| 21. |
- Handl, Verena, et al.
(författare)
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Continuous iontronic chemotherapy reduces brain tumor growth in embryonic avian in vivo models
- 2024
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Ingår i: Journal of Controlled Release. - : ELSEVIER. - 0168-3659 .- 1873-4995. ; 369, s. 668-683
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Tidskriftsartikel (refereegranskat)abstract
- Local and long-lasting administration of potent chemotherapeutics is a promising therapeutic intervention to increase the efficiency of chemotherapy of hard-to-treat tumors such as the most lethal brain tumors, glioblastomas (GBM). However, despite high toxicity for GBM cells, potent chemotherapeutics such as gemcitabine (Gem) cannot be widely implemented as they do not efficiently cross the blood brain barrier (BBB). As an alternative method for continuous administration of Gem, we here operate freestanding iontronic pumps - "GemIPs" - equipped with a custom-synthesized ion exchange membrane (IEM) to treat a GBM tumor in an avian embryonic in vivo system. We compare GemIP treatment effects with a topical metronomic treatment and observe that a remarkable growth inhibition was only achieved with steady dosing via GemIPs. Daily topical drug administration (at the maximum dosage that was not lethal for the embryonic host organism) did not decrease tumor sizes, while both treatment regimes caused S-phase cell cycle arrest and apoptosis. We hypothesize that the pharmacodynamic effects generate different intratumoral drug concentration profiles for each technique, which causes this difference in outcome. We created a digital model of the experiment, which proposes a fast decay in the local drug concentration for the topical daily treatment, but a long-lasting high local concentration of Gem close to the tumor area with GemIPs. Continuous chemotherapy with iontronic devices opens new possibilities in cancer treatment: the long-lasting and highly local dosing of clinically available, potent chemotherapeutics to greatly enhance treatment efficiency without systemic side-effects. Significance statement: Iontronic pumps (GemIPs) provide continuous and localized administration of the chemotherapeutic gemcitabine (Gem) for treating glioblastoma in vivo. By generating high and constant drug concentrations near the vascularized growing tumor, GemIPs offer an efficient and less harmful alternative to systemic administration. Continuous GemIP dosing resulted in remarkable growth inhibition, superior to daily topical Gem application at higher doses. Our digital modelling shows the advantages of iontronic chemotherapy in overcoming limitations of burst release and transient concentration profiles, and providing precise control over dosing profiles and local distribution. This technology holds promise for future implants, could revolutionize treatment strategies, and offers a new platform for studying the influence of timing and dosing dependencies of already -established drugs in the fight against hard -to -treat tumors.
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| 22. |
- Holmquist, Björn, et al.
(författare)
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Approximating Noncentral Chi-Squared to the Moments and Distribution of the Likelihood Ratio Statistic for Multinomial Goodness of Fit
- 2020
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Ingår i: Recent Developments in Multivariate and Random Matrix Analysis : Festschrift in Honour of Dietrich von Rosen - Festschrift in Honour of Dietrich von Rosen. - Cham : Springer International Publishing. - 9783030567736 - 9783030567729
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Bokkapitel (refereegranskat)abstract
- The chi-square distribution is often assumed to hold for the asymptotic distribution of two times the log likelihood ratio statistic under the null hypothesis. Approximations are derived for the mean and variance of G2, the likelihood ratio statistic for testing goodness of fit in a s category multinomial distribution. The first two moments of G2 are used to fit the distribution of G2 to a noncentral chi-square distribution. The fit is generally better than earlier attempts to fit to scaled versions of asymptotic central chi-square distributions. The results enlighten the complex role of the dimension of the multivariate variable in relation to the sample size, for asymptotic likelihood ratio distribution results to hold.
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| 23. |
- Högdahl, Karin, et al.
