready for on-field testing and further refinement. It can be anticipated that it will help in collecting data on bruxism in such a comprehensive way to have an impact on several clinical and research fields.
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| 14. |
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| 15. |
- Svensson, J. Peter, et al.
(författare)
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Analysis of gene expression using gene sets discriminates cancer patients with and without late radiation toxicity
- 2006
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Ingår i: PLoS Medicine. - : Public Library of Science (PLoS). - 1549-1277 .- 1549-1676. ; 3:10, s. 1904-1914
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Tidskriftsartikel (refereegranskat)abstract
- Background Radiation is an effective anti-cancer therapy but leads to severe late radiation toxicity in 5%-10% of patients. Assuming that genetic susceptibility impacts this risk, we hypothesized that the cellular response of normal tissue to X-rays could discriminate patients with and without late radiation toxicity. Methods and Findings Prostate carcinoma patients without evidence of cancer 2 y after curative radiotherapy were recruited in the study. Blood samples of 21 patients with severe late complications from radiation and 17 patients without symptoms were collected. Stimulated peripheral lymphocytes were mock-irradiated or irradiated with 2-Gy X-rays. The 24-h radiation response was analyzed by gene expression profiling and used for classification. Classification was performed either on the expression of separate genes or, to augment the classification power, on gene sets consisting of genes grouped together based on function or cellular colocalization. X- ray irradiation altered the expression of radio-responsive genes in both groups. This response was variable across individuals, and the expression of the most significant radio-responsive genes was unlinked to radiation toxicity. The classifier based on the radiation response of separate genes correctly classified 63% of the patients. The classifier based on affected gene sets improved correct classification to 86%, although on the individual level only 21/38 (55%) patients were classified with high certainty. The majority of the discriminative genes and gene sets belonged to the ubiquitin, apoptosis, and stress signaling networks. The apoptotic response appeared more pronounced in patients that did not develop toxicity. In an independent set of 12 patients, the toxicity status of eight was predicted correctly by the gene set classifier. Conclusions Gene expression profiling succeeded to some extent in discriminating groups of patients with and without severe late radiotherapy toxicity. Moreover, the discriminative power was enhanced by assessment of functionally or structurally related gene sets. While prediction of individual response requires improvement, this study is a step forward in predicting susceptibility to late radiation toxicity.
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| 16. |
- Tercero, M., et al.
(författare)
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5G systems: The mmMAGIC project perspective on use cases and challenges between 6-100 GHz
- 2016
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Ingår i: IEEE Wireless Communications and Networking Conference, WCNC. - 1525-3511. ; 2016-September, s. 200-205
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Konferensbidrag (refereegranskat)abstract
- mmMAGIC (Millimetre-Wave Based Mobile Radio Access Network for Fifth Generation Integrated Communications) is an EU funded 5G-PPP project, whose overall objective is to design and pre-develop a mobile radio access technology (RAT) operating in the 6-100 GHz range, capable of impacting standards and other relevant fora. The focus of the project is on extreme Mobile Broadband, which is expected to drive the 5G requirements for massive increase in capacity and data-rates. This paper elaborates on some 5G key research areas such as: identification of the most compelling use-cases and Key Performance Indicators (KPIs) for future 5G systems, advantages and challenges of millimeter-wave (mmWave) technologies, channel measurements and channel modeling, network architecture; and the design of a new mobile radio interface including multi-node and multi-Antenna transceiver architecture.
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| 17. |
- Uhlén, Mathias, et al.
(författare)
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The human secretome
- 2019
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Ingår i: Science Signaling. - : American Association for the Advancement of Science (AAAS). - 1945-0877 .- 1937-9145. ; 12:609
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Tidskriftsartikel (refereegranskat)abstract
- The proteins secreted by human cells (collectively referred to as the secretome) are important not only for the basic understanding of human biology but also for the identification of potential targets for future diagnostics and therapies. Here, we present a comprehensive analysis of proteins predicted to be secreted in human cells, which provides information about their final localization in the human body, including the proteins actively secreted to peripheral blood. The analysis suggests that a large number of the proteins of the secretome are not secreted out of the cell, but instead are retained intracellularly, whereas another large group of proteins were identified that are predicted to be retained locally at the tissue of expression and not secreted into the blood. Proteins detected in the human blood by mass spectrometry-based proteomics and antibody-based immuno-assays are also presented with estimates of their concentrations in the blood. The results are presented in an updated version 19 of the Human Protein Atlas in which each gene encoding a secretome protein is annotated to provide an open-access knowledge resource of the human secretome, including body-wide expression data, spatial localization data down to the single-cell and subcellular levels, and data about the presence of proteins that are detectable in the blood.
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| 18. |
- Abbott, Peter M., et al.
