| 1. |
|
|
| 2. |
|
|
| 3. |
- Modvig, S, et al.
(författare)
-
Value of Flow Cytometry for MRD-Based Relapse Prediction in B-Cell Precursor Acute Lymphoblastic Leukemia in a Multi-Center Setting
- 2019
-
Ingår i: Blood. - 0006-4971 .- 1528-0020.
-
Konferensbidrag (refereegranskat)abstract
- Background: PCR of rearranged antigen receptor genes is the method of choice for MRD quantification in ALL. Although FCM-MRD is faster and biologically more informative than PCR, the analysis requires a high level of training. The only larger published studies using FCM-MRD based stratification (Borowitz, Blood, 2008 and 2015) showed a clear association with clinical outcome in BCP-ALL. However, MRD analyses were centralized and these studies included only one MRD-based stratification (MRD levels at the end of induction). Patients and methods: We examined FCM-MRD as stratification tool in BCP-ALL at various timepoints in a large-scale multicenter (18 MRD centers) study. A total of 1487 patients with BCP-ALL (1298 children (younger than 18 years) and 189 adults (18-45 years) are included in the study and were treated according to the NOPHO ALL2008 protocol between July 2008 and February 2016. The median follow-up time for patients in first remission was 51 months (IQR 32-75). MRD was measured by FCM and/or real time quantitative PCR on days 15, 29 (end of induction) and 79 (for standard (SR) and intermediate risk (IR) patients) and prior to and after high risk blocks. A 6-colour FCM analysis including 3 standardized antibody combinations was used and performed in 18 laboratories. Patients were stratified by FCM-MRD, or by PCR-MRD if no FCM-MRD marker was available. End-of-induction MRD (cut-off 10-3) was used to stratify patients to standard risk (SR) vs intermediate risk (IR) or IR vs high risk consolidation therapy (in case of WBC > 100 x 109/L at diagnosis). Patients with MRD >=2.5x10-1 on day 15 were stratified to high risk block therapy. Patients with MRD >=5x10-2 on day 29 or day 79/post high risk-2 block MRD >=10-3 were stratified to HSCT. Primary outcomes were 5year event-free survival (5y EFS) and 5year cumulative incidence of relapse (5y CIR). Results: Only two patients (0.14% of total) had neither an informative FCM nor a PCR marker, and an informative FCM marker combination for MRD monitoring was identified in 96.2% of patients. There was a significant correlation between FCM- and PCR-MRD levels on day 15 (r=0.77, p<0.0001, n=153) and 29 (r=0.81, p<0.0001, n=140). Based on FCM-MRD only, the median MRD level on day 15, 29 and 79/post high risk-2 block was 5x10-3, 1.1x10-4, and below detection limit, respectively. Adults had significantly higher MRD levels at all time-points (p<0.0001 for day 15 and 29, p=0.0019 for day 79, Mann-Whitney). The 5y EFS was 86.1% (95% CI 84.1-88.1) with a 5y CIR of 9.5% (95% CI 7.8-11.3, n=1487). The day 29 FCM-MRD level was closely associated with clinical outcome and a higher hazard of relapse was seen independently for a FCM-MRD >=10-3 (hazard ratio (HR) 2.4, CI 1.6-3.7, p<0.0001), age>18 year (HR 3.0, CI 1.7-5.3, p<0.0001), WBC>=100 (HR 2.7, CI 1.6-4.6, p=0.0001), and B-other (HR 2.1, CI 1.2-3.5, p=0.0052) or high risk B-ALL cytogenetic aberration (rearranged KMT2A/iAMPchr21/hypodiploid) (HR 3.2, CI 1.6-6.1, p=0.0006) (multivariate cause-specific Cox regression, n=1328). Patients with a day 79 FCM-MRD >=10-4 and <10-3 had a significantly higher CIR (22.1%, CI 10.8-33.5%, n=68) compared to FCM-MRD <10-4 (7.5%, CI 2.1-12.8%, n=110) or undetectable (6.3%, CI 4.5-8.2%, n=999, p=0.0087 for FCM-MRD >=10-4 and <10-3vs <10-4 or undetectable). After adjusting for WBC, age, and the day 29 FCM-MRD level, a day 79 FCM-MRD >=10-4 and <10-3 was still significantly associated with a worse 5y CIR for non-transplanted patients (HR 2.3, CI 1.19-4.36, p=0.012 compared to undetectable FCM-MRD, n=1171). Patients with day 15 FCM-MRD <10-3 had a significantly better 5y EFS (92.0%, CI 89.2-95.0%) and CIR (3.9%, CI 1.7-6.1%, n=432) than patients with FCM-MRD >=10-3 and <2.5x10-1, who had a 5y EFS of 85.5% (CI 82.7-88.3%, p=0.0016, n=837) and a 3-fold higher 5y CIR (11.0%, CI 8.4-13.5%, p<0.0001, n=432). Among patients with day 15 FCM-MRD<10-3, the relapse incidence was comparable for patients with FCM-MRD 10-4 - <10-3 and below 10-4 (CIR 3.6, CI 0.5-6.7 vs. CIR 4.1, CI 1.0-7.2, p=0.83, n=432). Conclusion: FCM-MRD performed in a multi-center setting is a clinically useful method for disease monitoring and MRD-based treatment stratification in BCP-ALL. Moreover, FCM-MRD is a reliable indicator of outcome in BCP-ALL independently of other key risk factors. Residual disease >=10-4 and <10-3 at day 79 in SR/IR patients not allocated to HSCT further identifies patients with a high risk of relapse.
|
|
| 4. |
- Tulstrup, M., et al.
(författare)
-
NT5C2 germline variants alter thiopurine metabolism and are associated with acquired NT5C2 relapse mutations in childhood acute lymphoblastic leukaemia
- 2018
-
Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 32:12, s. 2527-2535
-
Tidskriftsartikel (refereegranskat)abstract
- The antileukaemic drug 6-mercaptopurine is converted into thioguanine nucleotides (TGN) and incorporated into DNA (DNA-TG), the active end metabolite. In a series of genome-wide association studies, we analysed time-weighted means ((wm)) of erythrocyte concentrations of TGN (Ery-TGN) and DNA-TG in 1009 patients undergoing maintenance therapy for acute lymphoblastic leukaemia (ALL). In discovery analyses (454 patients), the propensity for DNA-TG incorporation ((wm)DNA-TG/(wm)Ery-TGN ratio) was significantly associated with three intronic SNPs in NT5C2 (top hit: rs72846714; P - 2.09 x 10(-10), minor allele frequency 15%). In validation analyses (555 patients), this association remained significant during both early and late maintenance therapy (P - 8.4 x 10(-6) and 1.3 x 10(-3), respectively). The association was mostly driven by differences in (wm)Ery-TGN, but in regression analyses adjusted for wmEry-TGN (P < 0.0001), rs72846714-A genotype was also associated with a higher (wm)DNA-TG (P - 0.029). Targeted sequencing of NT5C2 did not identify any missense variants associated with rs72846714 or (wm)Ery-TGN/(wm)DNA-TG. rs72846714 was not associated with relapse risk, but in a separate cohort of 180 children with relapsed ALL, rs72846714-A genotype was associated with increased occurrence of relapse-specific NT5C2 gain-of-function mutations that reduce cytosol TGN levels (P = 0.03). These observations highlight the impact of both germline and acquired mutations in drug metabolism and disease trajectory.
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
- Le Roch, Sarah, et al.
