| 511. |
- Condoluci, Adalgisa, et al.
(författare)
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International prognostic score for asymptomatic early-stage chronic lymphocytic leukemia
- 2020
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 135:21, s. 1859-1869
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Tidskriftsartikel (refereegranskat)abstract
- Most patients with chronic lymphocytic leukemia (CLL) are diagnosed with early-stage disease and managed with active surveillance. The individual course of patients with early-stage CLL is heterogeneous, and their probability of needing treatment is hardly anticipated at diagnosis. We aimed at developing an international prognostic score to predict time to first treatment (TTFT) in patients with CLL with early, asymptomatic disease (International Prognostic Score for Early-stage CLL [IPS-E]). Individual patient data from 11 international cohorts of patients with early-stage CLL (n = 4933) were analyzed to build and validate the prognostic score. Three covariates were consistently and independently correlated with TTFT: unmutated immunoglobulin heavy variable gene (IGHV), absolute lymphocyte count higher than 15 x 10(9)/L, and presence of palpable lymph nodes. The IPS-E was the sum of the covariates (1 point each), and separated low-risk (score 0), intermediate-risk (score 1), and high-risk (score 2-3) patients showing a distinct TTFT. The score accuracy was validated in 9 cohorts staged by the Binet system and 1 cohort staged by the Rai system. The C-index was 0.74 in the training series and 0.70 in the aggregate of validation series. By meta-analysis of the training and validation cohorts, the 5-year cumulative risk for treatment start was 8.4%, 28.4%, and 61.2% among low-risk, intermediate-risk, and high-risk patients, respectively. The IPS-E is a simple and robust prognostic model that predicts the likelihood of treatment requirement in patients with early-stage CLL. The IPS-E can be useful in clinical management and in the design of early intervention clinical trials.
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| 512. |
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| 513. |
- Huang, Miller, et al.
(författare)
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Engineering Genetic Predisposition in Human Neuroepithelial Stem Cells Recapitulates Medulloblastoma Tumorigenesis
- 2019
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Ingår i: Cell Stem Cell. - : CELL PRESS. - 1934-5909 .- 1875-9777. ; 25:3, s. 433-
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Tidskriftsartikel (refereegranskat)abstract
- Human neural stem cell cultures provide progenitor cells that are potential cells of origin for brain cancers. However, the extent to which genetic predisposition to tumor formation can be faithfully captured in stem cell lines is uncertain. Here, we evaluated neuroepithelial stem (NES) cells, representative of cerebellar progenitors. We transduced NES cells with MYCN, observing medulloblastoma upon orthotopic implantation in mice. Significantly, transcriptomes and patterns of DNA methylation from xenograft tumors were globally more representative of human medulloblastoma compared to a MYCN-driven genetically engineered mouse model. Orthotopic transplantation of NES cells generated from Gorlin syndrome patients, who are predis- posed to medulloblastoma due to germline-mutated PTCH1, also generated medulloblastoma. We engineered candidate cooperating mutations in Gorlin NES cells, with mutation of DDX3X or loss of GSE1 both accelerating tumorigenesis. These findings demonstrate that human NES cells provide a potent experimental resource for dissecting genetic causation in medulloblastoma.
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| 514. |
- Johnsson, A., et al.
(författare)
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Anal cancer in Sweden 2015-2019. Implementation of guidelines, structural changes, national registry and early results
- 2022
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 61:5, s. 575-582
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Tidskriftsartikel (refereegranskat)abstract
- Background Squamous cell cancer of the anus is an uncommon malignancy, usually caused by human papilloma virus (HPV). Chemoradiotherapy (CRT) is the recommended treatment in localized disease with cure rates of 60-80%. Local failures should be considered for salvage surgery. With the purpose of improving and equalizing the anal cancer care in Sweden, a number of actions were taken between 2015 and 2017. The aim of this study was to describe the implementation of guidelines and organizational changes and to present early results from the first 5 years of the Swedish anal cancer registry (SACR). Methods The following were implemented: (1) the first national care program with treatment guidelines, (2) standardized care process, (3) centralization of CRT to four centers and salvage surgery to two centers, (4) weekly national multidisciplinary team meetings where all new cases are discussed, (5) the Swedish anal cancer registry (SACR) was started in 2015. Results The SACR included 912 patients with a diagnosis of anal cancer from 2015 to 2019, reaching a national coverage of 95%. We could show that guidelines issued in 2017 regarding staging procedures and radiotherapy dose modifications were rapidly implemented. At baseline 52% of patients had lymph node metastases and 9% had distant metastases. Out of all patients in the SACR 89% were treated with curative intent, most of them with CRT, after which 92% achieved a local complete remission and the estimated overall 3-year survival was 85%. Conclusions This is the first report from the SACR, demonstrating rapid nation-wide implementation of guidelines and apparently good treatment outcome in patients with anal cancer in Sweden. The SACR will hopefully be a valuable source for future research.
