| 1. |
|
|
| 2. |
- Lundstedt-Enkel, Katrin, et al.
(författare)
-
A Statistical Resampling Method To Calculate Biomagnification Factors Exemplified with Organochlorine Data from Herring (Clupea harengus) Muscle and Guillemot (Uria aalge) Egg from the Baltic Sea
- 2005
-
Ingår i: ENVIRONMENTAL SCIENCE & TECHNOLOGY. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 39:21, s. 8395-8402
-
Tidskriftsartikel (refereegranskat)abstract
- A novel method for calculating biomagnification factors is presented and demonstrated using contaminant concentration data from the Swedish national monitoring program regarding organochlorine contaminants (OCs) in herring (Clupea harengus) muscle and guillemot (Uria aalge) egg, sampled from 1996 to 1999 from the Baltic Sea. With this randomly sampled ratios (RSR) method, biomagnification factors (BMFRSR) were generated and denoted with standard deviation (0) as a measure of the variation. The BMFRSR were calculated by randomly selecting one guillemot egg out of a total of 29 and one herring out of a total of 74, and the ratio was determined between the concentration of a given OC in that egg and the concentration of the same OC in that herring. With the resampling technique, this was performed 50 000 times for any given OC, and from this new distribution of ratios, BMFRSR for each OC were calculated and given as geometric mean (GM) with GM standard deviation (GMSD) range, arithmetic mean (AM) with AMSD range, and minimum (BMFMIN) as well as maximum (BMFMAX) biomagnification factors. The 14 analyzed OCs were p,p'DDT and its metabolites p,p'DDE and p,p'DDD, polychlorinated biphenyls (PCB congeners: CB28, CB52, CB101, CB118, CB138, CB153, and CB180), hexachlorocyclohexane isomers (alpha-, beta-, and gamma HCH), and hexachlorobenzene (HCB). Multivariate data analysis (MVDA) methods, including principal components analysis (PCA), partial least squares regression (PLS), and PLS discriminant analyses (PLS-DA), were first used to extract information from the complex biological and chemical data generated from each individual animal. MVDA were used to model similarities/dissimilarities regarding species (PCA, PLS-DA), sample years (PLS), and sample location (PLS-DA) to give a deeper understanding of the data that the BMF modeling was based upon. Contaminants that biomagnify, that had BMFRSR significantly higher than one, were p,p'DDE, CB118, HCB, CB138, CB180, CB153, beta HCH, and CB28. The contaminants that did not biomagnify were p,p'DDT, p,p'DDD, alpha HCH, CB101, and CB52. Eventual biomagnification for gamma HCH could not be determined. The BMFRSR for OCs present in herring muscle and guillemot egg showed a broad span with large variations for each contaminant. To be able to make reliable calculations of BMFs for different contaminants, we emphasize the importance of using data based upon large numbers of, as well as well-defined, individuals.
|
|
| 3. |
|
|
| 4. |
- Moberg, Christina, et al.
(författare)
-
De unga gör helt rätt när de stämmer staten
- 2022
-
Ingår i: Aftonbladet. - 1103-9000.
-
Tidskriftsartikel (populärvet., debatt m.m.)abstract
- 1 620 forskare och lärare i forskarvärlden: Vi ställer oss bakom Auroras klimatkrav
|
|
| 5. |
|
|
| 6. |
- Anastasopoulou, Stavroula, et al.