(författare)
-
European survey on criteria of aesthetics for periodontal evaluation: The ESCAPE study
- 2019
-
Ingår i: Journal of Clinical Periodontology. - : Wiley. - 0303-6979 .- 1600-051X. ; 46:11, s. 1116-1123
-
Tidskriftsartikel (refereegranskat)abstract
- © 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd Objective: The ESCAPE multicentre survey was designed to (a) compare the agreement of three relevant aesthetic scoring systems among different centres, and (b) evaluate the reproducibility of each question of the questionnaires. Materials and Methods: EFP centres (n=14) were involved in an e-survey. Forty-two participants (28 teachers, 14 postgraduate students) were asked to score the one-year aesthetic outcomes of photographs using the Before–After Scoring System (BASS), the Pink Esthetic Score (PES) and the Root coverage Esthetic Score (RES). Mean values of kappa statistics performed on each question were provided to resume global agreement of each method. Results: Between teachers, a difference of kappa≥0.41 (p=.01) was found for BASS (75%) and PES (57%). Similarly, RES (84%) and PES (57%) were different (p<.001). No difference was found between BASS (75%) and RES (84%). No difference was found between students, whatever the scoring system. Questions of each scoring system showed differences in their reproducibility. Conclusions: The outcomes of this study indicate that BASS and RES scoring systems are reproducible tools to evaluate aesthetic after root coverage therapies between different centres. Among the various variables, lack of scar, degree of root coverage, colour match and gingival margin that follows the CEJ show the best reliability.
|
|
| 8. |
- Reid, G., et al.
(författare)
-
How do probiotics and prebiotics function at distant sites?
- 2017
-
Ingår i: Beneficial Microbes. - : WAGENINGEN ACADEMIC PUBLISHERS. - 1876-2883 .- 1876-2891. ; 8:4, s. 521-533
-
Tidskriftsartikel (refereegranskat)abstract
- The realisation that microbes regarded as beneficial to the host can impart effects at sites distant from their habitat, has raised many possibilities for treatment of diseases. The objective of a workshop hosted in Turku, Finland, by the International Scientific Association for Probiotics and Prebiotics, was to assess the evidence for these effects and the extent to which early life microbiome programming influences how the gut microbiota communicates with distant sites. In addition, we examined how probiotics and prebiotics might affect the skin, airways, heart, brain and metabolism. The growing levels of scientific and clinical evidence showing how microbes influence the physiology of many body sites, leads us to call for more funding to advance a potentially exciting avenue for novel therapies for many chronic diseases.
|
|
| 9. |
|
|
| 10. |
- Abrahamsson, Thomas, 1956, et al.
(författare)
-
Calibration and Validation of a Car Subframe Finite Element Model Using Frequency Responses
- 2015
-
Ingår i: Conference Proceedings of the Society for Experimental Mechanics Series. - Cham : Springer International Publishing. - 2191-5644 .- 2191-5652. - 9783319152516 ; 10, s. 9-22
-
Konferensbidrag (refereegranskat)abstract
- A finite element model of a car front subframe has been calibrated against test data. Stepped-sine testing has been used to give frequency response function estimates on an ensemble of seemingly identical subframes. Therefore, the deviation between test data and simulation results can be compared in a meaningful way by the outcome of model calibration and cross-validation. Emphasis has been put on the preparation of the test pieces for high fidelity testing and on bettering the chances of getting a calibration outcome that provides insight into the physical processes that govern the subframe dynamics. The front subframe model has more than 200,000 degrees-of-freedom and 17 model calibration parameters. The efficiency of the calibration procedure under these conditions is reported. To achieve efficiency, a calibration with a smooth deviation metric is used together with a damping equalization method that eliminates the need for matching of experimental and analytical eigenmodes. The method is combined with surrogate model frequency response evaluation based on model reduction for increased speed. The Matlab based open-domain software tool FEMcali that employs the Levenberg-Marquardt minimizer with randomized starts has been used for calibration and an unregularized Gauss-Newton minimizer has been used in the cross-validation.
|
|
| 11. |
|
|
| 12. |
- Burlen, J., et al.
(författare)
-
Efficacy of Gastric Electrical Stimulation for Gastroparesis: US/European Comparison
- 2018
-
Ingår i: Gastroenterology Research. - : Elmer Press, Inc.. - 1918-2805 .- 1918-2813. ; 11:5, s. 349-354
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Gastric electrical stimulation (GES) is used in both the US and Europe, but little research has investigated the demographics of gastroparesis patients receiving GES by geographic location. Methods: We compared data from 380 patients, 296 female and 84 males, mean age 42 years, 246 idiopathic (ID), 107 diabetic (DM), and 27 post-surgical (PS). The statistical significance was calculated by Chi-square test and a P-value obtained for ID, DM, and PS. The statistical significance was calculated by Fischer exact test and a P-value obtained comparing male vs. female. Results: European centers had 61 GES patients compared to 319 from the US. In Europe, 100% of patients had gastric emptying test (GET) values available; in the US, it was 75% of patients. European centers had more DM patients (59%) than the US (22%), and a smaller proportion of ID patients (25%) than the US (72%). There was a statistical difference between the causes of gastroparesis in the patients receiving GES (P-value < 0.00001). There was also significant difference in the gender of the patients receiving GES, with a greater proportion of women in the US (P value = 0.0023). Conclusions: Comparing GES in US vs. Europe demonstrated significant differences in gastroparesis demographics and percentage of patients with GET data. After analyzing the previously discussed results and reviewing recent updates in evidence-based medicine guidelines, the discrepancy and variance in patient populations in the US and Europe emphasizes the need for a database that allows better analysis and treatment of gastroparesis patients worldwide including stimulation therapies.
|
|
| 13. |
- Creutzig, Ursula, et al.
(författare)
-
Characteristics and outcome in patients with central nervous system involvement treated in European pediatric acute myeloid leukemia study groups.
- 2017
-
Ingår i: Pediatric blood & cancer. - : Wiley. - 1545-5017 .- 1545-5009. ; 64:12
-
Tidskriftsartikel (refereegranskat)abstract
- There is no consensus on the treatment for pediatric patients with acute myeloid leukemia and initial central nervous system (CNS) involvement.To evaluate different CNS-directed treatment options (intrathecal [IT] therapy, CNS irradiation, hematopoietic stem cell transplantation [HSCT]), 261 patients (excluding acute promyelocytic leukemia) with initial CNS involvement treated in trials with similar intensive chemotherapy by four cooperative European study groups (1998-2013) were studied and compared with CNS-negative patients from the Berlin-Frankfurt-Münster group.Patient characteristics in the different study groups were comparable. Young age, high white blood cell count, extramedullary involvement other than the CNS, monoblastic morphology, and inv(16) were associated with CNS involvement (each P < 0.0001). There were no major differences in outcome between the study groups. The cumulative incidence of relapse (CIR) regarding the CNS was higher in initially CNS-positive versus initially CNS-negative patients (all: 8 ± 2% vs. 3 ± 1%, P(Gray) = 0.001; isolated: 4 ± 1% vs. 1 ± 0%, P(Gray) = 0.03). However, global outcome of the CNS-positive cohort (overall survival, 64 ± 3%; event-free survival 48 ± 3%; and CIR 33% ± 3%) did not differ significantly from CNS-negative patients. Risk groups defined by cytogenetics were of likewise prognostic significance in CNS-positive and -negative patients. CNS treatment with cranial irradiation was not superior compared to IT therapy and systemic chemotherapy (± HSCT).Although CNS relapses occurred more frequently in initially CNS-positive patients, their global outcome was similar as in CNS-negative patients. Intensified IT therapy was heterogeneous; however, at least eight applications, preferably with triple IT chemotherapy, seem to be appropriate to accompany dose-intensive systemic chemotherapy.
|
|
| 14. |
- Darwich, Adam S., et al.