(författare)
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A detailed framework of Marine Isotope Stages 4 and 5 volcanic events recorded in two Greenland ice-cores
- 2012
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Ingår i: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791 .- 1873-457X. ; 36, s. 59-77
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Tidskriftsartikel (refereegranskat)abstract
- Sulphate records from Greenland ice-cores indicate that Marine Isotope Stages 4 and 5 were charactensed by a higher incidence of large volcanic eruptions than other periods during the last glacial period, however, few investigations have focused on tephra deposits associated with these volcanic eruptions and the nature and origin of the events. Here we present a detailed tephrochronological framework of the products of 15 volcanic events spanning this interval: the majority of which have been preserved as cryptotephra horizons within the Greenland records. The major element compositions of individual glass shards within these horizons indicate that 13 of the eruptions originated from Iceland and 6 of these events can be correlated to the specific volcanic systems of Katla, Grimsvotn, Grimsvotn-Kverkfjoll and either Reykjanes or Veidivotn-Bardarbunga. For the remaining Icelandic horizons a source from either the rift zone or a flank zone can be suggested based on rock suite affinities. Two horizons have been correlated to a source from the Jan Mayen volcanic system which represents the first discovery of material from this system within any Greenland ice-cores. The robust geochemical characterisations, independent ages for these horizons (derived from the GICCO5 ice-core chronology) and stratigraphic positions relative to the Dansgaard-Oeschger climate events recorded in the Greenland ice-cores represent a critical framework that provides new information on the frequency and nature of volcanic events occurring in the North Atlantic region during MIS 4 and 5. This framework can now be utilised in the assessment of the differential timing and rate of response to the millennial-scale climatic events that characterised this period, through the use of the tephra horizons as time-synchronous tie-lines to other palaeoclimatic sequences.
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| 19. |
- Cadrin-Tourigny, Julia, et al.
(författare)
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A new prediction model for ventricular arrhythmias in arrhythmogenic right ventricular cardiomyopathy
- 2019
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 1522-9645 .- 0195-668X. ; 40:23, s. 1850-1858
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVC) is characterized by ventricular arrhythmias (VAs) and sudden cardiac death (SCD). We aimed to develop a model for individualized prediction of incident VA/SCD in ARVC patients. METHODS AND RESULTS: Five hundred and twenty-eight patients with a definite diagnosis and no history of sustained VAs/SCD at baseline, aged 38.2 ± 15.5 years, 44.7% male, were enrolled from five registries in North America and Europe. Over 4.83 (interquartile range 2.44-9.33) years of follow-up, 146 (27.7%) experienced sustained VA, defined as SCD, aborted SCD, sustained ventricular tachycardia, or appropriate implantable cardioverter-defibrillator (ICD) therapy. A prediction model estimating annual VA risk was developed using Cox regression with internal validation. Eight potential predictors were pre-specified: age, sex, cardiac syncope in the prior 6 months, non-sustained ventricular tachycardia, number of premature ventricular complexes in 24 h, number of leads with T-wave inversion, and right and left ventricular ejection fractions (LVEFs). All except LVEF were retained in the final model. The model accurately distinguished patients with and without events, with an optimism-corrected C-index of 0.77 [95% confidence interval (CI) 0.73-0.81] and minimal over-optimism [calibration slope of 0.93 (95% CI 0.92-0.95)]. By decision curve analysis, the clinical benefit of the model was superior to a current consensus-based ICD placement algorithm with a 20.6% reduction of ICD placements with the same proportion of protected patients (P < 0.001). CONCLUSION: Using the largest cohort of patients with ARVC and no prior VA, a prediction model using readily available clinical parameters was devised to estimate VA risk and guide decisions regarding primary prevention ICDs (www.arvcrisk.com).
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| 20. |
- Cadrin-Tourigny, Julia, et al.
(författare)
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A new prediction model for ventricular arrhythmias in arrhythmogenic right ventricular cardiomyopathy
- 2022
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 43:32, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVC) is characterized by ventricular arrhythmias (VAs) and sudden cardiac death (SCD). We aimed to develop a model for individualized prediction of incident VA/SCD in ARVC patients. Methods and results: Five hundred and twenty-eight patients with a definite diagnosis and no history of sustained VAs/SCD at baseline, aged 38.2 ± 15.5 years, 44.7% male, were enrolled from five registries in North America and Europe. Over 4.83 (interquartile range 2.44-9.33) years of follow-up, 146 (27.7%) experienced sustained VA, defined as SCD, aborted SCD, sustained ventricular tachycardia, or appropriate implantable cardioverter-defibrillator (ICD) therapy. A prediction model estimating annual VA risk was developed using Cox regression with internal validation. Eight potential predictors were pre-specified: Age, sex, cardiac syncope in the prior 6 months, non-sustained ventricular tachycardia, number of premature ventricular complexes in 24 h, number of leads with T-wave inversion, and right and left ventricular ejection fractions (LVEFs). All except LVEF were retained in the final model. The model accurately distinguished patients with and without events, with an optimism-corrected C-index of 0.77 [95% confidence interval (CI) 0.73-0.81] and minimal over-optimism [calibration slope of 0.93 (95% CI 0.92-0.95)]. By decision curve analysis, the clinical benefit of the model was superior to a current consensus-based ICD placement algorithm with a 20.3% reduction of ICD placements with the same proportion of protected patients (P < 0.001). Conclusion: Using the largest cohort of patients with ARVC and no prior VA, a prediction model using readily available clinical parameters was devised to estimate VA risk and guide decisions regarding primary prevention ICDs (www.arvcrisk.com).
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