(författare)
-
Acute central nervous system toxicity during treatment of pediatric acute lymphoblastic leukemia : phenotypes, risk factors and genotypes
- 2020
-
Ingår i: Haematologica. - : Ferrata Storti Foundation. - 0390-6078 .- 1592-8721. ; 107:10, s. 2318-2328
-
Tidskriftsartikel (refereegranskat)abstract
- Central nervous system (CNS) toxicity is common at diagnosis and during treatment of pediatric acute lymphoblastic leukemia (ALL). We studied CNS toxicity in 1,464 children aged 1.0-17.9 years, diagnosed with ALL and treated according to the Nordic Society of Pediatric Hematology and Oncology ALL2008 protocol. Genome-wide association studies, and a candidate single-nucleotide polymorphism (SNP; n=19) study were performed in 1,166 patients. Findings were validated in an independent Australian cohort of children with ALL (n=797) in whom two phenotypes were evaluated: diverse CNS toxicities (n=103) and methotrexate-related CNS toxicity (n=48). In total, 135/1,464 (9.2%) patients experienced CNS toxicity for a cumulative incidence of 8.7% (95% confidence interval: 7.31-10.20) at 12 months from diagnosis. Patients aged >= 10 years had a higher risk of CNS toxicity than had younger patients (16.3% vs. 7.4%; P < 0.001). The most common CNS toxicities were posterior reversible encephalopathy syndrome (n=52, 43 with seizures), sinus venous thrombosis (n=28, 9 with seizures), and isolated seizures (n=16). The most significant SNP identified by the genome-wide association studies did not reach genomic significance (lowest P-value: 1.11x10(-6)), but several were annotated in genes regulating neuronal functions. In candidate SNP analysis, ATXN1 rs68082256, related to epilepsy, was associated with seizures in patients < 10 years (P=0.01). ATXN1 rs68082256 was validated in the Australian cohort with diverse CNS toxicities (P=0.04). The role of ATXN1 as well as the novel SNP in neurotoxicity in pediatric ALL should be further explored.
|
|
| 7. |
- Anastasopoulou, Stavroula, et al.
(författare)
-
Does minimal central nervous system involvement in childhood acute lymphoblastic leukemia increase the risk for central nervous system toxicity?
- 2022
-
Ingår i: Pediatric Blood & Cancer. - : John Wiley & Sons. - 1545-5009 .- 1545-5017. ; 69:7
-
Tidskriftsartikel (refereegranskat)abstract
- Central nervous system (CNS) involvement in childhood acute lymphoblastic leukemia (ALL) implicates enhanced intrathecal chemotherapy, which is related to CNS toxicity. Whether CNS involvement alone contributes to CNS toxicity remains unclear. We studied the occurrence of all CNS toxicities, seizures, and posterior reversible encephalopathy syndrome (PRES) in children with ALL without enhanced intrathecal chemotherapy with CNS involvement (n = 64) or without CNS involvement (n = 256) by flow cytometry. CNS involvement increased the risk for all CNS toxicities, seizures, and PRES in univariate analysis and, after adjusting for induction therapy, for seizures (hazard ratio [HR] = 3.33; 95% confidence interval [CI]: 1.26-8.82; p = 0.016) and PRES (HR = 4.85; 95% CI: 1.71-13.75; p = 0.003).
|
|
| 8. |
- Anastasopoulou, Stavroula, et al.
(författare)
-
Posterior reversible encephalopathy syndrome in children with acute lymphoblastic leukemia : Clinical characteristics, risk factors, course, and outcome of disease
- 2019
-
Ingår i: Pediatric Blood & Cancer. - : WILEY. - 1545-5009 .- 1545-5017. ; 66:5
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Posterior reversible encephalopathy syndrome (PRES) is a distinct entity with incompletely known predisposing factors. The aim of this study is to describe the incidence, risk factors, clinical course, and outcome of PRES in childhood acute lymphoblastic leukemia (ALL).Procedure: Patients aged 1.0 to 17.9 years diagnosed with ALL from July 2008 to December 2015 and treated according to the Nordic Society of Pediatric Hematology and Oncology (NOPHO) ALL2008 protocol were included. Patients with PRES were identified in the prospective NOPHO leukemia toxicity registry, and clinical data were collected from the medical records.Results: The study group included 1378 patients, of whom 52 met the criteria for PRES. The cumulative incidence of PRES at one month was 1.7% (95% CI, 1.1-2.5) and at one year 3.7% (95% CI, 2.9-4.9). Older age (hazard ratios [HR] for each one-year increase in age 1.1; 95% CI, 1.0-1.2, P = 0.001) and T-cell immunophenotype (HR, 2.9; 95% CI, 1.6-5.3, P = 0.0005) were associated with PRES. Central nervous system (CNS) involvement (odds ratios [OR] = 2.8; 95% CI, 1.2-6.5, P = 0.015) was associated with early PRES and high-risk block treatment (HR = 2.63; 95% CI, 1.1-6.4, P = 0.033) with late PRES. At follow-up of the PRES patients, seven patients had epilepsy and seven had neurocognitive difficulties.Conclusion: PRES is a neurotoxicity in the treatment of childhood ALL with both acute and long-term morbidity. Older age, T-cell leukemia, CNS involvement and high-risk block treatment are risk factors for PRES.
|
|
| 9. |
- Anastasopoulou, Stavroula, et al.