(författare)
-
IMI - Oral biopharmaceutics tools project - Evaluation of bottom-up PBPK prediction success part 3 : Identifying gaps in system parameters by analysing In Silico performance across different compound classes
- 2017
-
Ingår i: European Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0928-0987 .- 1879-0720. ; 96, s. 626-642
-
Tidskriftsartikel (refereegranskat)abstract
- Three Physiologically Based Pharmacokinetic software packages (GI-Sim, Simcyp (R) Simulator, and GastroPlus (TM)) were evaluated as part of the Innovative Medicine Initiative Oral Biopharmaceutics Tools project (OrBiTo) during a blinded "bottom-up" anticipation of human pharmacokinetics. After data analysis of the predicted vs. measured pharmacokinetics parameters, it was found that oral bioavailability (F-oral) was underpredicted for compounds with low permeability, suggesting improper estimates of intestinal surface area, colonic absorption and/or lack of intestinal transporter information. Foralwas also underpredicted for acidic compounds, suggesting overestimation of impact of ionisation on permeation, lack of information on intestinal transporters, or underestimation of solubilisation of weak acids due to less than optimal intestinal model pH settings or underestimation of bile micelle contribution. F-oral was overpredicted for weak bases, suggesting inadequate models for precipitation or lack of in vitro precipitation information to build informed models. Relative bioavailability was underpredicted for both high logP compounds as well as poorly water-soluble compounds, suggesting inadequate models for solubility/dissolution, underperforming bile enhancement models and/or lack of biorelevant solubility measurements. These results indicate areas for improvement in model software, modelling approaches, and generation of applicable input data. However, caution is required when interpreting the impact of drug-specific properties in this exercise, as the availability of input parameters was heterogeneous and highly variable, and the modellers generally used the data "as is" in this blinded bottom-up prediction approach.
|
|
| 15. |
|
|
| 16. |
- Margolskee, Alison, et al.
(författare)
-
IMI - Oral biopharmaceutics tools project - Evaluation of bottom-up PBPK prediction success part 2 : An introduction to the simulation exercise and overview of results
- 2017
-
Ingår i: European Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0928-0987 .- 1879-0720. ; 96, s. 610-625
-
Tidskriftsartikel (refereegranskat)abstract
- Orally administered drugs are subject to a number of barriers impacting bioavailability (F-oral), causing challenges during drug and formulation development. Physiologically-based pharmacokinetic (PBPK) modelling can help during drug and formulation development by providing quantitative predictions through a systems approach. The performance of three available PBPK software packages (GI-Sim, Simcyp (R), and GastroPlus (TM)) were evaluated by comparing simulated and observed pharmacokinetic (PK) parameters. Since the availability of input parameters was heterogeneous and highly variable, caution is required when interpreting the results of this exercise. Additionally, this prospective simulation exercise may not be representative of prospective modelling in industry, as API information was limited to sparse details. 43 active pharmaceutical ingredients (APIs) from the OrBiTo database were selected for the exercise. Over 4000 simulation output files were generated, representing over 2550 study arm-institution-software combinations and approximately 600 human clinical study arms simulated with overlap. 84% of the simulated study arms represented administration of immediate release formulations, 11% prolonged or delayed release, and 5% intravenous (i.v.). Higher percentages of i.v. predicted area under the curve (AUC) were within two-fold of observed (52.9%) compared to per oral (p.o.) (37.2%), however, F-oral and relative AUC (F-rel) between p.o. formulations and solutions were generally well predicted (64.7% and 75.0%). Predictive performance declined progressing from i.v. to solution and immediate release tablet, indicating the compounding error with each layer of complexity. Overall performance was comparable to previous large-scale evaluations. A general overprediction of AUC was observed with average fold error (AFE) of 1.56 over all simulations. AFE ranged from 0.0361 to 64.0 across the 43 APIs, with 25 showing overpredictions. Discrepancies between software packages were observed for a few APIs, the largest being 606, 171, and 81.7-fold differences in AFE between SimCYP and GI-Sim, however average performance was relatively consistent across the three software platforms.
|
|
| 17. |
- Modvig, S, et al.
(författare)
-
Minimal residual disease quantification by flow cytometry provides reliable risk stratification in T-cell acute lymphoblastic leukemia
- 2019
-
Ingår i: Leukemia. - : Nature Publishing Group. - 0887-6924 .- 1476-5551. ; 33:6, s. 1324-1336
-
Tidskriftsartikel (refereegranskat)abstract
- Minimal residual disease (MRD) measured by PCR of clonal IgH/TCR rearrangements predicts relapse in T-cell acute lymphoblastic leukemia (T-ALL) and serves as risk stratification tool. Since 10% of patients have no suitable PCR-marker, we evaluated flowcytometry (FCM)-based MRD for risk stratification. We included 274 T-ALL patients treated in the NOPHO-ALL2008 protocol. MRD was measured by six-color FCM and real-time quantitative PCR. Day 29 PCR-MRD (cut-off 10-3) was used for risk stratification. At diagnosis, 93% had an FCM-marker for MRD monitoring, 84% a PCR-marker, and 99.3% (272/274) had a marker when combining the two. Adjusted for age and WBC, the hazard ratio for relapse was 3.55 (95% CI 1.4-9.0, p = 0.008) for day 29 FCM-MRD ≥ 10-3 and 5.6 (95% CI 2.0-16, p = 0.001) for PCR-MRD ≥ 10-3 compared with MRD < 10-3. Patients stratified to intermediate-risk therapy on day 29 with MRD 10-4-<10-3 had a 5-year event-free survival similar to intermediate-risk patients with MRD < 10-4 or undetectable, regardless of method for monitoring. Patients with day 15 FCM-MRD < 10-4 had a cumulative incidence of relapse of 2.3% (95% CI 0-6.8, n = 59). Thus, FCM-MRD allows early identification of patients eligible for reduced intensity therapy, but this needs further studies. In conclusion, FCM-MRD provides reliable risk prediction for T-ALL and can be used for stratification when no PCR-marker is available.
|
|
| 18. |
- Nielsen, S. N., et al.
(författare)
-
Children with low-risk acute lymphoblastic leukemia are at highest risk of second cancers
- 2017
-
Ingår i: Pediatr Blood Cancer. - : Wiley. - 1545-5009 .- 1545-5017. ; 64:10
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe improved survival rates for childhood acute lymphoblastic leukemia (ALL) may be jeopardized by the development of a second cancer, which has been associated with thiopurine therapy. ProcedureWe retrospectively analyzed three sequential Nordic Society of Paediatric Haematology and Oncology's protocols characterized by increasing intensity of thiopurine-based maintenance therapy. We explored the risk of second cancer in relation to protocols, risk group, thiopurine methyltransferase (TPMT) activity, ALL high hyperdiploidy (HeH), and t(12;21)[ETV6/RUNX1]. ResultsAfter median 9.5 years (interquartile range, 5.4-15.3 yrs) of follow-up, 40 of 3,591 patients had developed a second cancer, of whom 38 had non-high-risk B-cell precursor ALL. Patients with standard-risk ALL, who received the longest maintenance therapy, had the highest adjusted hazard of second cancer (hazard ratio [HR], intermediate vs. standard risk: 0.16, 95% CI: 0.06-0.43, P < 0.001; HR, high vs. standard risk: 0.09, 95% CI: 0.02-0.49, P = 0.006); no significant effects of protocol, age, or white blood cell count at diagnosis, ALL HeH, or t(12;21)[ETV6/RUNX1] were observed. A subset analysis on the patients with standard-risk ALL did not show an increased hazard of second cancer from either HeH or t(12;21) (adjusted HR 2.02, 95% CI: 0.69-5.96, P = 0.20). The effect of low TPMT low activity was explored in patients reaching maintenance therapy in clinical remission (n = 3,368); no association with second cancer was observed (adjusted HR 1.43, 95% CI: 0.54-3.76, P = 0.47). ConclusionsThe rate of second cancer was generally highest in patients with low-risk ALL, but we could not identify a subset at higher risk than others.
|
|
| 19. |
|
|
| 20. |
|
|
| 21. |
|
|
| 22. |
|
|
| 23. |
- Abrahamsson, Johanna, 1990, et al.