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| 515. |
- Pais, Jorge C., et al.
(författare)
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Crumb Rubber Modified Binders
- 2023
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Ingår i: RILEM State-of-the-Art Reports. - : Springer Nature. ; , s. 37-67
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- RILEM Technical Committee 279 WMR is dedicated to the Valorization of Waste and Secondary Materials for Roads. Its Task Group 2 investigated Crumb Rubber (CR) as an additive to enhance the performance of bitumen. CR recycled from end-of-life tires (ELTs) was chosen for this investigation because crumb rubber modified bitumen (CRMB) has been used to improve bituminous mixtures performance for fatigue and reflective cracking. The success of these mixtures is due to the CRMB viscosity that allows the use of an increased amount of bitumen compared to conventional mixtures. Because the viscosity of the CRMB is a function of the CR surface, and presently various types of CRs are produced, it is crucial to verify how these materials perform as a bitumen modifier. Interlaboratory experiments were performed on four types of CR, obtained from mechanical grinding, cryogenic process, waterjet pulverization and reacted and activated rubber. Three base, 35/50, 50/70 and 70/100, bitumen were used for the modification. Mechanical and chemical properties of CRMB were investigated. Despite some differences in the non-mechanical tests, i.e., penetration, softening point and viscosity, the results of the mechanical tests (complex shear modulus) suggest that the bitumen penetration grade ultimately dictates CRMB response.
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| 516. |
- Rodriguez-Fernandez, Israel, et al.
(författare)
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Microstructure analysis and mechanical performance of crumb rubber modified asphalt concrete using the dry process
- 2020
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Ingår i: Construction and Building Materials. - : Elsevier BV. - 0950-0618 .- 1879-0526. ; 259
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Tidskriftsartikel (refereegranskat)abstract
- Globally, the vast majority of waste tires are landfilled, with catastrophic ecological consequences and in particular, serious threats to human health (e.g. fire, pests and soil contamination). Because of the increasing environmental awareness, the use of crumb rubber modified asphalt has become an important recycling strategy for waste tires. The so-called crumb rubber (CR), which is the recycled rubber from tires, has become a common additive in hot mix asphalt mixture due to its improvement of the mechanical performances of asphalt mixtures. The purpose of this study is to investigate the effect of adding crumb rubber to asphalt mixtures using the dry process by relating mechanical performances with microstructural characterizations. It was possible to observe the influence of conditioning process (time during which the asphalt mixture is kept at a high temperature after mixing) on the mechanical performance of the mixtures that depend primarily on the properties of the crumb rubber used. Specifically, it is shown that the conditioning time has an influence on the Marshall test results as well as the viscosity measurements. By using the Environmental Scanning Electron Microscope (ESEM), the distribution of the crumb rubber within the mixture has been investigated. In particular, the distribution of the crumb rubber by changing the conditioning time is of interest. The results showed that crumb rubber is well dispersed in the asphalt mixture when the conditioning time is increased. The effect of crumb rubber on the microstructure using Atomic Force Microscopy-Infrared Spectroscopy (AFM-IR) indicated that the main chemical change takes place in the para domain and catana or the so-called bee structures diminish on the CR modified bitumen as a consequence of more conditioning time.
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| 517. |
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| 518. |
- Sinnegger-Brauns, MJ, et al.