(författare)
-
Seizures during treatment of childhood acute lymphoblastic leukemia : A population-based cohort study
- 2020
-
Ingår i: European journal of paediatric neurology. - : ELSEVIER SCI LTD. - 1090-3798 .- 1532-2130. ; 27, s. 72-77
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Seizures are common in children with acute lymphoblastic leukemia (ALL). As ALL survival rates are improving, the challenge to minimize treatment related side effects and late sequelae rises. Here, we studied the frequency, timing, etiology and risk factors of seizures in ALL patients. Methods: The study included children aged 1-17.9 years at diagnosis of B-cell-precursor and T cell ALL who were treated according to the Nordic Society of Pediatric Hematology and Oncology (NOPHO) ALL2008 protocol between 2008 and 2015. Detailed patient data were acquired from the NOPHO ALL2008 registry and by review of medical records. Results: Seizures occurred in 81/1464 (5.5%) patients. The cumulative incidence of seizures at one months was 1.7% (95% CI: 1.2-2.5) and at one year 5.3% (95% CI 4.2-6.5%). Patients aged 10-17.9 years, those with T cell immunophenotype, CNS involvement, or high-risk induction with dexamethasone had higher risk for seizures in univariable analyses. Only age remained a risk factor in multivariable analyses (the cumulative incidence of seizures for patients 10-17.9 years old at one year was 9.0% (95% CI: 6.2-12.9)). Of the 81 patients with seizures, 43 had posterior reversible encephalopathy syndrome (PRES), 15 had isolated seizures, nine had sinus venous thrombosis (SVT), three had stroke-like syndrome, and 11 had other neurotoxicities. Epilepsy diagnosis was reported in totally 11 ALL survivors at last follow up. Conclusion: Seizures are relatively common in ALL patients and occur most often in patients with PRES, SVT, or as an isolated symptom. Older children have higher risk of seizures. (C) 2020 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.
|
|
| 10. |
- Basu, Samar, et al.
(författare)
-
Effects of melagatran, a novel direct thrombin inhibitor, during experimental septic shock
- 2000
-
Ingår i: Expert Opinion on Investigational Drugs. - : Informa Healthcare. - 1354-3784 .- 1744-7658. ; 9:5, s. 1129-1137
-
Tidskriftsartikel (refereegranskat)abstract
- Sepsis and endotoxaemia initiate the generation of thrombin, which is responsible for the conversion of fibrinogen to fibrin, platelet aggregation and acts as an inflammatory mediator affecting numerous types of cells, including myocardial, smooth muscle and endothelial cells. Human Gram-negative septic shock, frequently seen in intensive care units, is a condition with high mortality. This condition can be replicated in the endotoxaemic pig. As many of the toxic effects of sepsis are due to thrombin generation, it was of interest to study, using this porcine experimental septic shock model, whether inhibition of thrombin could alleviate the effects of endotoxaemia. For this purpose melagatran, a direct synthetic thrombin inhibitor with a molecular weight of 429 Da, was employed. Melagatran does not significantly interact with any other enzymes in the coagulation cascade or fibrinolytic enzymes aside from thrombin. Furthermore, melagatran does not require endogenous co-factors such as antithrombin or heparin co-Factor II for its antithrombin effect, which is important, as these inhibitors are often consumed in septic patients. We have shown that melagatran exerts a beneficial effect on renal function, as evaluated by plasma creatinine and urinary output, during experimental septic shock. These effects were most pronounced during the later phase of the experimental period, after the infusion of melagatran had been discontinued. Prevention of intrarenal coagulation may be attributable to this finding. In addition, melagatran had beneficial effects on systemic haemodynamics (left ventricular stroke work index, pulmonary capillary wedge pressure and systemic vascular resistance index) in endotoxaemic pigs. This result may be explained by the ability of melagatran to inhibit thrombin, thereby counteracting thrombin's cellular effects. Thus, it can be seen, using this experimental model of septic shock, that melagatran may help to alleviate some of the damaging effects of endotoxaemia, although more research is required to test this further.
|
|