(författare)
-
A Raman spectroscopic approach to investigate the production of biodiesel from soybean oil using 1-alkyl-3-methylimidazolium ionic liquids with intermediate chain length
- 2015
-
Ingår i: Applied Energy. - : Elsevier BV. - 1872-9118 .- 0306-2619. ; 154, s. 763-770
-
Tidskriftsartikel (refereegranskat)abstract
- We present a Raman spectroscopic study of the conversion of soybean oil into biodiesel by methanol using the lipase B enzyme pseudomonas cepacia as the bio-catalyst and 1-alkyl-3-methylimidazolium ionic liquids (CnC1Im) as co-solvents, where the alkyl chain length is varied from ethyl (n=2) to decyl (n=10). We have limited this study to a low reaction temperature, 40°C, and a low enzyme concentration to investigate the possibility of producing biodiesel with low energy and cost demands. We also demonstrate that Raman spectroscopy is a powerful and straightforward method to estimate the yield of the transesterification reaction, by analysis of the characteristic CO stretching mode found in the range ~1730-1750cm-1. Our results indicate that both reaction yield and reaction rate increase with the chain length, but also that for chains longer than decyl further improvements are marginal. We discuss these results from the viewpoint of local interactions and local structure of the investigated ionic liquids.
|
|
| 24. |
- Abrahamsson, Per, 1985, et al.
(författare)
-
Analysis of mesoscale effects in high-shear granulation through a computational fluid dynamics–population balance coupled compartment model
- 2018
-
Ingår i: Particuology. - : Elsevier BV. - 2210-4291 .- 1674-2001. ; 36, s. 1-12
-
Tidskriftsartikel (refereegranskat)abstract
- There is a need for mesoscale resolution and coupling between flow-field information and the evolution of particle properties in high-shear granulation. We have developed a modelling framework that compartmentalizes the high-shear granulation process based on relevant process parameters in time and space. The model comprises a coupled-flow-field and population-balance solver and is used to resolve and analyze the effects of mesoscales on the evolution of particle properties. A Diosna high-shear mixer was modelled with microcrystalline cellulose powder as the granulation material. An analysis of the flow-field solution and compartmentalization allows for a resolution of the stress and collision peak at the impeller blades. Different compartmentalizations showed the importance of resolving the impeller region, for aggregating systems and systems with breakage. An independent study investigated the time evolution of the flow field by changing the particle properties in three discrete steps that represent powder mixing, the initial granulation stage mixing and the late stage granular mixing. The results of the temporal resolution study show clear changes in collision behavior, especially from powder to granular mixing, which indicates the importance of resolving mesoscale phenomena in time and space.
|
|
| 25. |
- Abrahamsson, S., et al.
(författare)
-
Multifocus structured illumination microscopy for fast volumetric super-resolution imaging
- 2017
-
Ingår i: Biomedical Optics Express. - : OSA - The Optical Society. - 2156-7085. ; 8:9, s. 4135-4140
-
Tidskriftsartikel (refereegranskat)abstract
- We here report for the first time the synergistic implementation of structured illumination microscopy (SIM) and multifocus microscopy (MFM). This imaging modality is designed to alleviate the problem of insufficient volumetric acquisition speed in superresolution biological imaging. SIM is a wide-field super-resolution technique that allows imaging with visible light beyond the classical diffraction limit. Employing multifocus diffractive optics we obtain simultaneous wide-field 3D imaging capability in the SIM acquisition sequence, improving volumetric acquisition speed by an order of magnitude. Imaging performance is demonstrated on biological specimens.
|
|
| 26. |
- Abrahamsson, Thomas, et al.
(författare)
-
Microbiota in Functional Gastrointestinal Disorders in Infancy: Implications for Management
- 2017
-
Ingår i: INTESTINAL MICROBIOME: FUNCTIONAL ASPECTS IN HEALTH AND DISEASE. - : KARGER. - 9783318060317 - 9783318060300 ; , s. 107-115
-
Konferensbidrag (refereegranskat)abstract
- The complex and diverse intestinal microbiome is recognized as important in promoting human health. An altered gut microflora, referred to as dysbiosis, is increasingly recognized as having an etiologic role in a variety of conditions, including functional gastrointestinal disorders: colic in infants and irritable bowel syndrome in older children. Probiotics are defined as live microorganisms that, if ingested in sufficient amounts, restore microbial homeostasis and have a benefit on health. Randomized controlled trials indicate that probiotics can be effective in a variety of intestinal conditions, including colic and irritable bowel syndrome. Probiotics may promote gut microbial diversity, but timing of the intervention appears crucial. Strain-specific effects on colonization resistance, epithelial barrier integrity, modulation of signal transduction, impacts on innate and adaptive immune responses, and effects on visceral hyperalgesia likely explain the observed variability in various probiotic strains. In the future, probiotics are likely to be chosen for use in a defined clinical setting based on underlying mechanism(s) of action. The precise component of the probiotic agent mediating observed effects is the subject of current research. Unresolved issues relate to optimal dosages, timing of ingestion, single versus combination formulations, maintenance of viability in storage, and the merits of employing probiotic- derived products. (C) 2017 Nestec Ltd., Vevey/S. Karger AG, Basel
|
|
| 27. |
- Adolfsen Løhmann, DJ, et al.
(författare)
-
Associations between Pre-therapeutic Body Mass Index, Outcome and Cytogenetic Abnormalities in Pediatric Acute Myeloid Leukemia
- 2019
-
Ingår i: 38th NOPHO Annual meeting. Aalborg, Denmark 3-7 May.
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: Associations between body mass index (BMI), outcome and leukemia-related factors in children with acute myeloid leukemia (AML) are unclear. Aim: To investigate associations between pre-therapeutic BMI, cytogenetic abnormalities, and outcome in a large multinational cohort of children with AML. Methods: We included patients age 2–17 years, diagnosed with de novo AML from the five Nordic countries (2004–2016), Hong Kong (2007–2016), the Netherlands and Belgium (2010–2016), and Canada and USA (1995–2012). Cases with Down syndrome, acute promyelocytic leukemia, or isolated granulocytic sarcoma were excluded. Cases with missing data on pre-therapeutic BMI (n=7) were also excluded. BMI standard deviations score for age and sex was calculated and categorized according to the World Health Organization. Cumulative incidence functions, Cox regression and logistic regression were used to investigate associations. Results: In total, 867 patients were included. The median age was 10 years (range 2–17 years) and 53% were male. At diagnosis, 4% were underweight, 73% were healthy weight, 15% were overweight, and 9% were obese. Patients were treated on 17 different protocols with AAML0531, COG9421, NOPHO-AML 2004, DB AML-01 and NOPHO-DBH AML 2012 accounting for 79%. There was no difference in relapse risk, treatment-related mortality or overall mortality across BMI groups. The frequency of t(8;21) and inv(16) increased with increasing BMI. For obese patients, the sex, age and country adjusted odds ratio of having t(8;21) or inv(16) were 1.9 (95% confidence interval (CI) 1.1–3.4) and 2.8 (95% CI 1.3–5.8) respectively compared to healthy weight patients. Conclusion: This multi-institutional study of 867 pediatric patients with de novo AML did not confirm previous reports of associations between overweight and increased treatment-related or overall mortality in children. Obesity was associated with a higher frequency of t(8;21) and inv(16). AML cytogenetics appear to differ by BMI status.
|
|
| 28. |
- Albertsen, B. K., et al.