(författare)
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Continental margin magmatism and migmatisation in the west-central Fennoscandian Shield
- 2008
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Ingår i: Lithos. - : Elsevier BV. - 0024-4937 .- 1872-6143. ; 102:3-4, s. 435-459
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Tidskriftsartikel (refereegranskat)abstract
- The Ljusdal Batholith (LjB) is a major component of the central Svecofennian Domain in Sweden. It is separated from the Bothnian Basin to the north by the 1.82-1.80 Cia crustal-scale Hassela Shear Zone (HSZ). The LjB has emplacement ages of 1.86-1.84 Cia, is mainly alkali-calcic, metaluminous, has epsilon(Nd) values between -0.3 and + 1.2 and was formed in a magmatic arc setting. During the Svecokarelian orogeny the LjB was affected by at least three fold episodes. Large-scale folded screens of migmatised metasedimentary rocks occur in the eastern part of the batholith, and to the north of the HSZ, there is a 50 km wide diatexite belt. The Transition Belt (TrB), consisting of 1.88-1.85 Ga granitoids, is located at the northwestern extension of this belt. A calc-alkaline and peraluminous composition combined with negative epsilon(Nd) values (- 1.7 to -0.8) indicates a large proportion of metasediments in the source for these granitoids. U-Pb SIMS data on zircon rims from migmatites and leucogranites to the north and east of LjB yield ages of 1.87-1.86 Ga, i.e. coeval with the granitoids of the LjB and the TrB. There is thus a close relationship between the LjB, the TrB and the migmatites in both space and time. Syn-migmatitic shearing along the HSZ indicates that a proto-HSZ was initiated already at c. 1.86 Ga, and the location of the proto-HSZ is inferred to be controlled by two older nuclei present in the lower parts of the crust. As crustal-scale shear zone systems are known to act as ascent pathways for sheet-like flow in active orogenies the TrB may represents accumulations of melts that were attracted and extracted by the proto-HSZ and intruded in a block that was not pervasively affected by subsequent shear along the HSZ. An active continental margin setting for the LjB implies subduction at c. 1.86 Ga, and provides a heat source for both the migmatites and the TrB. A later migmatisation at 1.82 Ga has been recorded to the south of the HSZ. Within the LjB the 1.82 Ga stromatic migmatites are folded by F-2 folds, and the fabric is truncated by 1.80 Cia pegmatites.
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| 24. |
- Jakobsson, Martin, et al.
(författare)
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Potential links between Baltic Sea submarine terraces and groundwater seeping
- 2020
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Ingår i: Earth Surface Dynamics. - : Copernicus GmbH. - 2196-6311 .- 2196-632X. ; 8:1, s. 1-15
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Tidskriftsartikel (refereegranskat)abstract
- Submarine groundwater discharge (SGD) influences ocean chemistry, circulation, and the spreading of nutrients and pollutants; it also shapes sea floor morphology. In the Baltic Sea, SGD was linked to the development of terraces and semicircular depressions mapped in an area of the southern Stockholm archipelago, Sweden, in the 1990s. We mapped additional parts of the Stockholm archipelago, areas in Blekinge, southern Sweden, and southern Finland using high-resolution multibeam sonars and sub-bottom profilers to investigate if the sea floor morphological features discovered in the 1990s are widespread and to further address the hypothesis linking their formation to SGD. Sediment coring and sea floor photography conducted with a remotely operated vehicle (ROV) and divers add additional information to the geophysical mapping results. We find that terraces, with general bathymetric expressions of about 1 m and lateral extents of sometimes > 100 m, are widespread in the surveyed areas of the Baltic Sea and are consistently formed in glacial clay. Semicircular depressions, however, are only found in a limited part of a surveyed area east of the island of Asko, southern Stockholm archipelago. While submarine terraces can be produced by several processes, we interpret our results to be in support of the basic hypothesis of terrace formation initially proposed in the 1990s; i.e. groundwater flows through siltier, more permeable layers in glacial clay to discharge at the sea floor, leading to the formation of a sharp terrace when the clay layers above seepage zones are undermined enough to collapse. By linking the terraces to a specific geologic setting, our study further refines the formation hypothesis and thereby forms the foundation for a future assessment of SGD in the Baltic Sea that may use marine geological mapping as a starting point. We propose that SGD through the submarine sea floor terraces is plausible and could be intermittent and linked to periods of higher groundwater levels, implying that to quantify the contribution of freshwater to the Baltic Sea through this potential mechanism, more complex hydrogeological studies are required.