(författare)
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Isoform-specific regulation of mood behavior and pancreatic beta cell and cardiovascular function by L-type Ca2+ channels
- 2004
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Ingår i: Journal of Clinical Investigation. - 0021-9738. ; 113:10, s. 1430-1439
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Tidskriftsartikel (refereegranskat)abstract
- Ca(v)1.2 and Ca(v)1.3 L-type Ca2+ channels (LTCCs) are believed to underlie Ca2+ currents in brain, pancreatic beta cells, and the cardiovascular system. In the CNS, neuronal LTCCs control excitation-transcription coupling and neuronal plasticity. However, the pharmacotherapeutic implications of CNS LTCC modulation are difficult to study because LTCC modulators cause card iovascular (activators and. blockers) and neurotoxic (activators) effects. We selectively eliminated high dihydropyridine (DHP) sensitivity from Ca(v)1.2 alpha1 subunits (Ca(v)1.2DHP(-/-)) without affecting function and expression. This allowed separation of the DHP effects of Ca(v)1.2 from those of Ca(v)1.3 and other LTCCs. DHP effects on pancreatic P cell LTCC currents, insulin secretion, cardiac inotropy, and arterial smooth muscle contractility were lost in Ca(v)1.2DHP(-/-) mice, which rules out a direct role of Ca(v)1.3 for these physiological processes. Using Ca(v)1.2DHP(-/-) mice, we established DHPs as mood-modifying agents: LTCC activator-induced neurotoxicity was abolished and disclosed a depression-like behavioral effect without affecting spontaneous locomotor activity. LTCC activator BayK 8644 (BayK) activated only a specific set of brain areas. In the ventral striatum, BayK-induced release of glutamate and 5-HT, but not dopamine and noradrenaline, was abolished. This animal model provides a useful tool to elucidate whether Ca(v)1.3-selective channel modulation represents a novel pharmacological approach to modify CNS function without major peripheral effects.
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| 519. |
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| 520. |
- Yttri, K. E., et al.
(författare)
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Elemental and organic carbon in PM10 : a one year measurement campaign within the European Monitoring and Evaluation Programme EMEP
- 2007
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Ingår i: Atmospheric Chemistry And Physics. - 1680-7316 .- 1680-7324. ; 7:22, s. 5711-5725
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Tidskriftsartikel (refereegranskat)abstract
- In the present study, ambient aerosol (PM10) concentrations of elemental carbon (EC), organic carbon (OC), and total carbon (TC) are reported for 12 European rural background sites and two urban background sites following a one-year (1 July 2002 & ndash;1 July 2003) sampling campaign within the European Monitoring and Evaluation Programme, EMEP (http://www.emep.int/). The purpose of the campaign was to assess the feasibility of performing EC and OC monitoring on a regular basis and to obtain an overview of the spatial and seasonal variability on a regional scale in Europe. Analyses were performed using the thermal-optical transmission (TOT) instrument from Sunset Lab Inc., operating according to a NIOSH derived temperature program. The annual mean mass concentration of EC ranged from 0.17 +/- 0.19 mu G m(-3) (mean +/- SD) at Birkenes (Norway) to 1.83 +/- 1.32 mu g m(-3) at Ispra (Italy). The corresponding range for OC was 1.20 +/- 1.29 mu g m(-3) at Mace Head (Ireland) to 7.79 +/- 6.80 mu g m-3 at Ispra. On average, annual concentrations of EC, OC, and TC were three times higher for rural background sites in Central, Eastern and Southern Europe compared to those situated in the Northern and Western parts of Europe. Wintertime concentrations of EC and OC were higher than those recorded during summer for the majority of the sites. Moderate to high Pearson correlation coefficients (r(p)) (0.50-0.94) were observed for EC versus OC for the sites investigated. The lowest correlation coefficients were noted for the three Scandinavian sites: Aspvreten (SE), Birkenes (NO), and Virolahti (FI), and the Slovakian site Stara Lesna, and are suggested to reflect biogenic sources, wild and prescribed fires. This suggestion is supported by the fact that higher concentrations of OC are observed for summer compared to winter for these sites. For the rural background sites, total carbonaceous material accounted for 30 +/- 9% of PM10, of which 27 +/- 9% could be attributed to organic matter (OM) and 3.4 +/- 1.0% to elemental matter (EM). OM was found to be more abundant than SO42- for sites reporting both parameters.
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