(författare)
-
Intermittent Versus Continuous PEG-Asparaginase to Reduce Asparaginase-Associated Toxicities: A NOPHO ALL2008 Randomized Study
- 2019
-
Ingår i: Journal of Clinical Oncology. - 0732-183X. ; 37:19, s. 1638-1646
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE Asparaginase is an essential drug in childhood acute lymphoblastic leukemia (ALL) therapy and is frequently given for months to obtain continuous asparagine depletion. We randomly assigned patients to continuous versus intermittent pegylated-asparaginase (PEG-asp) treatment, hypothesizing there would be decreased toxicity with unchanged efficacy. METHODS Children (median age, 4.2 years) treated for non-high-risk ALL according to the Nordic Society for Pediatric Hematology and Oncology ALL2008 protocol received five intramuscular PEG-asp injections (1,000 IU/m(2)) every two weeks and were then randomly assigned to additional three doses (6-week intervals [experimental arm], n = 309) versus 10 doses (2-week intervals [standard arm], n = 316). The primary end point was noninferior (6% margin) disease-free survival. Toxicity reduction was a secondary end point. Occurrence of asparaginase-associated hypersensitivity, pancreatitis, osteonecrosis, and thromboembolism were prospectively registered. RESULTS After a median follow-up of 4.1 years, the 5-year disease-free survival was 92.2% (95% CI, 88.6 to 95.8) and 90.8% (95% CI, 87.0 to 94.6) in the experimental and standard arms, respectively. The 3-year cumulative incidence of any first asparaginase-associated toxicity (hypersensitivity [n = 13]; osteonecrosis [n = 29]; pancreatitis [n = 24]; thromboembolism [n = 17]) was 9.3% in the experimental arm and 18.1% in the standard arm (P = .001). Asparaginase-associated toxicity reduction was confirmed in sex- and risk-group-adjusted Cox regression analysis stratified by age (>= 10 and < 10 years; hazard ratio, 0.48; P = .001). The experimental arm had the lowest incidences of all four toxicities, reaching significance for pancreatitis (6-month risk, 5.8% v 1.3%; P = .002). CONCLUSION The excellent cure rates and reduced toxicity risk support the use of intermittent PEG-asp therapy after the first 10 weeks in future childhood ALL trials that apply prolonged PEG-asp therapy.
|
|
| 29. |
- Bager, Ninna, et al.
(författare)
-
Complex and monosomal karyotype are distinct cytogenetic entities with an adverse prognostic impact in paediatric acute myeloid leukaemia : A NOPHO-DBH-AML study
- 2018
-
Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 183:4, s. 618-628
-
Tidskriftsartikel (refereegranskat)abstract
- Data on occurrence, genetic characteristics and prognostic impact of complex and monosomal karyotype (CK/MK) in children with acute myeloid leukaemia (AML) are scarce. We studied CK and MK in a large unselected cohort of childhood AML patients diagnosed and treated according to Nordic Society for Paediatric Haematology and Oncology (NOPHO)-AML protocols 1993-2015. In total, 800 patients with de novo AML were included. CK was found in 122 (15%) and MK in 41 (5%) patients. CK and MK patients were young (median age 2.1 and 3.3 years, respectively) and frequently had FAB M7 morphology (24% and 22%, respectively). Refractory disease was more common in MK patients (15% vs. 4%) and stem cell transplantation in first complete remission was more frequent (32% vs. 19%) compared with non-CK/non-MK patients. CK showed no association with refractory disease but was an independent predictor of an inferior event-free survival (EFS; hazard ratio [HR] 1.43, P = 0.03) and overall survival (OS; HR 1.48, P = 0.01). MK was associated with a poor EFS (HR 1.57, P = 0.03) but did not show an inferior OS compared to non-MK patients (HR 1.14, P = 0.62). In a large paediatric cohort, we characterized AML with non-recurrent abnormal karyotype and unravelled the adverse impact of CK and MK on prognosis.
|
|
| 30. |
- Bettucci, Ottavia, et al.
(författare)
-
Organic dye-sensitized solar cells containing alkaline iodide-based gel polymer electrolytes: Influence of cation size
- 2018
-
Ingår i: Physical Chemistry Chemical Physics. - : Royal Society of Chemistry (RSC). - 1463-9084 .- 1463-9076. ; 20:2, s. 1276-1285
-
Tidskriftsartikel (refereegranskat)abstract
- The electrolyte used in dye-sensitized solar cells (DSSCs) plays a key role in the process of current generation, and hence the analysis of charge-transfer mechanisms both in its bulk and at its interfaces with other materials is of fundamental importance. Because of solvent confinement, gel polymer electrolytes are more practical and convenient to use with respect to liquid electrolytes, but in-depth studies are still necessary to optimize their performances. In this work, gel polymer electrolytes of general formulation polyacrylonitrile (PAN)/ethylene carbonate (EC)/propylene carbonate (PC)/MI, where M + is a cation in the alkaline series Li-Cs, were prepared and used in DSSCs. Their ionic conductivities were determined by impedance analysis, and their temperature dependence showed Arrhenius behavior within the experimental window. FT-IR studies of the electrolytes confirmed the prevalence of EC coordination around the cations. Photo-anodes were prepared by adsorbing organic sensitizer D35 on nanocrystalline TiO 2 thin films, and employed to build DSSCs with the gel electrolytes. Nanosecond transient spectroscopy results indicated a slightly faster dye regeneration process in the presence of large cations (Cs + , Rb + ). Moreover, a negative shift of TiO 2 flat-band potential with the decreasing charge density of the cations (increasing size) was observed through Mott-Schottky analysis. In general, results indicate that cell efficiencies are mostly governed by photocurrent values, in turn depending on the conductivity increase with cation size. Accordingly, the best result was obtained with the Cs + -containing cell, although in this case a slight reduction of photovoltage compared to Rb + was observed.
|
|
| 31. |
|
|
| 32. |
- Brewick, P., et al.
(författare)
-
Hybrid Time/Frequency Domain Identification of Real Base-Isolated Structure
- 2016
-
Ingår i: Conference Proceedings of the Society for Experimental Mechanics Series. - Cham : Springer International Publishing. - 2191-5644 .- 2191-5652. - 9783319297514 ; 2, s. 303-311
-
Konferensbidrag (refereegranskat)abstract
- This paper presents a case study using hybrid time-and frequency-domain identifications in a synergistic manner to develop models of a full-scale experimental base-isolated structure. This four-story reinforced-concrete building on an isolation layer (of rubber bearings, elastic sliding bearings, passive metallic yielding dampers, and controllable oil dampers) was designed and constructed at the large-scale Japanese NIED E-Defense earthquake engineering laboratory. A variety of sensors, including accelerometers, were mounted within the structure to measure building response to shake table excitations. While the building was ultimately subjected to historical and synthetic ground motions, the recorded table and building accelerations during a number of random excitation tests are used to identify the structure's natural frequencies, damping ratios and mode shapes. The substantial damping provided by the isolation layer necessitates adopting a hybrid time-and frequency-domain approach for identification. The modes of the structure are separated by frequency content wherein lower frequency modes are identified using time domain approaches from the subspace identification family of methods and higher frequency modes are identified using frequency response functions. Individually, neither approach is able to successfully identify all of the desired modes but, through their combination, the modal properties of the structure are successfully characterized.
|
|
| 33. |
- Dahlgren, David, et al.