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| 25. |
- Johansson, Eric, et al.
(författare)
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Quality of life after orthognathic surgery in Swedish patients : a register-based cohort
- 2024
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Ingår i: Clinical and Experimental Dental Research. - : John Wiley & Sons. ; 10:4
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Tidskriftsartikel (refereegranskat)abstract
- Materials and Methods: Patients subjected to orthognathic surgery due to dentofacial deformity (DFD) and registered in the National Register of Orthognathic Surgery (NROK) in Sweden between 2017 and 2020 were eligible for inclusion in this study. The Swedish-validated Orthognathic Quality of Life Questionnaire (S-OQLQ) was used to evaluate patient quality of life before and after surgery. The S-OQLQ measured each patient's subjective experience regarding social aspects.Results: Eighty-four participants were included in this cohort study, including 45 men (mean age 24.7 years), 48 women (mean age 23.4 years), and eight patients who stated no gender. Women generally graded several aspects of the S-OQLQ higher than men, including facial aesthetics p = 0.029), oral function (p < 0.001), and awareness of facial deformity (p = 0.0054). For all domains of the questionnaire (social, facial aesthetics, function, and awareness), a significant improvement was seen 6–24 months after surgery (p < 0.001). Women rated improvement of function and awareness of facial deformity higher than men (p < 0.001 and p = 0.039, respectively).Conclusion: Quality of life aspects of orthognathic surgery have a strong impact on the treatment outcome. Although functional impairment is often considered a major indication for surgery, the social and aesthetic influence of DFD is highly rated by patients, whereas pain is not an issue before or after treatment.
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| 26. |
- Johansson, Eric, et al.
(författare)
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Quality of Life After Orthognathic Surgery in Swedish Patients: A Register-Based Cohort
- 2024
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Ingår i: CLINICAL AND EXPERIMENTAL DENTAL RESEARCH. - : WILEY. - 2057-4347. ; 10:4
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Tidskriftsartikel (refereegranskat)abstract
- Objective: This study aimed to evaluate the effect of orthognathic surgery on quality of life among Swedish patients. Materials and Methods: Patients subjected to orthognathic surgery due to dentofacial deformity (DFD) and registered in the National Register of Orthognathic Surgery (NROK) in Sweden between 2017 and 2020 were eligible for inclusion in this study. The Swedish-validated Orthognathic Quality of Life Questionnaire (S-OQLQ) was used to evaluate patient quality of life before and after surgery. The S-OQLQ measured each patient's subjective experience regarding social aspects. Results: Eighty-four participants were included in this cohort study, including 45 men (mean age 24.7 years), 48 women (mean age 23.4 years), and eight patients who stated no gender. Women generally graded several aspects of the S-OQLQ higher than men, including facial aesthetics p = 0.029), oral function (p < 0.001), and awareness of facial deformity (p = 0.0054). For all domains of the questionnaire (social, facial aesthetics, function, and awareness), a significant improvement was seen 6-24 months after surgery (p < 0.001). Women rated improvement of function and awareness of facial deformity higher than men (p < 0.001 and p = 0.039, respectively). Conclusion: Quality of life aspects of orthognathic surgery have a strong impact on the treatment outcome. Although functional impairment is often considered a major indication for surgery, the social and aesthetic influence of DFD is highly rated by patients, whereas pain is not an issue before or after treatment.
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| 27. |
- Johansson, Martin, et al.