(författare)
-
Regional Intestinal Permeability of Three Model Drugs in Human
- 2016
-
Ingår i: Molecular Pharmaceutics. - : American Chemical Society (ACS). - 1543-8384 .- 1543-8392. ; 13:9, s. 3013-3021
-
Tidskriftsartikel (refereegranskat)abstract
- Currently there are only a limited number of determinations of human P-eff in the distal small intestine and none in the large intestine. This has hindered the validation of preclinical models with regard to absorption in the distal parts of the intestinal tract, which can be substantial for BCS class II-IV drugs, and drugs formulated into modified-release (MR) dosage forms. To meet this demand, three model drugs (atenolol, metoprolol, and ketoprofen) were dosed in solution intravenously, and into the jejunum, ileum, and colon of 14 healthy volunteers. The P-eff of each model drug was then calculated using a validated deconvolution method. The median P-eff of atenolol in the jejunum, ileum, and colon was 0.45, 0.15, and 0.013 X 10(-4) cm/s, respectively. The corresponding values for metoprolol were 1.72, 0.72, and 1.30 X 10(-4) cm/s, and for ketoprofen 8.85, 6.53, and 3.37 X 10(-4) cm/s, respectively. This is the first study where the human Peff of model drugs has been determined in all parts of the human intestinal tract in the same subjects. The jejunal values were similar to directly determined values using intestinal single-pass perfusion, indicating that the deconvolution method is a valid approach for determining regional P-eff. The values from this study will be highly useful in the validation of preclinical regional absorption models and in silico tools.
|
|
| 34. |
- Dellenmark-Blom, Michaela, 1983, et al.
(författare)
-
The Esophageal-Atresia-Quality-of-life Questionnaires: Feasibility, Validity and Reliability in Sweden and Germany.
- 2018
-
Ingår i: Journal of pediatric gastroenterology and nutrition. - 1536-4801. ; 67:4, s. 469-477
-
Tidskriftsartikel (refereegranskat)abstract
- Esophageal atresia (EA) is a rare malformation characterized of discontinuity of the esophagus, concurrent with or without a tracheoesophageal fistula (TEF). We report the feasibility validity and reliability of a condition-specific quality-of-life (QOL) tool for EA/TEF children, the age-adapted EA-QOL-questionnaires, when used in Sweden and Germany.A total of 124 families of children with EA/TEF participated in the study; 53 parents completed the EA-QOL-questionnaire for children aged 2 to 7 years; 62 children/71 parents the EA-QOL-questionnaire for children 8 to 17 years. Feasibility was determined from the percentage of missing item responses. Based on clinical data and previously validated generic QOL-instruments (PedsQL 4.0, DISABKIDS-12), the final EA-QOL scores were evaluated against hypotheses of validity (known-groups/concurrent/convergent) and reliability (internal consistency/retest reliability of scores for 3 weeks). Significant level was P < 0.05.In the questionnaire for EA/TEF children aged 2 to 7 years, 16/18 items were completed with missing values <6% (range 0%-7.5%), and in the questionnaire for 8 to 17-year-olds, 24/24 child-reported items (range 0%-4.8%) and 21/24 parent-reported items (range 0%-7.0%). In both age-specific EA-QOL-questionnaires, desirable standards for known-groups and concurrent validity were fulfilled; digestive symptoms and feeding difficulties negatively impacted EA-QOL-Total-scores (P < 0.001), and as hypothesized, in 2 to 7-year-olds, respiratory symptoms decreased EA-QOL-Total-scores (P=0.002). Correlations between the EA-QOL and generic QOL questionnaires supported convergent validity. Internal consistency reliability was satisfactory. The level of agreements of EA-QOL-scores between the field- and retest study were good to excellent.The overall psychometric performance of the EA-QOL-questionnaires for EA/TEF children is satisfactory and can enhance outcome evaluations in future research and clinical practice.
|
|
| 35. |
|
|
| 36. |
- Dzidic, Majda, et al.
(författare)
-
Oral microbiota maturation during the first 7 years of life in relation to allergy development
- 2018
-
Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : WILEY. - 0105-4538 .- 1398-9995. ; 73:10, s. 2000-2011
-
Tidskriftsartikel (refereegranskat)abstract
- Background Allergic diseases have become a major public health problem in affluent societies. Microbial colonization early in life seems to be critical for instructing regulation on immune system maturation and allergy development in children. Even though the oral cavity is the first site of encounter between a majority of foreign antigens and the immune system, the influence of oral bacteria on allergy development has not yet been reported. Objective Methods We sought to determine the bacterial composition in longitudinally collected saliva samples during childhood in relation to allergy development. Illumina sequencing of the 16S rDNA gene was used to characterize the oral bacterial composition in saliva samples collected at 3, 6, 12, 24 months, and 7 years of age from children developing allergic symptoms and sensitization (n = 47) and children staying healthy (n = 33) up to 7 years of age. Results Conclusion Children developing allergic disease, particularly asthma, had lower diversity of salivary bacteria together with highly divergent bacterial composition at 7 years of age, showing a clearly altered oral microbiota in these individuals, likely as a consequence of an impaired immune system during infancy. Moreover, the relative amounts of several bacterial species, including increased abundance of Gemella haemolysans in children developing allergies and Lactobacillus gasseri and L. crispatus in healthy children, were distinctive during early infancy, likely influencing early immune maturation. Early changes in oral microbial composition seem to influence immune maturation and allergy development. Future experiments should test the probiotic potential of L. gasseri and L. crispatus isolates.
|
|
| 37. |
- Gobbo, Marina, et al.
(författare)
-
Influence of Melatonin on the Proliferative and Apoptotic Responses of the Prostate under Normal and Hyperglycemic Conditions.
- 2015
-
Ingår i: Journal of Diabetes Research. - : Hindawi Limited. - 2314-6753 .- 2314-6745. ; 2015
-
Tidskriftsartikel (refereegranskat)abstract
- The antitumor properties of melatonin (MLT) are known for prostate cancer cells. This study investigated whether MLT affects prostate maturation and interferes with tissue injuries induced by diabetes. MLT was administered to Wistar rats from 5 weeks of age in the drinking water (10 μg/kg b.w.), and diabetes was induced at the 13th week by streptozotocin (4.5 mg/100g b.w., i.p.). The animals were euthanized in the 14th and 21st weeks. MLT reduced the immunostained cells for androgen receptor (AR) by 10% in younger rats. Diabetes decreased cell proliferation and increased apoptosis. MLT treatment impeded apoptosis (p = 0.02) and augmented proliferation (p = 0.0008) and PCNA content in prostate following long-term diabetes due to restoration of testosterone levels and expression of melatonin receptor type 1B. The effect of MLT (500 µM, 5 mM, and 10 mM) on androgen-dependent (22Rv1) and androgen-independent (PC3) cancer cells and human prostate epithelial cells (PNTA1) under normal and hyperglycemic conditions (HG, 450 mg/dL) was analyzed. Contrary to PNTA1 and 22Rv1 cells, MLT improved the proliferation of PC3 cells in hyperglycemic medium. The combined data indicated that MLT had proliferative and antiapoptotic effects in prostate cells subjected to HG levels and it seems to involve specific MLT pathways rather than AR.
|
|
| 38. |
- Gray, Victor, 1988, et al.
(författare)
-
CdS/ZnS core-shell nanocrystal photosensitizers for visible to UV upconversion
- 2017
-
Ingår i: Chemical Science. - : Royal Society of Chemistry (RSC). - 2041-6539 .- 2041-6520. ; 8:8, s. 5488-5496
-
Tidskriftsartikel (refereegranskat)abstract
- Herein we report the first example of nanocrystal (NC) sensitized triplet-triplet annihilation based photon upconversion from the visible to ultraviolet (vis-to-UV). Many photocatalyzed reactions, such as water splitting, require UV photons in order to function efficiently. Upconversion is one possible means of extending the usable range of photons into the visible. Vis-to-UV upconversion is achieved with CdS/ZnS core-shell NCs as the sensitizer and 2,5-diphenyloxazole (PPO) as annihilator and emitter. The ZnS shell was crucial in order to achieve any appreciable upconversion. From time resolved photoluminescence and transient absorption measurements we conclude that the ZnS shell affects the NC and triplet energy transfer (TET) from NC to PPO in two distinct ways. Upon ZnS growth the surface traps are passivated thus increasing the TET. The shell, however, also acts as a tunneling barrier for TET, reducing the efficiency. This leads to an optimal shell thickness where the upconversion quantum yield (Phi(UC)') is maximized. Here the maximum Phi(UC)' was determined to be 5.2 +/- 0.5% for 4 monolayers of ZnS shell on CdS NCs.
|
|
| 39. |
|
|
| 40. |
- Ho, Son, et al.
(författare)
-
Proof-Producing Synthesis of CakeML with I/O and Local State from Monadic HOL Functions
- 2018
-
Ingår i: Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics). - Cham : Springer International Publishing. - 1611-3349 .- 0302-9743. ; 10900, s. 646-662
-
Konferensbidrag (refereegranskat)abstract
- We introduce an automatic method for producing stateful ML programs together with proofs of correctness from monadic functions in HOL. Our mechanism supports references, exceptions, and I/O operations, and can generate functions manipulating local state, which can then be encapsulated for use in a pure context. We apply this approach to several non-trivial examples, including the type inferencer and register allocator of the otherwise pure CakeML compiler, which now benefits from better runtime performance. This development has been carried out in the HOL4 theorem prover.
|
|
| 41. |
|
|
| 42. |
- Højfeldt, Sofie G., et al.
(författare)
-
Genetic predisposition to PEG-asparaginase hypersensitivity in children treated according to NOPHO ALL2008
- 2019
-
Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 184:3, s. 405-417
-
Tidskriftsartikel (refereegranskat)abstract
- Asparaginase is essential in childhood acute lymphoblastic leukaemia (ALL) treatment, however hypersensitivity reactions to pegylated asparaginase (PEG-asparaginase) hampers anti-neoplastic efficacy. Patients with PEG-asparaginase hypersensitivity have been shown to possess zero asparaginase enzyme activity. Using this measurement to define the phenotype, we investigated genetic predisposition to PEG-asparaginase hypersensitivity in a genome-wide association study (GWAS). From July 2008 to March 2016, 1494 children were treated on the Nordic Society of Paediatric Haematology and Oncology ALL2008 protocol. Cases were defined by clinical hypersensitivity and no enzyme activity, controls had enzyme activity ≥ 100 iu/l and no hypersensitivity symptoms. PEG-asparaginase hypersensitivity was reported in 13·8% (206/1494) of patients. Fifty-nine cases and 772 controls fulfilled GWAS inclusion criteria. The CNOT3 variant rs73062673 on 19q13.42, was associated with PEG-asparaginase allergy (P = 4·68 × 10-8 ). We further identified two signals on chromosome 6 in relation to HLA-DQA1 (P = 9·37 × 10-6 ) and TAP2 (P = 1·59 × 10-5 ). This study associated variants in CNOT3 and in the human leucocyte antigen (HLA) region with PEG-asparaginase hypersensitivity, suggesting that not only genetic variations in the HLA region, but also regulation of these genes are of importance in the biology of this toxicity. Furthermore, our study emphasizes the importance of using asparaginase enzyme activity measurements to identify PEG-asparaginase hypersensitivity.
|
|
| 43. |
- Johnson-Henry, Kathene C., et al.
(författare)
-
Probiotics, Prebiotics, and Synbiotics for the Prevention of Necrotizing Enterocolitis
- 2016
-
Ingår i: ADVANCES IN NUTRITION. - : AMER SOC NUTRITION-ASN. - 2161-8313. ; 7:5, s. 928-937
-
Forskningsöversikt (refereegranskat)abstract
- Necrotizing enterocolitis (NEC) is a devastating intestinal disease in preterm infants characterized by barrier disruption, intestinal microbial dysbiosis, and persistent inflammation of the colon, which results in high mortality rates. Current strategies used to manage this disease are not sufficient, although the use of human breast milk reduces the risk of NEC. Mothers milk is regarded as a fundamental nutritional source for neonates, but pasteurization of donor breast milk affects the composition of bioactive compounds. Current research is evaluating the benefits and potential pitfalls of adding probiotics and prebiotics to pasteurized milk so as to improve the functionality of the milk and thereby reduce the burden of illness caused by NEC. Probiotics (live micro-organisms that confer health to the host) and prebiotics (nondigestible oligosaccharides that stimulate the growth of healthy bacteria) are functional foods known to mediate immune responses and modulate microbial populations in the gut. Clinical research shows strain-and compound specific responses when probiotics or prebiotics are administered in conjunction with donor breast milk for the prevention of NEC. Despite ongoing controversy surrounding optimal treatment strategies, randomized controlled studies are now investigating the use of synbiotics to reduce the incidence and severity of NEC. Synbiotics, a combination of probiotics and prebiotics, have been proposed to enhance beneficial health effects in the intestinal tract more than either agent administered alone. This review considers the implications of using probiotic-, prebiotic-, and synbiotic-supplemented breast milk as a strategy to prevent NEC and issues that could be encountered with the preparations.
|
|
| 44. |
|
|
| 45. |
- Lennernäs, Hans, et al.
(författare)
-
In Vivo Predictive Dissolution (IPD) and Biopharmaceutical Modeling and Simulation : Future Use of Modern Approaches and Methodologies in a Regulatory Context
- 2017
-
Ingår i: Molecular Pharmaceutics. - : American Chemical Society (ACS). - 1543-8384 .- 1543-8392. ; 14:4, s. 1307-1314
-
Tidskriftsartikel (refereegranskat)abstract
- The overall objective of OrBiTo, a project within Innovative Medicines Initiative (IMI), is to streamline and optimize the development of orally administered drug products through the creation and efficient application of biopharmaceutics tools. This toolkit will include both experimental and computational Models developed on improved understanding of the highly dynamic gastrointestinal (GI) physiology relevant to the GI absorption of drug products in both fasted and fed states. A part of the annual OrBiTo meeting in 2015 was dedicated: to the presentation of the most recent progress in the development of the regulatory use of PBPK in silk() modeling, in vivo predictive dissolution (IPD) tests, and their application to biowaivers. There are still several areas for improvement of in vitro dissolution testing by means of generating results relevant for the intraluminal conditions in the GI tract. The major opportunity is probably in combining IPD testing and physiologically based in silico models where the in vitro data provide input to the absorption predictions. The OrBiTo project and other current research projects include-definition of test media representative for the more distal parts of the GI tract, models capturing supersaturation and precipitation phenomena, and influence of motility waves on shear and other forces of hydrodynamic origin, addressing the inter individual variability in composition and characteristics of GI fluids, food effects, definition of biorelevant buffer systems, and intestinal water volumes. In conclusion, there is currently a mismatch between the extensive industrial usage of modern in vivo predictive tools and very limited inclusion of such data in regulatory files. However, there is a great interest among all stakeholders to introduce recent progresses in prediction of in vivo GI drug absorption into regulatory context.
|
|
| 46. |
- Levinsen, Mette, et al.