(författare)
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MAX IV 3 GeV storage ring magnet block production series measurement results
- 2015
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Ingår i: 6th International Particle Accelerator Conference, IPAC 2015. - 9783954501687 ; , s. 3069-3071
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Konferensbidrag (refereegranskat)abstract
- The magnet design of the MAX IV 3 GeV storage ring replaces the conventional support girder + discrete magnets scheme of previous third-generation synchrotron radiation light sources with a compact (Ø25 mm aperture) integrated design having several consecutive magnet elements precision-machined out of a common solid iron block. The production series of 140 integrated magnet block units, which was totally outsourced to industry, was completed mid-2014. This article presents mechanical and magnetic field measurement results of the full production series.
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| 28. |
- Johansson, Martin, et al.
(författare)
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MAX IV 3 GeV storage ring magnet block production series measurement results
- 2016
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Ingår i: IPAC 2016 - Proceedings of the 7th International Particle Accelerator Conference. - 9783954501472 ; , s. 1157-1159
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Konferensbidrag (refereegranskat)abstract
- The MAX IV 3 GeV storage ring magnets are integrated "magnet block" units consisting of several consecutive magnet elements precision-machined out of a common solid iron block. In the 3 GeV ring, there are 140 magnet blocks containing a total of 1320 magnet elements. During the manufacturing phase of the project, a field measurement was performed for each magnet element, by Hall probe and/or by rotating coil. This article presents an overview of the magnetic field measurement results that were obtained for the full production series.
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| 29. |
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| 30. |
- Kovács, Anikó, 1961, et al.
(författare)
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Effect of Radiotherapy After Breast-Conserving Surgery Depending on the Presence of Tumor-Infiltrating Lymphocytes : A Long-Term Follow-Up of the SweBCG91RT Randomized Trial
- 2019
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Ingår i: Journal of Clinical Oncology. - 0732-183X. ; 37:14, s. 1179-87
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The effects of radiotherapy (RT) on the basis of the presence of stromal tumor infiltrating lymphocytes (TILs) have not been studied. The purpose of this study was to analyze the association of TILs with the effect of postoperative RT on ipsilateral breast tumor recurrence (IBTR) in a large randomized trial. METHODS: In the SweBCT91RT (Swedish Breast Cancer Group 91 Radiotherapy) trial, 1,178 patients with breast cancer stage I and II were randomly assigned to breast-conserving surgery plus postoperative RT or breast-conserving surgery only and followed for a median of 15.2 years. Tumor blocks were retrieved from 1,003 patients. Stromal TILs were assessed on whole-section hematoxylin-eosin-stained slides using a dichotomized cutoff of 10%. Subtypes were scored using immunohistochemistry on tissue microarray. In total, 936 patients were evaluated. RESULTS: Altogether, 670 (71%) of patients had TILs less than 10%. In a multivariable regression analysis with IBTR as dependent variable and RT, TILs, subtype, age, and grade as independent variables, RT (hazard ratio [HR], 0.42; 95% CI, 0.29 to 0.61; P < .001), high TILs (HR, 0.61; 95% CI, 0.39 to 0.96, P = .033) grade (3 v 1; HR, 2.17; 95% CI, 1.08 to 4.34; P = .029), and age (≥ 50 v < 50 years; HR, 0.55; 95% CI, 0.38 to 0.80; P = .002) were predictive of IBTR. RT was significantly beneficial in the low TILs group (HR, 0.37; 95% CI, 0.24 to 0.58; P < .001) but not in the high TILs group (HR, 0.58; 95% CI, 0.28 to 1.19; P = .138). The test for interaction between RT and TILs was not statistically significant (P = .317). CONCLUSION: This study shows that high values of TILs in the primary tumor independently seem to reduce the risk for an IBTR. Our findings further suggest that patients with breast cancer with low TILs may derive a larger benefit from RT regarding the risk of IBTR.
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