(författare)
-
Leukemic blasts are present at low levels in spinal fluid in one-third of childhood acute lymphoblastic leukemia cases
- 2016
-
Ingår i: Pediatric Blood & Cancer. - : Wiley. - 1545-5009 .- 1545-5017. ; 63:11, s. 1935-1942
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Central nervous system (CNS) involvement is associated with relapse in childhood acute lymphoblastic leukemia (ALL) and is a diagnostic challenge. Procedure: In a Nordic/Baltic prospective study, we assessed centralized flow cytometry (FCM) of locally fixed cerebrospinal fluid (CSF) samples versus local conventional cytospin-based cytology (CC) for detecting leukemic cells and evaluating kinetics of elimination of leukemic cells in CSF. Results: Among 300 patients with newly diagnosed ALL, 87 (29%) had CSF involvement by FCM, while CC was positive in 30 (10%) of 299 patients with available CC data (P < 0.001). Patients with FCM+/CC+ had higher CSF leukemic blast counts compared to patients positive by FCM only (medians: 0.10 vs. 0.017 leukemic blasts/μl, P = 0.006). Patients positive by FCM had higher white blood cell counts in peripheral blood than patients negative by FCM (medians: 45 × 109/l vs. 10 × 109/l, P < 0.001), were younger (medians: 3 years vs. 4 years, P = 0.03), and more frequently had T-cell ALL (18/87 vs. 16/213, P = 0.001). At treatment day 15, five of 52 patients (10%) who had CSF positive by FCM at diagnosis remained so despite at least two doses of weekly intrathecal chemotherapy. Conclusions: Longer follow-up is needed to clarify whether FCM positivity has prognostic significance and is an indicator for intensified CNS-directed therapy.
|
|
| 47. |
- Levinsen, Mette, et al.
(författare)
-
Myelotoxicity after high-dose methotrexate in childhood acute leukemia is influenced by 6-mercaptopurine dosing but not by intermediate thiopurine methyltransferase activity
- 2015
-
Ingår i: Cancer Chemotherapy and Pharmacology. - : Springer Science and Business Media LLC. - 0344-5704 .- 1432-0843. ; 75:1, s. 59-66
-
Tidskriftsartikel (refereegranskat)abstract
- Through enhancement of 6-mercaptopurine (6MP) bioavailability and inhibition of purine de novo synthesis, high-dose methotrexate (HD-MTX) may increase incorporation into DNA of 6-thioguanine nucleotides, the cytotoxic metabolites of 6MP. Patients with intermediate activity of thiopurine methyltransferase (TPMTIA) have higher cytosol 6-thioguanine nucleotide levels. We investigated toxicity following HD-MTX during MTX/6MP maintenance therapy in relation to 6MP and TPMT. Using linear mixed models, we explored myelo- and hepatotoxicity in relation to 6MP dosage and TPMT phenotype following 1,749 HD-MTX courses to 411 children with acute lymphoblastic leukemia on maintenance therapy. The degree of myelosuppression following HD-MTX was similar for patients with TPMTIA and patients with high TPMT activity (TPMTHA), when HD-MTX started with same blood counts and 6MP doses. However, since TPMTIA had lower blood counts at initiation of HD-MTX compared with TPMTHA patients (median WBC 2.8 vs. 3.3 x 10(9)/L, P = 0.01; median ANC 1.4 vs. 1.7 x 10(9)/L, P = 0.02), TPMTIA continued to have lower WBC and ANC levels compared with TPMTHA during all 28 days after HD-MTX [relative difference 9 % (95 % CI 2-17), P = 0.02 and 21 % (95 % CI 6-39), P = 0.005]. Still, the fractional decrease in WBC and ANC levels after HD-MTX did not differ between TPMTIA and TPMTHA patients (P = 0.47; P = 0.38). The degree of leukopenia, neutropenia, thrombocytopenia and rise in aminotransferases were all significantly related to 6MP dose (P < 0.001 for all analyses). For both TPMTIA and TPMTHA patients, dose of 6MP prior to HD-MTX should be guided by pre-HD-MTX blood counts, but not by TPMT activity.
|
|
| 48. |
|
|
| 49. |
- Lockowandt, C., et al.
(författare)
-
The stratospheric balloon mission PoGO+ from Esrange to Victoria Island, Canada
- 2017
-
Ingår i: AIAA Balloon Systems Conference, 2017. - Reston, Virginia : American Institute of Aeronautics and Astronautics.
-
Konferensbidrag (refereegranskat)abstract
- PoGO is a stratospheric balloon project with a cosmic ray experiment from KTH, Stockholm, Sweden. The PoGO+ mission was launched on July 12th, 2016 for a 7 day flight from Sweden to Canada. The payload mass was 1728 kg and an Aerostar SF-39.57 balloon was used to reach the float altitude of 40 km. In 2013 a similar experiment flew from Esrange to Norilsk in Russia in a circumpolar flight that lasted 2 weeks. That balloon mission was called PoGOLite. The experiment on PoGO+ was a balloon-borne hard X-ray polarimeter operating in the 25 - 240 keV energy band from a stabilized observation platform. Observations were conducted from a stabilized stratospheric balloon platform at an altitude of approximately 40 km. The primary targets were the Crab - a pulsar and associated wind nebula in the constellation of Taurus, 6500 light years from Earth, and Cygnus X-1 - a black hole binary system. A custom attitude control system kept the polarimeter field-of-view aligned to targets of interest, compensating for sidereal motion and perturbations such as torsional forces in the balloon rigging. After a launch at 03:17 UTC, the balloon reached float altitude after more than 5 hours, due to a cold stratosphere with slow ascent. A slower than anticipated wind took the balloon over the Atlantic for a landing in Canada on July 18th at 22:26 UTC. Landing latitude was 71.84747 N, longitude 110.885 E on Victoria Island. The mission was very successful with all systems both scientific and support and balloon systems working nominal during the complete flight. A huge amount of scientific data was collected during the flight that are analyzed. The landing and recovery was performed nominal and the scientific data were recovered and delivered to the science team within 12 days after landing. The mission was managed by SSC and SSC was also responsible for the gondola structure, housekeeping and communication systems, power systems and of the balloon flight systems. SSC was handling the launch, flight and recovery operations. KTH was responsible for the instrument, X-ray polarimeter, including all subsystems for controlling and monitoring the systems including thermal management. DST Control was responsible for the dual axis pointing system. New Mexico State University, USA, was delivering part of the balloon flight systems.
|
|
| 50. |
- MacGregor-Ramiasa, M., et al.
(författare)
-
Magnetic alignment of nontronite dispersions
- 2015
-
Ingår i: Applied Clay Science. - : Elsevier BV. - 0169-1317. ; 116-117, s. 167-174
-
Tidskriftsartikel (refereegranskat)abstract
- The time dependent alignment of exfoliated nontronite dispersions subjected to moderate magnetic field strengths (B.
|
|
